Judicature Genes and Justice
The Growing Impact of the New Genetics on the Courts
November-December 1999 Vol 83(3)
GENES, DREAMS, AND REALITY
The promises and risks of the NEW GENETICS
by Denise K. Casey
Headlines about DNA, genes, and the new powers of scientists to analyze and manipulate these fundamental elements of life vie for our attention daily. The dazzling diversity of applications of DNA science to fields ranging from medicine and agriculture to forensics and environmental restoration undoubtedly will have resounding impacts on society and each of our own lives.
Many of the new genetic discoveries stem from data and tools generated by the massive international Human Genome Project (HGP), whose goal is to describe in intricate detail the DNA from humans and other selected organisms by 2003. Because DNA is the information molecule that carries instructions for creating and maintaining all life, resources and analytical technologies generated by the HGP and other genetic research can be applied to the DNA of all organisms on earth. Other important HGP goals are to develop tools for data analysis and to address some of the ethical, legal, and social issues that may arise from the project.
This article offers some basic information on the Human Genome Project and DNA science that will help the reader understand why genetic information is so powerful. It also describes a few current applications and some developments we can expect to see in the next few years, and presents some of the potentially troubling societal concerns surrounding this work.
The Human Genome Project
The HGP began in 1986 as a way for scientists in the U.S. Department of Energy (DOE) to use newly developing DNA analytical technologies to fulfill a long-standing mandate from Congress to assess the health effects of radiation. For decades DOE and its predecessors have developed international standards for the use of advanced medical diagnostic tools and treatments involving radiation and the protection of workers in the federal and civilian nuclear industry.
As the potential benefits of human genetics research became more apparent, Congress requested that DOE and the U. S. National Institutes of Health develop a joint genome project. The U.S. Human Genome Project began formally in 1990 with expanded goals to describe all human genetic material (DNA) by 2005. However, rapid technological achievements advanced the expected completion date to 2003, and a draft product is eagerly anticipated by 2000. International research teams, particularly those from the United Kingdom but also from France, Germany, and Japan joined U.S. scientists to make significant contributions to the HGP.
Today researchers worldwide are using HGP data and powerful analytical technologies to devise creative applications in an expanding array of fields.The claims and promises of these new capabilities are diverse and bold. But the new technologies and the data they generate also present complex ethical and policy issues that individuals and society, including the courts, have begun to confront (see "Societal concerns of the new genetics").
A brief glossary
The following primer will help ground the reader in the terms used throughout this article. It may also be helpful to refer to the figure "DNA: The molecule of life").
Genome. A genome is a complete set of coded instructions for making and maintaining an organism. It is made up of the chemical DNA.
Chromosome. The complete human genome is packaged into 46 pieces of DNA called chromosomes. Humans receive a set of 23 chromosomes from each parent. A complete set of 46 chromosomes is found in almost every one of our trillions of cells. Most cell types—skin, bone, hair, brain, heart—contain a complete human genome. Exceptions are sperm and egg cells, which contain 23 chromosomes, half the amount of DNA found in other cells; and mature red blood cells, which lack DNA.
DNA. DNA is the chemical that stores coded information on how, when, and where an organism should make the many thousands of different proteins required for life. DNA contains four different chemical building blocks called bases and abbreviated A, T, C, and G. In humans and other higher organisms, a DNA molecule consists of two strands of DNA whose bases connect with each other to form base pairs (see figure). With the exception of identical twins, each person's sequence of DNA bases—the order of As, Ts, Cs, and Gs along a single DNA strand—is different. This is what makes each person unique.
Genes. A gene is a piece of DNA that contains instructions for building a particular protein. Proteins are essential for all aspects of life. All organisms are made up largely of proteins, which provide the structural components of all cells and tissues as well as specialized enzymes for all essential chemical reactions. Through these proteins, our genes dictate not only how we look but also how well we process foods, detoxify poisons, and respond to infections.
Genes constitute only a tiny fraction, a mere 3 percent, of our DNA. The gene (coding) regions in our DNA are interspersed among millions of noncoding DNA bases whose functions are still largely unknown. Scientists estimate that we have from 80,000 to 100,000 genes whose sizes range from fewer than one thousand to several million bases.
DNA and disease
For all our apparent outward diversity, humans are surprisingly alike at the DNA level. We differ by only one or two tenths of one percent of our DNA—some three to six million bases—yet these tiny DNA variations are responsible for all our physical differences and may inßuence many of our behaviors as well.
Most DNA variation among individuals is normal, but harmful variations called mutations can cause or contribute to many different diseases and conditions. Depending on their size and where in the DNA they occur, mutations can have devastating effects or none at all. If they occur within genes, the result can be the creation of faulty proteins that function at less-than-normal levels or are completely nonfunctional and result in disease.
All diseases have a genetic basis. We may inherit a particular condition, such as the lung disease cystic fibrosis, or an increased likelihood for developing such disorders as heart disease or colon cancer. We also inherit the particular ability to respond to such environmental stresses as viruses, bacteria, and toxins. Understanding how DNA inßuences every aspect of health eventually will lead to far more effective ways to treat, cure, or even prevent the thousands of diseases that afflict humankind.
Some 4000 rare diseases are due to a single mutation in a single gene. These include cystic fibrosis, sickle cell anemia, and Tay Sachs. The causes are much more complex for common disorders such as heart disease, diabetes, hypertension, cancers, Alzheimer's disease, schizophrenia, and manic depression. These diseases are thought to be due to a variety of gene mutations, perhaps acting in concert, or to a combination of genes and such environmental factors as diet or exposure to radiation or toxins. Untangling the genetic and environmental contributions to complex disease will be one of the greatest challenges for medical researchers in the next century.
DNA science applied: Medicine and health
Gene tests. DNA-based tests are among the first commercial applications of the new genetic discoveries to medicine. These tests are employed to diagnose a condition or estimate the likelihood for developing one. Test results already are being offered as evidence to support medical and nonmedical cases in courts, including medical malpractice, discrimination, privacy violations, child custody disputes, and criminal cases.
Gene tests involve direct examination of the DNA molecule itself. A DNA sample can be obtained from any tissue, including blood. To do a gene test, scientists scan the sample, looking for a specific mutation in a particular DNA region that has been linked to a disorder. Cost can range from hundreds to thousands of dollars, depending on the sizes of the genes examined and the number of mutations tested for, which can vary from a few to hundreds. Although there are several hundred DNA-based tests for different conditions, most are still offered as research tools only. Fewer than 100 gene tests are available commercially, and most are for mutations associated with rare diseases in which just a single gene is involved (see "Some currently available gene tests").
Even though some current gene tests have been beneficial and their potential benefit enormous, the science is very new and dynamic. Researchers themselves are unsure how to interpret the results of some commercially available gene tests (see "Gene tests: the power and the limits").
Another limitation is the lack of medical options to treat or prevent many of the disorders for which gene tests are used. Researchers acknowledge the long lag time between linking a gene mutation with a disease and developing effective therapeutics. Additionally, patients agreeing to undergo gene testing face significant risks of jeopardizing their employment and insurance status. Patients face an additional burden as well: the psychological impact of testing can be devastating. Because genetic information is shared, all these risks extend to family members as well.
Many in the medical establishment feel that uncertainties surrounding test interpretation, the current lack of available medical options for most of these diseases, the potential for provoking anxiety, and the risks of discrimination and social stigmatization could outweigh the early benefits of testing (also see "Who's regulating gene tests").
Preventive medicine and customized therapies. Studies of gene function will lead to a deeper understanding of normal biological processes and how they go awry in disease states. These insights will allow the development of better and earlier predictive tests and eventually usher in a field of prevention-based medicine and diagnostics.
Within the next decade, researchers also will begin to understand how DNA variations underlie our individual responses to medical treatments. Tens of thousands of people are hospitalized each year as a result of toxic responses to medications that are beneficial to others. Some cancers respond dramatically to current therapeutic regimens while the same treatment has no effect on disease progression in others. Scientists in major pharmaceutical companies are trying to sort out the specific regions of DNA associated with drug responses, identify particular subgroups of patients, and develop drugs customized for those populations. These capabilities are expected to make drug development faster, cheaper, and more effective while drastically reducing the number of adverse reactions.
Drug design itself will be revolutionized as researchers use gene sequence and protein structure information to create new classes of medicines based on a reasoned approach rather than the traditional trial-and-error methods for finding new drugs. The new drugs, targeted to specific sites in the body and to particular points in the cascade of biochemical events leading to disease, will likely cause fewer side effects than many current medicines. Ideally, they would act earlier in the disease process.
Gene therapy and genetic enhancement. The potential for using genes themselves to treat disease has captured the imagination of the public and the biomedical community. This rapidly developing field—called gene transfer or gene therapy—holds great potential for treating or even curing such genetic and acquired diseases as cancers and AIDS by using normal genes to replace or supplement defective genes or bolster a normal function like immunity.
Over 350 clinical gene-therapy trials are now in progress worldwide, most for different kinds of cancers. Performed on patients in advanced stages of disease, most current studies aim to establish the safety of gene-delivery procedures rather than determine their effectiveness. The technology itself still faces many obstacles before it can become a practical approach for treating disease; however, novel experimental approaches look very promising (see "Gene therapy: using genes to treat disease").
Besides preventing and treating inherited and infectious diseases, gene-transfer technologies probably will make possible the enhancement or replacement of genes that inßuence other traits such as height, weight, strength, stamina, and even intelligence. These capabilities will generate many questions about the regulation of such technologies and the fairness of access to these expensive protocols, as well as safety and privacy issues, among others.
"Pharming" animals to produce human drugs. Gene-transfer technologies already are being used to transfer human genes into farm animals such as sheep and goats for the purpose of generating large quantities of expensive human proteins for use as pharmaceuticals. (The process has been called "pharming.") The animals carrying human genes are called "transgenics" and are very difficult and expensive to develop. This situation has encouraged biotechnology companies to explore more efficient ways to reproduce the animals; cloning technologies such as those used to create the famous Scottish sheep Dolly and other cloned mammals like mice, goats, and cows are the results of these efforts. And a reasonable assumption is that many of the new reproductive technologies being perfected in our mammalian cousins will be effective in—and applied to—humans.
Xenotransplants: from pigs to people. Some 18,000 organ transplants take place each year, not nearly accommodating the 40,000 who wait for appropriate donors. Ten people die each day waiting for suitable human donor organs. Transplanting such organs as hearts and kidneys from genetically altered pigs and other animals into humans, a process called xenotransplantation, may have the potential to save lives. Current research is aimed at using DNA technologies to grow organs having human genes that make the organ's surface more "human like" and may help to minimize the chance for rejection upon transplantation into a human host. A concern is the unintended transfer of animal viruses to humans and the effects this might have beyond the patient to the population at large.
Multiple uses across species. DNA technology can be used to identify any type of organism, from humans and whales to plants, viruses, and bacteria. One important use is for identifying organisms contaminating soil, air, water, and food. Pinpointing a disease source in an epidemic, for example, is critical for its rapid control. These analyses are not limited to diseases affecting humans: they can be used to identify disease sources in livestock, poultry, and plants as well.
Some uses of human DNA identification are to establish paternity and other family ties in adoption and immigration cases, identify victims of wars and other catastrophes, and aid the courts in criminal cases where biological evidence (e.g., blood and sperm) is left behind. Interestingly, DNA data gathered from other species present at a crime scene, such as plants, dogs, cats, and viruses (HIV) also have been used as evidence in trials.
A controversial DNA databank. In July, police linked a dead Florida man's DNA to eight unsolved rapes in Washington, using only the data available from a national DNA databank, called CODIS (Combined DNA Index System). No other investigative leads were available. CODIS, which came online in late 1998, contains DNA descriptions, or "profiles," of offenders convicted of certain serious crimes. While many agree that this use of DNA technology can be of great benefit to society, one controversy surrounding DNA profiling stems from the potential of a DNA sample to reveal much more about an individual (and their family) than just their identity. While today's practices scan specific DNA regions that do not currently reveal such additional information, the human genome is still relatively unknown territory, and no one knows what types of information future technology may be able to uncover from stored samples.
Another source of concern over DNA databanking is the potential for expanding the use of databases beyond that originally intended. Thought-provoking historical examples of expanding database functions include the now pervasive social security number system that was originally started in the 1930s to help with a newly established retirement program, and the use of census records to round up Japanese-Americans for placement in interment camps during World War II.
Agriculture and animals
Stronger cotton, healthier livestock. For thousands of years people have modified traits in plants and animals indirectly through selective breeding. Today, our growing ability to directly alter an organism's genetic makeup, called genetic engineering, is having a major impact worldwide on agriculture and animal husbandry. A number of ongoing projects aim to decipher and manipulate the genomes of such economically important organisms as rice, corn, wheat, soy, cotton, sheep, goats, cows, pigs, and fish.
Some of these explorations have led to the development of genetically modified plants that are providing higher yields, are more nutritious, and have increased resistance to herbicides, pests, and extremes of weather and temperature. In the United States this year, about half of all soybeans and a third of all corn planted were from genetically modified seeds, with most modifications aimed at pest and herbicide resistance.
Genetic alterations have produced ornamental crops such as carnations whose "aging genes" have been identified and turned off to allow an extended shelf life. Other plants are being genetically modified to produce biodegradable plastics, industrial oils and chemicals, low-calorie sweeteners, and human pharmaceuticals. Genetically modified animals are more nutritious and leaner, produce more milk, and are sometimes larger and more resistant to disease.
In a few recent examples, researchers reported adding rabbit genes to cotton plants to make the fiber as bright and soft as rabbit hair but stronger and warmer. A new strain of rice announced this spring contains a soybean gene for iron incorporation. This new rice can be used to treat the 30 percent of the world's population who are iron deficient and lack the means for expensive iron supplements.
Growing concerns. Consumer resistance to genetically modified plants and resulting foods, sometimes called "Frankenfoods," is strong in Europe and may be growing in the United States. Concerns center around environmental and consumer safety issues. Particularly in the United Kingdom, the strength of resistance to genetically modified foods stems from a lack of trust in the government to protect its citizens, following the "mad cow" disease scare.
Although genetically modified plants can decrease the use of pesticides and herbicides and thereby benefit the environment, a concern is that plants engineered to be more resistant to herbicides may pass on that trait through cross-pollination to related weed species in the wild. This could result in the creation of extremely resistant weeds requiring treatment with even more herbicides. Also, the impact of new pest-resistance traits on such nontarget organisms as visiting butterßies or birds is not known.
A potential health concern is that genes producing allergy-inducing proteins (such as those from peanuts) could be introduced into other food plants and consumers might unknowingly ingest a substance to which they could be allergic. (In the United States, the federal government is considering voluntary labeling of products derived from genetically modified organisms.) Another controversial issue is that genes introduced from one species into another may cause some consumers to violate religious restrictions against, for example, eating pork or beef.
A careful balance
Genetic data and tools offer enormous potential benefits to humankind but pose significant risks as well. As the impact of the new genetics grows, we can expect the courts to be increasingly confronted with many novel, challenging, and sometimes disturbing issues.
Scientific progress continues to advance rapidly as society scrambles to keep apace. But no one can anticipate some of the ways current and ever more powerful future DNA technologies will be put to use, nor their unintended and potentially controversial or adverse effects. As we begin to realize the benefits of the new genetics, maintaining a cautious approach will help minimize the risks.
Denise K. Casey is a science writer, editor, and educator with the DOE Human Genome Program Human Genome Management Information System at Oak Ridge National Laboratory. She has written numerous articles for technical and lay readers on genetics and its applications and has served as a faculty member at judicial education seminars.
|The online presentation of this publication is a special feature of the Human Genome Project Information Web site.|