Wednesday, April 9, 2008

ETHICAL ISSUES AND RISK ASSESSMENT IN BIOTECHNOLOGY


ETHICAL ISSUES AND RISK ASSESSMENT IN BIOTECHNOLOGY
There is a rich public debate about how the potential risks associated with biotechnology methods and bioindustry products should be assessed and about whether and how bioethics should influence public policy. A general structure for guiding public policy discourse is emerging but is not fully developed. Groups perceive risks differently depending on their culture, scientific background, perception of government, and other factors. Expert opinion supports a range of positions. Deeply and honestly held but often conflicting beliefs and values about nature, animals, and the community good animate the debate. The result is that biotechnology issues are often highly contentious and debated on both scientific and ethical grounds. Two contemporary examples are:
Do human social benefits such as living a longer and leading more productive life due to biotechnology outweigh the harm that an animal or groups of animals must experience to produce those benefits?
Should an insurance company require information about an individual's genetic inheritance as a condition of eligibility for health insurance?
Biotechnology's risks are sometimes purely conjectural. Without research and clinical trials, risks cannot be fully assessed. Yet conjectural and ethical issues are important because biotechnology affects not only human practices and economic sectors, but also medical practices and the relationship between humanity, animals and the environment. In Paul Thompson's view,
[Biotechnology] is not simply another type of mechanical or chemical creation aimed at making the world better for us. In this instance, we are not simply reshaping matter, but are harnessing life. By manipulating life and natural evolution, we are taking the process that shaped our existence and that of every other living organism on the planet and restructuring it for our own benefit.
Public Policy Debate
There are many complex and emotionally charged ethical issues that the development of biotechnology poses for the first time or reframes. This paper can only touch on some of them. Federal and state governments are attempting to grapple with these issues and create a framework to deal with them.
Three Federal panels addressed bioethical issues prior to 1983:
The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research;
The Ethics Advisory Board for the Secretary of the Department of Health, Education, and Welfare; and
The President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research.
These federal panels had a major impact on bioethical debate and risk assessment. For example, the President's Commission:
. . . supplied ethical premises and moral frameworks to reform the determination of death to include whole brain death, to formulate the evolving consensus on criteria for decisions to forgo life-supports (including artificial feeding and hydration) in incapacitated patients, and to lead the way to national policy on recombinant DNA research and the ethical aspects of human gene therapy.
Except for the National Institutes of Health-Department of Energy Working Group on Ethical, Legal, and Social Implications of the Human Genome Project, bioethical issues have been analyzed since 1983 on an ad hoc basis by temporary panels leading to delayed discussions, restricted scope, and inconsistent policy positions between panels. Congressional attempts to create a new national commission in 1990 to examine bioethical issues were unsuccessful, primarily due to a highly contentious debate over fetal research.
Bioethics examines broad issues such as animal rights and welfare, human testing, and the potential effects of genetically engineered species on other species and the environment. Risk assessments analyze the relative risks posed by possible toxic, pathogenic, and ecological effects of biotechnology and bioindustry. There are three broad analytical approaches to risk assessment:
Examine the processes which design and develop the new organism and the organism's effect on the environment;
Study only the effects of the organism on the environment; or
Determine if the organism has inherent rights (ethical evaluation) and its relationship to the environment and other organisms.
States and the federal government generally focus on the second approach, the characteristics and environmental risks of the altered organism, and not on the processes used to produce it or on possible natural rights. This "organism-in the environment" approach to risk assessment involves evaluation of any of the following: The probability of the survival and growth of genetically engineered organisms beyond intended environments;
The extent to which genetically engineered organisms may be harmful to humans, the environment, or to other organisms or species that they come in contact with; and
The extent to which genetically engineered organisms may exchange genetic material or information with other organisms, resulting in possible harmful effects.
Creation of New Genomes and Genetically Engineered Biologically Active Substances
The science of developing transgenic animals is just beginning. Critics contend that it raises both animal physiological (possible loss of function or generation of deformities) or psychological problems (unacceptable levels of stress or loss of function) and associated ethical issues. A 1989 statement, "Consultation on Respect for Life and the Environment," signed by the National Council of Churches, the Foundation on Economic Trends, and the Center for the Respect of Life and the Environment, called for a moratorium on transgenic animal research. The statement asserted that such technology "portends fundamental changes in the public's perception of, and attitude towards animals, which would be regarded as human creations, inventions, and commodities, rather than God's creation and subjects of nature." For example, during their development transgenic swine had many serious problems:
Those animals developed abnormally and exhibited deformed bodies and skulls. Some had swollen legs; others had ulcers, crossed eyes, renal disease, or arthritis. Many seemed to suffer from decreased immune function and were susceptible to pneumonia. All were sterile
Should we understand animal well-being to include an animal's entitlement to certain key traits that it would be unethical to select against or to seriously weaken? Should transgenic animal research and use be restricted to certain species? How are each of these questions to be reconciled with potential improvements in human health that could result from such research?
In contrast, the U.S. Department of Agriculture, the Biotechnology Industry Organization, and the American Medical Association argue that the creation of altered animals is medically and economically beneficial for humans and should continue.
Is the legal status of a transgenic animal that is owned by its creating company different from a domesticated animal? How do existing animal welfare statutes (humane treatment) apply to such animals? Each of these issues are magnified by the emerging ability to mass-produce large numbers of bioengineered animals such as genetically identical sheep and cattle that could become a primary source of fiber and food.
The deliberate manipulation of the gene line to achieve desirable human characteristics by altering sperm genes or to inserting genes from other species into human sex cells also has serious ethical implications. For example, is it ethical to make inheritable changes in the human genome affecting the characteristics of individuals that would be born with it? Who has the right to make a genetic therapy decision involving a fetus, children, or other? Should such guidelines extend to fetuses not brought to term for experimental purposes? Some of these issues may be addressed in guidelines being developed by the National Institutes of Health.
Ethical Debate On Patenting Life
In May 1995, a large coalition of religious leaders--Catholic bishops, Protestant and Jewish leaders and groups of Muslims, Hindus and Buddhists--announced its opposition to patents on human and animal life. The coalition did not oppose genetic engineering or biotechnology, but rather patenting human genes or organisms. It contends that such patents violate the sanctity of human life and reduce the "blueprint of evolution" to a marketable commodity. The group argues that life is a gift from God that should be cherished and nurtured. To reduce life to a commodity is to turn it into a product that can be owned and manipulated for profit alone, according to the group.
A second broad coalition of U.S. and international indigenous peoples, consumer, environmental, and other non-government groups issued the "Blue Mountain Declaration" in June 1995, declaring, in part,
The humans, animals, microorganisms and plants comprising life on the earth are part of the natural world into which we were all born. The conversion of these life forms, their molecules or parts into corporate property throughout patent monopolies is counter to the interests of the peoples of the world.
No individual, institution, or corporation should be able to claim ownership over species or varieties of living organisms. Nor should they be able to hold patents on organs, cells, genes or proteins, whether naturally occurring, genetically altered or otherwise modified.
This group also strongly opposes federal funding for the Human Genome Diversity Project. In particular, it is concerned about gathering samples of human genetic material from indigenous communities around the world. Related issues include ownership of cell lines, informed consent before providing the sample, patenting of genetic sequences, and who should benefit from the sale of related products.
Counter arguments are presented in the patenting (p. 38), human biological materials ownership (p. 41), and human and animal related products (p. 3-1) portions of this paper. These issues are currently under consideration by the courts and various professional organizations. Generally, the trend appears to be in the direction of allowing private ownership of laboratory-created organisms and the continued collection of human genetic material, on the grounds that the results are beneficial to humanity.
Organ Transplants And Embryological Tissue
Organ transplants and the availability of embryological tissue for research are important and difficult issues for modern medicine. Many lives are prolonged or saved every year through organ transplants. The National Organ Transplantation Act prohibits the sale of human tissue and organs for transplantation. This prohibition does not apply to non-transplantation purposes, including the sale of organs and other parts, such as embryological tissue, for research.
Fetal organs and tissue are believed by some researchers to be essential to research that might lead to alleviation of Parkinson's disease, diabetes, and other serious illnesses.
The federal government banned federally funded human embryology research for 15 years, (1979 to 1994), although some research continued with private funding. President Clinton has ordered that no federal funds be spent on embryos created for research. 208However, the order did not specifically forbid support for research on human embryos.
The National Institutes of Health convened an ad hoc Human Embryo Research Panel to examine the issue of embryo research. In 1994, the panel found that such research could make substantial contributions and agreed that pre-implantation embryos should receive serious moral consideration but not to the same degree as infants and children. The panel restricted its attention to research on pre-implantation embryos, or multi-cell clusters that are less than 14 days old and that are without a definite nerve system. The panel recommended an advisory process similar to that being followed for gene therapy, and contended that federal funding would help to establish consistent public review of the research.
Researchers obtain fetal tissue from hospitals and clinics. Some clinics have developed an informed consent form for patients giving permission to use fetal tissue from an aborted fetus for research or organ transplant. However, one author contends that, "there has been virtually no effective policing of fetal organ harvesting by the federal government or any state agency," and that such appears unlikely.
Animal to Human Organ Transplants
The area of organ transplants from animals to humans is developing so rapidly that the National Academy of Science's Institute of Medicine has created a committee to examine the practice. Issues that the Institute will examine include, "How to protect the rights of the first 'pioneer' patients? How to prevent the introduction of dangerous animal pathogens into the human population? And will the public find the idea of transplanting animal organs into humans acceptable?"
The FDA has also expressed concerns about animal-to-human transplants. Transplants might allow dangerous pathogens in animals to enter humans. Researchers plan to screen tissues for known viruses and to monitor recipients for infectious disease. However, screening for known viruses may not be adequate to apprehend new pathogens. The FDA wants stricter safeguards that could include improved tests for pathogens, protocols to quarantine patients, and the creation of colonies of "clean" animals. 21
Bioethics and Human Diagnostics
Testing for genetic defects is generally considered to be helpful and to increase possible treatment options. The issue becomes much more complex when genetic information has implications for reproductive choice or portends an unhealthy future for a currently healthy person (for example, having a mastectomy to prevent the potential future occurrence of a genetically-based cancer). Related issues include: disclosure of a genetic defect; availability and affordability of genetic counseling and health insurance; and employee screening. Screening for genetic diseases is controlled by the National Genetic Diseases Act, which provides for research, screening, counseling, and professional education for people with Tay-Sachs disease, Cystic Fibrosis, Huntington's disease, and a number of other conditions in which genetic mutations may be involved.
The use of genetic testing in the workplace can involve genetic screening or genetic monitoring. Screening involves a one-time test to detect a pre-existing trait in a worker or job applicant. Genetic monitoring involves multiple tests of a worker over time to determine if an occupational exposure has induced a genetic change. In 1989 five percent of the Fortune 500 companies surveyed either were using or had used employee genetic monitoring. [214] Genetic monitoring is reliable at the population level, not the individual employee level. There are three principal issues: [
Whether and how the decision is made to implement genetic screening and monitoring in the workplace and the use of the information which is generated;
How the information is disseminated and stored; and
The role of genetic counseling for both employers and employees.
The implementation of genetic testing can affect job applicants and workers, employers, and society differently. The impact varies according to whether the test performed is for genetic monitoring for chromosomal damage due to workplace conditions, genetic screening for susceptibilities to occupational illness, or genetic screening for inherited conditions or traits unrelated to the workplace but that could affect health insurance costs. Employees may wish to be genetically tested to track their health status but be concerned that the information could be used to remove them from the workplace, to deny insurance or keep them from being hired. On the other hand, employers contend that they need such information for hiring purposes and may wish to use genetic screening tests, establish conditions for employee participation, and implement consequences. Such employer practices are consistent with existing pre-employment medical testing practices. The Office of Technology Assessment (OTA), after a review of the issues involved, found:
A balance must be struck between promoting one party's autonomy and compromising that of another. If employers are free to implement and enforce genetic monitoring or screening policies, the autonomy of job applicants and employees will be limited. Conversely, giving the applicant or employee complete freedom to protect his or her own interests would restrict the freedom of the employer and, in some instances, present risk to co-workers or family. [Guidelines could] minimiz [e] occupational illness without threatening privacy or confidentiality, denying equality of opportunity, or stigmatizing workers.
Federal legislation (including the Occupational Safety and Health Act, the Rehabilitation Act of 1973, Title VI of the Civil Rights Act of 1964, the National Labor Relations Act, and the Americans with Disabilities Act) provides some protections against genetic testing and screening abuses, particularly against unilateral employer imposition of genetic monitoring and screening, discrimination, and breaches in confidentiality. States have also been active in this area, adopting legislation concerning genetic screening and employment.
The ability to test for possible inherited tendencies such as high blood pressure and other heart-related diseases, diabetes, and cancer has important implications for access to health insurance. Health insurance could become too expensive for some people. In the 1970s some people were denied insurance, charged higher premiums, or denied jobs because they tested positive as carriers of sickle cell anemia (a genetic condition inherited by some African Americans). More recent studies have documented cases of genetic descrimination against healthy persons with a gene that predisposes them or their children to an illness. "In a recent survey of people with a known genetic condition in the family, 22% indicated that they had been refused health insurance coverage because of their genetic status, whether they were sick or not."
Genetic information is already requested on health insurance applications. According to a 1992 OTA survey:
. . . insurers generally believe that it is fair for them to use genetic tests to identify those at increased risk of disease, and that they should decide how to use that information in risk classification. . . . [However,] over the next decade, O.T.A.'s survey indicates the vast majority of health insurers that offer individual coverage or medically underwrite groups do not anticipate requiring applicants to undergo genetic screening for disease, predisposition, or carrier status. Thus, whether or not genetic information is available to health insurers hinges on whether individuals who seek personal policies, or are part of medically underwritten groups, become aware of their genetic status because of general family history, because they have sought a genetic test because of family history, or because they have been screened in some other context. Even then, a majority of respondents to O.T.A.'s survey reported they thought it "somewhat unlikely" or "very unlikely" that they would be using genetic information for underwriting. [Italics in the original.]
Thirteen states have passed genetic testing laws. Most of the laws are narrowly drawn and attempt to prevent discrimination such as denial of insurance or employment because of a genetically identified disease. For example, an Ohio law prohibits insurers from requiring potential clients to submit to genetic tests as a condition of coverage. Recent state actions regarding genetic testing include:
In 1989, Arizona added "genetic" to its list of conditions insurers may not consider when assessing an application.
In the same year Oregon added genetic screening to its list of tests employers may not require as a condition of employment.
Montana passed legislation in 1991 prohibiting discrimination in insurance underwriting on the basis of genetic condition.
In 1992, Florida required informed consent for genetic analysis and confidentiality of test results.
In a related decision, "...the U.S. Equal Employment Opportunity Commission has concluded that healthy people carrying abnormal genes are protected against employment discrimination by the Americans with Disabilities Act." The decision seems to limit the use of genetic screening. California Department of Fair Employment and Housing regulations protect employees who have an increased likelihood of developing a physical handicap, but it is not clear whether this rule applies to genetic monitoring.
In January 1995, a new California law took effect prohibiting health insurers from discriminating against an applicant by increasing rates because of genetic traits when the person has no symptoms of any disease or disorder. Insurance companies are also prohibited from requesting or providing genetic information without prior authorization. Chaptered legislation introduced by Senator Johnston in the 1995 session (SB 1020) extends this provision by prohibiting insurance companies from requiring a higher rate or charge or offering or providing different terms, conditions, or benefits on the basis of a person's genetic characteristics. SB 970 (Johnston, 1995) would expand the definition of medical condition under the Department of Fair Employment and Housing to include discrimination against people who have an increased likelihood of developing a physical handicap due to genetic problems.
Federal law limits state protection against insurance coverage genetic discrimination. Self-funded insurance plans are exempted from state law by the federal Employee Retirement Income Security Act. Nationally, about one-third of the non-elderly insured are covered by such plans. In addition, most state laws prohibit discrimination based on genetic tests carried out in a laboratory. However these laws often do not extend that protection to use of genetic information gathered by other methods that trace genetic inheritance or to disclosure of a request to have a genetic test.
Recently, the National Action Plan on Breast Cancer and the Working Group on Ethical, Legal, and Social Implications of the Human Genome Project developed a set of recommendations and definitions for state policy makers to protect against genetic discrimination.
"Genetic information is information about genes, gene products, or inherited characteristics that may derive from the individual or a family member."
"Insurance provider means an insurance company, employer, or any other entity providing a plan of health insurance or health benefits including group and individual health plans whether fully insured or self-insured."
"Insurance providers should be prohibited from using genetic information, or an individual's request for genetic services, to deny or limit any coverage or establish eligibility, continuation, enrollment, or contribution requirements."
"Insurance providers should be prohibited from establishing differential rates or premium payments based on genetic information or an individual's request for genetic services."
"Insurance providers should be prohibited from requesting or requiring collection or disclosure of genetic information."
Insurance providers and other holders of genetic information should be prohibited from releasing genetic information without prior written authorization of the individual. Written authorization should be required for each disclosure and include to whom the disclosure would be made."
Genetic counseling services are important to individuals and families for understanding the results of genetic tests. These services also face serious ethical dilemmas. For example, a parent may refuse to share a diagnosis of an inherited tendency for colon cancer with the family, including the children. To honor the patient's request might harm the rest of the family.
In 1993, a panel of the National Academy of Sciences concluded that federal oversight of gene testing needs to be improved. The Health Care Financing Administration and the Food and Drug Administration are both responsible for ensuring the quality of testing in commercial laboratories. Currently the Health Care Financing Administration has no specific standards for laboratories that analyze DNA, and inspectors are not trained to evaluate the appropriate execution of DNA tests. The Food and Drug Administration requires that manufacturers obtain approval before marketing laboratory test kits and that laboratories offering experimental genetic tests be cleared and approved by the FDA.
Field Testing and Growing Genetically Engineered Crops
The field testing and release of genetically engineered plants and crops remains controversial but is widespread. Small-scale field tests of genetically-engineered crops have been under way in the U.S. for almost six years. Regulatory standards have been developed, and crops approved for testing and release. Since 1987, the U.S. Department of Agriculture has approved more than 860 applications and notifications to field-test transgenic crops. More than 1,025 field tests of genetically modified plants were conducted in 32 countries between 1986 and 1993. Thirty-eight different plant species with nearly 200 different engineered properties have been tested in the field to date. By the year 2000, there may be as many as 400 different, economically important genetically modified plants under field evaluation.
As noted above, the USDA has recently expedited approvals for field-test permits. In 1995, the EPA approved the first pesticidal transgenic plants (corn, potato, and cotton plants) for "limited" commercialization. Approval for full scale production is expected by 1996. 2
The U.S. National Academy of Sciences concluded in 1987, "There is no evidence of the existence of unique hazards either in the use of RDNA techniques or in the movement of genes between unrelated organisms." The U.S. National Research Council agreed: "No conceptual distinction exists between genetic modification of plants and microorganisms by classical methods or by molecular techniques that modify DNA and transfer genes," whether in the laboratory, in the field, or in large-scale environmental introductions.
The EPA,
. . . does not believe that there will be adverse effects to humans, nontarget organisms, or the environment from the limited use of the products. . . . [T] here is no unreasonable risk of unplanned pesticide production through gene capture and expression of Bt [the pesticide plant gene] in wild relatives of the transformed plants.
Nevertheless, there is still considerable public disagreement over the implications of introducing genetically-engineered species into the environment for testing or commercial purposes. Critics have been successful at obtaining court injunctions to stop the release of biological materials into the environment. Some scientists and ecologists claim that unlike risk assessment for synthetic chemicals, "there is no commensurate methodology for assessing the risks of released organisms." However, the overall likelihood of harm could rise as the number and variety of crop releases increase. If a problem occurs it could be high-risk with long-term unexpected consequences. Among the possibilities:
Altered crops could produce a toxic secondary metabolite or protein toxin;
Unrestricted self-perpetuation and spread of the organism might take place if the plant escapes the controlled field setting;
Transgenic crops could pass new genes to wild plants, in the process creating new and costly weed problems;
Novel transgenes might affect wild organisms and ecosystems in ways that are difficult to evaluate;
Altered plants, containing virus particles, might lead to creation of new viruses damaging to important crops and could require expensive control measures;
The risks to other organisms posed by plants engineered to express potentially toxic substances, including drugs and pesticides, are unknown; and
Commercialization of transgenic crops could threaten global crop diversity, particularly if the industry becomes more vertically integrated from the farmer through the food processor.
There is preliminary evidence that seems to support some of these concerns. Some exchanges of genetic information between plants in the field may occur by way of bacteria or viruses:
Evidence is rapidly accumulating that a blizzard of genetic material blows freely through the microbial world--not only between bacteria of the same species but also between members of distantly related species and between bacteria and viruses. "In terms of the flux of DNA, the general impression is that it goes anywhere and everywhere," says Julian E. Davies, a microbiologist at the University of British Columbia. . . . If environmental stress promotes gene exchange between bacterial species, genes deliberately engineered into microorganisms might spread more easily in nature than they do in the laboratory. . . . Experiments reported in Science in March [1994] indicate that plant viruses can combine the RNA that constitutes their genes with RNA from genes of genetically engineered plants.
Other scientists believe that the problem may not be significant, as "the potential benefits of engineered resistance genes far outweigh the vanishingly small risk of creating new and harmful viruses."
In some cases, a permit must be obtained from the USDA to begin limited field testing. The review often includes assessment of whether the product meets federal environmental-assessment standards and the environmental requirements of the Plant Pest Act. The EPA has developed guidelines for evaluating modified microorganisms under the Toxic Substances Control Act and for small-scale field testing of plants that produce pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act. 2These processes are considered by the respective agencies and industry to be more than adequate for evaluating new organisms, detecting any viral recombination that might create new, potentially high-risk viruses, and for field testing pesticide producing plants.
Regulatory decisions on field testing seriously affect research agendas. For example, after the Environmental Protection Agency refused Monsanto's request to field test a new genetically engineered bacterium to improve plant resistance to frost, the company dismantled its entire research program on microbial biocontrol agents. (Monsanto remains very involved in other biotechnology research areas.)
Some ecologists remain concerned about the need for additional information beyond that required by the USDA and EPA on a species' ability to survive, proliferate, and disperse in nature, and about the potential for genetic exchange of materials between species. 2One analysis concludes,
. . . the standard approaches to risk assessment and management employed by the regulatory agencies are inadequate to the task of properly assessing the advisability of such experiments, as well as the even more significant prospect of widespread commercial use of genetically engineered organisms in agriculture.
Jack Dekker and Gary Comstock, of Iowa State University, propose that ethical and technical criteria be developed and included in the regulatory process to address the issue:
We . . . need a rational basis on which to make evaluations of this new biotechnology. The technical aspects of their release require a logical guide to the ecological, environmental, and biological effects the release might have in sustainable agroeconsystems. The initial step should include an assessment of effects associated with population ecology, population genetics, environmental degradation, consumer health and farm economic viability due to the resistant crop-herbicide pair.
Existing field experiments have not resolved the debate. There are conflicting studies with differing answers. These findings show just how complex and unresolved the issue is. For example, one research effort found that transgenic sugar beets could transfer genes to weed relatives. Other evidence indicates that viral RNA or DNA inserted in a plant to make it virus-resistant may combine with genetic material from an invading virus to form new, more virulent strains. But, recent work on the transgenic squash has "found no evidence that wild squash have bred with transgenic plants to form virus-resistant wild squash." Despite concerns expressed by some observers, scientists consider it highly unlikely that the squash's wild relatives could obtain genetically engineered benefits from commercial relatives or that "novel recombinant viruses could crop up from [squashes] infected by wild viruses." It might take a number of unlikely conditions occurring in the environment before new or damaging recombinant viruses could spread. A more recent Danish study found that a commercial crop called oil seed rape containing a herbicide resistant gene can cross-fertilize with a weed called Brassica Campetris. Both plants are from the same mustard family. The bioengineered gene is present in the crossbreeds and is passed on to subsequent generations.
Large scale plantings of transgenic crops might resolve some of these questions:
Researchers are divided on just how seriously to take fears [associated with large scale release of biological engineered plant releases into the environment] , but they agree on one thing: small, carefully managed experimental plots have yielded insufficient data on transgenic hazards. What's needed to gain a complete picture of genetic exchanges between transgenic crops and other plants and to measure the true environmental impacts are tests covering thousands of acres--or commercialization of several transgenic crops.
According to a report in Science, "Chinese scientists have recently launched massive field trials of transgenic tobacco, tomatoes, and rice on thousands of hectares." Scientists in developing countries who are faced with food production problems may take more risks than others, the report notes.
Recent research also raises questions about the adequacy of models used to predict the dispersion of genetically engineered plants into the environment.
A recent Scottish study shows that a previously used pollen dispersion model--which would probably have been used to predict how fast genes from a transgenic crop leak into the environment--badly underestimated the amount of pollen that spreads from large oilseed rape fields. The study's authors discovered that pollen can disperse much farther than the model predicts; pollen levels that had been expected no more than 100 meters away were observed at distances up to 2.5 kilometers. The study thus demonstrates the principle that any genes that scientists introduce into a crop can quickly spread into wild populations. A herbicide-resistant strain might cause "superweeds" that would be difficult to contain. 2
The possible accidental release of potentially damaging organisms into the environment extends to other organisms as well. For example, efforts by Australian scientists to restrict a deadly virus (used in experiments against wildly proliferating European rabbits) to an off coast island failed. "Officials foresaw little possibility of the virus's escaping from the island, but escape it did."
Reframing Bioethical Issues for Public Policy
There are inherent conflicts involved in how biotechnology develops as an industry and the way ethical questions and public policy positions are discussed and adopted. Key factors include, for example:
How to define and evaluate man's fundamental long term relationships to his genetic heritage, other species and his ecological system;
How to address the pressure to rapidly advance scientific research and to exploit new product applications as they emerge;
What priority to grant commercial needs to quickly realize a high return on a very expensive investment in a turbulent market place.
The conflict between the ethical issues that emerge as research proceeds and discoveries are made, and the time and other pressures to immediately move products to the market place create public policy issues that cannot be easily resolved for a number of complex and interacting reasons:
Potential health, economic, and business benefits are huge. The potential human and financial rewards that could emerge from curing serious diseases, increasing the food supply, and substantially extending and improving the quality of human life are very large. It is this possibility that drives researchers, investors, and potential benefactors.
Biotechnology/bioethical issues are not simple. The underlying science is complex, as are the resulting issues. Bioethics is a new field that is developing right along with biotechnology.
It is difficult to know which biotechnology-induced changes in an organism or production technology might result in large scale social or economic changes. The often new relationship of the discovery to the greater environment, human health, marketplace, and to future generations is unknown. The law of unintended consequences is a major concern.
Measurements of the socio-economic and market effects of a new technology are hard to make. Methods for measuring expected human, ecological, industrial, and financial risks, short and long term costs/benefits, and other relevant factors are just being developed. It may be particularly difficult to estimate the long terms costs of biotechnology innovations, given their often unpredictable effects.
There is pressure to achieve immediate short term economic gains that might have essentially unknowable long-term effects. For example, patenting corn, rice, potatoes and wheat and the accompanying farming and marketing methods might reorder the entire agricultural industry and rural life.
Issues are set within conflicting time horizons and value systems. Research and marketing time horizons are relatively short, emphasizing immediate financial pay-off and scientific prestige. In contrast, bioethics and public policy questions often involve a long-term time horizon (generations of people), whole systems (ecological or industry), and the quality of individual and community life.
The definition of what "safe" means and how to evaluate an acceptable level of risk is still evolving. For example, how should manufacturers label bioengineered products and other products that may use genes inserted from plants to which people might be allergic? The large scale availability of genetic testing and its implications for the workplace and for inherited health problems are issues that are just now being addressed.
There is strong competitive pressure to go forward with new and potentially risky technology in a global market. European, Asian and other nations are fiercely competing with each other to develop and dominate a segment of the biotechnology industry, if not the industry itself. As noted, China has already embarked on a series of field tests that would probably not be approved in the West.

BIOTECHNOLOGY IN ANIMALS,VACCINESAND MEDICINE


Biotechnology has yielded new and improved medicines for animals that help lower production costs and improve animal well being by fighting diseases caused by bacteria and parasites. For example, scientists have identified a new anti-bacterial compound that may serve as a substitute for using some antibiotics in animals, a practice that has been criticized for contributing to the increased prevalence of drug-resistant bacteria in human infections.
New or enhanced animal vaccines have also been developed through modern biotechnology techniques. Vaccines are now used to prevent diseases including: foot and mouth disease, scours, brucellosis, shipping fever, feline leukemia, rabies, and infections affecting cultivated fish.
Biotechnology has led to the development of rapid test kits to diagnose the health of livestock and companion animals. Some kits are commercially available, but they will have to be low cost and easy to use if they are to be widely accepted.

Making aTransgenic Animal

One way to produce transgenic animals is through a technique called microinjection. Once scientists have identified and isolated the piece of DNA comprising the gene to be transferred, it is injected into a fertilized egg of the desired animal using a very small glass needle visualized under a microscope. In approximately one percent of the injected eggs, the gene becomes a new "word" in the egg's "instruction manual" by physically combining with the egg's genome. Ideally, the new gene integrates into the genome before the egg begins to divide. If this occurs, every cell in the animal can contain the new protein and the animal will pass the gene on to its offspring. After injection of the gene, the fertilized egg is implanted into a surrogate mother where it fully develops into a transgenic animal.

Traits Being Introduced Into Animals

Currently, the only routine commercial use of transgenic animals (primarily mice) is in the area of human disease research. One way to characterize the range of genetic modifications that are being considered for use in animals is in the three broad areas of input, output, and value-added traits. Examples of each are described below.

Inputs Traits

An "input" trait helps livestock and dairy producers by increasing production efficiency.
Input traits that are being investigated for use in animals:
Faster, more efficient growth rates
Increased production of milk or wool Resistance to diseases caused by viruses and bacteria

Output Traits

An output trait helps consumers or downstream processors by enhancing the quality of the animal product.
Output traits that may prove to be beneficial:
Leaner, more tender beef and pork
Milk that lacks allergenic proteins, or results in increased amounts of cheese and yogurt

Value-Added Traits

By adding or modifying genes, animals can function in completely new ways.
Producing large amounts of therapeutic proteins in animal milk may be an efficient, relatively low cost method to manufacture many proteins used to treat human diseases or proteins that have industrial value.
Transplanting animal organs into humans, or xenotransplantation, can be made more successful by genetically modifying the organs so that they are not as readily rejected by the human immune system. Development of animals that serve as models for human diseases to help scientists better understand prevention and treatment strategies.

Biotechnology and Cloning of Animals

Advances in biotechnology have allowed scientists to make genetically identical copies or clones of animals. Duplication of an organism's genome occurs naturally when identical twins are born or when a plant is grown from a cutting of another plant. However, the world really took notice of cloning in 1997 when a group of Scottish researchers announced the birth of Dolly the sheep, which had been cloned using a single cell from an adult sheep. Dolly had only one "parent;" her nuclear genome was exactly like her "mother's" instead of being a combination of two parents. Therefore, Dolly could generally be thought of as her mother's identical twin.
To produce Dolly, scientists took an egg from a sheep and removed its nucleus (which contains the genome or instruction manual), rendering it unable to function or develop. Next, they took a cell with an intact genome from a different adult sheep (Dolly's "mother") and fused it to the sheep egg which lacked a genome. The egg, with its new genome, was stimulated to begin developing into an embryo and was implanted into a surrogate sheep where it grew normally, resulting in the birth of Dolly. Dolly later gave birth to normal lambs.

Benefits and Risks of Cloning

Researchers have cloned other mammals including cows, goats, pigs, and mice. However, the overall low rate of successful cloning and frequent occurrence of developmental abnormalities in cloned animals demonstrate the need for further research before cloning will be practical.
It has also been reported that cloned animals may exhibit health problems throughout their life. Cloned animals may age prematurely as Dolly was diagnosed with arthritis at a seemingly young age and cloned mice had a shorter than normal life span. Additionally, it was demonstrated that cloned mice were both larger in size and heavier than a control group of non-cloned mice.
If advances in animal cloning technology were to overcome the current obstacles, the most obvious benefit would be the ability of a farmer to have a herd of superior performing animals in one generation. Breeding companies could sell cloned embryos in a manner similar to the way in which semen is currently marketed. A potential drawback of this practice would be the loss of genetic diversity in livestock herds, but this could be avoided by limiting the number of cloned embryos of a given animal that were sold.
It has also been proposed that cloning could be used to increase the population of animals in an endangered species. The mouflon sheep, which is a wild Mediterranean sheep with less than 1000 animals remaining, was successfully cloned. Additionally, scientists are attempting to clone an endangered wild Asian ox, called the guar (the first cloned guar died of an intestinal illness shortly after birth) and possibly the giant Panda. Although possible, a recovering population of cloned animals would be hindered by a lack of genetic diversity and would not address the larger issue of how the animal became endangered.

PLANT AND BIOTECHNOLOGY







Today, biotechnology is being used as a tool to give plants new traits that benefit agricultural production, the environment, and human nutrition and health.



The goal of plant breeding is to combine desirable traits from different varieties of plants to produce plants of superior quality. This approach to improving crop production has been very successful over the years. For example, it would be beneficial to cross a tomato plant that bears sweeter fruit with one that exhibits increased disease resistance. To do this, it takes many years of crossing and backcrossing generations of plants to obtain the desired trait. Along the way, undesirable traits may be manifested in the plants because there is no way to select for one trait without affecting others. Another limitation of traditional plant selection is that breeding is restricted to plants that can sexually mate.
Advances in scientific discovery and laboratory techniques during the last half of the twentieth century led to the ability to manipulate the deoxyribonucleic acid (DNA) of organisms, which accelerated the process of plant improvement through the use of biotechnology.


GENES AND THE GENOME

Plants are made of millions of cells all working together. Every cell of a plant has a complete "instruction manual" or genome (pronounced "JEE-nom") that is inherited from the parents of the plant as a combination of their genomes.
Genes are found within the genome and serve as the "words" of the instruction manual. When a cell reads a word, or in scientific terms "expresses a gene," a specific protein is produced. Proteins give an individual cell, and therefore the plant, its form and function. Genes (words) are written using the four-letter alphabet A, C, G, T. The letters are abbreviations for four chemicals called bases, which together make up DNA. DNA is universal in nature, meaning that the four chemical bases of DNA are the same in all living organisms. Consequently, a gene from one organism can function in any other organism. The ability to move genes into plants from other organisms, thereby producing new proteins in the plant, has resulted in significant achievements in plant biotechnology that were not possible using traditional breeding practices.

METHODS OF INTRODUCING GENES INTO THE CELL


To genetically modify a plant, the thousands of bases of DNA comprising an individual gene are transferred into an individual plant cell where the new gene becomes a permanent part of the cell's genome. This process makes the resulting plant "transgenic." Transfer of DNA into plant cells is done using various "transformation" techniques that are the result of discoveries in basic science

Natures way

One method to transfer DNA into plants takes advantage of a system found in nature. The bacterium that causes "crown gall tumors" injects its DNA into a plant genome, forcing the plant to create a suitable environment for the bacterium to live. After discovering this process, scientists were able to "disarm" the bacterium, put new genes into it, and use the bacterium to harmlessly insert the desired genes into the plant genome.

Cellular target practice

In the biolistic" or "gene gun" method, microscopic gold beads are coated with the gene of interest and shot into the plant cell with a burst of helium. Once inside the cell, the gene comes off the bead and integrates into the cell's genome.

Electroporating


It was also discovered that plant cells could be "electroporated" or mixed with a gene and "shocked" with a pulse of electricity, causing holes to form in the cell through which the DNA could flow. The cell is subsequently able to repair the holes and the gene becomes a part of the plant genome


Selecting the right cells


When using these methods, new genes are successfully introduced into only a small percentage of the cells, so scientists must be able to "pick out" or "select" the transformed cells before proceeding. This is often done by concurrently introducing an additional gene into the cell that will make it resistant to an antibiotic. A cell that survives antibiotic treatment will most likely have received the gene of interest as well; that cell is subsequently used to propagate the new plant. There is a concern that the gene giving antibiotic resistance could naturally be transferred to bacteria once the transgenic plant is in the wild, making bacteria resistant to antibiotics that are used to fight human infection. Scientists are currently devising ways to select for transformed cells that will alleviate this issue.

BIOTECHNOLOGY ON ENVIORNMENT

The use of new biotechnology for cleaning up major environmental concerns may be in its infancy, but practical applications are underway. Many problems associated with water, air, and soil contaminants can be fixed with new biotechnology. Modern biotechnology is currently being used in soils for growing better crops, in wastewater for eliminating odors and meeting regulatory requirements, in toxic waste clean-up and many other areas.
There is a dilemma with biotechnology concerning on-going research. What takes place on a small scale under controlled laboratory conditions is completely different than what occurs in a large scale "real world" situation. An example is in cheese manufacturing where thousands of pounds are made at one time with microbes added prior to aging. It would be very difficult to make a one pound batch with the same characteristics as a large batch because of the transformations caused by the microbes and enzymes. With new biotechnology, large projects generally outperform smaller test projects.
Agriculture is the big winner as modern biotechnology progresses. Past attempts for the long term control of nematode and phylloxera in vineyards with strong chemicals have had limited success. However, safe methods, using biotechnology, can supply special nutrients for the beneficial microbes in the soil. Several microbial strains, including actinomycetes, which are typically native in the soil, produce enzymes that open the skin of the damaging nematode or phylloxera, diminishing their population. The soil comes alive with beneficial creatures that can naturally control pest and disease problems. In addition, the trillions of beneficial microbes work to adjust pH, make nutrients more available, improve plant health and increase crop quality and yields.
Historically, industry has had difficulty dealing with wastewater problems. Sewage treatment plants around the world have included the use of native microbes that exist in their conventional treatment systems. By using biotechnology, the treatment process can be optimized with the proper strains of selected microbes. These microbes are more efficient at eating the waste, which causes high Biochemical Oxygen Demand (BOD) in the water. Special nutrients enable the microbes to reproduce and thrive in the system. The treatment plant becomes more efficient without incurring the major expense of building larger facilities. The waste is more completely broken down for safer discharge, the BOD is decreased, and the corresponding odors are significantly reduced or eliminated.
Dairy and hog operations that discharge wastewater into ponds or fields are also able to benefit from new biotechnology by lowering the nitrate concentration of their waste stream as well as eliminating odors associated with the waste. For instance, dairy wastewater is loaded with sanitizers and disinfectants that keep our milk supply safe for drinking. While these products help ensure the safety of our milk, they cause problems for the useful microbes in the wastewater. By treating the wastewater with the proper strains of microbes and nutrients, the sanitizers, disinfectants, and manure are broken down prior to field application. As a result, the crops benefit from a more productive soil. Food processing companies can also handle many of their environmental waste problems by using modern biotechnology.
The world faces many environmental challenges that can be effectively resolved using biotechnology. The focus on handling these challenges should be to treat the waste on-site and avoid transferring the problem to a landfill or municipal sewer system. Modern biotechnology can meet these challenges. This safe method of resolving complex problems is rapidly emerging as the most cost effective solution available.

BIOTECHNOLOGY IN DIAGNOSTICS FOR FOOD TESTING

ENZYME LINKED IMMUNOSORBENT ASSAY

Many of the classical food microbiological methods used in the past were culture-based, with microorganisms grown on agar plates and detected through biochemical identification. These methods are often tedious, labour-intensive and slow. Genetic based diagnostic and identification systems can greatly enhance the specificity, sensitivity and speed of microbial testing. Molecular typing methodologies, commonly involving the polymerase chain reaction (PCR), ribotyping (a method to determine homologies and differences between bacteria at the species or sub-species (strain) level, using restriction fragment length polymorphism (RFLP) analysis of ribosomal ribonucleic acids (rRNA) genes) and pulsed-field gel electrophoresis (PFGE, a method of separating large DNA molecules that can be used for typing microbial strains), can be used to characterise and monitor the presence of spoilage flora (microbes causing food to become unfit for eating), normal flora and microflora in foods. Random amplified polymorphic DNA (RAPD) or amplified fragment length polymorphism (AFLP) molecular marker systems can also be used for the comparison of genetic differences between species, subspecies and strains, depending on the reaction conditions used. The use of combinations of these technologies and other genetic tests allows the characterisation and identification of organisms at the genus, species, sub-species and even strain levels, thereby making it possible to pinpoint sources of food contamination, to trace microorganisms throughout the food chain or to identify the causal agents of foodborne illnesses. Monoclonal and polyclonal antibodies can also be used for diagnostics, e.g. in enzyme-linked immunosorbent assay (ELISA) kits.

Microarrays are biosensors which consist of large numbers of parallel hybrid receptors (DNA, proteins, oligonucleotides). Microarrays are also referred to as biochip, DNA chip, DNA microarray or gene arrays and offer unprecedented opportunities and approaches to diagnostic and detection methods. They can be used for the detection of pathogens, pesticides and toxins and offer considerable potential for facilitating process control, the control of fermentation processes and monitoring the quality and safety of raw materials.

BIOTECHNOLOGY IN PRODUCTION OF ENZYMES AND FOOD ADDITIVES

Enzymes are biological catalysts used to facilitate and speed up metabolic reactions in living organisms. They are proteins and require a specific substrate on which to work. Their catalysing conditions are set within narrow limits, e.g. optimum temperature, pH conditions and oxygen concentration. Most enzymes are denatured at temperatures above 42°C. However, certain bacterial enzymes are tolerant to a broader temperature range. Enzymes are essential in the metabolism of all living organisms and are widely applied as processing aids in the food and beverage industry.
The industrial production of enzymes from microorganisms involves culturing the microorganisms in huge tanks where enzymes are secreted into the fermentation medium as metabolites of microbial activity. Enzymes thus produced are extracted, purified and used as processing aids in the food industry and for other applications. Purified enzymes are cell free entities and do not contain any other macromolecules such as DNA.
Genetic technologies have not only improved the efficiency with which enzymes can be produced, but they have increased their availability, reduced their cost and improved their quality. This has had the beneficial impact of increasing efficiency and streamlining processes which employ the use of enzymes as processing aids in the food industry.
flavouring agents, organic acids, food additives and amino acids are all metabolites of microorganisms during fermentation processes. Microbial fermentation processes are therefore commercially exploited for production of these food ingredients. Metabolic engineering, a new approach involving the targeted and purposeful manipulation of the metabolic pathways of an organism, is being widely researched to improve the quality and yields of these food ingredients. It typically involves alteration of cellular activities by the manipulation of the enzymatic, transport and regulatory functions of the cell using recombinant DNA and other genetic techniques. Understanding the metabolic pathways associated with these fermentation processes, and the ability to redirect metabolic pathways, can increase production of these metabolites and lead to production of novel metabolites and a diversified product base

FERMENTATION TECHNOLOGY THE MAJOR TOOL IN FOOD BIOTECHNOLOGY

Fermentation is the process of bioconversion of organic substances by microorganisms and/or enzymes (complex proteins) of microbial, plant or animal origin. It is one of the oldest forms of food preservation which is applied globally. Indigenous fermented foods such as bread, cheese and wine, have been prepared and consumed for thousands of years and are strongly linked to culture and tradition, especially in rural households and village communities. It is estimated that fermented foods contribute to about one-third of the diet worldwide.
During fermentation processes, microbial growth and metabolism (the biochemical processes whereby complex substances and food are broken down into simple substances) result in the production of a diversity of metabolites (products of the metabolism of these complex substances). These metabolites include enzymes which are capable of breaking down carbohydrates, proteins and lipids present within the substrate and/or fermentation medium; vitamins; antimicrobial compounds (e.g. bacteriocins and lysozyme); texture-forming agents (e.g. xanthan gum); amino acids; organic acids (e.g. citric acid, lactic acid) and flavour compounds (e.g. esters and aldehydes). Many of these microbial metabolites (e.g. flavour compounds, amino acids, organic acids, enzymes, xanthan gums, alcohol etc.) are produced at the industrial level in both developed and developing countries for use in food processing applications. A considerable volume of current research both in academia and industry targets the application of microbial biotechnology to improve the production, quality and yields of these metabolites.
Fermentation is globally applied in the preservation of a range of raw agricultural materials (cereals, roots, tubers, fruit and vegetables, milk, meat, fish etc.). Commercially produced fermented foods which are marketed globally include dairy products (cheese, yogurt, fermented milks), sausages and soy sauce. Certain microorganisms associated with fermented foods, in particular strains of the Lactobacillus species, are probiotic i.e. used as live microbial dietary supplements or food ingredients that have a beneficial effect on the host by influencing the composition and/or metabolic activity of the flora of the gastrointestinal tract. Probiotic bacterial strains are also produced and commercially marketed in many developed countries.