Biotechnology

MITHUN KHATRI
Issues on Open Source

2010

“To hear always, to think always, to learn always,

It is thus that we live truly; he who aspires to
nothing, and learns nothing, is not worthy of
living.”
A. Helps
Introduction

Biotechnology in one form or another has flourished since prehistoric times. When the
first human beings realized that they could plant their own crops and breed their own
animals, they learned to use biotechnology. The discovery that fruit juices fermented into
wine or that milk could be converted into cheese or yogurt, or that beer could be made by
fermenting solutions of malt and hops began the study of biotechnology. When the first
bakers found that they could make soft, spongy bread rather than a firm, thin cracker,
they were acting as fledgling biotechnologists. The first animal breeders, realizing that
different physical traits could be either magnified or lost by mating appropriate pairs of
animals, engaged in the manipulations of biotechnology.

What then is biotechnology? The term brings to mind many different things. Some think
of developing new types of animals. Others dream of almost unlimited sources of human
therapeutic drugs. Still others envision the possibility of growing crops that are more
nutritious and naturally pest-resistant to feed a rapidly growing world population. This
question elicits almost as many first-thought responses as there are people to whom the
question can be posed.

In its purest form, the term "biotechnology" refers to the use of living organisms or their
products to modify human health and the human environment. Prehistoric
biotechnologists did this as they used yeast cells to raise bread dough and to ferment
alcoholic beverages, and bacterial cells to make cheeses and yogurts and as they bred
their strong, productive animals to make even stronger and more productive offspring.

In the field of biotechnology, fledgling efforts are under way to establish open source
projects. Borrowing concepts from the open source software movement, these projects
create cooperative exchanges in which life science inventions are openly available to a
broad research community. The projects are aimed at solving problems in underserved
communities, cutting through patent thickets, and ensuring that the biotechnology tools
required for research and innovation are openly available.

Open Source Technology in Biotechnology

A number of issues in the innovation policies of modern biotechnology, particularly the

impact of patent thickets and anti-commons effects, have emerged lately. Partially as a
response to such issues, partially as a natural consequence of biotech shifting towards an
information-intensive sector, attempts have emerged, trying - more or less consciously -
to adapt the licensing practices and development dynamics of Free, Libre and Open
Source Software (FLOSS) to the brave new world of the life sciences. The question
remains whether such approaches make sense for profit-maximizing firms and whether it

is conceptually and practically useful to use the "Open Source" meme as a basis for
discussion and policy-making in this sector.

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Open source as an alternative to intellectual property:

Biotechnology and Intellectual Property Rights (IPR) & Intellectual Property

Protection (IPP) - One of the most important issues, which has been raised due to the
emergence of modern biotechnology, is the legal characterization and treatment of trade
related biotechnological processes and products, popularly described as Intellectual
Property its protection (Intellectual Property Protection = IPP) and the Rights
(Intellectual Property Rights = IPR), available to protect this property have been the
subject of discussion in recent years.

In this connection, one may like to compare biotechnology with other technologies, the
advances in which are covered by the patent system and are, therefore, routinely licensed
and marketed.

The term property is often found associated with physical objects only, such as household
goods or land, for which ownership and associated rights are guaranteed and protected by
law prevalent in a country. This property is described as tangible. Intellectual property,
on the other hand, is intangible and includes 'patents', 'trade secrets', 'copyrights' and
'trademarks'. The right to protect this property prohibits others from making, copying,
using or selling the proprietary subject matter. Under biotechnology, one of the most
important examples of intellectual property is the processes and products, which result
from the development of genetic engineering techniques through the use of restriction
enzymes to create recombinant DNA. The characterization of these research results as
intellectual properties encourages industries to allocate labor, research and development
(R&D) units and funding to facilitate the production of commercially marketable items.

Due to these intellectual properties, many legal and public policies, which are
impediments to biotechnological research are also being challenged and are, therefore,
undergoing changes. This is understandable, because if public policies do not allow the
development and commercial use of an intellectual property, no industry would like to
invest funds in this research.

Another example of intellectual property is the development of crop varieties, which are
protected through 'plant breeder's rights' or PBRs (PBRs are available in developed
countries, not in India). Through PBR, the plant breeder who developed a variety enjoys
the exclusive right for marketing the variety, although use of the variety for further
breeding or for replantation of seed saved by a farmer (farmer's exemption) is
permissible.

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Benefits of Using Open Source Approaches

1. Scientific Benefits
a. Peer evaluation and valuation of findings
b. Increase intellectual curiosity and motivation
c. Maximize rational development
d. Facilitate sharing of technical information
e. Facilitate technology transfer and access to health in developing countries.

2. Economic Benefits
a. Reduce duplication
b. Develop market for complementary goods and services
c. Enhance reputation and public relations
d. Share financial risk in projects
e. Attract volunteer labor
f. Eliminate time consuming negotiations
g. customizable
h. Produce usable output at lower cost

3. Social Benefits
a. Increase respect of peers
b. Compatible with the scientific ethos of open science
c. Improve coordination
d. Facilitates access to information for learning and education process
e. Increase motivation of employees

Issues and Bioethics

Issues focus on scientific breakthrough that has propelled biotechnology at a dizzying

pace into the 21st century. Evolving in tandem with biotech innovations, ethics looks at
complex decisions that affect a few individual or an entire social group or society.

Issues
Some of the important issues in the important fields are as under:

Agricultural and Chemical Industries

The bio-revolution resulting from advances in molecular biosciences and biotechnology

has already outstripped the advances of the "Green Revolution." In the early 1960s, the
pioneering studies of Nobel prize winner Norman Borlaug, using cross-breeding
techniques based on classical genetics, offered for the first time a weapon against hunger
in the countries of Latin America, Asia, and Africa. As a direct result of the

comprehensive studies of Borlaug and his contemporaries, new wheat hybrids began to
transform the harvests of India and China, although they had a relatively minor influence

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on agriculture in more temperate climates. There is little doubt that genetic manipulation
will open more new doors in this field, and will dramatically alter farming worldwide.

It does not require a crystal ball to imagine the potential of the immediate
biotechnological future. From the advances in recent years, it is possible to extrapolate to
a number of likely developments based on research now in progress. In the plant world,
the 1978 development of the "pomato," a laboratory-generated combination of two
members of the Solanaceae family (the potato and the tomato), was a significant advance.
The Flavr Savr tomato was reviewed by the FDA in the spring of 1994 and found to be as
safe as conventionally produced tomatoes. This is the first time the FDA has evaluated a
whole food produced by biotechnology.

Exciting prospects are likely to result from industrial-scale plant tissue culture. This may
soon obviate the need for rearing whole plants in order to generate valuable commodities
such as dyes, flavorings, drugs, and chemicals. Cloning techniques could prove to be the
way to tackle some of the acute problems of reforesting in semi-desert areas. Seedlings
grown from the cells of mature trees could greatly speed up the process. In the summer of
1987, a Belgian team introduced into crop plants a group of genes encoding for insect
resistance and resistance to widely used herbicides. This combination of advantageous
genes could bring about a new era in plant protection. The crop can be treated safely with
more effective doses of weed killer, and it is also engineered to be less susceptible to
insect damage.

Dairy farming is also benefiting from advances in biotechnology. Bovine somatotropin

(growth hormone) will enhance milk yields, with no increase in feed costs. Embryo
duplication methods mean that cows will bear more calves than in the past, and embryo
transfer techniques are enabling cattle of indifferent quality to rear good quality stock, a
potentially important development for nations with less advanced agriculture. Genetic
manipulation of other stock, such as sheep and pigs, appears to be feasible, and work is in
progress on new growth factors for poultry.

The outcome of this intense activity will be improvements in the texture, quality, variety,
and availability of traditional farm products, as well as the emergence of newly
engineered food sources. Such bioengineered super-foods will be welcomed, and will
offer new varieties, and hence find new markets in the quality-conscious advanced
countries. Despite the enormous potential gains, the economic consequences of possible
overproduction in certain areas must also be faced. It will be essential for those
concerned with making agricultural policies to keep abreast of the pace of modern
biotechnology. Short-term benefits to the consumer of lower agricultural prices must be
weighed against a long-term assessment of the impact of new discoveries on the farming
industry.

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Medicine

In the medical field, considerable efforts will be devoted to the development of vaccines
for killer diseases such as AIDS. Monoclonal antibodies will be used to boost the body's
defenses and guide anti-cancer drugs to their target sites. This technology may also help
to rid the human and animal world of a range of parasitic diseases by producing specific
antibodies to particular parasites. Synthesis of drugs, hormones, and animal health
products, together with drug-delivery mechanisms, are all advancing rapidly. Enzyme
replacement and gene replacement therapy are other areas where progress is anticipated.
The next decade will see significant advances in medicine, agriculture, and animal health
directly attributable to biotechnology.

Mining and Waste Management

The impact of the new technology will not, however, be confined to bio-based industries.
Genetically engineered microbes may become more widely used to extract oil from the
ground and valuable metals from factory wastes. In short, the lives of every one of us will
be influenced by biotechnology.

Gene Therapy - An Overview

Altered Genes

Each of us carries about half a dozen defective genes. We remain blissfully unaware of
this fact unless we, or one of our close relatives, are amongst the many millions who
suffer from a genetic disease. About one in ten people has, or will develop at some later
stage, an inherited genetic disorder, and approximately 2,800 specific conditions are
known to be caused by defects (mutations) in just one of the patient's genes. Some single
gene disorders are quite common - cystic fibrosis is found in one out of every 2,500
babies born in the Western World - and in total, diseases that can be traced to single gene
defects account for about 5% of all admissions to children's hospitals.

In the U.S. and Europe, there are exciting new programs to 'map' the entire human
genome - all of our genes. This work will enable scientists and doctors to understand the
genes that control all diseases to which the human race is prone, and hopefully develop
new therapies to treat and predict diseases.

Diseases of Genetic Origin

Most of us do not suffer any harmful effects from our defective genes because we carry
two copies of nearly all genes, one derived from our mother and the other from our
father. The only exceptions to this rule are the genes found on the male sex
chromosomes. Males have one X and one Y chromosome, the former from the mother

and the latter from the father, so each cell has only one copy of the genes on these
chromosomes. In the majority of cases, one normal gene is sufficient to avoid all the
symptoms of disease. If the potentially harmful gene is recessive, then its normal

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counterpart will carry out all the tasks assigned to both. Only if we inherit from our
parents two copies of the same recessive gene will a disease develop.

On the other hand, if the gene is dominant, it alone can produce the disease, even if its
counterpart is normal. Clearly only the children of a parent with the disease can be
affected, and then on average only half the children will be affected. Huntington's chorea,
a severe disease of the nervous system, which becomes apparent only in adulthood, is an
example of a dominant genetic disease.

Finally, there are the X chromosome-linked genetic diseases. As males have only one
copy of the genes from this chromosome, there are no others available to fulfill the
defective gene's function. Examples of such diseases are Duchenne muscular dystrophy
and, perhaps most well known of all, hemophilia.

Queen Victoria was a carrier of the defective gene responsible for hemophilia, and
through her it was transmitted to the royal families of Russia, Spain, and Prussia. Minor
cuts and bruises, which would do little harm to most people, can prove fatal to
hemophiliacs, who lack the proteins (Factors VIII and IX) involved in the clotting of
blood, which are coded for by the defective genes. Sadly, before these proteins were
made available through genetic engineering, hemophiliacs were treated with proteins
isolated from human blood. Some of this blood was contaminated with the AIDS virus,
and has resulted in tragic consequences for many hemophiliacs. Use of genetically
engineered proteins in therapeutic applications, rather than blood products, will avoid
these problems in the future.

Not all defective genes necessarily produce detrimental effects, since the environment in
which the gene operates is also of importance. A classic example of a genetic disease
having a beneficial effect on survival is illustrated by the relationship between sickle-cell
anemia and malaria. Only individuals having two copies of the sickle-cell gene, which
produces a defective blood protein, suffer from the disease. Those with one sickle-cell
gene and one normal gene are unaffected and, more importantly, are able to resist
infection by malarial parasites. The clear advantage, in this case, of having one defective
gene explains why this gene is common in populations in those areas of the world where
malaria is endemic.

Gene Therapy

Much attention has been focused on the so-called genetic metabolic diseases in which a
defective gene causes an enzyme to be either absent or ineffective in catalyzing a
particular metabolic reaction effectively. A potential approach to the treatment of genetic
disorders in man is gene therapy. This is a technique whereby the absent or faulty gene is

replaced by a working gene, so that the body can make the correct enzyme or protein and
consequently eliminate the root cause of the disease.

The most likely candidates for future gene therapy trials will be rare diseases such as
Lesch-Nyhan syndrome, a distressing disease in which the patients are unable to

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manufacture a particular enzyme. This leads to a bizarre impulse for self-mutilation,
including very severe biting of the lips and fingers. The normal version of the defective
gene in this disease has now been cloned.

If gene therapy does become practicable, the biggest impact would be on the treatment of
diseases where the normal gene needs to be introduced into only one organ. One such
disease is phenylketonuria (PKU). PKU affects about one in 12,000 white children, and if
not treated early can result in severe mental retardation. The disease is caused by a defect
in a gene producing a liver enzyme. If detected early enough, the child can be placed on a
special diet for their first few years, but this is very unpleasant and can lead to many
problems within the family.

The types of gene therapy described thus far all have one factor in common: that is, that
the tissues being treated are somatic (somatic cells include all the cells of the body,
excluding sperm cells and egg cells). In contrast to this is the replacement of defective
genes in the germline cells (which contribute to the genetic heritage of the offspring).
Gene therapy in germline cells has the potential to affect not only the individual being
treated, but also his or her children as well. Germline therapy would change the genetic
pool of the entire human species, and future generations would have to live with that
change. In addition to these ethical problems, a number of technical difficulties would
make it unlikely that germline therapy would be tried on humans in the near future.

Before treatment for a genetic disease can begin, an accurate diagnosis of the genetic
defect needs to be made. It is here that biotechnology is also likely to have a great impact
in the near future. Genetic engineering research has produced a powerful tool for
pinpointing specific diseases rapidly and accurately. Short pieces of DNA called DNA
probes can be designed to stick very specifically to certain other pieces of DNA. The
technique relies upon the fact that complementary pieces of DNA stick together. DNA
probes are more specific and have the potential to be more sensitive than conventional
diagnostic methods, and it should be possible in the near future to distinguish between
defective genes and their normal counterparts, an important development.

The Human Genome Program in the U.S. will provide about $200 million each year to
scientists in multidisciplinary research centers who are attempting to determine the
makeup of all human genes. Together with similar programs in Europe, it is hoped that in
15 years time we shall be able to identify and treat all diseases to which humans are
susceptible. This will revolutionize modern medicine, and hopefully improve the quality
of life of all men, women, and children. Already, the genes for Duchenne muscular
dystrophy, cystic fibrosis, and retinoblastoma have been identified, and more such
information is emerging all the time.

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Bioethics

Talking and Teaching Biotech

Biotechnology Education with the Public: Generating Insight in the Age of

Information

We hear a common lament: Why does the public understand so little about
biotechnology? But in this era of customer focus, perhaps we should ask: Why do we
understand so little about communicating with the public about biotechnology?

Perhaps we talk too much - and in the language of Ph.D. biologists. Perhaps we need to
listen better.

At the beginning of a presentation I usually ask the audience, "What questions do you
have about biotechnology?" The most common one is also the fundamental one: "What is
biotechnology?" We need to be very careful when answering this question, for several
reasons. First, how we answer it sets the tone for all our educational activities. Do we
lecture, or do we inquire? Do we tell, or do we engage the audience? Second, defining
biotechnology also defines the community resources available for learning about
biotechnology. If it's defined solely as applied recombinant DNA, then we seem to
exclude biotechnology from most American communities - those without a college or a
research hospital or a hard-core biotech company.

To help define biotechnology broadly, I ask my audiences for five things beginning with
"F" that we get from plants, animals, or microbes. They eventually get to:

• Food
• Fiber
• Fuel
• Feedstocks
• Pharmaceuticals

That brings biotechnology home, and we expand the list of communities with local
resources for learning about it.

Most people know what a radar detector is. I'd like to have a "biotechnology detector" to
help raise awareness. A little box that could fit on the dashboard, it would go off when
the car goes by a place where biotechnology is used. Like a radar detector, the biotech
detector could be adjusted for sensitivity. At the "classical" setting, any place that uses
fermentations would set it off: a bakery, brewery, or a cheese plant. Adjust the sensitivity
to "recombinant DNA" and you might have to drive past a university or company doing
molecular biology research to set it off.

Third, the language we use is critical. Avoid bio babble when providing information. Use
analogies when giving analyses. Effective teachers often start with the familiar, and use
what their audience knows to bring them to topics they want to learn more about. For

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example, when describing genetic engineering you can either launch into descriptions of
restriction endonucleases, or you can compare DNA to videotape. Both DNA and
videotape are linear informational tapes that carry encoded information that can be
decoded, expressed, copied, spliced, edited, and you can make copies of the edits.

Savvy businesses and individuals take the time to learn the local language when they
move into international markets. Communicating in the new language demonstrates their
commitment and concern for their new customers. Before heading off to Europe or Asia,
you might take a Berlitz course in German or Japanese. You might seek the help of tutors
or fluent colleagues. Agreeing to work with a local education program may involve a
similar commitment to learning to use a new language, in this case, ordinary English. I
don't know if there's a Berlitz for Biotechers yet. But at the UWBC we're beginning to
develop a program to help people meet a language challenge: how to explain their work
using words and images that students, teachers and the public quickly understand.

Once they've learned the language, what role can businesses and their employees play in
education programs? Businesses can provide materials, money, apprenticeships, and
advocacy. Individual employees give the most precious component: their time, expertise,
and commitment. Learning other people's language is useful in another way: you can hear
and understand their concerns in their own tongue. And that will contribute to the
educational partnership, whether the contribution is in materials, money or expertise.

Biotechnology's Impact on Society

The effects of any new technology introduced on the scale anticipated for biotechnology
extend beyond the factories and research centers influencing our everyday lives.
Biotechnology has, for example, made it possible to detect, and in some cases treat,
diseases such as sickle-cell anemia, Tay-Sachs disease, diabetes, and cystic fibrosis.
Following initial concerns that genetic engineering could give rise to infectious
organisms - the spread of which would be difficult to contain - a stringent set of
guidelines was drawn up by the government and leading scientists in the mid-1970s to
regulate research in this field. While it is not possible to eliminate completely the risk of
a genetic engineering accident, the experience of the last ten or so years of research has
indicated that the chances of constructing a disease-producing organism by accident are
very remote. This is because such pathogens require an extremely complex set of distinct
characteristics, and are effective only when all are present.

A High-Tech, Low-Risk Technology

Containment of experiments is the key to safety. Microbiologists have gained valuable

experience over many years in handling extremely dangerous natural organisms, such as
smallpox virus and cholera bacteria. Physical containment (airtight chambers and
sterilization of all equipment) is backed up by biological containment. The K-12 strain of
E. coli used for the vast majority of experiments, although originating from the E. coli

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organism present in the human intestine, has become accustomed to laboratory
"penthouse" conditions. These optimum conditions are provided by microbiologists
concerned with minimizing variation in laboratory data. As a result, scientists have
shown that such strains cannot survive in the harsher conditions of the human body or the
external environment. Other approaches include the use of strains that specifically require
for their survival chemicals not present in the human body. Thus, current research carried
out under the strictest guidelines carries minimal risk to workers and the public at large.

Concern has been voiced that biotechnology might increase the risk of biological warfare,
and some have speculated that biologists today are stepping into the shoes of the nuclear
physicists of 40 years ago. It is undoubtedly a daunting aspect of the deployment of
biotechnology that will require continued vigilance.

Improved genetic tests based on biotechnological advances can be used to track down
criminals in assault cases based on the uniqueness of their DNA. Genetic counseling can
provide advice on heritable diseases, and genetic screening of workers in possible risk
industries is being considered. DNA probes are providing breakthroughs in early
diagnosis of disease. As detection of genetic predispositions becomes more predictable, a
great deal may be known at birth of an individual's prospects in life. The moral question
then arises as to who has access to this information and how this will affect the
individual's quality of life.

Is Biotechnology Safe?

Many people have voiced concern about biotechnology and genetic engineering.
Scientists have considered the issue of safety over recent years. A special committee of
the National Academy of Sciences specifically reviewed the issues on the introduction
into the environment of organisms genetically engineered using recombinant
DNA technology. They concluded that "there is no evidence that unique hazards exist
either in the use of R-DNA technique or in the transfer of genes between unrelated
organisms," and that "the risks associated with the introduction of R-DNA engineered
organisms are the same kind as those associated with the introduction of unmodified
organisms."

The committee concluded that R-DNA techniques constitute a powerful and safe new
means for the modification of organisms for the benefit of animals and humans. They

Also stated that there is adequate scientific knowledge to guide the safe and prudent use
of such organisms outside research laboratories.

Legal Implications

It will be essential that such issues are aired in public debate as the technology develops.
Many countries are actively reviewing the safety and ethics of biotechnology research
and its applications. Some countries have already established research guidelines for
work on embryo transplantation, embryo research, and surrogate motherhood. Lawyers

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and the public at large will be required to face up to these and similar questions as the
biosciences and biotechnology in particular, move forward.

Legal problems have already emerged regarding patent laws. In 1980, for example, a U.S.
court overturned existing practice and ruled that genetically-engineered microbes may be
patented.

The Benefits

The potential benefits include solving world food shortages, and improvements in
medicine, agriculture, and veterinary sciences. We can confidently expect
biotechnological solutions to many essential industrial processes that currently produce
toxic effluents. An increasing role for biotechnology in environmental management will
undoubtedly follow. Because the prospect of serious biohazards appears to be receding, it
does not mean that strict regulation of the new technology should be relaxed. Provided
such vigilance is maintained, mankind can look forward to a wide range of exciting
prospects that stem from biotechnology.

Conclusion:

Fighting disease, combating hunger, preserving the balance of life on Earth: the future of
biotechnological innovation may well be the future of our planet itself. In the not so
distant future, biotechnology will come to look much like present day software
development. This is somewhat inevitable, given the falling cost of computing power.
While a great deal of the newest biotechnology is powered by advances in computational
technology, ultimately everything bio will benefit.
The most important result of open information sharing and falling costs is the way in
which it opens up the priesthood – be it of programmers or biotech researchers – and
allows a much wider range of people to add their skills, time, desires and ideas to the
mix. Just as open sources of software development has led to a melting pot of innovative
designs, better software and a blurring of traditional lines, so too will the open biotech
movement of the future.

References:

• Public Perception Issues in Biotechnology : Charles Hagendorn and Susan

Allender Hagedorn
• Wizard of OS: Open Source Biotechnology
• Open Source Science: A New Model for Innovation by Martha Lagace
• Groombridge, B., ed. 1992. Intellectual Property Rights for Biotechnology
London: Chapman and Hall
• Issues and Bioethics: www.accessexcellence.org

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