SCHOOL OF BIO AND CHEMICAL ENGINEERING

DEPARTMENT OF BIOTECHNOLOGY

UNIT – I – Bioethics Biosafety and IPR – SBTA7011

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 UNIT 1 - BIOETHICS
Bioethics-Introduction. Animal Ethics, Animal Rights, Biotechnology and Ethics, Ethical
issues related to research in embryonic stem cell cloning. Ethical, Legal and Social
Implications (ELSI) of Human Genome Project.
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Bioethics
• Bioethics is the study of the typically controversial ethical issues emerging from new
situations and possibilities brought about by advances in biology and medicine.
• It is also moral discernment as it relates to medical policy and practice.
• Bioethicists are concerned with the ethical questions that arise in the relationships
among life sciences, biotechnology, medicine, politics, law, and philosophy.
• It also includes the study of the more commonplace questions of values ("the ethics of
the ordinary") which arise in primary care and other branches of medicine.

Etymology
• The term Bioethics (Greek bios, life; ethos, behavior) was coined in 1926 by Fritz Jahr,
who "anticipated many of the arguments and discussions now current in biological
research involving animals" in an article about the "bioethical imperative," as he called
it, regarding the scientific use of animals and plants.
• In 1970, the American biochemistVan Rensselaer Potter also used the term with a
broader meaning including solidarity towards the biosphere, thus generating a "global
ethics," a discipline representing a link between biology, ecology, medicine and human
values in order to attain the survival of both human beings and other animal species.

Purpose and scope

• The field of bioethics has addressed a broad swathe of human inquiry, ranging from
debates over the boundaries of life (e.g. abortion, euthanasia), surrogacy, the allocation
of scarce health care resources (e.g. organ donation, health care rationing) to the right
to refuse medical care for religious or cultural reasons.
• Bioethicists often disagree among themselves over the precise limits of their discipline,
debating whether the field should concern itself with the ethical evaluation of all
questions involving biology and medicine, or only a subset of these questions.[4]

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• Some bioethicists would narrow ethical evaluation only to the morality of medical
treatments or technological innovations, and the timing of medical treatment of
humans. Others would broaden the scope of ethical evaluation to include the morality
of all actions that might help or harm organisms capable of feeling fear.

Scope
The scope of bioethics can expand with biotechnology, including cloning, gene
therapy, life extension, human genetic engineering, astroethics and life in space,[5] and
manipulation of basic biology through altered DNA, XNA and proteins.[6] These
developments will affect future evolution, and may require new principles that address
life at its core, such as biotic ethics that values life itself at its basic biological processes
and structures, and seeks their propagation.

Principles
• One of the first areas addressed by modern bioethicists was that of human
experimentation.
• The National Commission for the Protection of Human Subjects of Biomedical and
Behavioral Research was initially established in 1974 to identify the basic ethical
principles that should underlie the conduct of biomedical and behavioral research
involving human subjects.
• However, the fundamental principles announced in the Belmont Report (1979)—
namely, autonomy, beneficence and justice—have influenced the thinking of
bioethicists across a wide range of issues.
• Others have added non-maleficence, human dignity and the sanctity of life to this list
of cardinal values.
• Another important principle of bioethics is its placement of value on discussion and
presentation.
• Numerous discussion based bioethics groups exist in universities across the United
States to champion exactly such goals.
• Examples include the Ohio State Bioethics Society[8] and the Bioethics Society of
Cornell.[9]
• Professional level versions of these organizations also exist

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 Medical ethics
• Medical ethics is the study of moral values and judgments as they apply to medicine.
• As a scholarly discipline, medical ethics encompasses its practical application in
clinical settings as well as work on its history, philosophy, theology, and sociology.
• Medical ethics tends to be understood narrowly as an applied professional ethics,
whereas bioethics appears to have worked more expansive concerns, touching upon the
philosophy of science and issues of biotechnology
• Still, the two fields often overlap and the distinction is more a matter of style than
professional consensus.
• Medical ethics shares many principles with other branches of healthcare ethics, such
as nursing ethics.
• A bioethicist assists the health care and research community in examining moral issues
involved in our understanding of life and death, and resolving ethical dilemmas in
medicine and science.

Perspectives and methodology

Bioethicists come from a wide variety of backgrounds and have training in a diverse
array of disciplines. The field contains individuals trained in philosophy such as H.
Tristram Engelhardt, Jr. of Rice University, Baruch Brody of Rice University, Peter
Singer of Princeton University, Daniel Callahan of the Hastings Center, and Daniel
Brock of Harvard University, medically trained clinician ethicists such as Mark
Siegler of the University of Chicago and Joseph Fins of Cornell University, lawyers
such as Nancy Dubler of Albert Einstein College of Medicine or Jerry Menikoff of the
federal Office of Human Research Protections, political scientists like Francis
Fukuyama, religious studies scholars includingJames Childress, public intellectuals
like Amitai Etzioni of The George Washington University, and theologians like Lisa
Sowle Cahill and Stanley Hauerwas.
• The field, once dominated by formally trained philosophers, has become
increasingly interdisciplinary, with some critics even claiming that the methods
of analytic philosophy have had a negative effect on the field's development.
Leading journals in the field include The Journal of Medicine and Philosophy,
The Hastings Center Report, the American Journal of Bioethics, the Journal of
Medical Ethics and the Cambridge Quarterly of Healthcare Ethics. Bioethics

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 has also benefited from the process philosophy developed by Alfred North
Whitehead.
• Many religious communities have their own histories of inquiry into bioethical issues
and have developed rules and guidelines on how to deal with these issues from within
the viewpoint of their respective faiths.
• The Jewish, Christian and Muslim faiths have each developed a considerable body of
literature on these matters.
• In the case of many non-Western cultures, a strict separation of religion from
philosophy does not exist.
• In many Asian cultures, for example, there is a lively discussion on bioethical issues.
• Buddhist bioethics, in general, is characterised by a naturalistic outlook that leads to a
rationalistic, pragmatic approach.
• Buddhist bioethicists include Damien Keown.
• In India, Vandana Shiva is a leading bioethicist speaking from the Hindu tradition.
• In Africa, and partly also in Latin America, the debate on bioethics frequently focuses
on its practical relevance in the context of underdevelopment and geopolitical power
relations.
• Masahiro Morioka argues that in Japan the bioethics movement was first launched by
disability activists and feminists in the early 1970s, while academic bioethics began in
the mid-1980s.
During this period, unique philosophical discussions on brain death and disability
appeared both in the academy and journalism.
• Bioethics has also had its critics.
• Paul Farmer has pointed out that bioethics tends to focus its attention on problems that
arise from "too much care," for patients in industrialized nations, while giving little or
no attention to the ethical problem of too little care for the poor.
• Farmer characterizes the bioethics of handling difficult clinical situations, normally in
hospitals in industrialized countries, as "quandary ethics."
• And he refers to bioethicists as "endlessly rehashing the perils of too much care."
• He does not regard quandary ethics and clinical bioethics as unimportant; he argues,
rather, that bioethics must be balanced and give due weight to the poor.

Issues

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• Areas of health sciences that are the subject of published, peer-reviewed bioethical
analysis include:
• Abortion • Eugenics
• Alternative Medicine • Euthanasia (human, non-
• Animal rights human animal)
• Artificial insemination • Exorcism
• Artificial life • Faith Healing
• Artificial womb • Feeding tube
• Assisted suicide • Gene theft
• Biocentrism • Gene therapy
• Biological agent • Genetically modified food
• Biological patent • Genetically modified
• Biopiracy organism
• Biorisk • Genomics
• Biotic ethics • Great Ape Project
• Blood transfusion • Human cloning
• Body modification • Human enhancement
• Brain-computer interface • Human experimentation
• Chimeras in the United States
• Circumcision • Human genetic
• Cloning engineering
• Confidentiality (medical • Iatrogenesis
records) • Infertility treatments
• Consent • Intersex
• Contraception (birth control) • Life extension
• Cryonics • Prescription drug prices in
• Disability the United States
• Lobotomy • Life support
• Medicalization • Procreative beneficence
• Medical malpractice • Professional ethics
• Medical research • Psychosurgery
• Medical torture • Quality of Life
• Mediation (Healthcare)

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 • Mitochondrial donation • Quaternary prevention
• Moral obligation • Recreational drug use
• Moral status of animals • Reproductive rights
• Nanomedicine • Reproductive technology
• Nazi human experimentation • Reprogenetics
• Ordinary and extraordinary • Sex reassignment therapy
care • Sperm and egg donation
• Overtreatment • Spiritual drug use
• Organ donation • Stem cell research
• Organ transplant • Suicide
• Pain management • Surrogacy
• Parthenogenesis • Transexuality
• Patients' Bill of Rights • Transhumanism
• Placebo • Transplant trade
• Pharmacogenetics • Vaccination controversy
• Political abuse of psychiatry • Xenotransfusion
• Population control • Xenotransplantation

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ANIMAL ETHICS

Animal ethics is a branch of ethics which examines human-animal relationships, the moral
consideration of animals and how nonhuman animals ought to be treated. The subject matter
includes animal rights, animal welfare, animal law, speciesism, animal cognition, wildlife
conservation, wild animal suffering,[1] the moral status of nonhuman animals, the concept of
nonhuman personhood, human exceptionalism, the history of animal use, and theories
of justice.[2][3] Several different theoretical approaches have been proposed to examine this
field, in accordance with the different theories currently defended in moral and political
philosophy.[4][5][6] There is no theory which is completely accepted due to the differing
understandings of what is meant by the term ethics; however, there are theories that are more
widely accepted by society such as animal rights and utilitarianism.[

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Animal rights

The first animal rights laws were first introduced between 1635–1780. In 1635, Ireland was the
first country to pass animal protection legislation, "An Act against Plowing by the Tayle, and
pulling the Wooll off living Sheep".[10] In 1641, Massachusetts colony's called Body of
Liberties that includes regulation against any "Tirranny or Crueltie" towards animals.[11] In
1687, Japan reintroduced a ban on eating meat and killing animals.[12] In 1789,
philosopher Jeremy Bentham argued in An Introduction to the Principles of Morals and
Legislation, that an animal's capacity to suffer—not their intelligence—meant that they should
be granted rights: "The question is not, Can they reason? nor, Can they talk? but, Can
they suffer? Why should the law refuse its protection to any sensitive being?"[13]

Between 1822–1892, more laws were passed to protect animals. In 1822, the British Parliament
passed the Cruel Treatment of Cattle Act.[14] In 1824, the first animal rights society was
founded in England by Richard Martin, Arthur Broome, Lewis Gompertz and William
Wilberforce, the Society for the Prevention of Cruelty to Animals, which later became
the RSPCA.[15] The same year, Gompertz published Moral Inquiries on the Situation of Man
and of Brutes, one of the first books advocating for what will be more than a century later
known as veganism.[16] In 1835, Britain passed the first Cruelty to Animals Act.[17] In 1866,
the American Society for the Prevention of Cruelty to Animals was founded by New
Yorker Henry Bergh.[18] In 1875, Frances Power Cobbe established the National Anti-
Vivisection Society in Britain.[19] In 1892, English social reformer Henry Stephens
Salt published Animal Rights: Considered in Relation to Social Progress.[20]

In 1970, Richard D. Ryder coined speciesism, a term for discrimination against animals based
on their species-membership.[21] This term was popularized by the philosopher and
ethicist Peter Singer in his 1975 book Animal Liberation. The late 1970s marked the
beginnings of the animal rights movement, which portrayed the belief that animals must be
recognised as sentient beings and protected from unessential harm.[22] Since the 18th century,
many groups have been organised supporting different aspects of animal rights and carrying
out their support in differing ways. On one hand, "The Animal Liberation Front" is an English
group that took the law into their own hands, orchestrating the Penn break-in, while a group
such as "People for Ethical Treatment of Animals" founded in the US, although supporting the
same goals, aim for legislative gains.

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Ethical guidelines for animal research

There is a wide range of ethical assessments regarding animals used in research. There are
general opinions that animals do have a moral status and how they are treated should be
subjected to ethical consideration; some of the positions include:

 Animals have intrinsic values that must be respected.

 Animals can feel pain and their interests must be taken into consideration.
 Our treatment of all animals/lab animals reflects on our attitudes and influences us on our
moral beings.[31]

The Norwegian National Committee for Research Ethics in Science and Technology (NENT)
have a set of ethical guidelines for the use of animals in research:

1. Respect Animal Dignity: Researchers must have respect towards the animals' worth,
regardless of their value and the animals' interests as living, sentient creatures.
Researchers have to have respect when choosing their topics/methods, and when
expanding their research. Researchers also have to supply care that is adapted to needs
to each laboratory animal.[31]
2. Responsibility for considering options (Replace): When there are alternatives
available, researchers are responsible for studying those alternatives for animal
experimentation. When there are no good alternatives available, researchers have to
consider if the research can be postponed until a good alternative are developed. While
being able to justify the experiments on animals, researchers then have to be
accountable for the absence of alternative options and the urge to obtain the knowledge
immediately.[31]
3. The principle of proportionality: responsibility for considering and balancing
suffering and benefit: Researchers have to consider both the risks of pain and
suffering that laboratory animals will face and assess them in the value of the
relationship to the research of animals, people, and the environment. Researchers have
a responsibility on whether or not the research will have improvements for the animals,
people or the environment. All of the possible benefits of the study has to be
considered, substantiated and specified in both the short and long run. This
responsibility also entails the obligation to consider both the scientific quality of the
experiment and whether or not the experiment will have relevant scientific benefits.

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 Suffering can only be caused by animals if there is a counterbalance of substantial and
probable benefits for animals, people or the environment. Since there are many
methods of analyzing the harm and the benefits, research institutions have to provide
training on suitable models and researchers have the responsibility to use the methods
of analysis when planning any experiments on animals.
4. Responsibility for considering reducing the number of animals
(Reduce): Researchers have the responsibility to consider whether or not it's acceptable
to reduce the number of animals that an experiment's plan on using and include the
number necessary to both the scientific quality of the experiments and the relevance to
the results only. Before the experiment, researchers have to conduct reading studies
and consider alternative designs and perform the calculations that are needed before
beginning an experiment.[31]
5. Responsibility for minimizing the risk of suffering and improving animal welfare
(Refine): Researchers have the responsibility to assess the expected effect on
laboratory animals. Researchers have to lessen the risk of suffering and provide
excellent animal welfare. Suffering includes pain, hunger, malnutrition, thirst,
abnormal cold/heat. fear, stress, illness, injury, and restrictions to where the animal
can't be able to behave naturally and normally. To find out what is a considerable
amount of suffering, a researcher's assessment should be based on which animal suffers
the most. Considering the animals is the deciding factor if there are any doubts about
regarding the suffering the animals will face. Researchers have to consider the direct
suffering that the animal might endure during an experiment, but there are risks before
and after the suffering, including breeding, transportation, trapping, euthanizing,
labeling, anesthetizing, and stabling. This means that all the researchers have to take
into account the needs of periods for adaptation before and after an experiment.[31]
6. Responsibility for maintaining biological diversity: Researchers are also responsible
for ensuring that the use of laboratory animals don't disrupt or endanger biological
diversity. This means that researchers have to consider the consequences to the stock
and their ecosystem as a whole. The use of endangered species has to be reduced to a
minimum. When there is credible and uncertain knowledge that the inclusion of
animals in research and the use of certain methods may have ethically unacceptable
consequences for the stock and the ecosystem as a whole, researchers must observe
the precautionary principle.

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 7. Responsibility when intervening in a habitat: Researchers have a responsibility for
reducing the disruption and any impact of the natural behaviors of the animals,
including those who aren't direct test subjects in research, as well as the population and
their surroundings. Most research and technology-related projects, like the ones
regarding environmental technology and surveillance, might impact the animals and
their living arrangements. In those cases, researchers have to seek to observe the
principle of proportionality and to decrease possible negative impact(see guideline
3).[31]
8. Responsibility for openness and sharing of data and material: Researchers have the
responsibility for ensuring the transparency of the research findings and facilitating
sharing the data and materials from all animal experiments. Transparency and sharing
are important in order to not repeat the same experiments on animals. Transparency is
also important in order to release the data to the public and a part of researchers'
responsibility for dissimulation. Negative results of the experiments on animals have
should be public knowledge. Releasing negative results to other researchers could give
them more on the information about which experiments that are not worth pursuing,
shine a light on unfortunate research designs, and can help reduce the number of
animals used in research.
9. Requirement of expertise on animals: Researchers and other parties who work and
handle live animals are required to have adequate and updated documentation expertise
on all animals. This includes knowledge about the biology of the animal species in
question, and willingly be able to take care of the animals properly.
10. Requirement of due care: There are many laws, rules, international convention, and
agreements regarding the laboratory animals that both the researchers and the research
managers have to comply with. Anyone who wants to use animals in experiments
should familiarize themselves with the current rules.[31
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Embryonic stem cell
From Wikipedia, the free encyclopedia

Embryonic stem cells (ES cells or ESCs) are pluripotent stem cells derived from the inner
cell mass of a blastocyst, an early-stage pre-implantation embryo.[1][2] Human embryos reach
the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells.
Isolating the embryoblast, or inner cell mass (ICM) results in destruction of the blastocyst, a
process which raises ethical issues, including whether or not embryos at the pre-implantation
stage should have the same moral considerations as embryos in the post-implantation stage of
development.[3][4]

Researchers are currently focusing heavily on the therapeutic potential of embryonic stem cells,
with clinical use being the goal for many laboratories.[5] Potential uses include the treatment
of diabetes and heart disease.[5] The cells are being studied to be used as clinical therapies,
models of genetic disorders, and cellular/DNA repair. However, adverse effects in the research
and clinical processes such as tumours and unwanted immune responses have also been
reported.[

Concern and controversy

Adverse effects

The major concern with the possible transplantation of ESC into patients as therapies is their
ability to form tumors including teratoma.[44] Safety issues prompted the FDA to place a hold
on the first ESC clinical trial, however no tumors were observed.

The main strategy to enhance the safety of ESC for potential clinical use is to differentiate the
ESC into specific cell types (e.g. neurons, muscle, liver cells) that have reduced or eliminated
ability to cause tumors. Following differentiation, the cells are subjected to sorting by flow
cytometry for further purification. ESC are predicted to be inherently safer than IPS
cells created with genetically-integrating viral vectors because they are not genetically
modified with genes such as c-Myc that are linked to cancer. Nonetheless, ESC express very
high levels of the iPS inducing genes and these genes including Myc are essential for ESC self-
renewal and pluripotency,[45] and potential strategies to improve safety by eliminating c-Myc
expression are unlikely to preserve the cells' "stemness". However, N-myc and L-myc have
been identified to induce iPS cells instead of c-myc with similar efficiency.[46] More recent

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protocols to induce pluripotency bypass these problems completely by using non-integrating
RNA viral vectors such as sendai virus or mRNA transfection.

Ethical debate

Due to the nature of embryonic stem cell research, there are a lot of controversial opinions on
the topic. Since harvesting embryonic stem cells necessitates destroying the embryo from
which those cells are obtained, the moral status of the embryo comes into question. Some
people claim that the 5-day old mass of cells is too young to achieve personhood or that the
embryo, if donated from an IVF clinic (which is where labs typically acquire embryos from),
would otherwise go to medical waste anyway. Opponents of ESC research claim that an
embryo is a human life, therefore destroying it is murder and the embryo must be protected
under the same ethical view as a more developed human being.[

Embryonic stem cell research and religion

The view concerning the moral status of the early human embryo before the time of its
implantation in the uterus differs depending on religion.

• Roman Catholic, Orthodox, conservative Protestant Churches: Since a human embryo is

believed to have a status of a human individual from the moment of the fertilization of the egg,
it has the right to its own life, and every intervention not in favor of the embryo is a violation
of that right. No end believed to be good (e.g. using stem cells to prepare other differentiated
cells to be applied in what look to be promising therapeutic procedures) can justify the
destruction of the embryo, which is believed to be a wrong action (15). The Orthodox
Christians as well as Roman Catholics and Conservative Protestants affirm the sanctity of
human life at all stages of development and believe that the process toward authentic human
personhood begins with the zygote, which is committed to a developmental course that will
ultimately lead to a human person.

• Less conservative Protestant Churches believe that the embryo has a potential human
status, reflecting its gradual development from basic cells to a fetus. Thus some embryo
research may be permitted. The life of the embryo is weighed against the possible benefit for
the society from embryo research. The life of the human embryo is sacred from conception,
but there are circumstances under which embryo research might be allowed prior to the

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“primitive streak” stage (around 14th day after the fertilization), bearing in mind the
seriousness of certain medical conditions that could possibly be treated.

• Judaism: The Jewish religious tradition emphasizes the importance of the saving of life and
considers the ultimate goal of human embryonic stem cell research to be life saving. Healing
in Judaism is not only permitted, it is required to be an active partner in the world’s repair and
perfection (8). Man is obliged to build and develop the world in every direction favorable to
humanity. Therefore, any activity that contributes to advancements in the world cannot be
considered as contradicting God’s decrees (16). It is also believed that it is God who has given
the power to create new technologies (10). Anything, which has no reason to be prohibited is
permitted without having to find a reason for its permissibility (16). In Judaism the human fetus
less than 40 days old (10) and certainly the pre-implantation embryo does not have a full human
status (17). After those first 40 days the embryo in the uterus is considered a part of the woman
until birth (9).

• Islam: The majority of Muslim thinkers through the ages have accepted the morality of
abortion through either the fortieth day or the fourth month of pregnancy (8). It is believed that
the soul is “breathed in” to the human embryo on the 40th day after fertilization and this is
when life becomes sacred (18). All schools of thought in Islam accept that the fetus is accorded
the status of a legal person only at later stages of its development, when perceptible form and
voluntary movements appear. The thinkers make a distinction between a biological and a moral
person, placing the stage of the moral person after the first trimester of pregnancy (8). However,
Muslim jurists differ over whether “breathing-in” of the soul takes place in 40 or 120 days (10).
Also, it is believed that there is no disease that does not have a cure, and therefore the cure
should be sought. Medical progress is a strong value and stem cell research is acceptable due
to its therapeutic benefits. According to the Muslim faith, the supernumerary embryos cannot
be donated to other couples, as the lineage of the father must be respected. In this view,
conducting research on supernumerary embryos that will no longer be used for in vitro
fertilization purposes rather than destroying them is choosing the lesser of two evils (18).

Buddhism and Hinduism: Buddhism prohibits harm to any sentient beings, which presents
possible restrictions on embryo and animal research (17). Also, every action (e.g. killing) that
treats human beings as non-humans is considered immoral. For Buddhists, however, not all
areas of medical biotechnology lead to ethical problems: more advanced medical
biotechnology (where research is conducted on molecular level) is likely to be acceptable.
Molecular human parts, such as cells, are hardly seen as human beings, thus their destruction

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in the process of research is not likely to be seen as morally wrong (19). Regarding the research
on human stem cells, the intention is important. If the intention of the research is to help and
benefit humankind, such research is considered ethical. On the contrary, if the research is done
just for the sake of making money out of it, it is considered as unethical. But since Buddhism
places great importance on the principle of non-harming, it has grave reservations about any
scientific technique or procedure that involves the destruction of life, whether human or animal.
However, the principle of non-harming can be interpreted as prohibiting only the harm on
sentient beings that is those who are able to feel. Therefore, Buddhism could accept research
on non-sentient embryos before the day 14 of their development (8). Hinduism, like Buddhism
prohibits injuring sentient beings. The Hindu tradition rejects both animal research and the
destruction of sentient embryos (17). Research on supernumerary embryos that will no longer
be used for in vitro fertilization purposes rather than destroying them is choosing the lesser of
two evils (18).

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The Human Genome Project (HGP) was an international scientific research project with the
goal of determining the base pairs that make up human DNA, and of identifying and mapping
all of the genes of the human genome from both a physical and a functional standpoint.[1] It
remains the world's largest collaborative biological project.[2] Planning started after the idea
was picked up in 1984 by the US government, the project formally launched in 1990, and was
declared complete on April 14, 2003.[3]

Funding came from the US government through the National Institutes of Health (NIH) as well
as numerous other groups from around the world. A parallel project was conducted outside the
government by the Celera Corporation, or Celera Genomics, which was formally launched in
1998. Most of the government-sponsored sequencing was performed in twenty universities and
research centres in the United States, the United
Kingdom, Japan, France, Germany, Spain and China.[4]

The Human Genome Project originally aimed to map the nucleotides contained in a
human haploid reference genome (more than three billion). The "genome" of any given
individual is unique; mapping the "human genome" involved sequencing a small number of
individuals and then assembling these together to get a complete sequence for each
chromosome. Therefore, the finished human genome is a mosaic, not representing any one
individual.

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ELSI Research Program Overview

The National Human Genome Research Institute's (NHGRI) Ethical, Legal and
Social Implications (ELSI) Research Program was established in 1990 as an integral part of the
Human Genome Project (HGP) to foster basic and applied research on the ethical, legal and
social implications of genetic and genomic research for individuals, families and communities.
The ELSI Research Program funds and manages studies, and supports workshops, research
consortia and policy conferences related to these topics.

ELSI Research Priorities

On February 10, 2011, Nature magazine published NHGRI's strategic plan for the future of
human genome research, called Charting a course for genomic medicine from base pairs to
bedside. This plan includes a section on Genomics and Society that outlines four areas that will
need to be addressed as genomic science and medicine move forward. Based on these areas,
the NHGRI has developed the following broad research priorities.

 Genomic Research. The issues that arise in the design and conduct of genomic
research, particularly as it increasingly involves the production, analysis and broad
sharing of individual genomic information that is frequently coupled with detailed
health information.
 Genomic Health Care. How rapid advances in genomic technologies and the
availability of increasing amounts of genomic information influence how health care is
provided and how it affects the health of individuals, families and communities.
 Broader Societal Issues. The normative underpinnings of beliefs, practices and
policies regarding genomic information and technologies, as well as the implications of
genomics for how we conceptualize and understand such issues as health, disease, and
individual responsibility.
 Legal, Regulatory and Public Policy Issues. The effects of existing genomic research,
health and public policies and regulations and the development of new policies and
regulatory approaches.

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Ethical, legal and social issues

At the onset of the Human Genome Project, several ethical, legal, and social concerns were
raised in regard to how increased knowledge of the human genome could be used to
discriminate against people. One of the main concerns of most individuals was the fear that
both employers and health insurance companies would refuse to hire individuals or refuse to
provide insurance to people because of a health concern indicated by someone's genes.[65] In
1996 the United States passed the Health Insurance Portability and Accountability
Act (HIPAA) which protects against the unauthorized and non-consensual release of
individually identifiable health information to any entity not actively engaged in the provision
of healthcare services to a patient.[66] Other nations passed no such protections

Along with identifying all of the approximately 20,000–25,000 genes in the human genome,
the Human Genome Project also sought to address the ethical, legal, and social issues that were
created by the onset of the project. For that, the Ethical, Legal, and Social Implications (ELSI)
program was founded in 1990. Five percent of the annual budget was allocated to address the
ELSI arising from the project.[22][67] This budget started at approximately $1.57 million in the
year 1990, but increased to approximately $18 million in the year 2014.[68]

Whilst the project may offer significant benefits to medicine and scientific research, some
authors have emphasized the need to address the potential social consequences of mapping the
human genome. "Molecularising disease and their possible cure will have a profound impact
on what patients expect from medical help and the new generation of doctors' perception of
illness.

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Human Gene Therapy

Introduction
Gene therapy is the use of genes to treat disease. It represents a quantum leap in our approach
to the treatment of human disease and will have a significant effect on medicine over the next
ten years. William French Anderson, Michael Biase, and Ken Culver performed the first
successful gene therapy on a human in 1990. They developed a protocol for treating Adenosine
deaminase (ADA) deficiency, severe combined immune deficiency, also known as the" Boy in
the Bubble disease". ADA deficiency is a result of inheriting two copies of the defective ADA
gene (in other words it is a recessive disease). Possession of a normal gene leads to the
continuous, regular production of ADA in cells throughout the body. Without at least one
properly functioning gene, children have no way of converting deoxyadenosine (a waste
product) into inosine. This leads to the rapid buildup deoxyadenosine in the system, which
becomes phosphoralysed into a toxic triphosphate which kills T-cell. The result is an almost
complete failure of the immune system and early death.

Concept of Gene Therapy

The term gene therapy originally referred to proposed treatments of genetic disorders that
would involve replacing a defective gene with its normal counterpart Current usage of the term
now extends to include all treatments in which there is an introduction of genetic material into
body cells to treat a variety of diseases. Gene therapy utilizes two theoretically possible
approaches:

1) Somatic gene therapy entails the transfer of a gene or genes into body cells other than germ
(egg or sperm) cells with effect only on the patient. The new genetic material cannot be passed
on to offspring. Examples of Somatic gene therapy have already proven to be clinically
effective. The first successful treatments of adenosine deaminase deficiency took place in 1990
in 1991 with two patients aged 4 and 11. Both are thriving with continuing treatment. The first
successful treatment of familial hypercholesterolemia, a genetic condition, which affects the
livers regulation of cholestrols in the blood, took place in 1992 of a 29-year-old woman. Her
improvement was stable for the 18 months of the study and liver biopsy demonstrated activity
of the inserted gene and no discernible abnormalities. Five patients have been treated as of
1994.Current research involving Somatic gene therapy is focusing on a number of areas.
Clinical trials are being performed on a treatment for cystic fibrosis, a chronic genetic disorder.

18
2) Germline gene therapy would involve the genetic modification of germ cells. Such therapy
would change the genetic makeup of the egg or sperm of an individual and would be carried
on to future generations. This would offer the possibility of removing an inherited disorder
from a family line forever. This could be achieved by other methods, such as, at present,
diagnosis when there is a known risk before embryo implantation during IVF. Germ line
therapy is a remote prospect and general opinion is strongly negative; such therapy is currently
illegal in most of Europe. Somatic and Germ line gene therapy raise different issues. Somatic
gene therapy offers the prospect of effective treatment and cure for previously fatal disorders.
Until now it has only been used experimentally for a small range of genetic disorders; even in
these cases treatment is complex, difficult and success uncertain.

Technical Aspects of Gene Therapy

The most fundamental requirement for gene therapy to be successful is that a therapeutic gene
can be effectively delivered to a target cell. Once delivered that gene must enter the nucleus of
cell wall where it will act as a template for production of protein molecule. The protein then
exerts the primary therapeutic effect. This may be, for example, cell killing in the case of tumor
therapy or cell preservation in the case of neurodegenerative disease.

There are several ways to get genes into cells. The most efficient of these uses disabled,
engineered viruses. These systems are efficient because viruses have evolved over long periods
of time to deliver their own genes to cells. Whenever, we get a viral disease, be it a cold or
AIDS, the particular virus concerned is placing its genes into our cells in order to
reprogrammed our cells to produce more virus. When we use viruses for gene therapy we
disable them so that they are unable to cause disease and we engineer them in such a way that
they pick up and deliver the genes of our choice rather than their own genes. These derivatives
of viruses that are used for gene delivery are known as viral vectors. The most frequently used
viral vectors are of two types. The vectors based on adenovirus are generally used for
therapeutic strategies that require the therapeutic gene to be active for only a short time. Gene
delivery by adenoviruses is very efficient but because the gene does not become integrated into
the chromosomes of the target cell the gene is lost overtime.

This not a disadvantage for some therapeutic strategies such as cell destruction in the treatment
of some cancers, restinosis or inflammatory disease. However, it is a disadvantage where

19
sustained gene activity required for many months such as in the treatment of some tumors,
neurodegenerative disease and HIV infection.

The second major type of vector is generally used and this is based on the retrovirus, murine
leukemia virus (MLV). When genes are delivered by derivatives of MLV they become
integrated into the chromosomes of target cell and are maintained for as long as the cell remains
alive. Gene activity is easy to control and continues over long periods of time. Many clinical
trials have been conducted with these MLV based systems and has been shown to be well
tolerated with no adverse side effects.

One of the major difference between adenovirus vectors and MLV vectors is that the former
can deliver genes to cells that are not multiplying by cell division whereas the latter cannot.
Until recently this has meant gene therapy strategies that demand long term gene activity in
cells that are not dividing have been feasible. Examples of important target cells that do not
divide are neurons, certain cells of the immune system and certain epithelial cells.

Lentiviruses are a subgroup with in the general family of retroviruses but they are distinct from
the MLV like viruses in that they are able to infect non-dividing cells. The best studied of the
lentiviruses is HIV and when observation was made, about 10 years ago, that HIV could infect
terminally differentiated macrophages, which do not divide, there was a move within the
research community to develop gene delivery vectors from HIV. There were number of early
technical difficulties and first generation vectors could not be used in the clinic as they had
potential to generate infectious HIV. Over past two years we have seen new HIV based vectors
emerge that are severely disabled containing only the few HIV components that are required
for efficient gene delivery to non dividing cells. These so called minimal vectors are now
candidates for gene delivery vehicles for clinical use in gene therapy.

The technique, called Chimeraplasty, was developed for mammalian gene therapy. It has an
advantage over current genetic engineering methods in that it can seek out any specific gene
and cause tiny mutations with high precision. Instead of adding a new gene to trick a plant into
doing something it would not normally do, Chimeraplasty simply switches on or off function
for which the plant already has a gene.

Until now, an entire gene had to hitch a ride into the nucleus on a defused viruses, which has
the ability to insert itself into the genome. However, the virus could settle anywhere on the

20
genome, sometimes choosing a location that is less than optimal for the replication of new
gene. Technique also eliminates the danger from inserting large sections of genes with
potentially undesirable side- effects, such as poisoning beneficial insects.

For Chimeraplasty, researchers start with small chunks of artificial genetic material, called
oligonucleotides or "oligos", with about 25 bases each. They mirror one specific plant gene
except for a mismatch of a few bases. The chunks are hooked up to tiny gold particles, which
are then shot into nucleus of cell with a particle gun. When the oligos attach their counterparts
in the cell, the DNA repair machinery tries to "fix" the mismatch, using the new sequence of
the bases as blueprint.

Boosting blood cell production does little good for patients, whose blood cells are malformed,
such as those of sickle cell anemic. The ultimate goal of gene therapy is not to compensate for
genetic diseases but to erase them completely. Preliminary work published in the September 6
issue of science offers a reason to hope that goal may be possible .A team led by Allyson Cole-
strauss and Kyonggeum Yoon of Thomas Jefferson University in Philadelphia experimented
on cells containing a mutant gene that causes sickle cell anemia .To make their genetic drug
they combined DNA for the normal version of this gene with RNA for the same gene. When
they injected the drug into the diseased cells, the RNA/DNA particles homed in on the
particular stretch of the genome that matched their codes and formed triple stranded DNA that
covered the mutation. The cells normal DNA repair machinery then apparently replaced the
mutation with the normal code thus permanently curing 10 to 20 percent of cells. The
researchers still have to demonstrate that this technique works in human cells and in human
bodies.

In about half of lung cancer cases, a gene called p53 has mutated and thus falls to encode a
protein that oversees programmed cell death. In the absence of this protein, which helps to curb
the growth of damaged or abnormal cells, cancer can gain a foothold. Replacing such defective
p53 genes with fresh ones has shown promise against a variety of cancers in animal
experiments and studies of a few patients.

Scientists now report further progress in such localized gene therapy. By enlisting a virus to
deliver p53 to tumor sites in 28 people with lung cancer, they temporarily stabilized or reversed
the course of the cancer in more than half patients. The patients, average age 65, had lung
cancer that was either inoperable or was no longer responding to radiation treatment or

21
chemotherapy. The researchers injected the tumors with an adenovirus engineered to contain
p53 genes. The virus was modified to prevent it from replicating and thus causing the upper
respiratory infection that it might otherwise bring about.

During the 6 months treatment period patients received one to six monthly injections of the
modified virus. The researchers delivered a range of doses -from 1 million to 100 billion viral
units to gauge any toxicity of the treatment. 3 of the 28 patients died of cancer before doctors
could make a 1-month follow up examination. Among the 25 others, tumors shrank in 2
patients, stabilized in 16 and continued to grow in the other 7.

The dose of virus mattered; cancer progressed unabated in three of five patients who received
injections of 10 million or fewer viral units. In contrast, only 4 of 20 patients getting larger
dose experienced cancer growth.

Argument of Human Gene Therapy

Consider what a nation would gain by permitting parents to genetically enhance their children.
By assumption, the genetic enhancement technology increases the ability of children to learn
and perform cognitive tasks, and thus to acquire and generate knowledge. Permitting or
facilitating genetic enhancement would therefore increase the collective human capital
embodied in nations workers .The increasing prevalence of high ability genotypes would also
multiply the effects of other national investments in education, training, and scientific or
engineering research. Because genetic enhancements are heritable, the effect of these
investments on the stock of human capital are cumulative unless enhanced offspring or their
descendants emigrate. Finally, permitting genetic enhancement would be a cheap way for a
state to increase aggregate human capital, because competition between parents would lead
some parents to pay for it out of their own pockets. If expanding stock of nations human capital
brings increasing returns in productivity and economic growth, it means that in economic
competitions among nations, small initial differences in the distribution of able people can
multiply, over time, to large international differences in the rate of economic growth. Thus
nations have an incentive to defect from an international ban on genetic enhancement to get a
jump on others in the accumulation of human capital.

It is said that the day is not far of when parents will be able to browse through gene catalogs to
special order a hazel eyed, red headed extrovert with perfect pitch. Every new discovery gives
shape and bracing focus to a debate we have barely begun. Even skeptics admit it's only matter

22
of time before these issues become real. If you could make your kids smatter, would you? If
everyone else did, would it be fair not to?

It's an ethical quandary and an economic one, about fairness and fate, about vanity and values.
Which side effects would we tolerate? What if making smarter kids also made them meaner?
What if only the rich could afford the advantage? Does god give us both the power to re-create
ourselves and moral muscles to resist? Self-improvement forever been an American religion,
but norms about what is normal keep changing.

While gene therapy shows a great deal of potential, opponents, biomedical reductionism will
undoubtedly have several responses. The way a person experiences a disease involves many
social and psychological elements (such as emotional impact of the disease, the stigmatism
attached to it, the cost and employment implications, etc). These important aspects of disease
are neglected by therapeutic approaches aimed strictly at the genetic level.

Today in many countries governments sets up committees, which included not only scientists
and doctors but also religious leaders, lawyers and ethicist, to consider the matter (Nichols
1988). A distinction should be drawn between making genetic changes in somatic cells and in
germinal cells. The purpose of somatic gene therapy is to treat an individual patient, e.g. by
inserting a properly functioning gene into patients bone marrow cells in vitro and then
introducing the cells into patients body. They differ, however, in that gene therapy an inherent
and probably permanent change in the body rather than requiring repeated applications of an
outside force or substance. An analogy is organ transplantation, which also involves the
incorporation into an individual of cells containing DNA of foreign origin. Germinal gene
therapy, in which the changes would be made in germ cells and would be passed on to the
offspring, is not allowed.

Reference:

https://www.ndsu.edu/pubweb/~mcclean/plsc431/students99/oberoi.htm

Golden rice is a variety of rice (Oryza sativa) produced through genetic

engineering to biosynthesize beta-carotene, a precursor of vitamin A, in the edible parts of
rice.[1][2] It is intended to produce a fortified food to be grown and consumed in areas with

23
a shortage of dietary vitamin A, a deficiency which each year is estimated to kill 670,000
children under the age of 5[3] and cause an additional 500,000 cases of irreversible childhood
blindness.[4] Rice is a staple food crop for over half of the world's population, providing 30–
72% of the energy intake for people in Asian countries, and becoming an effective crop for
targeting vitamin deficiencies.[5]

Golden rice differs from its parental strain by the addition of three beta-carotene biosynthesis
genes. The parental strain can naturally produce beta-carotene in its leaves, where it is involved
in photosynthesis. However, the plant does not normally produce the pigment in the
endosperm, where photosynthesis does not occur. Golden rice has met significant opposition
from environmental and anti-globalization activists. A study in the Philippines is aimed to
evaluate the performance of golden rice, whether it can be planted, grown and harvested like
other rice varieties, and whether golden rice poses risk to human health.[6] There has been little
research on how well the beta-carotene will hold up when stored for long periods between
harvest seasons, or when cooked using traditional methods.[7]

In 2005, Golden Rice 2 was announced, which produces up to 23 times as much beta-carotene
as the original golden rice.[8] To receive the USDA's Recommended Dietary
Allowance (RDA), it is estimated that 144 g/day of the high-yielding strain would have to be
eaten. Bioavailability of the carotene from golden rice has been confirmed and found to be an
effective source of vitamin A for humans.[9][10][11] Golden Rice was one of the seven winners
of the 2015 Patents for Humanity Awards by the United States Patent and Trademark
Office.[12][13] In 2018 came the first approvals as food in Australia, New Zealand, Canada and
the US.

NO TILLAGE FARMING

What is tillage?

Tillage is an agriculture land preparation through mechanical agitation which includes digging,
stirring and overturning.
Zero tillage is the process where the crop seed will be sown through drillers without prior land
preparation and disturbing the soil where previous crop stubbles are present. Zero tillage not
only reduce the cost of cultivation it also reduces the soil erosion, crop duration and irrigation
requirement and weed effect which is better than tillage. Zero Tillage (ZT) also called No
Tillage or Nil Tillage.

24
Zero tillage in India

No Till approach started from 1960s by farmers in India. The zero-tillage system is being
followed in the Indo-Gangetic plains where rice-wheat cropping is present. Wheat will be
planted after rice harvest without any operation. Hundreds of farmers are following the same
system and getting more yields and profits by reducing the cost of cultivation. In South, the
outhern districts like Guntur and some parts of West Godavari of Andhra Pradesh state follow
the ZT system in rice-maize cropping system.
The green revolution paved the way for the rice-wheat production system in the north-western
parts of India. But in due course of time, the yields of rice and wheat become stagnant due to
inappropriate soil and water management system and late planting of wheat, as in the hot season
rice is being grown and in the winter wheat follows the rice. In 1990’s the zero tillage came to
mitigate the problem, by planting the wheat by drilling without any land preparation and tillage.
The success of zero tillage depends on the machinery to drill seed in the uncultivated land. In
late 1980’s, CIMMYT introduced a prototype for drilling the seed. In India, the first localized
seed drill was manufactured by GB Pant University with a motor to reduce the cost and make
it available and affordable. The drills are tractor drawn and used in rice-wheat cropping system.
Zero tillage proves better for direct-seeded rice, maize, soybean, cotton, pigeonpea, mungbean,
clusterbean, pearlmillet during kharif season and wheat, barley, chickpea, mustard and lentil
during rabi season. Wheat sowing after rice can be advanced by 10-12 days by adopting this
technique compared to conventionally tilled wheat, and wheat yield reduction caused by late
sowing can be avoided. ZT provides opportunity to escape wheat crop from terminal heat
stress. Zero tillage reduces cost of cultivation by nearly Rs 2,500-3,000/ha through reduction
in cost of land preparation, and reduces diesel consumption by 50-60 litres per hectare. Zero
tillage reduces water requirement of crop and the loss of organic carbon by oxidation. Zero
tillage reduces Phalaris minor problem in wheat. The carbon status of soil is significantly
enhanced in surface soil (0-5 cm), particularly under crop residue retention with zero
tillage (Ref: Policy paper 31 - Doubling Strategy for Doubling Income of Farmers in India).
Advantages of zero tillage

1. Reduction in the crop duration and thereby early cropping can be obtained to get higher
yields.
2. Reduction in the cost of inputs for land preparation and therefore a saving of around
80%.

25
 3. Residual moisture can be effectively utilized and number of irrigations can be reduced.
4. Dry matter and organic matter get added to the soil.
5. Environmentally safe - Greenhouse effect will get reduced due to carbon sequestration.
6. No tillage reduces the compaction of the soil and reduces the water loss by runoff and
prevent soil erosion.
7. As the soil is intact and no disturbance is done, No Till lands have more useful flora
and fauna.

Conclusion

The natural resources are precious and therefore demand an effective and sustainable use. Zero
tillage is a potential technology in this scenario. Although the drawback of use of non-selective
herbicide is more, it still causes less effect than the conventional method of farming. In zero
tillage, more returns can be achieved and timely crop can be grown with higher yields.

Reference:
Madhu Kiran Tumma, PBRD Asia-Pacific Millet India, Pioneer Hibrid Pvt Ltd., Hyderabad
500082

K S V Poorna Chandrika, ICAR-Indian Institute of Oilseeds Research, Rajendranagar,

Hyderabad, Telangana 500030

Bt cotton

Strains of the bacterium Bacillus thuringiensis produce over 200 different Bt toxins, each
harmful to different insects. Most notably, Bt toxins are insecticidal to the larvae of moths and
butterflies, beetles, cotton bollworms and flies but are harmless to other forms of life.[1] The
gene coding for Bt toxin has been inserted into cotton as a transgene, causing it to produce this
natural insecticide in its tissues. In many regions, the main pests in commercial cotton
are lepidopteran larvae, which are killed by the Bt protein in the genetically modified
cotton they eat. This eliminates the need to use large amounts of broad-spectrum insecticides
to kill lepidopteran pests (some of which have developed pyrethroid resistance). This spares
natural insect predators in the farm ecology and further contributes to noninsecticide pest
management.

Bt cotton is ineffective against many cotton pests such as plant bugs, stink bugs, and aphids;
depending on circumstances it may be desirable to use insecticides in prevention. A 2006 study
done by Cornell researchers, the Center for Chinese Agricultural Policy and the Chinese

26
Academy of Science on Bt cotton farming in China found that after seven years these secondary
pests that were normally controlled by pesticide had increased, necessitating the use of
pesticides at similar levels to non-Bt cotton and causing less profit for farmers because of the
extra expense of GM seeds.[2]

Biological pest control

From Wikipedia, the free encyclopedia

Syrphus hoverfly larva (below) feed on aphids (above), making them natural biological control
agents.

A parasitoid wasp (Cotesia congregata) adult with pupal cocoons on its host, a tobacco
hornworm (Manduca sexta, green background), an example of a hymenopteran biological
control agent

Biological control or biocontrol is a method of controlling pests such

as insects, mites, weeds and plant diseases using other organisms.[1] It relies

27
on predation, parasitism, herbivory, or other natural mechanisms, but typically also involves
an active human management role. It can be an important component of integrated pest
management (IPM) programs.

There are three basic strategies for biological pest control: classical (importation), where a
natural enemy of a pest is introduced in the hope of achieving control; inductive
(augmentation), in which a large population of natural enemies are administered for quick pest
control; and inoculative (conservation), in which measures are taken to maintain natural
enemies through regular reestablishment.[2]

Natural enemies of insect pests, also known as biological control agents, include
predators, parasitoids, pathogens, and competitors. Biological control agents of plant diseases
are most often referred to as antagonists. Biological control agents of weeds include seed
predators, herbivores, and plant pathogens.

Biological control can have side-effects on biodiversity through attacks on non-target species
by any of the above mechanisms, especially when a species is introduced without a thorough
understanding of the possible consequences.

Genetically modified fish

Genetically modified fish (GM fish) are organisms from the taxonomic clade which includes
the classes Agnatha (jawless fish), Chondrichthyes (cartilaginous fish) and Osteichthyes (bony
fish) whose genetic material (DNA) has been altered using genetic engineering techniques. In
most cases, the aim is to introduce a new trait to the fish which does not occur naturally in the
species, i.e. transgenesis.

GM fish are used in scientific research and kept as pets. They are being developed as
environmental pollutant sentinels and for use in aquaculture food production. In 2015,
the AquAdvantage salmon was approved by the US Food and Drug Administration (FDA) for
commercial production, sale and consumption,[1] making it the first genetically modified
animal to be approved for human consumption. Some GM fish that have been created have
promoters driving an over-production of "all fish" growth hormone. This results in dramatic
growth enhancement in several species, including salmonids,[2] carps[3] and tilapias.[4][5]

28
 Critics have objected to GM fish on several grounds, including ecological concerns, animal
welfare concerns and with respect to whether using them as food is safe and whether GM fish
are needed to help address the world's food needs.

Delayed Ripening Technology

14
Ripening is a normal phase in the maturation process of fruits
and vegetables. Upon its onset, it only takes about a few days
before the fruit or vegetable is considered inedible. This
unavoidable process brings significant losses to both farmers
and consumers alike.

Scientists have been working to delay fruit ripening so that

farmers will have the flexibility in marketing their goods and ensure consumers of “fresh-from-
the-garden” produce.

Advantages of DR Technology

The increased shelf life of products offers several advantages to

both producers and consumers:

1. Assurance of top quality fruits and vegetables on the market.

Farmers can now wait for the fruits and vegetables to attain full
maturity before they are plucked from their vines thereby allowing
the fruits to exude full quality. Consumers will get value for their money.
2. Widening of market opportunities for farmers as their produce can now be transported for
longer periods of time, some of which would not even require refrigeration.
3. Reduction in postharvest losses. DR fruits do not go soft easily compared to conventional ones
and are therefore more resilient to damage during handling and transportation. This ensures a
significant percentage of the harvested fruits to end up on the market shelves.
4. Extension in shelf life as fruits or vegetables as they stay fresher and nutritious for longer
periods. These fruits will not easily go “over the hill”.

29
Safety Aspects of DR Technology

The first ever GM crop approved for marketing was the

Flavr-SavrTM tomato produced by Calgene, Inc. (U.S.) in
1994. After thoroughly studying DR technology and its
products, US regulatory agencies concluded that the DR
technology is safe, it produces tomatoes that have the same
nutritional composition as the conventional ones and that show no difference in levels of
allergens or toxins compared to normal fruit. In addition, field trials have shown that the DR
tomatoes do not pose any threat to other plants nor to any non-target organisms.

Other DR tomatoes that followed thereafter have also been granted deregulated status by
regulatory agencies in several countries including the U.S., Canada, and Mexico. In 1996, the
UK’s food safety regulators also gave their thumbs up to a DR tomato developed by Zeneca
Seeds but it is not currently being sold in supermarkets.

A European First

On February 5, 1996, branches of Safeway and Sainsbury’s supermarkets throughout the UK

started to sell tomato pureé made from genetically-modified tomatoes. This was the first time
that food made from a GM organism had been sold in Europe.

Labels on the cans clearly stated that the product had been made with
GM tomatoes. Although there was no legal requirement to label the
product, both supermarkets adopted an ‘open’ information policy
from the start. For the inquisitive customer there was no shortage of
information: leaflets were available describing the product, its
benefits to the environment and consumer, the technology, and the
regulatory processes through which the product had to pass.

According to the supermarkets, sales in around 80 stores in which supplies were initially
available were brisk. Figures indicated that once they bought the product, shoppers came back
30
for more. In November 1997, Safeway Stores announced that they had sold three quarters of a
million cans of the product, and that average sales per store of the modified tomato purée
exceeded those of the conventional equivalent. One reason might have been the price: the new
purée cost 29 pence for 170 grams while the traditional form cost slightly more: 29 pence for
a mere 142 grams.

Both supermarket chains pledged that the new product would always be offered alongside its
old-fashioned counterpart. This move pleased consumer groups, which had no objection to the
purée, provided that it was safe to eat and that consumers were always given a choice.

However, commercial pressures generated by public concern about GM foods early in 1999
forced Sainsbury’s to announce that it would withdraw the product from sale. Stocks were
exhausted by July 1999.

Source: http://www.ncbe.reading.ac.uk/NCBE/GMFOOD/tomato.html

Current Status of DR Technology

Delayed Ripening (DR) Technology has been applied for use in tomatoes, melons, and papaya.
An interesting application of DR technology is in floriculture where experiments are underway
to apply the technology to delay the withering of flowers.

In Southeast Asia, DR technology is being applied for use in papayas, a popular subsistence
food and part of the general diet in the region. This technology could significantly increase the
availability of this nutritious fruit to consumers and to small-scale and mostly resource-poor
farmers in the region.

Regulatory approval of countries for crops with the DR trait

Crop Countries Type of Approval

Carnation Australia Norway Cultivation Cultivation

31
Melon USA Food

Pineapple USA Food

China Canada Mexico Food, feed, cultivation Food Food Food, feed,
Tomato
USA cultivation

Source: ISAAA GM Approval Database. http://www.isaaa.org/gmapprovaldatabase.

Chymosin

Chymosin /ˈkaɪməsᵻn/ or rennin /ˈrɛnᵻn/ is a protease found in rennet. It is an aspartic

endopeptidase belongs to MEROPS A1 family. It is produced by newborn ruminant animals in
the lining of the fourth stomach to curdle the milk they ingest, allowing a longer residence in
the bowels and better absorption. It is widely used in the production of cheese. Bovine
chymosin is now producedrecombinantly in E. coli, Aspergillus niger var awamori, and K.
lactis as alternative resource.

Recombinant Chymosin

Because of the imperfections and scarcity of microbial and animal rennets, producers sought
replacements. With the development of genetic engineering, it became possible to extract
rennet-producing genes from animal stomach and insert them into
certain bacteria, fungi or yeasts to make them produce chymosin during fermentation. The
genetically modified microorganism is killed after fermentation and chymosin is isolated from
the fermentation broth, so that the fermentation-produced chymosin (FPC) used by cheese
producers does not contain any GM component or ingredient. FPC contains the identical
chymosin as the animal source, but produced in a more efficient way. FPC products have been
on the market since 1990 and have been considered in the last 20 years the ideal milk-clotting
enzyme.

FPC was the first artificially produced enzyme to be registered and allowed by the US Food
and Drug Administration. In 1999, about 60% of US hard cheese was made with FPC and it
has up to 80% of the global market share for rennet.

32
By 2008, approximately 80% to 90% of commercially made cheeses in the US and Britain
were made using FPC. Today, the most widely used fermentation-produced chymosin is
produced either by the fungus Aspergillus niger and commercialized under the trademark
CHY-MAX® by the Danish company Chr. Hansen, or produced byKluyveromyces lactis and
commercialized under the trademark MAXIREN® by the Dutch company DSM.

FPC contains only chymosin B, achieving a high degree of purity compared with animal rennet.
FPC can deliver several benefits to the cheese producer compared with animal or microbial
rennet, such as higher production yield, better curd texture and reduced bitterness.

***************************************************************************
***
Tryptophan
Tryptophan (abbreviated as Trp or W; encoded by the codon UGG) is an α-amino acid that is
used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated
–NH3+ form under biological conditions), an α-carboxylic acid group (which is in
the deprotonated –COO− form under biological conditions), and a side chain indole,
classifying it as a non-polar, aromatic amino acid. It is essential in humans, meaning the body
cannot synthesize it and thus it must be obtained from the diet.

33
Eosinophilia–myalgia syndrome

There was a large outbreak of eosinophilia-myalgia syndrome (EMS) in the U.S. in 1989, with
more than 1,500 cases reported to the CDC and at least 37 deaths. After preliminary
investigation revealed that the outbreak was linked to intake of tryptophan, the U.S. Food and
Drug Administration (FDA) banned most tryptophan from sale in the US in 1991, and other
countries followed suit.

Subsequent epidemiological studies suggested that EMS was linked to specific batches of L-
tryptophan supplied by a single large Japanese manufacturer, Showa Denko.[44][45][46][47] It
eventually became clear that recent batches of Showa Denko's L-tryptophan were contaminated
by trace impurities, which were subsequently thought to be responsible for the 1989 EMS
outbreak.[44][48][49] However, other evidence suggests that tryptophan itself may be a potentially
major contributory factor in EMS.

The FDA loosened its restrictions on sales and marketing of tryptophan in February 2001, but
continued to limit the importation of tryptophan not intended for an exempted use until 2005.

The fact that the Showa Denko facility used genetically engineered bacteria to produce the
contaminated batches of L-tryptophan later found to have caused the outbreak of eosinophilia-
myalgia syndrome has been cited as evidence of a need for "close monitoring of the chemical
purity of biotechnology-derived products."[51] Those calling for purity monitoring have, in turn,
been criticized as anti-GMO activists who overlook possible non-GMO causes of
contamination and threaten the development of biotech.

IGF-1
IGF-1, or insulin-like growth factor 1, is a growth hormone produced by the liver, and small
amounts are also found in the testes. It is an important hormone, involved in blood cell
production and the growth of blood vessels, but a 2008 study done by the Schneider Children's
Medical Center of Israel showed that a natural deficiency can actually help to increase the life
span, possibly by reducing the risk of certain cancers. People who use HCG as a bodybuilding
supplement sometimes use IGF-1 in conjunction, hoping to increase their body's ability to
absorb and use the HCg. When IGF-1 is isolated from milk, it resists breakdown by digestion.

34
General Side Effects
IGF-1 and HCG are steroids, and as such, have the potential to cause many undesirable side
effects, regardless of whether they are taken together or separately. They can damage your liver
and kidneys and keep your body from producing its own hormones. They can cause acne,
aggressive behavior and can trigger baldness in people who are genetically predisposed.
Because hormones are heavily involved in gender differentiation, IGF-1 and HCG
supplementation can cause the development of male breast tissue and the masculinization of
women. The masculinization includes the growth of excess body and facial hair and the
deepening of the voice, and the male breast tissue may need to be surgically removed.

***************************************************************************
*

Ice-minus Pseudomonas syringae

Ice-minus bacteria is a common name given to a variant of the

common bacterium Pseudomonas syringae (P. syringae). This strain of P. syringae lacks the
ability to produce a certain surface protein, usually found on wild-type P. syringae. The "ice-
plus" protein (Ina protein, "Ice nucleation-active" protein) found on the outer bacterial cell
wall acts as thenucleating centers for ice crystals.[1] This facilitates ice formation, hence the
designation "ice-plus." The ice-minus variant of P. syringae is a mutant, lacking
the gene responsible for ice-nucleating surface protein production. This lack of surface protein
provides a less favorable environment for ice formation. Both strains of P. syringae occur
naturally, butrecombinant DNA technology has allowed for the synthetic removal or alteration
of specific genes, enabling the creation of the ice-minus strain.

The ice nucleating nature of P. syringae incites frost development, freezing the buds of the
plant and destroying the occurring crop. The introduction of an ice-minus strain of P.
syringae to the surface of plants would reduce the amount of ice nucleate present, rendering
higher crop yields. The recombinant form was developed as a commercial product known
as Frostban. Field-testing of Frostban was the first release of a genetically modified
organism into the environment. The testing was very controversial and drove the formation of
US biotechnology policy. Frostban was never marketed.

35
Controversy

At the time of Lindow's work on ice-minus P. syringae, genetic engineering was considered to
be very controversial. Jeremy Rifkin and his Foundation on Economic Trends (FET) sued the
NIH in federal court to delay the field trials, arguing that NIH had failed to conduct an
Environmental Impact Assessment and had failed to explore the possible effects "Ice-minus"
bacteria might have on ecosystems and even global weather patterns.[4][7] Once approval was
granted, both test fields were attacked by activist groups the night before the tests occurred:
"The world's first trial site attracted the world's first field trasher".[5] The BBC quoted Andy
Caffrey from Earth First!: "When I first heard that a company in Berkley was planning to
release these bacteria Frostban in my community, I literally felt a knife go into me. Here once
again, for a buck, science, technology and corporations were going to invade my body with
new bacteria that hadn't existed on the planet before. It had already been invaded by smog, by
radiation, by toxic chemicals in my food, and I just wasn't going to take it anymore."[5]

Rifkin's successful legal challenge forced the Reagan Administration to more quickly develop
an overarching regulatory policy to guide federal decision-making about agricultural
biotechnology. In 1986, the Office of Science and Technology Policy issued the Coordinated
Framework for Regulation of Biotechnology, which continues to govern US regulatory
decisions.[4]

The controversy drove many biotech companies away from use of genetically engineering
microorganisms in agriculture.[8]

***************************************************************************
*

rBST

Recombinant Bovine Somatotropin (rBST)

recombinant bovine growth hormone (rBGH), or artificial growth hormone. Four large
pharmaceutical companies, Monsanto,American Cyanamid, Eli Lilly, and Upjohn, developed
commercial rBST products and submitted them to the US Food and Drug
Administration (FDA) for approval.[3][4] Monsanto was the first firm to receive approval. Other
countries (Mexico, Brazil, India, Russia, and at least ten others) also approved rBST for

36
commercial use.[5] Monsanto licensed Genentech's patent,[2] and marketed their product as
"Posilac".[6][7] In October 2008, Monsanto sold this business, in full, to Eli Lilly and
Company for $300 million plus additional consideration.

rBST has not been allowed on the market in Canada, Australia, New Zealand, Japan, Israel, or
the European Union since 2000. Argentina also banned the use of rBST.

The FDA,[9] World Health Organization,[4] and National Institutes of Health[10] have
independently stated that dairy products and meat from BST-treated cows are safe for human
consumption. In the United States, public opinion led some manufacturers and retailers to
market only milk that is rBST-free.

A European Union report on the animal welfare effects of rBST states that its use often results
in "severe and unnecessary pain, suffering and distress" for cows, "associated with serious
mastitis, foot disorders and some reproductive problems"

rBST is present in milk from both rBST-treated and untreated cows, but it is destroyed in the
digestive system and even if directly injected, has not been found to have any direct effect on
humans.[29] Researchers have found that "IGF-1 in milk is not denatured by pasteurization and
the extent to which intact, active IGF-1 is absorbed through the human digestive tract remains
still however uncertain" implicating that an extensive study on the nature of IGF-1 in relation
to rBST milk is required.[30]

FDA rBST labeling guidelines state, "FDA is concerned that the term 'rbST free' may imply a
compositional difference between milk from treated and untreated cows rather than a difference
in the way the milk is produced. Without proper context, such statements could be misleading.
Such unqualified statements may imply that milk from untreated cows is safer or of higher
quality than milk from treated cows. Such an implication would be false and misleading".[31]

The FDA[9] World Health Organization,[4] and National Institutes of Health[10] have
independently stated that dairy products and meat from rBST-treated cows are safe for human
consumption. The American Cancer Society issued a report declaring, "The evidence for
potential harm to humans [from rBGH milk] is inconclusive. It is not clear that drinking milk
produced using rBGH significantly increases IGF-1 levels in humans or adds to the risk of
developing cancer. More research is needed to help better address these concerns."[32]

37
Human health

The effects of rBGH on human health is an ongoing debate, in part due to the lack of conclusive
evidence. A few of the most debated issues include:

IGF-1 is a hormone found in humans that is responsible for growth promotion, protein
synthesis, and insulin actions over the lifecycle. The hormone has been shown to influence the
growth of tumors in some studies and may be linked to the development of
prostate,[33] colorectal, breast,[34][35] and other cancers.[36][37][38]

IGF-1 is also found in milk (soy included). Previous research has proposed an increase of IGF-
1 in rBST-treated cows, but this claim is currently not substantiated. In addition, no current
evidence shows that orally consumed IGF-1 is absorbed in humans and the dietary amount is
negligible when compared to what the body produces on its own. “IGF-1 in milk is not
denatured (inactivated) by pasteurization. The extent to which intact, active IGF-1 is absorbed
through the human digestive tract remains uncertain.

The American Cancer Society has reviewed the evidence concerning IGF-1 in milk from rBST-
treated cows, and found that: "While there may be a link between IGF-1 blood levels and
cancer, the exact nature of this link remains unclear. Some studies have shown that adults who
drink milk have about 10% higher levels of IGF-1 in their blood than those who drink little or
no milk. But this same finding has also been reported in people who drink soymilk. This
suggests that the increase in IGF-1 may not be specific to cow's milk, and may be caused by
protein, minerals, or some other factors in milk unrelated to rBGH. There have been no direct
comparisons of IGF-1 levels in people who drink ordinary cow's milk vs. milk stimulated by
rBGH. At this time, it is not clear that drinking milk, produced with or without rBGH treatment,
increases blood IGF-1 levels into a range that might be of concern regarding cancer risk or
other health effects.... IGF-1 concentrations are slightly higher (to variable degrees, depending
on the study) in milk from cows treated with rBGH than in untreated milk. This variability is
presumed to be much less than the normal range of variation of IGF-1 in cow's milk due to
natural factors, but more research is needed."[32]

Research is supportive of milk supplying vital nutrients used in childhood development.[39] At

this time, evidence does not link rBST-treated milk with adverse health outcomes for
children.[40] Several studies have looked at the relationship between type 1 diabetes and infant
feeding. Environmental triggers that may elicit an autoimmune reaction is the mechanism in

38
which is being studied. Some studies have shown early exposure to bovine milk may predispose
an infant to type 1 diabetes, whereas other studies show no causality.[41]

The American Society of Animal Science published an article in 2014 after reviewing health
issues arising from the rBST debate. The article indicated “there are no new human health
issues related to the use of rbST by the dairy industry. Use of rbST has no effect on the micro-
and macrocomposition of milk. Also, no evidence exists that rbST use has increased human
exposure to antibiotic residues in milk. Concerns that IGF-I present in milk could have
biological effects on humans have been allayed by studies showing that oral consumption of
IGF-I by humans has little or no biological activity. Additionally, concentrations of IGF-I in
digestive tract fluids of humans far exceed any IGF-I consumed when drinking milk.
Furthermore, chronic supplementation of cows with rbST does not increase concentrations of
milk IGF-I outside the range typically observed for effects of farm, parity, or stage of lactation.
Use of rbST has not affected expression of retroviruses in cattle or posed an increased risk to
human health from retroviruses in cattle. Furthermore, risk for development of type 1 or type
2 diabetes has not increased in children or adults consuming milk and dairy products from
rbST-supplemented cows. Overall, milk and dairy products provide essential nutrients and
related benefits in health maintenance and the prevention of chronic diseases.” [42]

Environmental impact

On an industry level, supplementing one million cows with rbST would result in the same
amount of milk produced using 157,000 fewer cows.[43] Farmers are, therefore, able to improve
milk production with a smaller dairy population.

Some studies show that rBST-treated cows reduce the impact of greenhouse gases in
comparison with conventional and organic dairy operations. Furthermore, excretion of nitrogen
and phosphorus, two major environmental pollutants arising from animal agriculture, was
reduced by 9.1 and 11.8%, respectively.[44] Carbon dioxide is recognized to be the most
important anthropogenic greenhouse gas,[45] and livestock metabolism and fossil fuel
consumption are the main sources of emissions from animal agriculture.

 Livestock metabolism-use of rBST in lactating cows decreases the quantity of energy and
protein needed in comparison to conventional dairy operations along with reducing the
total feedstuff used.
 Fossil fuel consumption-targets atmospheric pollution and resource sustainability
environmental concerns. With cows treated with rBST, producing a higher milk yield
39
 reduces the feed requirement which in turn decreases with electricity for milk production
and the energy required from fossil fuels for cropping. In addition, the global warming
potential is reduced equivalent to removing 400,000 family cars from the road.

When conventional, conventional with rBST, and organic dairy operations are compared, 8%
fewer cows are needed in an rBST-supplemented population, whereas organic production
systems require a 25% increase to meet production targets.[44] This is due to a lower milk yield
per cow due to the pasture-based system which is attributed with a greater maintenance energy
expenditure associated with grazing behavior

40
 SCHOOL OF BIO AND CHEMICAL ENGINEERING
DEPARTMENT OF BIOTECHNOLOGY

UNIT – II – Bioethics Biosafety and IPR – SBTA7011

1
 UNIT 2 BIOSAFETY
Introduction, Different levels of Biosafety, Biosafety levels of specific Microorganisms;
Recommended Biosafety levels for Infectious agents and Infected animals, Biosafety
Issues in Biotechnology, Biological Safety Cabinets; Containments- Types. Basic
Laboratory and Maximum Containment Laboratory.
----------------------------------------------------------------------------------------------------------------
-----

Biosafety level

From Wikipedia, the free encyclopedia

Essential features of a biosafety level 4 (BSL-4) laboratory[1]

A biosafety level (BSL), or pathogen/protection level, is a set of biocontainment precautions

required to isolate dangerous biological agents in an enclosed laboratory facility. The levels of
containment range from the lowest biosafety level 1 (BSL-1) to the highest at level 4 (BSL-4).
In the United States, the Centers for Disease Control and Prevention (CDC) have specified
these levels.[2] In the European Union, the same biosafety levels are defined in
a directive.[3] In Canada the four levels are known as Containment Levels.[4] Facilities with

2
these designations are also sometimes given as P1 through P4 (for pathogen or protection
level), as in the term P3 laboratory.[5]

At the lowest level of biosafety, precautions may consist of regular hand-washing and minimal
protective equipment. At higher biosafety levels, precautions may include airflow systems,
multiple containment rooms, sealed containers, positive pressure personnel suits, established
protocols for all procedures, extensive personnel training, and high levels of security to control
access to the facility.

History

The first prototype Class III (maximum containment) biosafety cabinet was fashioned in 1943
by Hubert Kaempf Jr., then a U.S. Army soldier, under the direction of Arnold G. Wedum,
Director (1944–69) of Industrial Health and Safety at the United States Army Biological
Warfare Laboratories, Camp Detrick, Maryland. Kaempf was tired of his MP duties at Detrick
and was able to transfer to the sheet metal department working with the contractor, the H.K.
Ferguson Co.[6]

On 18 April 1955, fourteen representatives met at Camp Detrick in Frederick, Maryland. The
meeting was to share knowledge and experiences regarding biosafety, chemical, radiological,
and industrial safety issues that were common to the operations at the three principal biological
warfare (BW) laboratories of the U.S. Army.[7] Because of the potential implication of the work
conducted at biological warfare laboratories, the conferences were restricted to top
level security clearances. Beginning in 1957, these conferences were planned to include non-
classified sessions as well as classified sessions to enable broader sharing of biological safety
information. It was not until 1964, however, that conferences were held in a government
installation not associated with a biological warfare program.[8]

Over the next ten years, the biological safety conferences grew to include representatives from
all federal agencies that sponsored or conducted research with pathogenic microorganisms. By
1966, it began to include representatives from universities, private laboratories, hospitals, and
industrial complexes. Throughout the 1970s, participation in the conferences continued to
expand and by 1983 discussions began regarding the creation of a formal
organization.[8] The American Biological Safety Association (ABSA) was officially
established in 1984 and a constitution and bylaws were drafted the same year. As of 2008,
ABSA includes some 1,600 members in its professional association.[8]

3
In 1977 Jim Peacock of the Australian Academy of Science asked Bill Snowdon, then Chief
CSIRO AAHL if he could have the newly released USA NIH and the British equivalent
requirements for the development of infrastructure for bio-containment reviewed by AAHL
personnel with a view to recommending the adoption of one of them by Australian authorities.
The review was carried out by CSIRO AAHL Project Manager Bill Curnow and CSIRO
Engineer Arthur Jenkins. They drafted outcomes for each of the levels of security. AAHL was
notionally classified as "substantially beyond P4". These were adopted by the Australian
Academy of Science and became the basis for Australian Legislation. It opened in 1985 costing
$185 million, built on Corio Oval.[9] The Australian Animal Health Laboratory is a Class 4/ P4
Laboratory.

Levels

Biosafety level 1

Biosafety level 1 (BSL-1) is suitable for work with well-characterized agents which do not
cause disease in healthy humans. In general, these agents should pose minimal potential hazard
to laboratory personnel and the environment.[10] At this level, precautions are limited relative
to other levels. Laboratory personnel must wash their hands upon entering and exiting the lab.
Research with these agents may be performed on standard open laboratory benches without the
use of special containment equipment. However, eating and drinking are generally prohibited
in laboratory areas.[10] Potentially infectious material must be decontaminated before disposal,
either by adding a chemical such as bleach or isopropanol or by packaging for decontamination
elsewhere.[10] Personal protective equipment is only required for circumstances where
personnel might be exposed to hazardous material.[10] BSL-1 laboratories must have a door
which can be locked to limit access to the lab. However, it is not necessary for BSL-1 labs to
be isolated from the general building.[11]

This level of biosafety is appropriate for work with several kinds of microorganisms including
non-pathogenic strains of Escherichia coli and Staphylococcus, Bacillus
subtilis, Saccharomyces cerevisiae and other organisms not suspected to contribute to human
disease.[12] Due to the relative ease and safety of maintaining a BSL-1 laboratory, these are the
types of laboratories generally used as teaching spaces for high schools and colleges.[11]

Biosafety level 2

At this level, all precautions used at Biosafety Level 1 are followed, and some additional
precautions are taken. BSL-2 differs from BSL-1 in that:

4
 Laboratory personnel have specific training in handling pathogenic agents and are directed
by scientists with advanced training.
 Access to the laboratory is limited when work is being conducted.
 Extreme precautions are taken with contaminated sharp items.
 Certain procedures in which infectious aerosols or splashes may be created are conducted
in biological safety cabinets or other physical containment equipment.[10]

Biosafety level 2 is suitable for work involving agents of moderate potential hazard to
personnel and the environment.[11] This includes various microbes that cause mild disease to
humans, or are difficult to contract via aerosol in a lab setting.[13] Examples include
Hepatitis A, B, and C viruses, human immunodeficiency virus (HIV), pathogenic strains
of Escherichia coli and Staphylococcus, Salmonella, Plasmodium falciparum,
and Toxoplasma gondii.[13][14]

Biosafety level 3

Researcher at US Centers for Disease Control, Atlanta, Georgia, working with influenza
virus under biosafety level 3 conditions, with respirator inside a biosafety cabinet (BSC).

Biosafety level 3 is appropriate for work involving microbes which can cause serious and
potentially lethal disease via the inhalation route.[10] This type of work can be done in clinical,
diagnostic, teaching, research, or production facilities.[11] Here, the precautions undertaken in
BSL-1 and BSL-2 labs are followed, as well as additional measures including:

5
 All laboratory personnel are provided medical surveillance and offered relevant
immunizations (where available) to reduce the risk of an accidental or unnoticed
infection.[10]
 All procedures involving infectious material must be done within a biological safety
cabinet.[10]
 Laboratory personnel must wear solid-front protective clothing (i.e. gowns that tie in the
back). This cannot be worn outside of the laboratory and must be discarded or
decontaminated after each use.[10]
 A laboratory-specific biosafety manual must be drafted which details how the laboratory
will operate in compliance with all safety requirements.[10]

In addition, the facility which houses the BSL-3 laboratory must have certain features to ensure
appropriate containment. The entrance to the laboratory must be separated from areas of the
building with unrestricted traffic flow.[10] Additionally, the laboratory must be behind two sets
of self-closing doors (to reduce the risk of aerosols escaping).[11] The construction of the
laboratory is such that it can be easily cleaned. Carpets are not permitted, and any seams in the
floors, walls, and ceilings are sealed to allow for easy cleaning and
decontamination.[10] Additionally, windows must be sealed, and a ventilation system installed
which forces air to flow from the "clean" areas of the lab to the areas where infectious agents
are handled.[10] Air from the laboratory must be filtered before it can be recirculated.[10]

Biosafety level 3 is commonly used for research and diagnostic work involving various
microbes which can be transmitted by aerosols and/or cause severe disease. These
include Francisella tularensis, Mycobacterium tuberculosis, Chlamydia psittaci, Venezuelan
equine encephalitis virus, Eastern equine encephalitis virus, SARS-CoV-1, SARS-CoV-
2, MERS-CoV, Coxiella burnetii, Rift Valley fever virus, Rickettsia rickettsii, several species
of Brucella, chikungunya, yellow fever virus, West Nile virus, Yersinia pestis.[14][15]

6
Biosafety level 4

CDC technician dons an older-model positive-pressure suit before entering one of the CDC's
earlier BSL-4 labs.

Biosafety level 4 (BSL-4) is the highest level of biosafety precautions, and is appropriate for
work with agents that could easily be aerosol-transmitted within the laboratory and cause
severe to fatal disease in humans for which there are no available vaccines or
treatments.[10] BSL-4 laboratories are generally set up to be either cabinet laboratories or
protective-suit laboratories.[10] In cabinet laboratories, all work must be done within a class III
biosafety cabinet.[10] Materials leaving the cabinet must be decontaminated by passing through
an autoclave or a tank of disinfectant.[10] The cabinets themselves are required to have seamless
edges to allow for easy cleaning. Additionally the cabinet and all materials within must be free
of sharp edges in order to reduce the risk of damage to the gloves.[10] In a protective-suit
laboratory, all work must be done in a class II biosafety cabinet by personnel wearing a positive
pressure suit.[10] In order to exit the BSL-4 laboratory, personnel must pass through a chemical
shower for decontamination, then a room for removing the positive-pressure suit, followed by
a personal shower.[10] Entry into the BSL-4 laboratory is restricted to trained and authorized
individuals, and all persons entering and exiting the laboratory must be recorded.[10]

As with BSL-3 laboratories, BSL-4 laboratories must be separated from areas that receive
unrestricted traffic. Additionally airflow is tightly controlled to ensure that air always flows
from "clean" areas of the lab to areas where work with infectious agents is being

7
performed.[10] The entrance to the BSL-4 lab must also employ airlocks to minimize the
possibility that aerosols from the lab could be removed from the lab. All laboratory waste,
including filtered air, water, and trash must also be decontaminated before it can leave the
facility.[10]

Biosafety level 4 laboratories are used for diagnostic work and research on easily transmitted
pathogens which can cause fatal disease. These include a number of viruses known to
cause viral hemorrhagic fever such as Marburg virus, Ebola virus, Lassa virus, and Crimean-
Congo hemorrhagic fever. Other pathogens handled at BSL-4 include Hendra virus, Nipah
virus, and some flaviviruses. Additionally, poorly characterized pathogens which appear
closely related to dangerous pathogens are often handled at this level until sufficient data are
obtained either to confirm continued work at this level, or to permit working with them at a
lower level.[14] This level is also used for work with Variola virus, the causative agent
of smallpox, though this work is only performed at the Centers for Disease Control and
Prevention in Atlanta, United States, and the State Research Center of Virology and
Biotechnology in Koltsovo, Russia.[16]

Regular inspection of positive-pressure suits to locate any leaks[17]

SPECT machine at BSL-4 imaging facility that separates subjects with pathogens from the
machines.[1]

8


The circular containment tube separates the patient table in the "hot" zone (pathogen
present) from the "cold" zone around this MRI machine.

Air pressure resistant (APR) door to separate the hot and cold zones

Working inside a BSL-4 lab with air hoses providing positive air pressure.

Inside a Class III biological safety cabinet with an aerosol control platform

9


Effluent decontamination system of a BSL-4 lab of NIAID

BSL-4 facilities for extraterrestrial samples

Sample-return missions that bring back to Earth samples obtained from a Category V body
must be curated at facilities rated BSL-4. Because the existing BSL-4 facilities in the world do
not have the complex requirements to ensure the preservation and protection of Earth and the
sample simultaneously,[18] there are currently at least two proposals to build a BSL-4 facility
dedicated to curation of restricted (potentially biohazardous) extraterrestrial materials.

The first is the European Sample Curation Facility (ESCF),[19][20] proposed to be built
in Vienna, which would curate non-restricted samples as well as perform BSL-4 processing of
restricted material obtained from Category V bodies such as Mars, Europa,
and Enceladus.[19] The other proposal is by NASA and is tentatively known as the Mars
Sample-Return Receiving facility (MSRRF).[21] At least three different designs were submitted
in 2009.[18] If funded, this American facility would be expected to take 7 to 10 years from
design to completion,[22][23] and an additional two years is recommended for the staff to become
proficient and accustomed to the facilities.[22] NASA is also assessing a 2017 proposal to build
a mobile and modular BSL-4 facility to secure a sample return capsule at the landing site to
conduct preliminary biohazard analyses.[24] After completion of biohazard testing, decisions
could be made to sterilize the sample or transport all or portions to a permanent quarantine
storage facility anywhere in the world.[24]

The systems of such facilities must be able to contain unknown biohazards, as the sizes of any
putative alien microorganisms are unknown. Ideally, it should filter particles down to
10 nanometers, and release of a particle 50 nanometers or larger is unacceptable under any
circumstance.[25]

List of BSL-4 facilities

According to a U.S. Government Accountability Office (GAO) report published on 4 October

2007, a total of 1,356 CDC/USDA registered BSL-3 facilities were identified throughout the

10
United States.[26] Approximately 36% of these laboratories are located in academia. 15 BSL-4
facilities were identified in the U.S. in 2007, including nine at federal labs.[26]

The following is a list of existing BSL-4 facilities worldwide.

Countr ye
Name Location Description
y ar

National Service of
Healthcare and
Buenos Diagnostic laboratory for Foot-and-mouth
Agriculture Argentina
Aires disease.[27]
Quality (SENASA
)

Capable of housing from large experimental

animals to insects under conditions that
exceed all BSL 4 requirements. The
antecedent of all such facilities developed
since the 1980s. Arguably the most
researched design and construction project
ever. AAHL is subdivided into a number of
Australian Centre
Geelong, V isolation zones that can be managed at
for Disease Australia 1985
ictoria differing containment levels concurrently.
Preparedness CSIRO AAHL Project Manager and
Architect, William Curnow, provided
technical reviews to Canadian, Indian, UK
and French Authorities and consulted with
Dr Jerry Callis [PIADC] to UN FAO on
matters of bio-containment. Formerly
known as the Australian Animal Health
Laboratory (AAHL) and renamed to

11
 Countr ye
Name Location Description
y ar

Australian Centre for Disease Preparedness

April 2020

University of
Melbourne –
Melbourne,
Doherty Institute Australia 2014 Diagnostic reference lab.[28][29]
Victoria
for Infection and
Immunity

National High Operates under the auspice of the Victoria

Melbourne,
Security Australia Infectious Diseases Reference
Victoria
Laboratory Laboratory.[30]

Laboratório
Nacional Pedro
Agropecuário de Leopoldo, Focus on Agropecuary diseases and
Brazil 2014
Minas Minas diagnostics.[31]
Gerais (Lanagro/M Gerais
G)

Located at the Canadian Science Centre for

National Human and Animal Health, it is jointly
Winnipeg, 1999
Microbiology Canada [32]
operated by the Public Health Agency of
Manitoba
Laboratory Canada and the Canadian Food Inspection
Agency.[33]

12
 Countr ye
Name Location Description
y ar

Wuhan Institute of Virology has existed

Wuhan Institute of
since 1956 and already hosted BSL3
Virology of the Wuhan, Hu
China 2015 laboratories. A BSL4 facility was completed
Chinese Academy bei
in 2015, and became the first BSL-4
of Sciences
laboratory in China.[34]

Harbin Veterinary
Research
Harbin Veterinary Research
Institute of
Harbin, Hei Institute researches prevention and control
the Chinese China 2018
longjiang of major infectious diseases. China's second,
Academy of
and the first for large animals, BSL-4 lab.[35]
Agricultural
Sciences

1971
,
Hospital and research facility. Located at the
Těchonín, rebui
Biological Defense Czech Centrum biologické ochrany (Biological
Pardubice lt
Center Republic Defense Center). Operated by Army of the
Region 2003
Czech Republic.[36]
–
2007

French Armed Brétigny-

sur-
Biomedical France French Army laboratory.[37]
Orge, Esso
Research
nne
Institute, French

13
 Countr ye
Name Location Description
y ar

Defence Health
Service

Lyon, Metr
Jean Mérieux BSL- Built and owned by the Fondation Mérieux.
opolis of France 1999
4 Laboratory Since 2004, operated by INSERM.[38]
Lyon

Vert-le-
Laboratoire de la
Petit, Esson France 2013 Operated by the Ministry of Defense.[39]
DGA
ne

Centre
Franceville, This facility is operated by a research
International de
Haut- organization supported by both Gabonese
Recherches Gabon
Ogooué (mainly) and French governments, and is
Médicales de
Province West Africa's only P4 lab (BSL-4).[40]
Franceville

Robert Koch
Berlin Germany 2015 Diagnostic and experimental lab facility.[41]
Institute

Bernhard Nocht Part of the Leibniz Center Infection.

Institute for Hamburg Germany 2014 National reference lab for tropical
Tropical Medicine viruses.[42]

Friedrich Loeffler Isle Focus on animal viral diseases and

Germany 2010
Institute of Riems, diagnostics.[43]
Greifswald,

14
 Countr ye
Name Location Description
y ar

Mecklenbu
rg-
Vorpomme
rn

Philipps
Marburg, H
University of Marb Germany 2008 Focuses on hemorrhagic fever viruses.[44]
esse
urg

Division of Virology operates three WHO

National Reference Laboratories. The BSL-
National Center for
Budapest Hungary 1998 4 biosafety laboratory provides a modern
Epidemiology
means to process dangerous imported
zoonotic viral pathogens.[45]

Opened in 2016, part of "Szentágothai János

University of Pécs Pécs Hungary 2016
Kutatóközpont".

High Security
Bhopal, Ma This facility deals especially to zoonotic
Animal Disease
dhya India 1998 organisms and emerging infectious disease
Laboratory
Pradesh threats.[46]
(HSADL)

Centre for Cellular

Hyderabad, National BSL-4 Containment Facility for
and Molecular India 2009
Telangana Human Infectious Diseases.[47]
Biology

15
 Countr ye
Name Location Description
y ar

National Institute Pune, Maha India's most advanced BSL-4 category

India 2012
of Virology rashtra lab.[48]

The "National Institute of Infectious

Diseases" used to operate within the
Istituto Nazionale
Rome, Lazi Lazzaro Spallanzani hospital; the facility is
per le Malattie Italy 1997
o now independent and is home to five BSL-3
Infettive
labs as well as a single BSL-4 laboratory,
which was completed in 1997.[49]

Located at National Institute for Infectious

National Institute Musashimu
Diseases, Department of Virology I. Built in
for Infectious rayama, To Japan 2015
1981; operated at BSL-3 until 2015 due to
Diseases kyo
opposition from nearby residents.[50]

Institute of
Tsukuba, Ib
Physical and Facility completed in 1984 but not operated
araki Japan 1984
Chemical as BSL-4 due to local opposition.[51]
Prefecture
Research (RIKEN)

State Research
Koltsovo,
Center of Virology One of two WHO-approved facilities for
Novosibirs Russia
and Biotechnology work on variola virus.[16]
k Oblast
(VECTOR)

16
 Countr ye
Name Location Description
y ar

National Institute
Johannesbu South [52]
for Communicable 2002
rg, Gauteng Africa
Diseases

Cheongju,
Korea Centers for
North South
Disease Control 2017 First BSL-4 Lab in South Korea
Chungcheo Korea
and Prevention
ng Province

Solna, Stoc The only BSL-4 facility in the Nordic

Public Health
kholm Sweden 2001 region. Constructed for research and
Agency of Sweden
County diagnostics of hemorrhagic fever viruses.[53]

Geneva, Ca
University Hospital Switzerla "Glove box" type laboratory; primarily for
nton of
of Geneva nd handling clinical samples.[54]
Geneva

Run by Federal Office for Civil

Spiez, Cant Switzerla
Spiez Laboratory 2013 Protection and the Federal Department of
on of Bern nd
Defence, Civil Protection and Sports.[55]

The Institute of
Mittelhäuse Part of the Food Safety and Veterinary
Virology and Switzerla
rn, Canton Office (FSVO).[57] Primary purpose is
Immunology nd
[56]
of Bern diagnostics of highly pathogenic viruses.[55]
IVI

17
 Countr ye
Name Location Description
y ar

Institute of National
[58]
Preventive Defense Taiwan 1983
Medicine University

Camden, G
Francis Crick United Has BSL-4 space but does not work on
reater 2015
Institute Kingdom human pathogens.[59]
London

Department of Health laboratory.

Public Health Colindale,
United Diagnostics for various viral
England's Centre Greater
Kingdom diseases.[60] Part of the European Network
for Infections London
of Biosafety-Level-4 Laboratories.[61]

Medical Research Council laboratory.

National Institute Mill Research and diagnostics for highly
United
for Medical Hill, Greate pathogenic viruses. Closed in 2017 and
Kingdom
Research r London work moved to the Francis Crick Institute.
Site demolished in 2018. [60]

National Institute
Potters Department of Health and Home Office
for Biological United
Bar, Hertfo laboratory. Develop assays and reagents for
Standards and Kingdom
rdshire research on virulent pathogens.[60]
Control

18
 Countr ye
Name Location Description
y ar

Department for Environment, Food and

Animal and Plant Addlestone, United
Rural Affairs laboratory. Diagnostics and
Health Agency Surrey Kingdom
research for animal diseases.[60]

Biotechnology and Biological Sciences

Institute for Pirbright, S United
Research Council laboratory. Research on
Animal Health urrey Kingdom
highly pathogenic animal diseases.[60]

Private lab. Produces vaccines against foot

Merial Animal Pirbright, S United
and mouth disease and bluetongue
Health urrey Kingdom
disease.[60]

Department of Health laboratory.

Centre for
Porton Diagnostics and research for haemorrhagic
Emergency United
Down, Wilt fever viruses.[60] Part of the European
Preparedness and Kingdom
shire Network of Biosafety-Level-4
Response
Laboratories.[61]

Defence Science Porton

United Ministry of Defence laboratory. Focuses on
and Technology Down, Wilt
Kingdom protection from biological weapons.[60]
Laboratory shire

Centers for Disease Fort United A BSL 3/4 facility that operates in
Control and Collins, Co States connection with some of Colorado State
lorado
Prevention, University's biomedical research programs.

19
 Countr ye
Name Location Description
y ar

Division of Vector The location specializes in arboviral and

Borne Diseases bacterial diseases.[62]

Centers for Disease Currently operates in two buildings. One of

Atlanta, Ge United
Control and two facilities in the world that officially
orgia States
Prevention hold smallpox.[16]

Georgia State Atlanta, Ge United

1997 Research focus on B virus.[63]
University orgia States

National Bio and Under construction. Facility to be operated

2022
Agro-Defense by the Department of Homeland Security,
Manhattan, United (exp
Facility (NBAF), and replace the Plum Island Animal Disease
Kansas States ected
Kansas State Center. Expected to be operational by 2022–
)
University 2023.[64]

National Institutes Bethesda, United Located on the NIH Campus, it currently

of Health (NIH) Maryland States only operates with BSL-3 agents.[65]

Fort Operated by National Institute of Allergy

Integrated United
Detrick, M and Infectious Diseases (NIAID). Focuses
Research Facility States
aryland on animal models of human diseases.[66]

Fort Operated by the Department of Homeland

National United
Detrick, M Security. Focus on potential bioterrorism
Biodefense States
threats.[67]
Analysis and aryland

20
 Countr ye
Name Location Description
y ar

Countermeasures
Center

US Army Medical
Research Institute Fort
United Run by the U.S. Army. Research focuses on
of Infectious Detrick, M 1969
States biological threats to the U.S. military.[68][69]
Diseases (USAMR aryland
IID)

Built
2008
,
Open
ed
National Emerging
2012
Infectious Diseases
Boston, Ma United ,[70] Focus on potential threats to public
Laboratory (NEID
ssachusetts States BSL- health.[72]
L), Boston
4
University
Appr
oval
in
2017
[71]

Rocky Mountain
Laboratories Integr Hamilton, United NIAID laboratory. Focus on vector-borne
2008
ated Research Montana States diseases.[73]
Facility

21
 Countr ye
Name Location Description
y ar

Galveston National
Laboratory,
Galveston, United Opened in 2008, facility is operated by
National
Texas States the University of Texas Medical Branch.[74]
Biocontainment
Facility

Galveston, United Operated by the University of Texas

Shope Laboratory 2004
Texas States Medical Branch.[75]

San
Texas Biomedical United The only privately owned BSL-4 lab in the
Antonio, T 1999
Research Institute States US.[76]
exas

Safety concerns

A North Carolina Mosquito & Vector Control Association (NCMVCA) study highlighted
safety concerns. In the United States, laboratories can be funded by federal, state, private, non-
profit, or academically. The last accounts for 72% of the funding. There is no central
monitoring agency accountable for monitoring laboratories and standards vary according to
funding, the age of the laboratory, and is dependent on the size and whether it is SA
approved.[77]

High-containment labs that are registered with the Centers for Disease Control and Prevention
(CDC) and the U.S. Department of Agriculture's (USDA) Select Agent Program must adhere
to Department of Defense standards.[78] No single federal agency, according to 12 agencies'
responses to a GSA survey, has the mission to track the overall number of BSL-3 and BSL-4
labs in the United States. This means no agency is responsible for determining the risks
associated with the proliferation of these labs.[79]

22
Biocontainment

From Wikipedia, the free encyclopedia

Researchers working in Class III cabinets at the U.S. Army Biological Warfare
Laboratories, Camp Detrick, Maryland (1940s). Biocontainment procedures were pioneered at
the USBWL in the 1940s and '50s.

One use of the concept of biocontainment is related to laboratory biosafety and pertains
to microbiology laboratories in which the physical containment of pathogenic organisms or
agents (bacteria, viruses, and toxins) is required, usually by isolation in environmentally and
biologically secure cabinets or rooms, to prevent accidental infection of workers or release into
the surrounding community during scientific research.

Another use of the term relates to facilities for the study of agricultural pathogens, where it is
used similarly to the term "biosafety", relating to safety practices and procedures used to
prevent unintended infection of plants or animals or the release of high-consequence
pathogenic agents into the environment (air, soil, or water).

Terminology

The World Health Organization's 2006 publication, Biorisk management: Laboratory

biosecurity guidance, defines laboratory biosafety as "the containment principles, technologies
and practices that are implemented to prevent the unintentional exposure to pathogens and
toxins, or their accidental release". It defines biorisk management as "the analysis of ways and
development of strategies to minimize the likelihood of the occurrence of biorisks".[1]

23
The term "biocontainment" is related to laboratory biosafety.[2][3] Merriam-Webster's online
dictionary reports the first use of the term in 1966, defined as "the containment of extremely
pathogenic organisms (such as viruses) usually by isolation in secure facilities to prevent their
accidental release especially during research".[4]

The term laboratory biosafety refers to the measures taken "to reduce the risk of accidental
release of or exposure to infectious disease agents", whereas laboratory biosecurity is usually
taken to mean "a set of systems and practices employed in legitimate bioscience facilities to
reduce the risk that dangerous that dangerous biological agents will be stolen and used
maliciously".[5]

Containment types

Laboratory context

Primary containment is the first container in direct contact with biohazardous material[6] as
well as protection of personnel and the immediate laboratory environment from exposure to
infectious agents. Primary containment requires using proper storage containers, good
microbiological technique, and the use of appropriate safety equipment such as biological
safety cabinets.

Secondary containment is the protection of the environment external to the laboratory from
exposure to infectious materials and is provided by a combination of facility design and
operational practices.

Biological safety cabinets (BSC), first commercially available in 1950,[7] are fairly common
devices designed to provide effective primary biocontainment in laboratories working with
highly infectious agents. Three general levels and types have been devised (Class I, Class II,
and Class III).

Biosafety suites are suites of laboratory rooms which are essentially equivalent to large Class
III cabinets in which positive pressure personnel suits ("space suits") serve as the "outside"
environment for workers. Examples include the biosafety suites at USAMRIID at Fort Detrick,
Maryland, USA and the Maximum Containment Facility (MCF) of the CDC in Atlanta,
Georgia, USA.

24
Agricultural context

The term “biocontainment” is used differently in facilities for the study of human pathogens
versus those used for the study of agricultural pathogens. In agricultural facilities, the definition
for “biocontainment” resembles that for “biosafety,” i.e., the safety practices and procedures
used to prevent unintended infection of plants or animals or the release of high-consequence
pathogenic agents into the environment (air, soil, or water). In the agricultural setting, worker
protection and public health are always considerations; however, emphasis is placed on
reducing the risk that agents under study could escape into the environment.

----------------------------------------------------------------------------------------------------------------

A genetically modified organism (GMO) is any organism whose genetic material has been
altered using genetic engineering techniques. The exact definition of a genetically modified
organism and what constitutes genetic engineering varies, with the most common being an
organism altered in a way that "does not occur naturally by mating and/or
natural recombination". A wide variety of organisms have been genetically modified (GM),
from animals to plants and microorganisms. Genes have been transferred within the same
species, across species (creating transgenic organisms), and even across kingdoms. New genes
can be introduced, or endogenous genes can be enhanced, altered, or knocked out.

Creating a genetically modified organism is a multi-step process. Genetic engineers must

isolate the gene they wish to insert into the host organism and combine it with other genetic
elements, including a promoter and terminator region and often a selectable marker. A number
of techniques are available for inserting the isolated gene into the host genome. Recent
advancements using genome editing techniques, notably CRISPR, have made the production
of GMO's much simpler. Herbert Boyer and Stanley Cohen made the first genetically modified
organism in 1973, a bacteria resistant to the antibiotic kanamycin. The first genetically
modified animal, a mouse, was created in 1974 by Rudolf Jaenisch, and the first plant was
produced in 1983. In 1994 the Flavr Savr tomato was released, the first
commercialized genetically modified food. The first genetically modified animal to be
commercialized was the GloFish (2003) and the first genetically modified animal to be
approved for food use was the AquAdvantage salmon in 2015.

Bacteria are the easiest organisms to engineer and have been used for research, food
production, industrial protein purification (including drugs), agriculture, and art. There is
potential to use them for environmental, purposes or as medicine. Fungi have been engineered

25
with much the same goals. Viruses play an important role as vectors for inserting genetic
information into other organisms. This use is especially relevant to human gene therapy. There
are proposals to remove the virulent genes from viruses to create vaccines. Plants have been
engineered for scientific research, to create new colors in plants, deliver vaccines, and to create
enhanced crops. Genetically modified crops are publicly the most controversial GMOs. The
majority are engineered for herbicide tolerance or insect resistance. Golden rice has been
engineered with three genes that increase its nutritional value. Other prospects for GM crops
are as bioreactors for the production of biopharmaceuticals, biofuels, or medicines.

Animals are generally much harder to transform and the vast majority are still at the research
stage. Mammals are the best model organisms for humans, making ones genetically engineered
to resemble serious human diseases important to the discovery and development of treatments.
Human proteins expressed in mammals are more likely to be similar to their natural
counterparts than those expressed in plants or microorganisms. Livestock is modified with the
intention of improving economically important traits such as growth rate, quality of meat, milk
composition, disease resistance, and survival. Genetically modified fish are used for scientific
research, as pets, and as a food source. Genetic engineering has been proposed as a way to
control mosquitos, a vector for many deadly diseases. Although human gene therapy is still
relatively new, it has been used to treat genetic disorders such as severe combined
immunodeficiency, and Leber's congenital amaurosis.

Many objections have been raised over the development of GMOs, particularly their
commercialization. Many of these involve GM crops and whether food produced from them is
safe and what impact growing them will have on the environment. Other concerns are the
objectivity and rigor of regulatory authorities, contamination of non-genetically modified food,
control of the food supply, patenting of life and the use of intellectual property rights.
Although there is a scientific consensus that currently available food derived from GM crops
poses no greater risk to human health than conventional food, GM food safety is a leading issue
with critics. Gene flow, impact on non-target organisms, and escape are the major
environmental concerns. Countries have adopted regulatory measures to deal with these
concerns. There are differences in the regulation for the release of GMOs between countries,
with some of the most marked differences occurring between the US and Europe. Key issues
concerning regulators include whether GM food should be labeled and the status of gene-edited
organisms.

26
----------------------------------------------------------------------------------------------------------------
-----

An Overview of the Legal and Socioeconomic Impacts of Biotechnology—Biosafety

Regulations
Biosafety, as currently discussed in the International “Convention on Biological Diversity”
(CBD) and designed to create internationally binding protocols on biosafety. The application
of biotechnology to food and agriculture can bring not only potential risks and benefits as any
technology can, but also concerns about the human dimensions coupled with biotechnology.
These include both positive and negative impacts on stake holders, social institutions, economy
and communities.

Different areas associated with biosafety include:

(i) Agriculture and food system issues
(ii) Market and consumer issues
(iii) Institutional issues, business issues and
(iv) Social issues

Agriculture and food system issues.

These include the impact of biotechnology on the organisation, structure and behaviour of
agricultural industry; further, the coexistence of conventional organic and biotechnology
oriented agriculture; the capacity of the food system to segregate genetically-modified
commodity and product of specific markets; impacts on competitions involved, trade in
agricultural commodities and the economical impacts of establishing oversight, standard
regulations and public policies concerning biotechnology.

Market and consumer issues.

These include various limitations which come to the rescue of consumer demand for overall
against the products of agricultural biotechnology, the needs, desires and concerns of
consumers in domestic and international markets; the influence of culture, advertising, product
labelling, scientific information and recent new events on consumer decision making about the
use of biotechnology products; different methods for most effectively increasing the
understanding on which publication and primary decision making concerning biotechnology is
based.

27
Institutional issues and business issues.
These include the impacts of biotechnology on individual forms or group of forms about buying
or selling biotechnology products and processes; changes in business practices, alliances and
domestic and international markets including markets in Third World countries.

Social issues.
These include the needs of various public to secure meaningful information for involvement in
decision making on development and by use of agricultural biotechnology; the role of civic
engagement at the local, state and national levels; perceived and actual risks benefits to
consumers and the general environmental protection, agro-terrorism; research vandalism, and
their impacts on Third World nations.

Genetically modified food controversies

There is controversy over GMOs, especially with regard to their release outside laboratory
environments. The dispute involves consumers, producers, biotechnology companies,
governmental regulators, non-governmental organizations, and scientists. Many of these
concerns involve GM crops and whether food produced from them is safe and what impact
growing them will have on the environment. These controversies have led to litigation,
international trade disputes, and protests, and to restrictive regulation of commercial products
in some countries.[328] Most concerns are around the health and environmental effects of
GMOs. These include whether they may provoke an allergic reaction, whether the transgenes
could transfer to human cells, and whether genes not approved for human consumption
could outcross into the food supply.[329]

28
A protester advocating for the labeling of GMOs

There is a scientific consensus[330][331][332][333] that currently available food derived from GM

crops poses no greater risk to human health than conventional food,[334][335][336][337][338] but that
each GM food needs to be tested on a case-by-case basis before
introduction.[339][340][341] Nonetheless, members of the public are much less likely than scientists
to perceive GM foods as safe.[342][343][344][345] The legal and regulatory status of GM foods varies
by country, with some nations banning or restricting them, and others permitting them with
widely differing degrees of regulation.[346][347][348][349]

Gene flow between GM crops and compatible plants, along with increased use of broad-
spectrum herbicides,[350] can increase the risk of herbicide resistant weed
populations.[351] Debate over the extent and consequences of gene flow intensified in 2001
when a paper was published showing transgenes had been found in landrace maize in Mexico,
the crop's center of diversity.[352][353] Gene flow from GM crops to other organisms has been
found to generally be lower than what would occur naturally.[354] In order to address some of
these concerns some GMOs have been developed with traits to help control their spread. To
prevent the genetically modified salmon inadvertently breeding with wild salmon, all the fish
raised for food are females, triploid, 99% are reproductively sterile, and raised in areas where
escaped salmon could not survive.[355][356] Bacteria have also been modified to depend on
nutrients that cannot be found in nature,[357] and genetic use restriction technology has been
developed, though not yet marketed, that causes the second generation of GM plants to be
sterile.[358]

Other environmental and agronomic concerns include a decrease in biodiversity, an increase in

secondary pests (non-targeted pests) and evolution of resistant insect pests.[359][360][361] In the
areas of China and the US with Bt crops the overall biodiversity of insects has increased and
the impact of secondary pests has been minimal. Resistance was found to be slow to evolve
when best practice strategies were followed.[362] The impact of Bt crops on beneficial non-
target organisms became a public issue after a 1999 paper suggested they could be toxic
to monarch butterflies. Follow up studies have since shown that the toxicity levels encountered
in the field were not high enough to harm the larvae.[363]

Accusations that scientists are "playing God" and other religious issues have been ascribed to
the technology from the beginning.[364] With the ability to genetically engineer humans now
possible there are ethical concerns over how far this technology should go, or if it should be

29
used at all.[365] Much debate revolves around where the line between treatment and
enhancement is and whether the modifications should be inheritable.[366] Other concerns
include contamination of the non-genetically modified food supply,[367][368] the rigor of the
regulatory process,[369][370] consolidation of control of the food supply in companies that make
and sell GMOs,[371] exaggeration of the benefits of genetic modification,[372] or concerns over
the use of herbicides with glyphosate.[373] Other issues raised include the patenting of
life[374] and the use of intellectual property rights.[375]

There are large differences in consumer acceptance of GMOs, with Europeans more likely to
view GM food negatively than North Americans.[376] GMOs arrived on the scene as the public
confidence in food safety, attributed to recent food scares such as Bovine spongiform
encephalopathy and other scandals involving government regulation of products in Europe,
was low.[377] This along with campaigns run by various non-governmental
organizations (NGO) have been very successful in blocking or limiting the use of GM
crops.[378] NGOs like the Organic Consumers Association, the Union of Concerned
Scientists,[379][380][381] Greenpeace and other groups have said that risks have not been
adequately identified and managed[382] and that there are unanswered questions regarding the
potential long-term impact on human health from food derived from GMOs. They propose
mandatory labeling[383][384] or a moratorium on such products.[371][369][385]

----------------------------------------------------------------------------------------------------------------
-----

Risks of Modern Biotechnology

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The following points highlight the four major risks of modern biotechnology. The risks are: 1.
Health Risks 2. Environmental Risks 3. Risks to Biodiversity 4. Socioeconomic Risks.

1. Health Risks:
Potential health risks of genetically improved organisms relate to assessing and minimizing the
risk of food allergens in genetically improved food. New biotechnology based methods allow
the identification, characterization, and minimization of risks of food allergens. Genetically

30
improved crops and food, and the risk of allergens associated with them, are now a concern
throughout the world, especially in industrial countries.

More than 90 per cent of food allergens that occur in 2 per cent of adults and 4-6 per cent of
children are associated with eight food groups. Allergenicity of genetically improved foods can
be raised in crops and foods either by raising the level of endogenous allergen or by introducing
a new allergen.

Assessment of the risk of allergens is a challenge. The International Life Sciences Institute
(ILSI) has developed a decision tree that provides a framework for risk assessment.

It uses the following criterion: that an introduced protein in a food is not a concern if
there is:
(1) No history of common allergenicity,

(2) No similar amino acid sequence to known allergens,

(3) Rapid digestion of the protein, and

(4) The protein is expressed at low levels.

Protocols enable assembly of the data to judge food against this criterion. It is also important
to inform consumers of any potential risk. A key concern of consumers is being able to identify
where allergens are found.

Consumers want to know where the potential for food allergens exists. Any protein added to
food should be assessed for potential allergenicity, whether it is added by genetic engineering
or by manufacturing.

There are several related areas of concern with regard to potential human health risks of
genetically improved foods: toxicity, carcinogenicity, food intolerances; the risk of the use of
gene markers for antibiotic resistance; other macromolecules aside from protein that could be
potential allergens; and nutritional value.

Methods of testing and evaluating risks of toxicity and carcinogenicity are well established for
food. The question remains as to whether developing countries can implement and use
currently available technologies and protocols to assess food allergens and other health risks.
31
The techniques are well established, and should be readily implementable by trained
professionals. Although no clear cases of harmful effects on human health have been
documented from new genetically improved food that does not mean that risks do not exist and
they should be assessed on a case by case basis.

2. Environmental Risks:
The risks policymakers and regulators need to assess include the potential for spread of traits
from genetically improved plants to the same or related species, plants, the build-up of
resistance in insect populations, and the potential threat to biodiversity posed by widespread
monoculture of genetically improved crops.

i. A transparent, science-based framework is required, which assesses risks on a case by case

basis and takes account of all stakeholder views.

ii. Environment-related issues to be considered in each case include the possibilities for gene
transfer, weediness, specific trait effects, genetic and phenotypic variability, and expression of
pathogenic genes.

iii. Risk management needs to consider the prospects for managing any specific risks identified
with a proposed release.

iv. Experience is accumulating in the management of the Bt genes in transgenic cotton varieties
in several countries and this needs to be closely monitored.

v. An agricultural sustainability protocol that balances risks and benefits may have value for
the approval and use of new crop varieties.

The risks lie in the management of the cropping system involving soil, water and other inputs.
There is a need for the establishment of baseline information in the environment where such
introductions are to be made. There is very little known on this, although some understanding
has been gained over recent years, and further R&D is required.

The information derived from such an assessment needs to be handled through risk
management associated with “plants as plants.” Risk management involves the consideration
of traditional cultural practices that have evolved over time, and new knowledge gained from

32
research in agronomy, plant pathology, entomology, weed science, plant biology, soils,
microbiology, and other disciplines.
3. Risks to Biodiversity:
Risks to biodiversity and wildlife are important issues in particular environments. Careful
assessment is necessary of the risks associated with the possible creation of new selection
pressures coming from the introduction of genetically improved organisms into the
environment.

Of special concern is the potential impact on biodiversity of genetically improved organisms

as the selection pressures wield influence in the species composition of the ecosystem. These
concerns merit further study, especially on the behaviour of genetically improved organisms in
the open environment.

The framework for strategic planning in the deployment of genetically improved organisms
should be formulated with sustain-ability as the primary concern. Both food safety and
biosafety regulations should reflect international agreements and best practice and a given
society’s acceptable risk levels, including the risks associated with not using biotechnology to
achieve desired goals.

The principles and practices for assessing the risks on a case-by-case basis are well established
in most Organization for Economic Cooperation and Development (OECD) countries and
several emerging economies. These principles and practices have been summarized in a series
of OECD reports published over the past decade or more.

National, regional, and international guidelines for risk assessment and risk management
provide a basis for national regulatory systems. Biosafety guidelines are available from several
international organizations including the OECD, United Nations Environment Program, United
Nations Industrial Development Organization, and the World Bank.

Regulatory trends to govern the safe use of biotechnology to date, include undertaking
scientifically based, case-by-case, hazard identification and risk assessments; regulating the
end product rather than the production process itself; developing a regulatory framework that
builds on existing institutions rather than establishing new ones; and building in flexibility to
reduce regulation of products after they have been demonstrated to be of low risk.

33
Biotechnology is not inherently different to other technologies with respect to economic and
social impacts, as long as it focuses on the problems that affect poor people.

One important difference is that research on biotechnology has largely taken place in the
private sector with proprietary technologies and an orientation to commercial agriculture. This
implies the need for a strong role for the public sector, including increased resources, to address
developing country priorities.

4. Socioeconomic Risks:
There is a risk that modern science may bypass the needs of poor people. Biotechnology is only
one tool in addressing the challenges of food security and poverty. There is a need for
biotechnology to be integrated with appropriate policies and other conventional R&D
programs.

The positive and negative impacts of biotechnology should be monitored over time in terms of
who and what are affected and how they are affected. Monitoring impact will provide guidance
for public policymakers in the future.

Unless countries have policies in place to ensure that small farmers have access to delivery
systems, extension services, productive resources, markets, and infrastructure, there is a risk
that the introduction of agricultural biotechnology could lead to increased inequality of income
and wealth.

In such cases, larger farmers are likely to capture most of the benefits through early adoption
of the technology, expanded production, and reduced unit costs.

Biotechnology has potential to reduce input use, reduce risk to biotic and abiotic stress, increase
yields, and enhance quality-all traits which should enable the development of new crop
varieties that are appropriate to poor producers and consumers.

Modern biotechnology is not a silver bullet for achieving food security, but, used in conjunction
with other agricultural research, it may be a powerful tool in the fight against poverty.

It has the potential to help enhance agricultural productivity in developing countries in a way
that further reduces poverty, improves food security and nutrition, and promotes sustainable

34
use of natural resources. Solutions to the problems facing small farmers in developing countries
could benefit both farmers and consumers.

The benefits and risks need to be assessed on a case by case basis, weighing the risks and
benefits for each particular situation. The benefits of new genetically improved food to
consumers are likely to vary according to how they earn their income and how much of their
income they spend on food.

Consumers outnumber farmers by a factor of more than 20 in the European Union, and
Europeans spend only a tiny fraction of their incomes on food.

Similarly, in the United States, farms account for less than 2 per cent of all households, and the
average consumer spends less than 12 per cent of income on food. In the industrial countries,
consumers can afford to pay more for food, increase subsidies to agriculture, and give up
opportunities for better tasting and better-looking food.

In developing countries, poor consumers depend heavily on agriculture for their livelihoods
and spend the bulk of their income on food. Strong opposition to genetically improved foods
in the European Union has resulted in restrictions on modern agricultural biotechnology in
some countries.

The opposition is driven in part by perceived lack of consumer benefits, uncertainty about
possible negative health and environmental effects, widespread perception that a few large
corporations will be the primary beneficiaries, and ethical concerns.

----------------------------------------------------------------------------------------------------------------

35
 SCHOOL OF BIO AND CHEMICAL ENGINEERING
DEPARTMENT OF BIOTECHNOLOGY

UNIT – III – Bioethics Biosafety and IPR – SBTA7011

1
 UNIT 3 BIOSAFETY GUIDELINES

Biosafety guidelines and regulations (National and International) – Operation at National

level; GMO’s and LMO’s – Definition, Institutional Biosafety Committee, RCGM,
GEAC, for GMO applications in Food and Agriculture, Assessment and management of
risks associated with GMO

Biosafety
‘Biosafety’ means the need to protect human and animal health and environment from the
possible adverse effects of the products of modern biotechnology
Environmental and Biosafety issues in modern Biotechnology
International Evolution
 Environmentalism emerged as a distinct development in the last forty
years.
 Emergence of “pressure groups” in the sixties
 First Earth Day (1970)
 The United Nations Conference on the Human Environment and
Development (1972)
 The Brundtland Report: our Common Future (1987)
 The Rio Earth Summit (1992)
 Convention on Biodiversity (CBD) [1992]
 Cartagena Protocol on Biosafety (CPB) [1993]
Convention of Biodiversity (CBD) [1992]
 Focus: conservation and sustainable use of biodiversity
 Recognized the potential of modern biotechnology for human well being
 Took cognizance that modern biotechnology could have serious effects on
environment and health
 Article 8(g) emphasized the need to regulate the risks associated with the use of
LMOS.
 Article 19(3) set the stage for a legally binding international instrument about
biosafety.
The Cartagena Protocol on Biosafety (CPB)
 Entered into force on 29th December 1993

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  Focus on transboundary movement of the LMOS.
Seeks to lay down an internationally acceptable framework to provide for an
adequate level of protection against the possible adverse effects of LMOS on
biodiversity and human health.
How is Genetic Engineering (GE) different from conventional breeding (CB)?
 Combining DNA in new combinations and introducing it into a new organism
are the GE tools.
 Main differences between CB and GE
 Ability to move across sexual barriers
 Amount of change: a specific gene embodying a particular trait or
thousands of genes embodying desirable and undesirable traits
 Occurrence of change in one or several generations.

Genetic engineering:Recombinant DNA technology

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Is GE inherently unsafe?
 Two diametrically opposite trends of thought
 US-Canada
 No new risks associated with GM crops
 New regulations not considered necessary
 Safety assessments
 ‘Product’ rather than ‘process’ based
 In comparison and contrast to their ‘familiarity’ and ‘substantial’
equivalence to conventional crops
 EU

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  GE crops considered new and special
 Existing legislation not considered sufficient
 Safety assessment
 Process based
 Principle of ‘substantial equivalence’ beginning rather than the end
 Adoption of ‘Precautionary Principle’ as guide
 GE technology carries certain inherent unpredictability
 Some facts
 Isolation of a gene from its natural environment and integration into entirely
different organism
 Possible transgenic instability due to triggering of the inbuilt defense
mechanisms of the host organism leading to inactivation or silencing of foreign
genes.
 Possibilities of integration of foreign gene at a site predisposed to silencing of
genes (position effect).
 Variance in the levels of expression of the transgene in different
environmental conditions (heat, humidity, light…..)
 Possibilities of silencing of genes arising in subsequent generations
 Case by case sound scientific assessment is of utmost significance

Biosafety issues in transgenic crops

 Relate to environmental, human and animal health consequences
 Both can have short and long term implications
 Biosafety risks involve the entire spectrum of biodiversity
 A universal ‘true for all’ approach may not be applicable

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 Risks

Known Unknown
Probability Probability

• Rigorous Scientific Assessment

• Risk Mitigation
• Precautionary Principle

Biosafety concerns arise from:

 Horizontal gene transfer
 Genetic contamination
 Transfer of allergens and toxins from one life form to another and creation of
new toxins and allergenic compounds
Main concerns
 Development of aggressive weeds/ wild relatives by transfer of
transgenic traits
 Erosion of land races/wild relatives by genetic pollution in centres of
origin/ diversity

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  Harm to the non-target organisms
 Development of pest resistance by prolonged use
 Monoculture and limitations to farmers’ choice in crop management
 Hazard to human and animal health by transfer of toxins and allergens
and by creation of new toxins and allergenic compounds
Assessment
 GE venturing into an unknown biological territory
 ASILOMAR Conference (1975): No research till safety guidelines in place
 Initially, focus on laboratory safety procedures
 Wider definition of biosafety with possibilities of commercialization of GM
products
 The broad format of biosafety parametres essentially the same in all regulations

Two main stages:

1. Laboratory/green house stage
2. Confined Trial Stage
IMPORTANT

Prevention of the spread of genetically engineered material outside lab/field

Laboratory/green house stage

 Different biosafety levels as per the degree of risk involved
 Two methods of containment
 Physical
 Biological
Confined Trial Stage

A confined trial is a small scale release of a transgenic plant species for research
purposes conducted under conditions that prevent spread of the organism and mitigate
its impact on the surrounding environment

Objective is to collect data to evaluate the crops’ performance

Focus on Risk Mitigation

Risk mitigation – the terms and conditions that are necessary to conduct the trial safely.

 Prevent Gene Flow

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  Prevent entry of GMOs into food chain

 Prevent Persistence of GMOs in the field

Bio-pharmaceutical therapeutics

Biosafety risk

 Survival, multiplication and dissemination of GMOs in contained/ open

environment

 Interaction of GMOs with biological systems

 Routes of dissemination: physical; biological

Risk depends upon

 Nature of organism invovled

 Extent of use of LMOs

 End product LMO or not?

Risk categorization of micro organisms:

 Determining factors

 Capability to cause disease

 Hazard to laboratory workers

 Risk of spread to community

 Availability of effective treatment

Health risks

 Toxigenicity Pathogenicity

 Allergenicity Antibiotic resistance

Environmental risks

 Outcrossing between GMOs and pathogens

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  Negative effects on populations of non target organisms

Risk assessment

 Access

 Expression

 Damage

Risk management and communication

 Physical

 Biological

GM foods: need for safety assessment

 Expressed proteins generally not a part of regular food supply

 Food complex mixtures e.g. nutrients, anti-nutrients and natural toxins

 Directly enter human system
 Assume different forms
 Involve storage, processing, transportation
.. Safety assessment of GM foods comprise
Guidelines by Codex Alimentarius Commission
 Assessment of possible allergenicity
 Assessment of possible toxicity
 Compositional analysis of key components
 Food processing
 Nutritional modification

….GM foods: Allergenicity; Toxicity

Allergy
It is a hypersensitive reaction initiated by immunologic mechanisms caused by specific
substances called allergens.
Assessment
 Is the gene source allergenic?

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  Expression level of introduced gene
 Unintended effect
 Digestibility and heat stability
Toxicity
 New proteins as a result of intended modification
 Unintended new proteins as a result of the modification
 Natural constituents beyond their level of normal variation

….GM foods: nutritional aspects; unintended effects

 Intended and unintended changes in nutrient levels

 Bioavailability of nutrients, stability and processing
 Presence and effect of anti-nutrients
 Impact of individual changes on overall nutritional profile
Unintended effects
Random integration of transgenes
 Insertional mutagenesis
 Disruption of gene functions
 Production of new proteins
 Changes in
o Phenotype Metabolites
o Enzymes Toxins
o Genotype
 Concluding Note……

 Biosafety is integral to modern biotechnology

 The adoption of modern biotech products needs to be balanced with adequate
biosafety safeguards
 Case by case scientific risk assessment and cost benefit analysis
 Greater acceptance of health care applications
 Need based adoption in GM crops and foods
 Participation of various stakeholders
 Dissemination of knowledge and information

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Genetically Modified Foods

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What are GM’s?
 are a result of technology that has altered the DNA of living organisms (animals, plants
or bacteria)
Other terms that mean the same thing:
 Genetically engineered
 Transgenic
 Recombinant DNA (rDNA) technology

How does this differ from Mendel and his peas?

GM vs. Selective breading
Selective breading
-slow
-imprecise
-modification of genes that naturally occur in the organism
GM
-very fast
-precise

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-can introduce genes into an organism that would not occur naturally!

Why do it?
 Rice- not high in essential nutrients
Modification:
 + daffodil genes and a bacterium = beta-carotene content drastically increased
 + genes from a french bean = double the iron content.
 Tomatoes- Introduce genes to increase shelf life.

How is this done?: Transgenic tomatoes

Other applications
 Potato - modified to produce a beetle killing toxin
 Yellow squash – modified to contain to viral genes that resistant the most common viral
diseases

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  Develop foods that contain vaccines and antibodies that offer valuable protection
against diseases such as cholera, hepatitis, and malaria
 Canola – modified to resist one type of herbicide or pesticide

A Local Example:

 Bayer CropScience produces genetically modified

canola in Australia for
the Canadian market. It is produced to resist the
Benefits of Genetic Engineering and Modifying
1. Higher yielding crops, more efficient use of land

2. Can save money and promote higher profits

3. Longer shelf life, less waste
Example: Tomatoes from genetically modified seeds stay fresh longer.
4. Enhanced taste and quality
5. Reduced maturation time
6. Increased and improved nutrients and stress tolerance
- A single gene genetically engineered into cauliflower can increase
production of beta-carotene 100 times.
- A gene can be implanted into a soybean upgrading the soy protein
to a quality equal to that of milk.
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 - Corn can be modified to contain its two limiting amino acids,
lysine or tryptophan
7. Improved resistance to disease or illness
- Foods can be enhanced with phytochemicals that help maintain
health and reduce the risks of chronic disease.
8. Improved crop resistance to disease, pests, weeds and herbicides
9. New products and growing techniques
- “Individuals allergic to milk may be able to buy milk that has been
treated with the lactase enzyme” (Whiney, 2002).
- Creating decaffeinated coffee beans are in a process of research.
Society
 Increased food security for growing populations and growth challenges
Who Uses this technology

The Countries that Grow 99% of the

World's Transgenic Crops

7% 1%

USA
23%
Argentina
Canada

69% China

Risks associated with Genetic Modification

1. Safety
 Potential human health implications.
 Potential environmental impact.
 Out-crossing
 Inevitable out-crossing of transgenic plants with naturally
occurring ones.
 Creation of super-weeds
 Creation of biological weapons.

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2. Access and Intellectual Property
 Domination of world food production by a few companies and developing
countries.
3. Ethics
 “Playing God”
 Tampering with nature by mixing genes among species.
4. Labeling
 Not mandatory in some countries (e.g., Canada and the United States).
 Mixing GM crops with non-GM confounds labeling attempts.
5. Society
 New advances may be skewed to the interests of rich countries.
(Human Genome Project Information (2003),
http://www.ornl.gov/sci/techresources/Human_Genome/elsi/gmfood.shtml)

Biodiversity
 Addition of Bt gene into plants including corn, potatoes and cotton to increase
resistance to plants
 Bt gene obtained from Bacillus thuringiensis (a soil bacterium that produces a natural
insecticide)
 Problem: plants producing Bt toxin are releasing toxin in pollen
(Draper, D. (2002). Our Environment: A Canadian Perspective 2nd Ed. Scarborough:
Thompson Canada Limited.)
 Pollen from a Bt plant was dusted on to milkweed:
- only 56% of young monarch butterfly larvae lived
- whereas pollen from organic plants dusted on the milkweed produced a survival rate of 100%.
Approximately half of the monarch butterfly population live in the “corn belt” of the USA
= this new gene could have serious repercussions for this organism

Canadian Food Inspection Agency

 Genetically modified foods are currently regulated by the CFIA
 works collaboratively with Environment Canada, Health Canada, and Fisheries and
Oceans

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  Goal: to ensure that products of biotechnology are considered safe to human and animal
health and the environment.
 According to the CFIA, the assessment process for GE foods is very rigorous

 Assessment process
 Criticisms of process

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**

Gene Expression Omnibus (GEO)

GEO is a public functional genomics data repository supporting MIAME-compliant data

submissions. Array- and sequence-based data are accepted. Tools are provided to help users
query and download experiments and curated gene expression profiles.

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**

Genetically Modified Organisms (GMO):

When a gene from one organism is purposely moved to improve or change another organism
in a laboratory, the result is a genetically modified organism (GMO). It is also sometimes called
"transgenic" for transfer of genes.

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There are different ways of moving genes to produce desirable traits. For both plants and
animals, one of the more traditional ways is through selective breeding. For example, a plant
with a desired trait is chosen and bred to produce more plants with the desirable trait. More
recently with the advancement of technology is another technique. This technique is applied in
the laboratory where genes that express the desired trait is physically moved or added to a new
plant to enhance the trait in that plant. Plants produced with this technology are transgenic.
Often, this process is performed on crops to produce insect or herbicide resistant plants, they
are referred to as Genetically Modified Crops (GM crops).

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NATIONAL AND INTERNATIONAL LEVEL BIOSAFETY REGULATIONS
In most of developing countries, biosafety regulation is still in its infancy. Appropriate
biosafety regulations are one of the prerequisites for a successful transfer of biotechnology to
and, among developing countries. Important issues in the debate on biotechnology regulation
are the uplifting
of field trials, systematising of regulations, and capacity development in developing countries.
The regulation of biosafety is a tool for the safe deployment of biotechnology applications into
the environment. It is rather a specialised form of Environmental Impact Assessment (EIA),
focussing on the biological consequences of applying Genetically Modified Organisms
(GMOs). As a part of EIA, the nature of the organism, the environment in which the organism
is to be released, and the interaction of such species, with reference to intraspecific and
interspecific are to be analysed. Field trials constitute a major part of the transgenic plants
impact assessments, however, biosafety concerns all Genetically Modified Organisms
(GMOs).

TRIALS ON–FIELD
Among several industrialized countries, biosafety regulations have been implemented since the
mid 1980s; however, there are significant differences among some of these countries. Good
experience has been established, both in the regulatory process as well as in analysing the
environmental impact of transgenic crops through small demonstration trials. Until December
1992, more than 1,180 small-scale demonstrations with transgenic plants have been conducted
in countries having Organisation for Economic Cooperation and Development (OECD).
Further, these trials are also conducted to test the expression of the newly-induced trait.

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 The most commonly tested traits in those demonstration trials are resistant to
herbicides, viruses and insects. Herbicide resistance alone accounts to 40 percent of the total
number of trials. This high percentage attracts both scientific and commercial interests. In
research on transgenic crops, herbicide resistance genes are often used as marker genes for the
selection of successfully modified plants. At the same time, commercial interest for herbicide
resistance draws from agrochemical companies seeking new markets or safeguarding the
existing market shares for their herbicides.

UPSCALING OF FIELD TRIALS

The ecological risks of transgenic crops depend on relatively rare events occasioned by the
interaction of particular plants with a particular environment. According to a report of the US
Union of Concerned Scientists (UCS), commercial use on a large scale increases the
opportunities for the rare harmful conjunctions of factors to occur. Even if a large number of
small scale demonstrations are conducted, their outcome does not predict necessarily safety on
a commercial scale. The number of plants involved in commercial use is in order of magnitude
larger than the number involved in field tests. Most of the field tests involve not more than 4
hectare plots. In contrast, commercial use of major crops such as maize and soya beans could
entail cultivation on millions of hectares in the United States alone. Usually field tests are
conducted under conditions that severely limit the escape of plants or genes from the test plots.
For example, test sites are far removed from other crops or wild relatives with which the
transgenic crop can interbreed. Developing countries, however, host many wild relatives of
crop plants. Also, sites are monitored to detect transgenic plants that escape. However, no such
restrictions apply to commercial use. Once available in the market, engineered plants are free
to migrate away from the farm, and their pollen may flow unimpeded to relatives in agricultural
and non-agricultural habitats.
Compared to field tests, commercial use will involve crops cultivated in far more diverse
environments, in proximity to a broader selection of relatives in different climates, and subject
to a greater variety of weather events, such as floods and hurricanes. Floods can expose seeds
and plants to many new, potentially congenial environments.
The UCS report offers a framework and guidelines for analyzing the environmental
risks of large scale, commercial use of transgenic crops. On discussing the issue of upscaling
within the OECD, the OECD has developed a set of scientific principles for the environmental
safety of the large scale use of transgenic plants. These guidelines contend that experience and

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knowledge gained by traditional plant breeding is essential. The more that is known about a
given plant, its traits, its environment and their likely interactions, the easier risk/safety analysis
and subsequent risk management will be harmonization.
Many non-governmental organizations, bilateral and multilateral agencies are presently
involved in providing direction and assistance in developing appropriate regulations and
technical expertise for implementing them. One of the major issues in these international
initiatives is harmonization of regulation. Harmonization means that regulatory requirements
are made compatible and that reviews are made consistent with each other. However, it does
not mean that all countries should have identical policies, priorities or strategies. The aim is
uniformity in requirements for data collection and testing procedures, and the exchange of
information. Eventually, the outcome of national regulations depends on public perceptions,
and public acceptance, as well as on cultural and institutional processes.

Harmonization of regulations has several advantages:

(a) Regulatory authorities may benefit from experiences in other countries, both on the
organization and the content of risk analysis.
(b) It may foster technology transfer as it installs confidence and simplifies the preparation of
field trial applications, and
(c) It may protect developing countries from being used as a testing ground for field trials that
would not be permitted in other countries.

DEVELOPING COUNTRIES
The developing countries, however, do not have regulatory or monitoring procedures, mainly
due to lack of monetary enforcement systems, including inadequate institutional facility. India
and Philippines which have established regulations and incorporated in their national laws, are
exceptions. Other countries viz., Argentina, Bolivia, Brazil, China, Colombia, Costa Rica,
Cuba, Indonesia, Malaysia, Thailand and Zimbabwe are in a more or less advanced stage of
drafting resolutions, or have formed adhoc committees. Adhoc committees are generally
formed to review field trial applications for transgenic plants. Although the number of field
trials cannot be matched with that of the OECD countries, it is gradually increasing. In the last
three to four years, in Latin America alone, over 60 field trials have been conducted.

COORDINATION AND CAPACITY ESTABLISHMENT

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Many of the developing countries are in a process of designing and implementing biosafety
regulations. This stage enables opportunities for international coordination of national
approaches. Such coordination is carried out by the Inter-American Institute for Cooperation
on Agriculture (IICA), for several regions within Latin America, and the International Service
for the Acquisition of Agribiotech Applications (ISAAA) for certain selected regions.
Harmonization i.e., the regulatory requirement issues were discussed at the “African Regional
Conference for International Cooperation on Safety in Biotechnology”, held in Zimbabwe in
October 1993.
The harmonization processes of IICA and ISAAA are mainly a process building
endeavour, since regulation is only as good as the public who develop and enforce it. Thus,
capacity building can be defined as (i) the training of those nationals who will be developing
and
implementing biosafety regulatory mechanisms and (ii) the sharing of experience with agencies
that are already for many years involved in developing and implementing such regulations.
This can be achieved through intensive workshops that would enable participants to gain hands
on experience pertaining to the issues and procedures.
There is also a clear-cut way in establishing and harmonizing biosafety regulations in
developing countries, by transnational biotech companies. Firstly, if a regulatory system is in
place, companies can share responsibility with regulatory authorities in case something
misfires. Secondly, supporting regulation may provide a chance to influence the content of the
regulation. And finally, implementing and harmonizing regulation can avoid unfair
competition from companies established in countries without strict safety regulation. As this is
interesting and attractive several international biotech companies contribute to the ISAAA
initiative.
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BIOSAFETY
RISKS VERSUS BENEFITS
The risk assessment procedures of transgenic plants should provide scientific quantitative
information about the chance of any adverse effect leading to an hazard. This information can
be gathered through field trials/demonstrations. There is a process of assessing these field trials.
This is the state of balancing risks against benefits. In this assessment, ecological effects are to
be mainly evaluated. Risk acceptance depends on several factors viz., the expected benefits,

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product kinds involved, different possibilities to prevent risks and the need for innovative
products through latest technologies. Public perception and reliability of information providing
agency, on risks and benefits, also are important. The evaluation of potential risks against
expected benefits may vary among different countries. In the application of biotechnology for
food production, industrialized countries can easily afford to place higher priority on health
and environmental quality management; whereas, developing countries have to concern more
with the production and distribution of food. If the application of biotechnology provides
enhanced food supplies, developing countries shall accept certain ecological risks. More often
the difference is not between south and north, but between entrepreneures and consumers and
between biotechnologists and environmentalists. As entrepreneurship is risk oriented,
entrepreneurs may accept certain risks than consumers. Consumers can “wait and see”; if their
risk perception of some product is too high, they can decide not to buy that product.
Biotechnologists focus on the genes of an individual plant and claim that genetic engineering
has opened wider options for improvement of plant production. Environmentalists focus their
attention on the effect of transgenic plants on ecosystem. Thus, the acceptance of risk and the
evaluation of risk against benefit is very much influenced by the position and interests of
producer and consumer.This also leads to discussion and deciding on biosafety regulation a
very difficult argumet.

HAZARDOUS MATERIALS USED IN BIOTECHNOLOGY — HANDLING AND

DISPOSAL
(A) Waste Categories
Hazardous waste can be broadly categorised into four categories: Chemical, radioactive,
biohazardous and material that is sharp. Each category has hazards which have an effect on
safer handling and safe disposal practices, and a specific waste may have properties of more
than one category.
Chemical waste:
Chemical wastes which are hazardous are disposed through a hazardous waste disposal
program managed by the safety department. The term “hazardous” refers to materials or
chemicals that are corrosive, flammable, reactive, explosive or toxic. The regulatory
description of hazardous waste, in a broader sense, includes the majority of known chemicals
when they are to be discarded.

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 The waste disposal of hazardous chemicals is managed in accordance with regulation
of the Cregon Department of Environmental Quality (DEQ) and the U.S. Environmental
Protection Agency. These regulations suggest specific methods for disposal of different types
of hazardous chemical wastes. Therefore, the safety department has specific guidelines which
must be strictly followed with reference to packaging, labelling, and disposal of hazardous
waste. Since generators are charged for costs associated with waste disposal, guidelines have
also been established by the safety department for recycling and waste minimizing methods.

Radioactive waste:
Radioactive substances are most toxic. As compared to organic poisons, infurious effects of
radio-nuclides are exceedingly high. For example, radium is 25,000 times more lethal than
arsenic. Nuclear war materials, test explosions, craze for power plants, radioisotope use in
medicine, industry and research are the main source of radioactive pollution that could threaten
our environmental security.
There is no suitable and cheap method of disposal of radioactive waste (spent nuclear
fuel
Gaseous effluents and low level wastes). At any time radioactivity is likely to escape from the
waste in water bodies, concrete cases and salt formations in high mountains. The nuclear waste
is thus likely to get leached into the biosphere.
Pollution control boards and environmental protection agencies must evolve certain
foolproof methods to prevent above mentioned pollution by handling radioactive wastes
carefully.

Biohazardous waste:
Biological hazard or biohazard means infectious agents causing a risk of death, injury or illness
to individuals who handle them. All waste materials which contain such agents must be
autoclaved or chemically sterilized before disposing into the general trash. A control viz.,
sterilizer indicator tape has to be used to assure the effectiveness of treatment.
Toxicity and radioactivity like hazards should not be ignored when disposing of
sterilized materials. Provided sterilization is not practical, then biohazardous material must be
incinerated in a DEQ-permitted infections waste incinerator.

Sharp materials:

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Sharp materials including needles, broken glass, and razor blades provide danger both to initial
users and to others who may come in contact with that. Besides causing physical damage, such
materials, when contaminated, can provide an entry route into the body for toxic or infectious
substances. Therefore, sharp materials should be enclosed in a rigid container and placed in
garbage dumpsters.

(B) Instructions for Hazardous Waste Disposal

Proper disposal of chemical wastes is required by central and state governmental laws. For
waste generators three steps are suggested: packaging the waste properly, filling out the
chemical collection request and sending the request to Linfield Safety Department. However,
there is no charge for the pickup service and department billing for hazardous waste disposal
will be only for the materials disposed off as billed by the disposal agency.
(a) Packaging the waste:
Package the waste in a leak-proof container with a screw-up lid or other secure closer.
However, snapcaps (such as those found on milk bottles), wrong size caps, parafilm, or
other loose-fitting lids, are not acceptable. Solid debris can be packaged into sealed
plastic bags. Biohazard bags are not to be used for chemically hazardous waste.
(b) Fill up the chemical collection request form:
The following information has to be filled legibly:
(i) Name: Name of the person to be contacted if any questions are to be clarified. He or she
should be knowledgeable about the chemical characteristics of the waste and the processes
used to generate the waste.
(ii) Date: State and federal law allows one to store waste on campus for not more than 90
days. If any container was used to accumulate waste, the date should indicate the last day
waste was added.
(iii) Department: Departments are charged for waste disposal. Therefore, it has to track
who generates a particular area-waste for billing and to help in pollution prevention
planning.
(iv) Phone details: List the number where the generator can be reached.
(v) Building and room. Please mention the building and room where the packed waste
product can be located when collectors arrive to pick it up the (not office/corporate office
address).

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Chemical Contents and Properties
Chemical name and common name:
Used as the basic identifiers for the waste product.
Constituents and percentages: List all the constituents in the container, including solvents
and water, by full name, not by abbreviation, initials or chemical formula. Mention their
approximate proportions, which should add up to 100%. If the proportions are unknown,
indicate that the container holds a mixture and identify the components as well as one can.
Properties, Number of Containers, Container type
Follow the check off and blank fill-in to complete these sections (they are self-explanatory):
Quantity per container: Indicate the amount of waste in the container, not the size of the
container, using one of the following units of measure: Litre (including ml etc.), gallon, gram
(including kg, etc.), pound. For example, two litres of waste in a four-litre container should be
entered as two litres.
• Total quantity: Amount in all containers.
• pH: Measure the pH and indicate.
• Major hazards: Be sure to indicate all hazards.
• Comments: Add any comments that you feel would be helpful in classification and handling
of the material.
The rest of the form will be completed by the Environmental Health and Safety Department
representative picking up the material.
Arranging for waste pickup
Send a copy of the completed request to safety department, unit 4002. Attach a copy of the
request to the waste container. The concerned agency will pickup the waste within a week of
receiving the request. The marked containers should be left in a visible place in the room noted
on the request form.
Problem request forms
While most chemical collection requests the agency receive are usable, there are some common
problems that create bad request; further there are some unusually ugly requests.

Common mistakes found on requests include:

(a) Signing initials or the name of a laboratory in the column designated for the
investigator/generator. A responsible person should be available to clarify any questions
regarding the waste.

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(b) Failure to list the building and room where the waste can be located.
(c) Failure to identify 100% of the chemical constituents.
(d) Failure to identify any of the constituents at all. Disposing of “unknown” chemicals is
extremely expensive.
(e) Using chemical formulas to identify the chemical constituents in the waste. For clear
communication and to comply with the applicable laws, rules and regulations, the names of the
chemical constituents must be written out completely.
(f) Using trade names, abbreviations, of waste instead of listing waste chemical constituents.
Refer to the MSDS for the chemical constituents, or attach a copy of MSDS within the
waste.

Hazardous Waste Disposal Guide

(a) Office and shop waste
Both office and shop settings typically utilize products that are found also in homes.
Environmental regulations allow homeowners greater leeway in disposal of materials than in
the
workplace environment. What people are used to legally throwing away at home may not be
legal to do at work.
(b) Aerosol-cans
All aerosol cans are considered hazardous waste until completely empty and punctured.
Campus departments may purchase devices to open aerosol cans and drain contents, except for
cans with pesticides or other highly toxic materials. Cans will be picked up as with other
hazardous wastes. Departments which produce a lot of aerosol cans are encouraged to purchase
their own opening device, in consultation with the Linfield College Safety Department.
(c) Office-products
In the past, correction fluid (“white-out”), duplicating fluid, glues, and various thinners for
these products were extensively used in offices. With the advent of word processing systems
and photocopiers, the use of these solvent-based products has decreased. Containers that are
not completely dry are typically hazardous waste when disposed. In addition, toner fluid (for
copiers and printers) may be hazardous, depending on constituents. Inks used for stamp pads
or certain pens are typically hazardous.
(d) Cleaning-products

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Many cleaning products have a high or low enough pH to qualify as hazardous waste. Any
cleaning product which smells of ammonia is likely to be above the pH allowed for sewer
disposal under McMinnville drain disposal regulations. This does not affect the use of these
products as intended, but should be kept in mind when getting rid of old or outdated stocks. In
addition, many cleaning products contain solvents which may be classified as hazardous waste
when disposed.
(e) Rags
Rags which are to be used for solvent-based purposes should be purchased, when possible,
through a laundering service which includes laundering the rags. If this is not feasible, rags
with flammable solvents or hazardous constituents should be collected in flammable rag
containers and disposed as hazardous waste.
(f) Paint Washers
Paint washers typically contain flammable or halogenated solvents. Whenever possible, users
should set up a recovery system to reclaim the solvent, or arrange for a commercial service
which does this. Manufacturers often market replacement solvents which they claim are “non-
toxic” or “biodegradable”. Their use is encouraged, especially if it results in less chlorinated
solvent use. Users must keep in mind, however, that the material they are cleaning may add
contaminants to the solvent, such as metals or grease, which make it a hazardous waste.
(g) Paint
Paint is typically hazardous before drying. The use of lead and mercury in paint has largely
disappeared, but the solvents used in both latex and oil-based paints are usually hazardous.
Excess unopened or scarcely used paint in good condition should be offered as surplus
property. Paint that has been opened should only be thrown away if it is completely dry. If not
dry, it can be painted on something or disposed as hazardous waste. There are methods to
recycle latex paint to groups that can use it.
Waste Reduction
(a) Waste-costs
The cost to dispose of hazardous chemical waste will often exceed the original purchase price
of a chemical or chemical product. The Linfield College Safety Department encourages waste
generators to use waste reduction techniques. If followed, the techniques listed below will help
reduce the volume of waste, which will have a corresponding effect on the cost of disposal.
Because the costs are variable, they are not listed here. Call the Linfield College Safety
Department for current disposal rates. In addition to disposal costs, there are fines from

27
regulatory agencies for not properly handling waste materials. These fines can be as much as
$10,000 per day, and are closely tied into storage and labeling guidelines.
(b) Purchasing
Purchase chemicals to match anticipated needs. This aspect of waste and cost reduction is
frequently overlooked. A substantial portion of hazardous waste generated at Linfield College
consists of chemicals that are in original containers, and are unused or of questionable purity
due to previous use. Projected savings from purchasing chemicals in a large size are often offset
by costs for disposal of unused portions of larger bottles, especially those with a limited shelf
life. It may not be possible to exactly determine future needs, but any effort will be beneficial.
(c) Change-procedures
A procedure which uses a hazardous substance can often be modified to lessen the hazard or
amount of waste products resulting from that procedure. In many cases, a less hazardous
material can be substituted and perform as well. An example is substituting a commercial lab
glass cleaner (e.g., NOCHROMIX) in place of chromic acid cleaning solution. The resulting
mixture is still hazardous because of its corrosive properties, but has no toxic chromium and
can therefore be neutralized. Reactive substances those that react with water or air or are
unstable are especially troublesome disposal items. Disposal costs associated with picric acid,
for example, can be as much as ten times the original purchase price.
(d) Unknowns
Unknowns are difficult and expensive to dispose. Unknowns can be prevented by good record
keeping and labeling, which includes designation of constituents and percentages. If unknowns
are found, the responsible department must make every effort to identify the material. If this is
not possible, then the responsible department will be billed for the cost of identification or
classification required for disposal of the unknown chemical, in addition to disposal costs.
(e) Recycling
Chemical recycling is possible if material is in unopened containers or partially used original
containers and of high quality. These materials are made available to interested parties at
Linfield College. Be careful not to obliterate any parts of labels. Chemicals and chemical
products should not be given or sold to the general public or offered as surplus property.
Commercial chemical products may be offered for surplus if reasonable cautions are followed.
(f) Segregate
Segregate wastes as much as possible. Mixing a low-cost disposal item with a higher one makes
the entire lot a higher-cost item.

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(g) Storage
The storage of hazardous materials must be in compliance with federal and state regulations.
Your methods of handling waste are subject to unannounced inspections by state regulatory
inspectors. All containers need to have a label at all time indicating contents. For waste
materials, this could be a simple label such as “WASTE SOLVENT” or “USED ACETONE”.
Put the label on the container BEFORE ADDING WASTE. All containers need a lid at all
times when not actively adding or removing waste. Evaporation in a hood is not a legal disposal
method. Funnels do not count as lids. Secondary containment is advised for liquid containers.
Storage limits and locations are the same for waste as for new materials. For example, storage
of flammable liquids in excess of 10 gallons requires a flammable liquid storage cabinet. Glass
bottles may not be stored on the floor because they can easily be broken by accidental kicking.
----------------------------------------------------------------------------------------------------------------
----

rDNA GUIDELINES

The National Institutes of Health (NIH) Guidelines for Research Involving

Recombinant DNA Molecules is the reference document for research compliance with
recombinant DNA molecules.
SCOPE AND APPLICABILITY
• If your institution receives Federal funding, then it must comply with the NIH
Guidelines for recombinant DNA research.
Even if a project is privately sponsored, that research experiment must still be conducted in
accordance with the NIH Guidelines.
Definition of recombinant DNA: Recombinant deoxyribonucleic acid (rDNA) by definition
involves in vitro introduction of different segments of DNA (one being the vector and the others
normally unrelated DNA sequences) that are capable of replication in a host cell either
autonomously or as an integral part of host's genome and maintenance of their continued
propagation. This will include all types of cell fusion, microinjection of DNA or RNA or parts
or all of chromosomes, genetic engineering including self cloning and deletion as well as cell
hybridation, transformation and other types of virus or pathogen introduction into unnatural
hosts.
The organisms involved may belong to these categories:
1. i) Intergeneric organisms

29
 ii) Well defined organisms with non-coding regulatory regions
2. i) Biological agents whose source of DNA is a pathogen
ii) Organisms that are generally recognised as non-pathogenic and may imbibe the
characteristics of a pathogen on genetic manipulation.
Recombinant DNA (rDNA):
Defined as either:
1. Molecules constructed outside living cells by joining natural or synthetic DNA
segments to DNA molecules that can replicate in a living cell; or
2. DNA molecules that result from the replication of those described above.

• Risk Levels:
I. Low Risk: risk level of agents and/or operations having minimal effect on personnel,
other animal or plants under ordinary use. This classification is restricted to all etiologic agents
designated as Biosafety Level 1 by the CDC.
II. Moderate Risk: risk level of agents and/or operations requiring special conditions
for control or containment because of (a) known pathogenicity to personnel, other animals or
plants; (b) concentration; or c) genetic alteration (synergistic effect) with other materials.
III. High Risk: risk level of agents and/or operations requiring additional control
measures beyond those for moderate risk. This classification includes all etiologic agents
designated Class 4 or 5 by the CDC and oncogenic viruses classified as high risk by the NCI.

SAFETY CONSIDERATIONS
Risk Group
• 1: not known to cause disease
• 2: rarely serious disease, with therapeutic intervention
• 3: serious, lethal disease with therapeutic intervention
• 4: serious, lethal disease with no therapeutic intervention
RISK ASSESSMENT
• Review classification of organism
• Review research procedures to be performed
• Assess available facility/physical barriers

30
 (biosafety levels)
• Potential for inadvertent release
• Other factors, such as volume, concentration, replication competency

CONTAINMENT
• Standard practices
• Special procedures, equipment
• Available facility/facility design
• Biological barriers

CLASSIFICATION OF EXPERIMENTS

Requires: IBC, RAC, NIH Director Review and Approval prior to the initiation of work
• Drug resistance to organisms
• Prevent compromise to agriculture/medicine

Requires: NIH/OBA, IBC Review and Approval Before Initiation of Work

• Containment determined by NIH/OBA
• Example: Deliberate Cloning of Toxin Molecules Lethal to Vertebrates at an LD50 of
Less Than 100 Nanograms/Kg of Body Weight (e.g., Botulinum Toxin)
Requires: RAC Review, IBC, and IRB Review and Approval Before Participant
Enrollment
• Requires RAC Review prior to local institutional review.
• Must be reviewed by NIH prior to research participant enrollment.
Requires: IBC Review and Approval prior to the initiation of work
• Involves RG 2-4 agents, host/vector system
• Cloned DNA from RG 2-4 agents into non-pathogenic prokaryotes
• RG 2-4 agents into whole animals, usually transgenic
• Recombinant plants
Requires: IBC notification at the initiation of work (BL-1 containment)
• DNA Contains Less than 2/3 viral genome
• Transgenic Rodents with ABSL1 containment

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 • Whole Plants-minimal containment required
Exempt from the NIH Guidelines and Does Not Require IBC Review and Approval
Recombinant DNA that is:
• Not in Organisms
• Not a risk to the environment
ROLES AND RESPONSIBILITIES
• Ensure compliance with NIH Guidelines
• Establish IBC
• Appoint a Biosafety Officer
• Ensure IBC has expertise in the research that is reviewed
• Establish a medical surveillance program as needed
• Report all accidents to the NIH

When the institution conducts recombinant DNA research at BL3, BL4, or Large Scale (greater
than 10 Liters), a Biological Safety Officer is mandatory and shall be a member of the
Institutional Biosafety Committee.

The Institutional Biosafety Committee must be composed of no fewer than five members so
selected that they collectively have experience and expertise in recombinant DNA technology
and the capability to assess the safety of recombinant DNA research and to identify any
potential risk to public health or the environment.

At least two members shall not be affiliated with the institution (apart from their membership
on the IBC) and who represent the interest of the surrounding community with respect to health
and protection of the environment (e.g. officials of state or local public health or environmental
protection agencies, members of other governmental bodies, or persons active in medical,
occupational health, or environmental concerns in the community).
No member of an Institutional Biosafety Committee may be involved (except to provide
information requested by the IBC) in the review or approval of a project in which he/she has
been or expects to be engaged or has a direct financial interest
Reviewing recombinant DNA research conducted at or sponsored by the institution for
compliance with NIH Guidelines as specified in Section III, Experiments Covered by the NIH
Guidelines.

32
This review shall include:
(i) independent assessment of the containment levels required by the NIH Guidelines
(ii) assessment of the facilities, procedures, practices, and training and expertise of personnel
involved in recombinant DNA research.

Certain experiments with animals require IBC review and approval:

• Section III-D-4, whole animals
• Section III-E-3, transgenic rodents
• Appendix Q: Containment requirements for large mammals
• Any introduction of biohazardous agents(shedding)
• While the IACUC traditionally examines pain and suffering, euthanasia and vivaria
housing, the safe work practices described in Biosafety Levels 1-3 should be followed.

The IBC and IACUC should also ensure:

• biohazard vivaria areas are kept clean
• animal carcasses are properly disposed of
• infected animals are housed separately
• infected animals are transported safely
• infected animals do not infect humans

REPORTING ACCIDENTS AND INCIDENTS

• All laboratory accidents or incidents involving recombinant DNA molecules must be
reported to NIH, OBA.
• All adverse events in gene transfer experiments must be reported to NIH, OBA, even
if thought not to be in conjunction with the gene transfer intervention.

RAC APPROVAL
The Institutional Biosafety Committee may not authorize initiation of experiments which are
not explicitly covered by the NIH Guidelines until NIH (with the advice of the RAC when
required) establishes the containment requirement.

CONCLUSION

33
This presentation was designed to inform the audience on the key provisions of the NIH
Guidelines. The IBC must interact as necessary with other institutional committees and ensure
that research involving recombinant DNA molecules is adequately reviewed.

34
 SCHOOL OF BIO AND CHEMICAL ENGINEERING
DEPARTMENT OF BIOTECHNOLOGY

UNIT – IV – Bioethics Biosafety and IPR – SBTA7011

1
 UNIT 4 INTELLECTUAL PROPERTY RIGHTS

Intellectual Property Rights (IPR)-Types, Patents, Trade Mark, Copyright & related
rights, Industrial design, Traditional knowledge, Geographical indications –.
Requirement of patentability, Patent application, Compulsory licenses, Biotechnological
examples.
----------------------------------------------------------------------------------------------------------------

Intellectual Property Rights

Intellectual property, often known as IP, allows people to own their creativity and innovation
in the same way that they can own physical property. The owner of IP can control and be
rewarded for its use, and this encourages further innovation and creativity to the benefit of us
all. In some cases, IP gives rise to protection for ideas but in other areas, there will have to be
more elaboration of an idea before protection can arise. It will often not be possible to protect
IP and gain IP rights (or IPRs) unless, they have been applied for and granted, but some IP
protection
such as copyright arises automatically, without any registration, as soon as there is a record in
some form of what has been created.

The four main types of IP are:

• Patents for inventions—new and improved products and processes that are capable of
industrial application
• Trade marks for brand identity—of goods and services allowing distinctions to be made
between different traders
• Designs for product appearance—of the whole or a part of a product resulting from the
features of, in particular, the lines, contours, colours, shape, texture or materials of the product
itself or its ornamentation
• Copyright for material—literary and artistic material, music, films, sound recordings and
broadcasts, including software and multimedia.

However, IP is much broader than this extending to trade secrets, plant varieties, geographical
indications, performers rights and so on. To understand exactly what can be protected by IP,

2
you will need to check the four main areas of copyright, designs, patents and trade marks as
well as other IP. Often, more than one type of IP may apply to the same creation.

Patent
A patent gives an inventor the right for a limited period to stop others from making, using or
selling an invention without the permission of the inventor. It is a deal between an inventor and
the state in which the inventor is allowed a short-term monopoly in return for allowing the
invention to be made public. Patents are about functional and technical aspects of products and
processes. Most patents are for incremental improvements in known technology—evolution
rather than revolution. The technology does not have to be complex.

• Specific conditions must be fulfilled to get a patent. Major ones are that the invention must
be new. The invention must not form part of the “state of the art”. The state of the art is
everything that has been made available to the public before the date of applying for the patent.
This includes published documents and articles, but can also include use, display, spoken
description, or any other way in which information is made available to the public.
• Involve an inventive step, as well as being new, the invention must not be obvious from the
state of the art. Obviousness is from the viewpoint of a person skilled in the area of technology
that the invention is in.
• Be industrially applicable. This condition requires that the invention can be made or used in
any kind of industry.

A patented invention is recorded in a patent document. A patent document must have

• description of the invention, possibly with drawings, with enough details for a person skilled
in the area of technology to perform the invention.
• claims to define the scope of the protection. The description is taken into account while
interpreting the claims.

The original patent document of a patent application is published by a patent office. The
application then adds to the state of the art for later applications and anyone can comment on
the application. Often the patent document needs altering or amending to meet the conditions
above before a patent can be granted. The final version of the granted patent document is then
republished. If more information about the state of the art is discovered after grant, the patent

3
document can be amended and republished again.

Patent rights are territorial; a UK patent does not give rights outside of the UK. Patent rights
last for up to 20 years in the UK. Some patents, such as those for medicinal products, may be
eligible for a further 5 years protection with a Supplementary Protection Certificate. A patent
can be of value to an inventor—as well as protecting his business, patents can be bought, sold,
mortgaged, or licenced to others. They also benefit people other than the inventor since large
amounts of information can be learnt from other peoples patents — they can stop you from
reinventing things or you can monitor what your competitors are doing. Patents also spur you
or others on to develop your idea further, and once the term of the patent expires it can be freely
performed by anyone which benefits the public and the economy.

TRADEMARK
A trademark is any sign which can distinguish the goods and services of one trader from those
of another. A sign includes words, logos, colours, slogans, three-dimensional shapes and
sometimes sounds and gestures. A trademark is therefore a “badge” of trade origin. It is used
as a
marketing tool so that customers can recognize the product of a particular trader. To be
registrable in the UK it must also be capable of being represented graphically, that is, in words
and/or pictures.

DESIGN
A design refers to the appearance of the whole or a part of a product resulting from the features
of, in particular, the lines, contours, colours, shape, texture or materials of the product or its
ornamentation.

In the United Kingdom, designs are protected by three legal rights:

(a) Registered designs rights
• gives the owner a monopoly on their product design.
• brings the right to take legal action against others who might be infringing the design and to
claim damages.
• may deter a potential infringement.

4
• also brings the exclusive right to make, offer, put on the market import, export, use or stock
any product to which the design has been applied or is incorporated or to let others use the
design under the terms agreed with the registered owner, in the UK and the Isle of Man.

Design registration gives the owner a monopoly on their product design, i.e., the right for a
limited period to stop others from making, using or selling a product to which the design has
been applied, or in which it has been incorporated without their permission and is additional to
any design right or copyright protection that may exist automatically in the design.

(b) Unregistered design right.

Is not a monopoly right but a right to prevent deliberate copying, and lasts until 10 years after
first marketing articles made to the design, subject to an overall limit of 15 years from creation
of the design. Unlike design registration, you do not have to apply to register design right. A
design right is a property that, like any other business commodity, may be bought, sold or
licensed.

(c) Artistic copyright.

Work can only be original if it is the result of independent creative effort. It will not be original
if it has been copied from something that already exists. If it is similar to something that already
exists but there has been no copying from the existing work either directly or indirectly, then
it may be original.

The term “original” also involves a test of substantiality—literary, dramatic, musical and
artistic works will not be original if there has not been sufficient skill and labour expended in
their creation. But, sometimes significant investment of resources without significant
intellectual input can still count as sufficient skill and labour.

Ultimately, only the courts can decide whether something is original, but there is much case
law indicating, for example, that names and titles do not have sufficient substantiality to be
original and that, where an existing work is widely known, it will be difficult to convince a
court that there has been no copying if your work is very similar or identical. Sound recordings,
films and published editions do not have to be original but they will not be new copyright works
if they have been copied from existing sound recordings, films and published editions.

5
Broadcasts do not have to be original, but there will be no copyright, if, or to the extent that,
they infringe copyright in another broadcast.

IMPLICATIONS OF IPRs AND AGRICULTURAL TECHNOLOGY

The dynamics and interplay of IPRs and technological innovations have multiple impacts.
These
can be categorized into social, economic and ecological. Due to peculiarities of Indian
agriculture, the magnitude of these impacts will be manifold. The IPR regime not only
influences research portfolio but also the contours of technology development. Primarily, the
underlying motive of protection is to share profits with innovators. Therefore, the economic
implications are not only predominant but also most obvious. The other two implications of
access to newer technologies are on social and ecological dimensions. These three impacts are
not mutually exclusive and often overlap.

Social Implications
Social impact of new technologies is manifested in terms of its influence on equity. Other
important issue pertains to “scale effect”. These issues can be explained by the illustration of
Green Revolution. This seed-fertiliser technology was predominantly applicable in the areas
with assured irrigation. These technologies contributed to the widening of the regional
disparity. Viewed from a macro-perspective, however, the revolution was a great success that
helped realize cherished goal of self-sufficiency in food grains. Therefore, the magnitude and
nature of
social implications vary according to the category of the technology (Table). Knowledge-based
technologies and technologies concerning conservation of natural resources have positive
impact
on the society. Because of their nature (public good), the net social welfare increases manifold.
Certain technologies like HYVs and hybrids require intensive input use and therefore have a
mixed impact on the society. The predominant positive impact (+ + –) clouds the negative
effects. Yield enhancement by conventional breeding is an ideal example. By the same
yardstick, if conventional breeding aims at preventing yield loss (pest- and disease-resistant
varieties) it becomes cost-reducing and has no negative impact (+). There are technologies
where the negative component impact is marked (– +). Current levels of technologies (and its

6
costs) in farm machinery and power precludes their accessibility to small and marginal farmers.
There is a distinct possibility that in the near future farm machinery is tailor-made to suit small
holdings ?

Economic Implications
Most technologies, excluding agricultural biotechnology and crop protection chemicals have a
net positive impact on the economy. There are also implicit benefits like savings from potential
losses due to pests and diseases. Newer techniques invariably shift production functions
thereby improving income of individuals and that of the nation. Research in the public domain
will concentrate in cost-reducing technologies that are helpful to the weaker sections.
Conservation
of genetic resources have huge positive externalities (both intra and inter generational).
Considering the market structure of crop varieties and crop protection chemicals and the nature
of potential technologies, the scope for market malpractice such as monopoly and cartelisation
is real. Generally embodied technologies are likely to have relatively more apparent impacts.
Active presence of the public sector is vital for the provision of disembodied technologies.

7
Ecological implications
Increased use of agrochemicals will accelerate environmental degradation (– – –).Though
biotechnological innovations minimise the use of agrochemicals to some extent (+ –), they are
feared for their contribution to gene pollution (– ? ?). Development of such resistant varieties
by conventional breeding has no negative impacts (++). Any technology encouraging the use
of improved varieties is likely to contribute to narrowing of genetic base (–). Increasingly, the
use of antibiotics, hormones, unconventional feeds and genetic engineering in livestock and
fisheries have raised questions about health hazards and animal biodiversity (– –). Destruction
of soil structure and groundwater depletion are serious ecological risks associated with the
excessive use of technologies associated with farm machinery and power. Technological
advancements in the conservation of soil, water and genetic resources have profound positive

8
impacts on the ecology (+++). Being locally evolved and practice based, knowledge based
technologies optimise resource use thereby imparting positive externalities to the environment.

Protection of Plant Varieties and Farmers' Rights Act, 2001

Introduction

In order to provide for the establishment of an effective system for the protection of plant
varieties, the rights of farmers and plant breeders and to encourage the development of new
varieties of plants it has been considered necessary to recognize and to protect the rights of the
farmers in respect of their contributions made at any time in conserving, improving and making
available plant genetic resources for the development of new plant varieties. The Govt. of India
enacted “The Protection of Plant Varieties and Farmers' Rights (PPV&FR) Act, 2001” adopting
sui generis system. Indian legislation is not only in conformity with International Union for the
Protection of New Varieties of Plants (UPOV), 1978, but also have sufficient provisions to
protect the interests of public sector breeding institutions and the farmers. The legislation
recognizes the contributions of both commercial plant breeders and farmers in plant breeding
activity and also provides to implement TRIPs in a way that supports the specific socio-

9
economic interests of all the stakeholders including private, public sectors and research
institutions, as well as resource-constrained farmers.
Objectives of the PPV & FR Act, 2001

1. To establish an effective system for the protection of plant varieties, the rights of
farmers and plant breeders and to encourage the development of new varieties of plants.
2. To recognize and protect the rights of farmers in respect of their contributions made at
any time in conserving, improving and making available plant genetic resources for the
development of new plant varieties.
3. To accelerate agricultural development in the country, protect plant breeders’ rights;
stimulate investment for research and development both in public & private sector for
the development new of plant varieties.
4. Facilitate the growth of seed industry in the country which will ensure the availability
of high quality seeds and planting material to the farmers.

Rights under the Act

1. Breeders’ Rights : Breeders will have exclusive rights to produce, sell, market,
distribute, import or export the protected variety. Breeder can appoint agent/ licensee
and may exercise for civil remedy in case of infringement of rights.
2. Researchers’ Rights : Researcher can use any of the registered variety under the Act
for conducting experiment or research. This includes the use of a variety as an initial
source of variety for the purpose of developing another variety but repeated use needs
prior permission of the registered breeder.
3. Farmers' Rights
o A farmer who has evolved or developed a new variety is entitled for registration
and protection in like manner as a breeder of a variety;
o Farmers variety can also be registered as an extant variety;
o A farmer can save, use, sow, re-sow, exchange, share or sell his farm produce
including seed of a variety protected under the PPV&FR Act, 2001 in the same
manner as he was entitled before the coming into force of this Act provided
farmer shall not be entitled to sell branded seed of a variety protected under the
PPV&FR Act, 2001;

10
 o Farmers are eligible for recognition and rewards for the conservation of Plant
Genetic Resources of land races and wild relatives of economic plants;
o There is also a provision for compensation to the farmers for non-performance
of variety under Section 39 (2) of the Act, 2001 and
o Farmer shall not be liable to pay any fee in any proceeding before the Authority
or Registrar or the Tribunal or the High Court under the Act.

Implementation of the Act

To implement the provisions of the Act the Department of Agriculture, Cooperation and
Farmers Welfare, Ministry of Agriculture and Farmers Welfare established the Protection of
Plant Varieties and Farmers' Rights Authority on 11" November, 2005. The Chairperson is the
Chief Executive of the Authority. Besides the Chairperson, the Authority has 15 members, as
notified by the Government of India (GOI). Eight of them are ex-officio members representing
various Departments/ Ministries, three from SAUs and the State Governments, one
representative each for farmers, tribal organization, seed industry and women organization
associated with agricultural activities are nominated by the Central Government. The Registrar
General is the ex-officio Member Secretary of the Authority.
General Functions of the Authority

1. Registration of new plant varieties, essentially derived varieties (EDV), extant varieties;
2. Developing DUS (Distinctiveness, Uniformity and Stability) test guidelines for new
plant species;
3. Developing characterization and documentation of varieties registered;
4. Compulsory cataloging facilities for all variety of plants;
5. Documentation, indexing and cataloguing of farmers' varieties;
6. Recognizing and rewarding farmers, community of farmers, particularly tribal and rural
community engaged in conservation and improvement;
7. Preservation of plant genetic resources of economic plants and their wild relatives;
8. Maintenance of the National Register of Plant Varieties and
9. Maintenance of National Gene Bank.

Registration of varieties

A variety is eligible for registration under the Act if it essentially fulfills the criteria of
Distinctiveness, Uniformity and Stability (DUS). The Central Government issues notification

11
in official Gazettes specifying the genera and species for the purpose of registration of varieties.
So far, the Central Government has notified 157 crop species for the purpose of registration. To
access the list, click here.
The PPV&FR Authority has developed "Guidelines for the Conduct of Species Specific
Distinctiveness, Uniformity and Stability" tests or "Specific Guidelines" for individual crop
species.
To know the time limit for registration of extant varieties, click here.
To know the registration process, click here
Fees for registration

Application for registration of plant varieties should be accompanied with the fee of registration
prescribed by the Authority. Fee for registration for different types of variety is as under:

S.No Types of Variety Fees for Registration

1 Extant Variety notified under section 5 of the Seeds Rs 2000/-

Act, 1966

2. New Variety/Essentially Derived Variety (EDV)/  Individual Rs. 7000/-

Extant Variety about  Educational Rs.10000/-
which there is common knowledge (VCK)  Commercial Rs.50000/-

3. Farmers Varieties No Fee

The Registration of a variety is renewable subject to payment of annual and renewal fee as
notified in the Plant Variety Journal of India of the Authority and Gazette of India dated
15.06.2015.
DUS Test Centers

Authority has notified DUS test Centers for different crops with a mandate for maintaining and
multiplication of reference collection, example varieties and generation of database for DUS
descriptors as per DUS guidelines of respective crops. To access the list of DUS test
Centers, click here.
Certificate of Registration

The certificate of registration issued will be valid for nine years in case of trees and vines and
six years in case of other crops. It may be reviewed and renewed for the remaining period on

12
payment of renewal fees subject to the condition that total period of validity shall not exceed
eighteen years in case of trees and vines from the date of registration of the variety, fifteen
years from the date of notification of variety under the Seeds Act, 1966 and in other cases
fifteen years from the date of registration of the variety.
Benefit Sharing

The benefit sharing is one of the most important ingredients of the farmers' rights. Section 26
provides benefits sharing and the claims can be submitted by the citizens of India or firms or
non-governmental organization (NGOs) formed or established in India. Depending upon the
extent and nature of the use of genetic material of the claimant in the development of the variety
along with commercial utility and demand in the market of the variety breeder will deposit the
amount in the Gene Fund. The amount deposited will be paid to the claimant from National
Gene Fund. The Authority also publishes the contents of the certificate in the PVJI for the
purpose of inviting claims for benefits sharing.
Rights of Community

1. It is compensation to village or local communities for their significant contribution in

the evolution of variety which has been registered under the Act.
2. Any person/group of persons/governmental or non- governmental organization, on
behalf of any village/local community in India, can file in any notified centre, claim for
contribution in the evolution of any variety.

Convention countries

Convention country means a country which has acceded to an international convention for the
protection of plant varieties to which India has also acceded or a country which has law of
protection of plant varieties on the basis of which India has entered into an agreements for
granting plant breeders’ rights to the citizen of both the countries. Any person if applies for the
registration of a variety in India within twelve months after the date on which the application
was made in the convention country, such variety shall, if registered under this Act, be
registered as of the date on which the application was made in convention country and that date
shall be deemed for the purpose of this Act to be the date of registration.
Plant Varieties Protection Appellate Tribunal

There is transitory provision by which it is provided that till the PVPAT is established the
Intellectual Property Appellate Board (IPAB) will exercise the jurisdiction of PVPAT.

13
Consequently the Plant Varieties Protection Appellate Tribunal (PVPAT) has been established
by appointing Technical Member. All orders or decisions of the Registrar of Authority relating
to registration of variety and orders or decisions of the Registrar relating to registration as agent
or licensee can be appealed in the Tribunal. Further, all orders or decisions of Authority relating
to benefit sharing, revocation of compulsory license and payment of compensation can also be
appealed in the Tribunal. The decisions of the PVPAT can be challenged in High Court. The
Tribunal shall dispose of the appeal within one year.
Source: Protection of Plant Varieties and Farmers’ Rights Authority
----------------------------------------------------------------------------------------------------------------
GOOD MANUFACTURING PRACTICES

What is GMP?

GMP refers to the Good Manufacturing Practice regulations promulgated by the US Food and
Drug Administration under the authority of the Federal Food, Drug, and Cosmetic Act (FDA).
These regulations, which have the force of law, require that manufacturers, processors, and
packagers of drugs, medical devices, some food, and blood take proactive steps to ensure that
their products are safe, pure, and effective. GMP regulations require a quality approach to
manufacturing, enabling companies to minimize or eliminate instances of contamination,
mixups, and errors. This in turn, protects the consumer from purchasing a product which is not
effective or even dangerous. Failure of firms to comply with GMP regulations can result in
very serious consequences including recall, seizure, fines, and jail time.
GMP regulations address issues including recordkeeping, personnel qualifications,
sanitation, cleanliness, equipment verification, process validation, and complaint handling.
Most GMP requirements are very general and open-ended, allowing each manufacturer to
decide individually how to best implement the necessary controls.

14
Approved drug manufacturing equipment
The GMPs require that equipment be of appropriate design to facilitate operations for its
intended use and for cleaning and maintenance and, that any equipment surface in contact with
components, in-process materials, or drug products not be reactive, additive, or absorptive so
as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official
or other established requirements.

GOOD LABORATORY PRACTICES (GLP)

During the 1970s, there were several problems which made some scientific reports unreliable.
These reports had been submitted to international regulatory authorities and decisions about
the safety of materials to man and the environment were made on the basis of this unreliable
information.
Consequently the US Government introduced the first Good Laboratory Practice
(GLP) regulations in 1978. Other countries followed with different GLP standards and the
Organisation for Economic Cooperation and Development (OECD) published the worldwide
principles of Good Laboratory Practice in 1981. Adherence to these OECD standards permits
international acceptability of safety testing from different countries.

15
 In the first part we will examine the nature of the problems that caused the introduction
of
GLP and how the international scientific and regulatory community responded to these
problems. We will also discuss how international co-operation in GLP is organised. GLP is
based on sound, common-sense principles. There is nothing required by GLP that exceeds what
any conscientious scientist would do when producing quality research and development.
GLP is concerned with how we organise our laboratories and how we organise our
studies. It addresses responsibilities for managing the people, facilities and equipment required
for good science and how we plan, perform and report our experiments and studies. Most
importantly, GLP does not interfere with the ability of scientists to make scientific decisions.

GOOD LABORATORY PRACTICE PRINCIPLES

1. Test Facility Organisation and Personnel

Management’s responsibilities Test facility management should ensure that the principles of
good laboratory practice is complied with in the test facility.

2. At minimum it should
(a) ensure that qualified personnel, appropriate facilities, equipment, and materials are
available;
(b) maintain a record of the qualifications, training, experience and job description for each
professional and technical individual;
(c) ensure that personnel clearly understand the functions they are to perform and, where
necessary, provide training for these functions;
(d) ensure that health and safety precautions are applied according to national and/or
international regulations;
(e) ensure that appropriate standard operating procedures are established and followed;
(f) ensure that there is a Quality Assurance Programme with designated personnel;
(g) where appropriate, agree to the study plan in conjunction with the sponsor;
(h) ensure that amendments to the study plan are agreed upon and documented;
(i) maintain copies of all study plans;
(j) maintain a historical file of all Standard Operating Procedures;

16
(k) for each study ensure that a sufficient number of personnel is available for its timely and
proper conduct;
(l) for each study designate an individual with the appropriate qualifications, training, and
experience as the Study Director before the study is initiated. If it is necessary to replace a
Study Director during a study, this should be documented;
(m) ensure that an individual is identified as responsible for the management of the
archives.

Study Director’s Responsibilities

1. The Study Director has the responsibility for the overall conduct of the study and for its
report.
2. These responsibilities should include, but not be limited to, the following functions:
(a) should agree to the study plan;
(b) ensure that the procedures specified in the study plan are followed, and that authorization
for any modification is obtained and documented together with the reasons for them;
(c) ensure that all data generated are fully documented and recorded;
(d) sign and date the final report to indicate acceptance of responsibility for the validity of the
data and to confirm compliance with these Principles of Good Laboratory Practice;
(e) ensure that after termination of the study, the study plan, the final report, raw data and
supporting material are transferred to the archives.

Personnel Responsibilities
1. Personnel should exercise safe working practice. Chemicals should be handled with suitable
caution until their hazard(s) has been established.
2. Personnel should exercise health precautions to minimise risk to themselves and to ensure
the integrity of the study.
3. Personnel known to have a health or medicinal condition that is likely to have an adverse
effect on the study should be excluded from operations that may affect the study.

Quality Assurance Programme

General

17
1. The test facility should have a documented quality assurance programme to ensure that
studies performed are in compliance with these Principles of Good Laboratory Practice.
2. The quality assurance programme should be carried out by an individual or by individuals
designated by and directly responsible to management and who are familiar with the test
procedures.
3. This individual(s) should not be involved in the conduct of study being assured.
4. This individual(s) should report any finding in writing directly to management and to the
Study Director.

Responsibilities of the quality assurance personnel

1. The responsibilities of the quality assurance personnel should include, but not be limited to,
the following functions:
(a) ascertain that the study plan and Standard Operating Procedures are available to personnel
conducting the study;
(b) ensure that the study plan and Standard Operating Procedures are followed by periodic
inspections of the test facility and/or by auditing the study in progress. Records of such
procedures should be retained.
(c) promptly report to management and the Study Director unauthorised deviations from the
study plan and from Standard Operation Procedures;
(d) review the final reports to confirm that the methods, procedures, and observations are
accurately described, and that the reported results accurately reflect the raw data of the study;
(e) prepare and sign a statement, to be included with the final report, which specifies the dates
inspections were made and the dates any findings were reported to management and to the
Study Director.

3. Facilities

General
1. The test facility should be of suitable size, construction and location to meet the requirements
of the study and minimise disturbances that would interfere with the validity of the study.
2. The design of the test facility should provide an adequate degree of separation of the different
activities to assure the proper conduct of each study.

18
Test system facilities
1. The test facility should have a sufficient number of rooms or areas to assure the isolation of
test systems and the isolation of individual projects, involving substances known or suspected
of being biohazardous.
2. Suitable facilities should be available for the diagnosis, treatment and control of diseases, in
order to ensure that there is no unacceptable degree of deterioration of test systems.
3. There should be storage areas as needed for supplies and equipment. Storage areas should
be separated from areas housing the test systems and should be adequately protected against
infestation and contamination. Refrigeration should be provided for perishable commodities.

Facilities for handling test and reference substances

1. To prevent contamination or mix-ups, there should be separate areas for receipt and storage
of the test and reference substances, and mixing of the test substances with a vehicle.
2. Storage areas for the test substances should be separated from areas housing the test systems
and should be adequated to preserve identity, concentration, purity, and stability, and ensure
safe storage for hazardous substances.

Archive facilities
1. Space should be provided for archives for the storage and retrieval of raw data, reports,
samples, and specimens.

Waste disposal
1. Handling and disposal of wastes should be carried out in such a way as not to jeopardize the
integrity of studies in progress.
2. The handling and disposal of wastes generated during the performance of a study should be
carried out in a manner which is consistent with pertinent regulatory requirements. This would
include provision for appropriate collection, storage, and disposal facilities, decontamination
and transportation procedures, and the maintenance of records related to the preceding
activities.

4. Apparatus, Material, and Reagents

Apparatus

19
1. Apparatus used for the generation of data, and for controlling environmental factors relevant
to the study should be suitably located and of appropriate design and adequate capacity.
2. Apparatus used in a study should be periodically inspected, cleaned, maintained, and
calibrated according to Standard Operating Procedures. Records of procedures should be
maintained.

Material
Apparatus and materials used in studies should not interfere with the test systems.

Reagents
Reagents should be labelled, as appropriate, to indicate source, identity, concentration, and
stability information and should include the preparation dates, earliest expiration date, specific
storage instructions.

5. Test Systems

Physical/Chemical
(a) Apparatus used for the generation of physical/chemical data should be suitably located and
of appropriate design and adequate capacity.
(b) Reference substances should be used to assist in ensuring the integrity of the
physical/chemical test systems.

Biological
(a) Proper conditions should be established and maintained for the housing, handling and care
of animals, plants, microbial as well as other cellular and sub-cellular systems, in order to
ensure the quality of the data.
(b) In addition, conditions should comply with appropriate national regulatory requirements
for the import, collection, care and use of animals, plants, microbial as well as other cellular
and sub-cellular systems.
(c) Newly-received animal and plant test systems should be isolated until their health status has
been evaluated. If any unusual mortality or morbidity occurs, this lot should not be used in
studies and, when appropriate, humanely destroyed.
(d) Records of source, date of arrival, and arrival condition should be maintained.

20
(e) Animal, plant, microbial, and cellular test systems should be acclimatised to the test
environment for an adequate period before a study is initiated.
(f) All information needed to properly identify the test systems should appear on their housing
or containers.
(g) The diagnosis and treatment of any disease before or during a study should be recorded.

6. Test and Reference Substances

Receipt, handling, sampling and storage

(a) Records including substance characterisation, date of receipt, quantities received, and used
in studies should be maintained.
(b) Handling, sampling, and storage procedures should be identified in order that the
homogeneity and stability is assured to the degree possible and contamination or mix-up are
precluded.
(c) Storage container(s) should carry identification information, earliest expiration date, and
specific storage instructions.

Characterisation
(a) Each test and reference substance should be appropriately identified (e.g., code, chemical
abstract number (CAS), name).
(b) For each study, the identity, including batch number, purity, composition, concentrations,
or other characterisations to appropriately define each batch of the test or reference substances
should be known.
(c) The stability of test and reference substances under conditions of storage should be known
for all studies.
(d) The stability of test and reference substances under the test conditions should be known for
all studies.
(e) If the test substance is administered in a vehicle, Standard Operating Procedures should be
established for testing the homogeneity and stability of the test substance in that vehicle.
(f) A sample for analytical purposes from each batch of test substance should be retained for
studies in which the test substance is tested longer than four weeks.

7. Standard Operating Procedures

21
General
(a) A test facility should have written Standard Operating Procedures approved by management
that are intended to ensure the quality and integrity of the data generated in the course of the
study.
(b) Each separate laboratory unit should have immediately available Standard Operating
Procedures relevant to the activities being performed therein. Published textbooks, articles and
manuals may be used as supplements to these Standard Operating Procedures.

Application
1. Standard Operating Procedures should be available for, but not limited to, the following
categories of laboratory activities. The details given under each heading are to be considered
as illustrative examples.
(a) Test and Reference Substance. Receipt, identification, labelling, handling, sampling, and
storage.
(b) Apparatus and Reagents.Use, maintenance, cleaning, calibration of measuring apparatus
and environmental control equipment; preparation of reagents.
(c) Record keeping. Reporting, Storage and Retrieval Coding of studies, data collection,
preparation of reports, indexing systems, handling of data, including the use of computerised
data systems.
(d) Test system (where appropriate):
(i) Room preparation and environmental room conditions for the test system.
(ii) Procedures for receipt, transfer, proper placement, characterisation, identification and care
of test system.
(iii) Test system preparation, observations examinations, before, during and at termination of
the study.
(iv) Handling of test system individuals found moribund or dead during the study.
(v) Collection, identification and handling of specimens including necropsy and
histopathology.
(e) Quality Assurance Procedures. Operation of quality assurance personnel in performing and
reporting study audits, inspections, and final study report reviews.
(f) Health and Safety Precautions. As required by national and/or international legislation or
guidelines.

22
8. Performance of the Study
Study plan
1. For each study, a plan should exist in a written form prior to initiation of the study.
2. The study plan should be retained as raw data.
3. All changes, modifications, or revisions of the study plan, as agreed to by the Study Director,
including justification(s), should be documented, signed and dated by the Study Directors, and
maintained with the study plan.
Content of the study plan
The study plan should contain, but not be limited to the following information:
1. Identification of the Study, the Test and Reference Substances
(a) A descriptive title;
(b) A statement which reveals the nature and purpose of the study;
(c) Identification of the test substance by code or name (IUPAC; CAS number, etc.);
(d) The reference substance to be used.
2. Information Concerning the Sponsor and the Test Facility
(a) Name and address of the Sponsor;
(b) Name and address of the Test Facility;
(c) Name and address of the Study Director.
3. Dates
(a) The date of agreement to the study plan by signature of the Study Director, and when
appropriate, of the sponsor and/or the test facility management;
(b) The proposed starting and completion dates.
4. Test Methods
Reference to OECD Test Guideline or other test guideline to be used.
5. Issues (where applicable)
(a) The justification for selection of the test system;
(b) Characterisation of the test system, such as the species, strain, sub-strain, source of supply,
number, body weight range, sex, age, and other pertinent information;
(c) The method of administration and the reason for its choice;
(d) The dose levels and/or concentration(s), frequency, duration of administration;

23
(e) Detailed information on the experimental design, including a description of the
chronological procedure of the study, all methods, materials and conditions, type and frequency
of analysis, measurements, observations and examinations to be performed.
6. Records
A list of records to be retained.

Conduct of the study

1. A unique identification should be given to each study. All items concerning this study should
carry this identification.
2. The study should be conducted in accordance with the study plan.
3. All data generated during the conduct of the study should be recorded directly, promptly,
accurately, and legibly by the individual entering the data. These entries should be signed or
initialled and dated.
4. Any change in the raw data should be made so as not to obscure the previous entry, and
should indicate the reason, if necessary, for change and should be identified by date and signed
by the individual making the change.
5. Data generated as a direct computer input should be identified at the time of data input by
the individual(s) responsible for direct data entries. Corrections should be entered separately
by the reason for change, with the date and the identity of the individual making the change.

9. Reporting of Study Results

General
1. A final report should be prepared for the study.
2. The use of the International System of Units (SI) is recommended.
3. The final report should be signed and dated by the Study Director.
4. If reports of principal scientists from co-operating disciplines are included in the final report,
they should sign and date them.
5. Corrections and additions to a final report should be in the form of an amendment. The
amendment should clearly specify the reason for the corrections or additions and should be
signed and dated by the Study Director and by the principal scientist from each discipline
involved.

Content of the final report

24
The final report should include, but not be limited to, the following information:
1. Identification of the Study, the Test and Reference Substance
(a) A descriptive title;
(b) Identification of the test substance by code or name (IUPAC; CAS number, etc.);
(c) Identification of the reference substance by chemical name;
(d) Characterisation of the test substance including purity, stability and homogeneity.
2. Information Concerning the Test Facility
(a) Name and address;
(b) Name of the Study Director;
(c) Name of other principal personnel having contributed reports to the final report.
3. Dates
(a) Dates on which the study was initiated and completed.

4. Statement
(a) A Quality Assurance statement certifying the dates inspections were made and the dates
any findings were reported to management and to the Study Director.
5. Description of Materials and Test Methods
(a) Description of methods and materials used;
(b) Reference to OECD Test Guidelines or other test guidelines.
6. Results
(a) A summary of results;
(b) All information and data required in the study plan;
(c) A presentation of the results, including calculations and statistical methods;
(d) An evaluation and discussion of the results and, where appropriate, conclusions.
7. Storage: The location where all samples, specimens, raw data, and the final report are to be
stored.

10. Storage and Retention of Records and Material

Storage and retrieval
1. Archives should be designed and equipped for the accommodation and the secure
storage of:
(a) the study plans;
(b) the raw data;
(c) the final reports;

25
(d) the reports of laboratory inspections and study audits performed according to the Quality
Assurance Programme;
(e) samples and specimens.
2. Material retained in the archives should be indexed so as to facilitate orderly storage and
rapid retrieval.
3. Only personnel authorised by management should have access to the archives. Movement
of material in and out of the archives should be properly recorded.
Retention
1. The following should be retained for the period specified by the appropriate authorities:
(a) The study plan, raw data, samples, specimens, and the final report of each study
(b) Records of all inspections and audits performed by the Quality Assurance Programme
(c) Summary of qualifications, training, experience and job description of personnel
(d) Records and reports of the maintenance and calibration of equipment
(e) The historical file of Standard Operating Procedures
2. Samples and specimens should be retained only as long as the quality of preparation permits
evaluation.
3. If a test facility or an archive contracting facility goes out of business and has no legal
successor, the archive should be transferred to the archives of the sponsor(s) of the study(s).

26
 SCHOOL OF BIO AND CHEMICAL ENGINEERING
DEPARTMENT OF BIOTECHNOLOGY

UNIT – V – Bioethics Biosafety and IPR – SBTA7011

1
 UNIT 5 AGREEMENTS, ACT AND AMENDEMENTS

Establishment and functions of GATT and TRIPS agreement; Madrid agreement; Hague
agreement; WIPO treaties; Budapest treaty; PCT, Indian patent Act 1970 and Recent
amendments. Role of a Country Patent Office. Patent infringement – meaning, scope,
litigation
--------------------------------------------------------------------------------------------------------------

WORLD TRADE ORGANISATION (WTO)

In brief, the World Trade Organisation (WTO) is the only international organisation dealing
with the global rules of trade between nations. Its main function is to ensure that trade flows as
smoothly, predictably and freely as possible.

Location: Geneva, Switzerland

Established: 1 January 1995
Created by: Uruguay Round negotiations (1986-94)
Membership: 146 countries (as of April 2003)
Budget: 155 million Swiss francs for 2003
Secretariat staff: 560
Head: Director-General, Supachai Panitchpakdi

Functions:
• Administering WTO trade agreements
• Forum for trade negotiations
• Handling trade disputes
• Monitoring national trade policies
• Technical assistance and training for developing countries
• Cooperation with other international organizations

The result is assurance. Consumers and producers know that they can enjoy secure supplies
and greater choice of the finished products, components, raw materials and services that they
use. Producers and exporters know that foreign markets will remain open to them. The result
is also a more prosperous, peaceful and accountable economic world. Decisions in the WTO

2
are typically taken by consensus among all member countries and they are ratified by members’
parliaments. Trade friction is channeled into the WTO’s dispute settlement process where the
focus is on interpreting agreements and commitments, and how to ensure that countries’ trade
policies confirm with them. That way, the risk of disputes spilling over into political or military
conflict is reduced. By lowering trade barriers, the WTO’s system also breaks down other
barriers between peoples and nations.

At the heart of the system—known as the multilateral trading system—are the WTO’s
agreements, negotiated and signed by a large majority of the world’s trading nations, and
gratified in their parliaments. These agreements are the legal ground-rules for international
commerce. Essentially, they are contracts, guaranteeing member countries important trade
rights.
They also bind governments to keep their trade policies within agreed limits to everybody’s
benefit. The agreements are negotiated and signed by governments. But their purpose is to help
producers of goods and services, exporters, and importers conduct their business. The goal is
to improve the welfare of the people of the member countries.

A Closer Look at These Principles

Trade without Discrimination

(a) Most-favoured-nation (MFN): Treating other people equally. Under the WTO
agreements, countries cannot normally discriminate between their trading partners. Grant
someone a special favour (such as a lower customs duty rate for one of their products) and you
have to do the same for all other WTO members. This principle is known as Most-Favoured-
Nation (MFN) treatment. It is so important that it is the first article of the General Agreement
on Tariffs and Trade (GATT), which governs trade in goods. MFN is also a priority in the
General Agreement

3
on Trade in Services (GATS) and the Agreement on Trade-Related Aspects of Intellectual
Property Rights (TRIPS), although in each agreement the principle is handled slightly
differently.
Together, these three agreement cover all the three main areas of trade handled by the
WTO. Some exceptions are allowed. For example, countries can set up a free-trade agreement
that applies only to goods traded within the group—discriminating against goods from outside.
Or they can give developing countries special access to their markets. Or a country can raise
barriers against products that are considered to be traded unfairly from specific countries. And
in services, countries are allowed, in limited circumstances, to discriminate. But the agreements
permit these exceptions only under strict conditions. In general, MFN means that every time a
country lowers a trade barrier or opens up a market, it has to do so for the same goods or
services from all its trading partners—whether rich or poor, weak or strong.

(b) National treatment: Treating foreigners and locals equally. Imported and locally produced
goods should be treated equally—at least after the foreign goods have entered the market. The
same should apply to foreign and domestic services, and to foreign and local trademarks,
copyrights and patents. This principle of “national treatment” (giving others the same treatment
as one’s own nationals) is also found in all the three main WTO agreements (Article 3 of
GATT, Article 17 of GATS and Article of 3 TRIPS), although once again the principle is
handled slightly differently in each of these. National treatment only applies once a product,
service or item of intellectual property has entered the market. Therefore, charging customs
duty on an import is not a violation of national treatment even if locally-produced products are
not charged an equivalent tax.

2. Free Trade: Gradually, Through Negotiation

Lowering trade barriers is one of the most obvious means of encouraging trade. The barriers
concerned include customs duties (or tariffs) and measures such as import bans or quotas that
restrict quantities selectively. From time to time other issues such as red tape and exchange rate
policies have also been discussed.
Since GATT’s creation in 1947-48 there have been eight rounds of trade negotiations.
A ninth round, under the Doha Development Agenda, is now underway. At first, these are
focused on lowering tariffs (customs duties) on imported goods. As a result of the negotiations,
by the mid-1990s industrial countries’ tariff rates on industrial goods had fallen steadily to less

4
than 4%. But by the 1980s, the negotiations had expanded to cover non-tariff barriers on goods,
and
to the new areas such as services and intellectual property. Opening markets can be beneficial,
but it also requires adjustment. The WTO agreements allow countries to introduce changes
gradually, through “progressive liberalization”. Developing countries are usually given longer
time period to fulfil their obligations.

3. Predictability: Through Binding and Transparency

Sometimes, promising not to raise a trade barrier can be as important as lowering one, because
the promise gives business a clearer view of their future opportunities. With stability and
predictability, investment is encouraged, jobs are created and consumers can fully enjoy the
benefits of competition—choice and lower prices. The multilateral trading system is an attempt
to governments to make the business environment stable and predictable.

Table 2.1. The Uruguay Round increased bindings. Percentages of tariffs

bound before and after the 1986–94 talks

(These are tariff lines, so percentages are not weighted according to trade volume or value) In
the WTO, when countries agree to open their markets for goods or services, they “bind” their
commitments. For goods, these bindings amount to ceilings on customs tariff rates. Sometimes
countries tax imports at rates that are lower than the bound rates. Frequently, this is the case in
developing countries. In developed countries, the rates actually charged and the bound rates
tend to be the same.
A country can change its bindings, but only after negotiating with its trading partners,
which could mean compensating them for loss of trade. One of the achievements of the
Uruguay
Round of multilateral trade talks was to increase the amount of trade under binding
commitments
(see Table 2.1). In agriculture, 100% of products now have bound tariffs. The result of all this:
a substantially higher degree of market security for traders and investors.

5
 The system tries to improve predictability and stability in other ways as well. One way
is
to discourage the use of quotas and other measures used to set limits on quantities of imports
administering quotas can lead to more red-tape and accusations of unfair play. Another is to
make countries’ trade rules as clear and public (transparent) as possible. Many WTO
agreements
require governments to disclose their policies and practices publicly within the country or by
notifying the WTO. The regular surveillance of national trade policies through the Trade Policy
Review Mechanism provides a further means of encouraging transparency both domestically
and at the multilateral level.

4. Promoting Fair Competition

The WTO is sometimes described as a “free trade” institution, but that is not entirely accurate.
The system does allow tariffs and, in limited circumstances, other forms of protection. More
accurately, it is a system of rules dedicated to open, fair and undistorted competition. The rules
on non-discrimination—MFN and national treatment – are designed to secure fair conditions
of trade. So too are those on dumping (exporting at below cost to gain market share) and
subsidies. The issues are complex, and the rules try to establish what is fair or unfair, and how
governments can respond, in particular by charging additional import duties calculated to
compensate for damage caused by unfair trade.
Many of the other WTO agreements aim to support fair competition: in agriculture,
intellectual property, services, for example. The agreement on government procurement (a
“plurilateral” agreement because it is signed by only a few WTO members) extends
competition
rules to purchases by thousands of government entities in many countries, and so on.

5. Encouraging Development and Economic Reform

The WTO system contributes to development. On the other hand, developing countries need
flexibility in the time they take to implement the system’s agreements. And the agreements
themselves inherit the earlier provisions of GATT that allow for special assistance and trade
concessions for developing countries.
Over three quarters of WTO members are developing countries and countries in
transition

6
to market economies. During the seven and a half years of the Uruguay Round, over 60 of these
countries implemented trade liberalization programmes autonomously. At the same time,
developing countries and transition economies were much more active and influential in the
Uruguay Round negotiations than in any previous round, and they are even more, so in the
current Doha Development Agenda.

At the end of the Uruguay Round, developing countries were prepared to take on most of the
obligations that are required of developed countries. But the agreements did give them
transition periods to adjust to the more unfamiliar and, perhaps, difficult WTO provisions-
particularly so for the poorest, “least-developed” countries. A ministerial decision adopted at
the end of the round says better-off countries should accelerate implementing market access
commitments on goods exported by the least-developed countries, and it seeks increased
technical assistance for them. More recently, developed countries have started to allow duty-
free and quota-free imports for almost all products from least-developed countries. On all of
this, the WTO and its members are still going through a learning process. The current Doha
Development Agenda includes developing countries’ concern about the difficulties they face
in implementing the Uruguay Round agreements.

WTO AGREEMENTS
How can you ensure that trade is as fair as possible, and as free as is practical? By negotiating
rules and abiding by them. The WTO’s rules—the agreements—are the result of negotiations
between the members.
The current set were the outcome of the 1986-94 Uruguay Round negotiations, which
included a major revision of the original General Agreement on Tariffs and Trade (GATT).
GATT is now the WTO’s principal rule-book for trade in goods. The Uruguay Round also
created new rules for dealing with trade in services, relevant aspects of intellectual property,
dispute settlement, and trade policy reviews. The complete set runs to some 30,000 pages
consisting of about 60 agreements and separate commitments (called schedules) made by
individual members in specific areas such as lower customs duty rates and services
marketopening.
Through these agreements, WTO members operate a non-discriminatory trading system
that spells out their rights and their obligations. Each country receives guarantees that its
exports will be treated fairly and consistently in other countries’ markets. Each promises to do

7
the same for imports into its own market. The system also gives developing countries some
flexibility in implementing their commitments.

Goods
It all began with trade in goods. From 1947 to 1994, GATT was the forum for negotiating lower
customs duty rates and other trade barriers; the text of the General Agreement spelt out
important rules, particularly non-discrimination. Since 1995, the updated GATT has become
the WTO’s umbrella agreement for trade in goods. It has annexes dealing with specific sectors
such as agriculture and textiles, and with specific issues such as state trading, product standards,
subsidies and actions taken against dumping.

Services
Banks, insurance firms, telecommunications companies, tour operators, hotel chains and
transport companies looking to do business abroad can now enjoy the same principles of freer
and fairer trade that originally only applied to trade in goods. These principles appear in the
new General Agreement on Trade in Services (GATS). WTO members have also made
individual commitments under GATS stating which of their services sectors they are willing to
open to foreign competition, and how open those markets are.

Intellectual Property
The WTO’s intellectual property agreement amounts to rules for trade and investment in ideas
and creativity. The rules state how copyrights, patents, trademarks, geographical names used
to identify products, industrial designs, integrated circuit layout-designs and undisclosed
information such as trade secrete–“intellectual property”–should be protected when trade is
involved.

Dispute Settlement
The WTO’s procedure for resolving trade quarrels under the Dispute Settlement Understanding
is vital for enforcing the rules and therefore for ensuring that trade flows smoothly. Countries
bring disputes to the WTO if they think their rights under the agreements are being infringed.
Judgements by specially-appointed independent experts are based on interpretations of the
agreements and individual countries’ commitments. The system encourages countries to settle
their differences through consultation. Failing that, they can follow a carefully mapped out,

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stage-by-stage procedure that includes the possibility of a ruling by a panel of experts, and the
chance to appeal the ruling on legal grounds. Confidence in the system is borne out by the
number of cases brought to the WTO—around 300 cases in eight years compared to the 300
disputes dealt with during the entire life of GATT (1947-94).

Policy Review
The Trade Policy Review Mechanism’s purpose is to improve transparency, to create a greater
understanding of the policies that countries are adopting, and to assess their impact. Many
members also see the reviews as constructive feedback on their policies. All WTO members
must undergo periodic scrutiny, each review containing reports by the country concerned and
the WTO Secretariat.

DEVELOPING COUNTRIES DEVELOPMENT AND TRADE

Over three quarters of WTO members are developing or least-developed countries. All WTO
agreements contain special provision for them, including longer time periods to implement
agreement and commitments, measures to increase their trading opportunities, provisions
requiring all WTO members to safeguard their trade interests, and support to help them build
the
infrastructure for WTO work, handle disputes, and implement technical standards. The 2001
Ministerial Conference in Doha set out tasks, including negotiations, for a wide range of issues
concerning developing countries. Some people call the new negotiations the Doha
Development Round. Before that part in 1997, a high-level meeting on trade initiatives and
technical assistance
for least-developed countries resulted in an “integrated framework” involving six
intergovernmental agencies, to help least-developed countries increase their ability to trade,
and some additional preferential market access agreements.
A WTO committee on trade and development, assisted by a sub-committee on least-developed
countries, looks at developing countries’ special needs. Its responsibility includes
implementation of the agreements, technical cooperation, and the increased participation of
developing countries in the global trading system.

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TECHNICAL ASSISTANCE AND TRAINING
The WTO organizes around 100 technical cooperation missions to developing countries
annually. It holds on average three-trade policy courses each year in Geneva for government
officials. Regional seminars are held regularly in all regions of the world with a special
emphasis
on African countries. Training courses are also organized in Geneva for officials from countries
in transition from central planning to market economies. The WTO set up reference centres in
over 100 trade ministries and regional organizations in capitals of developing and least-
developed countries, providing computers and internet-access to enable ministry officials to
keep
abreast of events in the WTO in Geneva through online access to the WTO’s immense database
of official documents and other material.
• Assisting developing countries in trade policy issues, through technical assistance and
training programmes.
• Cooperating with other international organizations.

THE ORGANIZATION FUNCTIONS

The WTO’s overriding objective is to help trade flow smoothly, freely, fairly and predictably.
It
does this by:
• administering trade agreements;
• acting as a forum for trade negotiations;
• settling trade disputes;
• reviewing national trade policies.

STRUCTURE
The WTO has nearly 150 members, accounting for over 97% of world trade. Around 30 others
are negotiating membership. Decisions are made by the entire membership. This is typically
by
consensus. A majority vote is also possible but it has never been used in the WTO, and was
extremely rare under the WTO’s predecessor, GATT. The WTO’s agreements have been
ratified

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in all members’ parliaments.
The WTO’s top level decision-making body is the Ministerial Conference which meets at
least once every two years. The Fifth WTO Ministerial Conference was held in Cancun,
Mexico from 10 to 14 September, 2003.
Below this is the General Council (normally ambassadors and heads of delegation in Geneva,
but sometimes officials sent from members’ capitals) which meets several times a year in the
Geneva headquarters. The General Council also meets as the Trade Policy Review Body and
the Dispute Settlement Body.
At the next level, the Goods Council, Services Council and Intellectual Property (TRIPS)
Council report to the General Council. Numerous specialized committees, working groups
and working parties deal with the individual agreements and other areas such as environment,
development, membership applications and regional trade agreements.

SECRETARIAT
The WTO Secretariat, based in Geneva has around 560 staff and is headed by a director general.
It does not have branch offices outside Geneva. Since decisions are taken by the members
themselves, the Secretariat does not have the decision-making role those other international
bureaucracies are given.
The secretariat’s main duties are to supply technical support for the various councils and
committees and the ministerial conferences, to provide technical assistance for developing
countries, to analyze world trade, and to explain WTO affairs to the public and media. The
Secretariat also provides some forms of legal assistance in the dispute settlement process and
advises governments wishing to become members of the WTO. The annual budget is roughly
155 million Swiss francs.

GENERAL AGREEMENT ON TARIFFS AND TRADE (GATT)

The General Agreement on Tariffs and Trade (GATT) was created in 1947. GATT is an
agreement between many nations, governing international trade. GATT provides a place for
negotiating trade issues and a framework for guiding the conduct of trade. Current GATT
membership includes 123 nations. One of the major beliefs behind GATT is that more
liberalized
trade would help the economies of participating nations grow (Banks 35). Some other
principles

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of GATT are nondiscrimination; what is meant by nondiscrimination is that no member of
GATT can discriminate against other nations or who favoritism or give any special privileges
to
any nations. This allows all trading partners to be put on an equal basis. A second principle,
tariff protection, favors the use of tariffs as a clear way to protect domestic industries, as
opposed to no tariff measures such as import quotas. A third and final principle behind GATT
is providing a stable basis for trade. This is achieved by binding all participating nations to
agree upon tariff levels by listing in “tariff schedules” the negotiated tariffs for each country’s
products (Banks 35).
There has been eight conferences, referred to as rounds or cycles of GATT, each of these rounds
resulted in new trade agreements. The most recent round is referred to as the Uruguay Round
because it was launched at a conference in Punte del Este, Uruguay in 1986. These negotiations
concluded with the signing by more than 100 of the Uruguay Round “Final Act” in Marrakesh,
Morocco in April 1994. The Uruguay Round Agreement has been described as the largest,
most comprehensive trade pact in history (Congressional Digest).
The United States had a number of objectives in entering into the Uruguay Round of trade
negotiations. These included broadening procedures relating to trade in agricultural products,
extending GATT rules to trade in services never before covered by GATT, increasing
protection
for patents, copyrights, and trademarks, and an improved way for settling disputes among
GATT participants. Most of the objectives that the United States brought to the Uruguay Round
were achieved. GATT was expanded to include services and new areas relating to the
protection of patents and foreign investment. The Uruguay Round also cut tariffs worldwide
by about one third; coverage for agriculture, textiles, and clothing was increased. And a new
World Trade Organization was created to administer the agreement, oversee dispute
settlements, and review
countries’ trade policies and practices (C.D.).
Nations signing the agreement must have it approved by their governments before they can be
subjected to its terms. In the U.S. Congress, consideration for the agreement is taking place
under “fast track” procedure, meaning that the House and the Senate must vote up or down on
the legislation dealing with the agreement, with no opportunity to introduce or consider
amendments. Opponents are concerned that the United States may lose more than it gains. They
fear that the World Trade Organization poses a threat to U.S. sovereignty in that the United

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States may be forced to lower its environmental, health, and safety standards to conform to
global rules. An example of this is that a Geneva based trade panel ruled that the U.S.
government must halt its boycott of tuna caught with fishing methods that kill large numbers
of dolphins (821). The reason that something like this can happen is that nations involved in
the GATT are subject to challenges of this sort as illegal trade barriers. The World Trade
Organization could also undermine food safety laws by forcing the United States to either
accept
food with dangerous pesticide levels or pay a substantial fee. They also argue that new taxes
may be needed to offset the loss in tariff revenue. Another concern is that U.S. measures to
prevent dumping or selling of a product in a foreign market at a price lower than its fair market
value could be weakened. But what the opponents of the World Trade Organization fail to
realize is that if the Congress passes the Uruguay Round the U.S. will have a much larger say
in environmental and food safety standards and the restriction of dumping. Members of
Congress who support the agreement believe that it will bring far reaching economic benefits
to the United States, including new employment opportunities and high paying jobs associated
with the increased production of goods and services for export (Banks 35).
Supporters also feel that import growth resulting from the agreement will keep prices
low and broaden consumer choices. A specific group of Americans that will benefit greatly
from the passage to GATT in Congress are the farmers. The United States is by far the most
efficient farming country with more prime cropland per capita than any other country in the
world. Last
year U.S. farm exports totaled 42.6 billion dollars which is lower than their 1981 peak. The
main reason for this has been the increase of Europe’s heavily subsidized farmers (Banks 35).
Using 1992 numbers, every one hundred dollars of Europe’s farm exports carried an average
twenty five dollar subsidy versus one dollar for the United States (Banks 35). If GATT was to
pass the gap wouldn’t disappear but it would shrink significantly.
Another positive aspect of GATT is that it will open up traditionally closed foreign
markets. For example, the U.S. will import three percent of its peanuts and Japan will import
at
least some of its rice and citrus products, Korea will import some almonds, and so on with
other countries. As a positive look to the future for farmers penetrating foreign markets a study
shows that Asians eat on average 11 grams of protein a day compared to 52 for Japanese and

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72 for Americans. As the Asian countries’ standard of living increases the study says so will
their protein intake.

With GATT in place, the likelihood is that an increasing amount of it will be American grown.
GATT will cost the United States Treasury about fourteen billion dollars over the next five
years in revenues lost because of reduced tariffs. Under budget rules, this tax cut for consumers
must be paid for with fourteen billion dollars in increased revenues or decreased spending.
Republicans feel that the government already has too much money so they are opposed to new
taxes. And the Democrats feel that the government could never have too much money to work
with so they oppose spending cuts.
GATT is not perfect but I feel that it would be devastating to allow these different outlooks to
impede a trade package that may enlarge the U.S. GDP by a cumulative one trillion dollars
over the first ten years (76). GATT will increase U.S. competitiveness in foreign markets and
create a great number of high paid, highly-skilled jobs for Americans. Because of these positive
factors and small speculative risks I feel that the General Agreement on Tariffs and Trade
should be supported by all Americans with great enthusiasm towards the economic future of
our nation.

The World Intellectual Property Organization (WIPO) is an international organization

dedicated to promoting the use and protection of works of the human spirit. These works—
intellectual property—are expanding the bounds of science and technology and enriching the
world of the arts. Through its work, WIPO plays an important role enhancing the quality and
enjoyment of life, as well as creating real wealth for nations. With headquarters in Geneva,
Switzerland, WIPO is one of the 16 specialized agencies of the United Nations system of
organizations.

It administers 23 international treaties dealing with different aspects of intellectual property

protection. The Organization counts 182 nations as member states. As of January 2000, all
developed and developing countries who are members of the World Trade Organization
(WTO) were obligated to have domestic laws and enforcement mechanisms that comply with
the international standards set forth under the Agreement on Trade-Related Aspects of
Intellectual Property Rights (TRIPS). TRIPS, which is the most comprehensive multilateral
agreement on intellectual property, includes a set of provisions dealing with domestic

14
procedures and remedies for the enforcement of intellectual property rights. TRIPS lays down
certain general principles applicable to all intellectual property rights enforcement procedures,
and contains provisions on civil and administrative procedures and remedies, provisional
measures, special requirements related to broader measures and criminal procedures. Because
of the January 2000 deadline for TRIPS compliance, during much of that year, USPTO
developed and implemented many training programs to help those countries with the January
2000 deadline to implement the TRIPS provisions. The USPTO will continue to cooperate with
other US agencies and regional and international organizations in the years to come to provide
similar programs to developing countries.

GENERAL PROVISIONS AND BASIC PRINCIPLES

Article 1
Nature and scope of obligations
1. Members shall give effect to the provisions of this Agreement. Members may, but shall not
be obliged to, implement in their law more extensive protection than is required by this
Agreement, provided that such protection does not contravene the provisions of this
Agreement. Members shall be free to determine the appropriate method of implementing the
provisions of this Agreement within their own legal system and practice.
2. For the purposes of this Agreement, the term “intellectual property” refers to all categories
of intellectual property that are the subject of Sections 1 through 7 of Part II.
3. Members shall accord the treatment provided for in this Agreement to the nationals of other
members. In respect of the relevant intellectual property right, the nationals of other members
shall be understood as those natural or legal persons that would meet the criteria for eligibility
for protection provided for in the Paris Convention (1967), the Berne Convention (1971), the
Rome Convention and the Treaty on Intellectual Property in Respect of Integrated Circuits,
were all members of the WTO members of those conventions. Any member availing itself of
the possibilities provided in paragraph 3 of Article 5 or paragraph 2 of Article 6 of the Rome

15
Convention shall make a notification as foreseen in those provisions to the Council for Trade-
Related Aspects of Intellectual Property Rights (the “Council for TRIPS”).

Article 2
Intellectual property conventions
1. In respect of Parts II, III and IV of this Agreement, members shall comply with Articles 1
through 12, and Article 19, of the Paris Convention (1967).
2. Nothing in Parts I to IV of this Agreement shall derogate from existing obligations that
members may have to each other under the Paris Convention, the Berne Convention, the Rome
Convention and the treaty on Intellectual Property in Respect of Integrated Circuits.

Article 3
National treatment
1. Each member shall accord to the nationals of other members treatment no less favorable than
that it accords to its own nationals with regard to the protection of intellectual property, subject
to the exceptions already provided in, respectively, the Paris Convention (1967), the Berne
Convention (1971), the Rome Convention or the Treaty on Intellectual Property in Respect of
Integrated Circuits. In respect of performers, producers of phonograms and broadcasting
organizations, this obligation only applies in respect of the rights provided under this
Agreement. Any member availing itself of the possibilities provided in Article 6 of the Berne
Convention (1971) or paragraph 1(b) of Article 16 of the Rome Convention shall make a
notification as foreseen in those provisions to the Council for TRIPS.
2. Members may avail themselves of the exceptions permitted under paragraph 1 in relation of
judicial and administrative procedures, including the designation of an address for service or
the appointment of an agent within the jurisdiction of a member, only where such exceptions
are necessary to secure compliance with laws and regulations which are not inconsistent with
the provisions of this Agreement and where such practices are not applied in a manner which
would constitute a disguised restriction on trade.

Article 4
Most-favoured-nation treatment
With regard to the protection of intellectual property, any advantage, favour, privilege or
immunity granted by a member to the nationals of any other country shall be accorded

16
immediately and unconditionally to the nationals of all other members. Exempted from this
obligation is any advantage, favour, privilege or immunity accorded by a member: (a) deriving
from international agreements on judicial assistance or law enforcement of a general nature
and not particularly confined to the protection of intellectual property; (b) granted in
accordance with the provisions of the Berne Convention (1971) or the RomeConvention
authorizing that the treatment accorded be a function not of national treatment but of the
treatment accorded in another country; (c) in respect of the rights of performers, producers of
phonograms and broadcasting organizations not provided under this Agreement;
(d) deriving from international agreements related to the protection of intellectual property
which entered into force prior to the entry into force of then WTO Agreement, provided that
such agreements are notified to the Council for TRIPS and do not constitute an arbitrary or
unjustifiable discrimination against nationals of other Members.

Article 5
Multilateral agreements on acquisition or maintenance of protection
The obligations under Articles 3 and 4 do not apply to procedures provided in multilateral
agreements concluded under the auspices of WIPO relating to the acquisition or maintenance
of intellectual property rights.

Article 6
Exhaustion
For the purposes of dispute settlement under this Agreement, subject to the provisions of
Articles 3 and 4 nothing in this Agreement shall be used to address the issue of the exhaustion
of intellectual property rights.

Article 7
Objectives
The protection and enforcement of intellectual property rights should contribute to the
promotion of technological innovation and to the transfer and dissemination of technology, to
the mutual advantage of producers and users of technological knowledge and in a manner
conductive to social and economic welfare, and to a balance of rights and obligations.

Article 8

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Principles
1. Members may, in formulating or amending their laws and regulations, adopt measures
necessary to protect public health and nutrition, and to promote the public interest in sectors of
vital importance to their socio-economic and technological development, provided that such
measures are consistent with the provisions of this Agreement.
2. Appropriate measures, provided that they are consistent with the provisions of this
Agreement, may be needed to prevent the abuse of intellectual property rights by right holders
or the resort to practices which unreasonably restrain trade or adversely affect the international
transfer of technology.

Does the TRIPS Agreement Apply to all WTO Members?

All the WTO agreements (except for a couple of “plurilateral” agreements) apply to all WTO
members. The members each accepted all the agreements as a single package with a single
signature—making it, in the jargon, a “single undertaking”. The TRIPS Agreement is part of
that package. Therefore it applies to all WTO members (more on the single undertaking). But
the agreement allows countries different periods of time to delay applying its provisions. These
delays define the transition from before the agreement came into force (before 1 January, 1995)
until it is applied in member countries.
The main transition periods are :
• Developed countries were granted a transition period of one year following the entry into
force of the WTO Agreement, i.e., until 1 January, 1996.
• Developing countries were allowed a further period of four years (i.e., to 1 January, 2000) to
apply the provisions of the agreement other than Articles 3, 4 and 5 which deal with general
principles such as non-discrimination.
• Transition economies, i.e., members in the process of transformation from centrallyplanned
into market economies, could also benefit from the same delay (also until 1 January, 2000) if
they met certain additional conditions.
• Least-developed countries are granted a longer transition period of a total of eleven years
(until 1 January, 2006), with the possibility of an extension. For pharmaceutical patents, this
has been extended to 1 January, 2016, under a decision taken by ministers at the Fourth
Ministerial Conference in November 2001.

What is the Place of the TRIPS Agreement in the Multilateral Trading System?

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One of the fundamental characteristics of the TRIPS Agreement is that it makes protection of
intellectual property rights an integral part of the multilateral trading system, as embodied in
the WTO.
The TRIPS Agreement is often described as one of the three “pillars” of the WTO, the other
two being trade in goods (the traditional domain of the GATT) and trade in services. The TRIPS
Agreement is part of the “single undertaking” resulting from the Uruguay Round negotiations.
That implies that the TRIPS Agreement applies to all WTO members. It also means that the
provisions of the agreement are subject to the integrated WTO dispute settlement mechanism
which is contained in the Dispute Settlement Understanding (the “Understanding on Rules and
Procedures Governing the Settlement of Disputes”).

What is the Relationship between the TRIPS Agreement and the Pre-existing
International Conventions that it Refers to?
The TRIPS Agreement says WTO member countries must comply with the substantive
obligations of the main conventions of WIPO—the Paris Convention on industrial property,
and the Berne Convention on copyright (in their most recent versions). With the exception of
the provisions of the Berne Convention on moral rights, all the substantive provisions of these
conventions are incorporated by reference. They therefore become obligations for WTO
member countries under the TRIPS Agreement – they have to apply these main provisions, and
apply them to the individuals and companies of all other WTO members.
The TRIPS Agreement also introduces additional obligations in areas which were not
addressed in these conventions, or were thought not to be sufficiently addressed in them. The
TRIPS Agreement is therefore sometimes described as a Berne and Paris-plus Agreement.

The text of the TRIPS Agreement also makes use of the provisions of some other international
agreements on intellectual property rights:
• WTO members are required to protect integrated circuit layout-designs in accordance with
the provisions of the Treaty on Intellectual Property in Respect of Integrated Circuits
(IPIC Treaty) together with certain additional obligations.
• The TRIPS Agreement refers to a number of provisions of the International Convention for
the Protection of Performers, Producers of Phonograms and Broad casting Organizations
(Rome Convention), without entailing a general requirement to comply with the substantive
provisions of that Convention. TRIPS Agreement specifies that nothing in Parts I to IV of the

19
agreement shall derogate from existing obligations that members may have to each other under
the Paris Convention, the Berne Convention, the Rome Convention and the Treaty on
Intellectual Property in respect of integrated circuits.

What is the Role of the TRIPS Council?

The TRIPS Council comprises all WTO members. It is responsible for monitoring the operation
of the agreement, and, in particular, how members comply with their obligations under it.

1. Monitoring: Members review each others’ laws. The reviews are central to the TRIPS
Council’s task of monitoring what is happening under the agreement. Each country has to make
sure its laws comply with the obligations of the agreement, according to the timetable spelt out
in the agreement. Most have to enact laws implementing the obligations. These laws are
notified to the TRIPS Council, allowing members to review each others’ legislation, and
promoting the transparency of members’ policies on intellectual property protection. The
requirement to notify comes under the TRIPS Agreement. Members have to supply the TRIPS
Council with copies of their laws and regulations that deal with the TRIPS Agreements’
provisions. These notifications are then used as the basis the Council’s reviews of members’
legislation. In these reviews, countries supply written questions about each others’ laws before
the review meetings. The answers are also in writing. Follow-up questions and replies are made
orally during the course of the meeting, and further follow-up is possible at subsequent
meetings.

PATENTING AND THE PROCEDURES INVOLVED IN THE APPLICATION FOR

GRANTING OF A PATENT

Overview of the Patenting Process

A patent is an exclusive right of its owner to exclude others from making, using, or selling the
invention as defined in the claims of the patent for a period of time, which in the United States
is 20 years from the date of filing the patent application.

There are three types of patents:

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1. Utility Patents may be granted to anyone who invents or discovers any new and useful
process, machine, article of manufacture, or composition of matter, or any new and useful
improvement thereof;

2. Design Patents may be granted to anyone who invents a new, original, and ornamental
design for an article of manufacture; and

3. Plant Patents may be granted to anyone who invents or discovers and asexually reproduces
any distinct and new variety of plant.

STEPS TO A PATENT
Introduction

There are several steps that help in securing a patent. The steps begin in the lab and move
through the legal process of patent prosecution and maintenance. This section describes the
steps that you should follow to help maximize the value of your invention and protect your
intellectual property rights.

(a) Patent success starts in the lab

Documentation is the beginning of strong patents because it authenticates with whom a theory
originates (conception) and the steps taken to test and produce results (diligent reduction to
practice). These documents are scrutinized to determine inventorship, reduction to practice,
and to support a patent’s validity.
Well-maintained laboratory records can document the date of conception of an invention and
also establish diligence in developing an idea. Such documentation is needed in case of a
question about which inventor should be entitled to pursue a patent. Records can be more useful
in this regard if the following steps are followed:

• Records have more value if they are meaningful to others. Entries should be complete,
accurate, and legible.
• Preface the record of each experiment with a brief purpose or statement of the problem.
• Use a permanently bound notebook with numbered pages.
• Make frequent entries (daily is best) in ink, and design and date each page.

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• Start a new page for each new experiment.
• Draw a continuous diagonal line through unused portions of pages remaining at the end of an
experiment.
• Don’t erase. Instead, where necessary, cross out with a single line.
• Initial and date all major changes.
• Record observations of physical results even if they are not fully appreciated or understood
at the time.
• Have work corroborated by having notebooks witnessed by dated signature of an associate
who understands the content, but not a co-worker or one who collaborates in the research area
and who could be a joint inventor.
• Think carefully before destroying any samples, run sheets, or records related to any
inventions.

(b) Plan to both publish and patent

Although the timing of publications may sometimes prohibit patenting, planning allows the
inventor to both publish and patent. Disclosing the idea to the Office of Technology Transfer
as soon as the invention is clearly conceptualized, or at least before submitting abstracts or
manuscripts disclosing the invention, allows time to complete a patentability and
commercialization assessment before being barred from a patent. In the United States, an
inventor has a grace period of one year to file a patent application after disclosure through
publication. However, if an invention is publicly disclosed before a U.S. patent application is
filed, patent rights in most other countries are lost.

What constitutes publication?

Articles in newspapers, newsletters, bulletins, textbooks, journals, theses, reports, and even
letters to the editor all qualify as publications. Oral presentations may constitute publication,
as would distribution of a paper at a public meeting. Some legal experts also think that
disclosure through electronic communications, such as e-mail, may be considered publication.
The key test is that the publication be enabling—it must describe the invention in sufficient
detail that it could be duplicated or put into use.

(c) Disclosing an invention

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The technology transfer process actually begins when the inventor discloses his or her potential
invention to the Office of Technology Transfer—a step required by IU’s intellectual property
policy. Discussions between the inventor and office staff members can help determine whether
an invention has been made and whether a formal disclosure should be completed. The office
staff supplies inventors with a formal disclosure form and assists in its preparation. An
invention disclosure is a written record of an invention containing a complete description of
the invention, the inventor’s dated signature, and dated signatures of witnesses who fully
understand the invention (but are not joint inventors).

(d) Invention evaluation

When the completed disclosure form has been reviewed by the Office of Technology Transfer
and discussed with the inventor, recommendations are formulated on ownership, patenting, and
licensing. Inventions are evaluated for novelty, likelihood of patentability, potential market,
usefulness, projected development time, and cost. The most effective way to bring the
invention’s benefits to the public will be determined, whether through patent, copyright, or
placing the invention in the public domain (usually through publication). The probability for
an invention’s economic success may be roughly gauged by these questions:

• How big is the potential market for the invention? Can the invention be sold to a large section
of the public or a large number of manufacturers? Can it be sold to different industries?
• What development will be required before the invention can be sold? How long will
development take? What will it cost? What regulatory requirements must be satisfied?
• How will the product be marketed? Can it be distributed through normal commercial
channels?
• What is the demand for the invention? Does it fill a real need and not just replace satisfactory
article? Does it contribute to the interest?
In most cases, before a patent application is prepared, the Office of Technology Transfer staff
will search for potential licensees to determine the level of industrial interest in the technology.
(A license is essentially an agreement by the patent owner not to sue the licensee for
infringement as long as the licensee abides by the agreement. Licensing is typically the way
the
university realizes an invention’s commercial potential). In most cases, commercial
organizations will underwrite patent expenses in return for the right to a license.

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(e) Patent prosecution (process of obtaining a patent)
The process of obtaining a patent is called patent prosecution. It consists of preparing and filing
the patent application, then filing responses and amendments to the objections of the patent
examiner. Patent prosecution will result in either the issuance of a published patent or the
rejection or abandonment of the application.
Under U.S. law, individual inventors are allowed to prosecute their own patent
applications. However, because the Patent and Trademark Office has specific and often
complex rules about the content and examination of applications and because patents are
interpreted and
enforced in court, inventors should be represented by a patent attorney or agent.
To qualify as a patent attorney, an individual must have a law degree and a degree in a
technical area, and the person must pass the rigorous patent bar exam. To become a patent
agent, a person still must pass the patent bar exam, but a law degree is not required. The patent
application is prepared by the patent attorney with the help of the inventor and is similar in
many respects to a detailed scientific paper (the specifications and drawings) accompanied by
one or more claims, which make-up the legal definition of the invention. The patent application
must make a full disclosure of the invention to teach others how to make and use the invention
and to clearly define the borders of the patent protection. Accomplishing both these objectives
requires the close collaboration of the inventor and the patent attorney. Although the make-up
of patent applications varies considerably, it is commonly divided into the following headings:

• Field of the invention — This describes the general technological field and the broad nature
of the invention.
• Background of the invention — The background describes the technological problem to be
solved and gives a brief description of present technology and its limitations.
• Objectives of the invention — The objectives indicate the nature of the improvements the
invention seeks to provide.
• Summary of the invention — The summary states the essential elements of the invention in
broad terms and often introduces the terminology to be used in the main claims of the patent.
• Detailed description of the invention and/or description of the drawings —These details
include the experimental data, given by way of example, describing the methodology of the
invention and the apparatus used (if any).

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• Claims — Claims define the invention in one or more single-sentence paragraphs and serve
as the legal definition of the invention.

When received in the Patent and Trademark Office, the application package is assigned to a
patent examiner with expertise in the invention’s technical field. Although workloads and
response times vary, usually six months or more pass before the application’s initial
examination.
In the initial examination, the examiner searches both the scientific and the patent
literature to determine whether the application discloses and claims new and patentable subject
matter, and the examiner judges the allowability of each claim. Most applications are initially
rejected. The basis for rejection is most often prior patents or publications which, in the
examiner’s view, render the new invention obvious. The patent attorney, with the assistance of
the inventor, responds to the examiner with arguments about why the invention is patentable.
The cycle can be repeated several times and the patent application can be amended, restricted,
divided, or continued in the process. On average, the examination of a patent application takes
two years in the United States, where the application is considered confidential throughout the
process. In many other countries, patent applications are published after a given period of time.
The Patent and Trademark Office allows, or approves, around 90,000 patents a year. The total
number of patents issued now exceeds 5 million. When the Patent and Trademark Office gives
notice of allowance, and the issue fee is paid, the patent is issued, or published in the Patent
Gazette.
The cost of the typical U.S. patent prosecution for university, conducted by outside
legal counsel, is $15,000 or more.

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PATENT COOPERATION TREATY (PCT)
Done at Washington on June 19, 1970, amended on October 2, 1979, and modified on February
3, 1984, and Regulations under the PCT (as in force on January 1, 1985) World Intellectual
Property Organization, Geneva 1985.

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Establishment of a Union
1. The States party to this Treaty (hereinafter called “the Contracting States”) constitute a
Union for cooperation in the filing, searching, and examination, of applications for the
protection of inventions, and for rendering special technical services. The Union shall be
known as the International Patent Cooperation Union.
2. No provision of this Treaty shall be interpreted as diminishing the rights under the Paris
Convention for the Protection of Industrial Property of any national or resident of any country
party to that Convention.

Definitions

For the purposes of this Treaty and the regulations and unless expressly stated otherwise:

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(i) “application” means an application for the protection of an invention; references to an
“application” shall be construed as references to applications for patents for inventions,
inventors’ certificates, utility certificates, utility models, patents or certificates of addition,
inventors’ certificates of addition, and utility certificates of addition;
(ii) references to a “patent” shall be construed as references to patents for inventions, inventors’
certificates, utility certificates, utility models, patents or certificates of addition, inventors’
certificates of addition, and utility certificates of addition;
(iii) “national patent” means a patent granted by a national authority;
(iv) “regional patent” means a patent granted by a national or an intergovernmental authority
having the power to grant patents effective in more than one State;
(v) “regional application” means an application for a regional patent;
(vi) references to a “national application” shall be construed as references to applications for
national patents and regional patents, other than applications filed under this Treaty;
(vii) “international application” means an application filed under this Treaty;
(viii) references to an “application” shall be construed as references to international
applications
and national applications;
(ix) references to a “patent” shall be construed as references to national patents and regional
patents.

Reference:

Sree Krishna, V. 2007. Bioethics and Biosafety in Biotechnology. New Age International (P)
Ltd., Publishers, New Delhi – 110002, India.135pp.

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