July 3, 1998

What Issues in Genetics Research Most Concern 13 Experts Right Now

FRANCIS COLLINS
Director, National Human Genome Research Institute, National Institutes of Health

As we approach the new millennium, we face an ever-multiplying number of ethical, legal, and social challenges that arise from the rapid advances that are occurring in human genetics. The following questions seem to me to be the most urgent:

* Will effective legislative solutions be found to prevent genetic discrimination?

* Will the therapeutic promise of genetics be realized?

* How can we effectively shepherd new genetic tests from research laboratories into clinical practice?

* Can health-care providers and the public learn enough about genetics for genetic medicine to be effectively integrated into the mainstream?

* Will we forget that environment and free will are critical contributors to health, disease, and behavior, and succumb to genetic determinism?

* Will the benefits of advances in genetics be available only to a privileged few?

* Will we reach a consensus about the ethical limits of using genetic technology to enhance particular physical traits?

Any one of these topics would be an appropriate subject for a large, complex research-and-policy initiative. We must apply the same amount of energy to answering these questions that we now are devoting to unraveling the secrets of the human genome. Then we can be confident of preventing unnecessary casualties of the genetic revolution.


RUTH HUBBARD
Professor emerita of biology, Harvard University

At present, I spend much of my time countering claims that exaggerate the significance of genes and DNA. Looking upon genes as control centers for various characteristics or activities within the body obscures the extent to which the functioning of genes depends on other substances and on physical and social forces. It also misrepresents the complex and often unpredictable ways that genes relate to health, disease, and behavior. The rising incidence of many cancers, for example, and the puzzling differences in their geographical distribution illustrate the importance of non-genetic factors.

Unfortunately, long before experiments can establish the degree of association between a disease and a specific variant of a gene, tests can be developed to detect that variant. And so we now have "predictive" tests for breast cancer or Alzheimer's disease. At best, however, these tests estimate the statistical probability of developing the condition, which is hardly more useful than knowing one's family history and no help in preventing the condition.

The overvaluing of genes is driven, at least in part, by the commercial importance of gene identification. Amid mounting conflicts of interest, researchers, universities, and the biotechnology industry vie for patents on genes and genetically engineered organisms. Research results often are announced first in the business pages of the newspapers, and the public is inundated with questionable claims about the importance of specific genes.


LAP-CHEE TSUI
Professor of molecular and medical genetics, University of Toronto, and geneticist-in-chief, Department of Genetics, Toronto's Hospital for Sick Children

One important issue in genetic research today is how to communicate the vast amount of information that is being accumulated in our laboratories each day. Because money is tight and competition keen, overly optimistic interpretations of experimental data and extrapolation of observations are common among both scientists in academic institutions and venture capitalists in biotech companies. Further, it is often difficult to explain a complex scientific issue to the public. Simplification is required, but not all the technical nuances can be explained in lay terms.

Breakthroughs in medical research are particularly difficult to report; they are not the same as the invention of a new computer system or a new type of battery. The latter sorts of discoveries will undoubtedly affect our lives in the future, but their emotional impact is much less than that of the identification of a gene that causes disease, or the cloning of an animal.

Scientists need to learn how to present their results to the public properly; journalists need to know how to present facts effectively; lawmakers need to know what is scientifically possible and what is ethically allowable; and citizens need to know where they can find the truth and what should be discarded as myth.


JEFFREY KAHN
Director, Center for Bioethics, and associate professor of medicine, public health, and philosophy, University of Minnesota

The genetic markers that increasingly will be used to predict health risks often are first identified through research on particular groups -- for example, research on women of Eastern European, Jewish ancestry led to the identification of increased breast-cancer risk in women with the BRCA-1 and BRCA-2 genes. Such discoveries point to only a few of what are probably many mutations that influence the development of diseases such as cancer, and it is only because of the genetic usefulness of members of a population that "their" mutations are catalogued first. But being first is double-edged.

Members of the group are the first to gain access to more information about future health risks and to be able to seek early testing and treatment. But they also are the first to have the information used against them -- for instance, to determine eligibility and premiums for insurance or to draw broad conclusions about whether or not they are healthy.

We must make sure that policies and practices do not overemphasize the significance of the genetic components of the diseases that we have studied thus far -- and do not penalize those whose genetic mutations have been studied first.


SIR COLIN CAMPBELL
Chairman, United Kingdom's Human Genetics Advisory Commission

The birth of the cloned sheep Dolly had a worldwide impact, being simultaneously hailed as a scientific breakthrough and a harbinger of doom. The United Kingdom's Human Genetics Advisory Commission, working with the Human Fertilisation and Embryology Authority, has consulted with experts and members of the public in an effort to improve public debate about cloning and to remove some of the confusion. For example, we have highlighted the distinction between reproductive cloning, or the reproduction of whole human beings, which is banned in the United Kingdom, and what may be broadly called therapeutic cloning, which includes techniques such as the production of replacement skin for victims of serious accidents.

In response to public concern about the implications of genetic testing for insurance, our commission considered a range of views and recommended a voluntary moratorium on insurance companies' requiring applicants to disclose the results of genetic tests. This moratorium would allow time to establish reliable evidence on the extent to which the results can be used to predict life expectancy or the onset of disease. It would also give us an opportunity to produce a robust appeals mechanism for applicants whom insurers turn down, and to develop a sound body of research on the ethical, legal, and social implications of advances in human genetics.


VICTOR A. MCKUSICK
Professor of medical genetics, Johns Hopkins University

The part of the Human Genome Project that most interests me is the research on non-human genomes, which arguably is doing the most to advance the project. Some of this research does not now receive enough financial support from the federal government. An example is the work on the dog genome, from which scientists hope to acquire useful information about the genetic basis of behavior.

We are studying the genomes of other organisms because we already have extensive genetic and biochemical information about those organisms. We can gain further information with less difficulty from non-human species than from humans because those species can be manipulated more easily in research.

We can use what we know about other species to help us identify human genes and understand their functions. When we find that a segment of human DNA of unknown function closely resembles a gene whose function we do know in another organism, such as yeast, we can make highly useful inferences as to the function of the human genetic material.

The first organism whose genome was completely sequenced -- in July 1995 -- was a bacterium. Yeast was the first organism with a nucleus to be sequenced completely, in April 1996. Those two organisms have approximately 1,800 and 6,000 genes, respectively, compared with the roughly 70,000 genes of a human being.

A tremendous body of sequence information from a large number of organisms -- plants as well as animals -- is now available in data bases, and searching those data bases has become a productive method of genomic research.


ARAVINDA CHAKRAVARTI
Professor of genetics and medicine, Case Western Reserve University School of Medicine

The rediscovery, in 1900, of Mendel's rules of genetic transmission began a bitter debate between Mendelians, who argued that evolution was responsible for large differences in traits, and biometricians, who supported the idea that Darwin's theory of natural selection operated on even small variations in traits. We still have only indirect and meager experimental evidence to support either view.

The Mendelian-biometrical debate is at the heart of our current difficulty in identifying the genes that underlie common disorders that run in families, such as hypertension or schizophrenia, as compared with the recent successes in isolating genes for rare diseases caused by single genes, such as cystic fibrosis. I am interested in the nature of genetic variation and suspect that we need new paradigms to discover the genes involved in the sorts of common, small variations that produce hypertension and other familial disorders.

The challenges to understanding the catalogue of human genes that the Human Genome Project is producing are formidable but surmountable. An even greater challenge is to explain how inherited variations in the human genetic code -- estimated to amount to about three million DNA units (nucleotides) -- between any two persons produce differences ranging from hair color to susceptibility to disease. I hope to contribute to our understanding of the genetic nature of familial disorders, and of how human evolutionary history has shaped the current distribution in the world of those disorders.


J. CRAIG VENTER
Director and president, Institute for Genomic Research, a not-for-profit research institution working on sequencing the human genome

Genetic research will touch so many aspects of society in the next century that it is difficult to predict where the greatest challenges will lie. Our increased knowledge of evolution, and ultimately of ourselves, will probably prompt many questions that we have not yet even considered.

Within the next few years, new applications of recent research will begin to have a significant impact in the form of medical advances. One of the exciting new developments is the identification of multiple genetic variations within subsets of the population. Using information about genetic variations will allow physicians to practice medicine that is tailored to specific individuals, selecting the most effective medications with the fewest side effects for the treatment of any disease. New diagnostic tools also will allow us to predict more accurately the outcome of many diseases based on specific genetic variations, determining which cancers are likely to metastasize to other organs, for example. Our improved understanding of how different genetic variations are related also will improve our understanding of individual traits and of how those are affected by interactions with the environment.

Ultimately, these new technologies will make it even clearer than it is now that we are more than just the sum total of our genes. But, in the short term, we must move beyond the current trend toward genetic reductionism, which results in oversimplified explanations of a disease or a behavioral trait. Unfortunately, such oversimplifications serve only to link new advances in genetics with the destructive, discriminatory aspects of past genetic research.

We are on the verge of an exciting new era, but, to discourage genetic reductionism, we must insure that our science is of the highest quality, appropriately reviewed by other scientists and accurately interpreted by the news media and the public. If we succeed, I believe that we can appropriately assimilate the wealth of new knowledge and technology that genetic research will provide.


PHILIP BEREANO
Professor of technical communication, College of Engineering, University of Washington

Transgenic organisms result from the breaching of natural barriers between species; many such laboratory-produced organisms are being inappropriately commercialized and patented today without democratic oversight. Although virtually all opinion polls show that Americans reject the idea of eating foods whose genes have been altered commercially, such novelties, unlabeled, are being added to our dinner plates.

The U.S. government does not monitor the effects of such food on consumers, nor does it scrutinize the release of other genetically altered organisms into the environment for commercial gain -- for example, micro-organisms engineered to assist in industrial processing. Citizens have no opportunity to acquire information about the release of these organisms and their possible negative consequences, or to participate in decisions about when and how to apply the technology.

Meanwhile, even human genes are being treated as raw material for corporate ownership and manipulation. Companies apply for patents on gene fragments of unknown function and on whole genomes of Third World peoples, distorting the idea of "invention."

Will such trends continue, producing a crisis, as powerful economic interests distort law and ethics? That depends almost completely on whether citizens' values and opinions are translated into political regulation and oversight programs. The situation in the United States differs considerably from that in Europe, where genetic engineering is a subject of lively public debate.

In the absence of regulation in the United States, a violation of public safety is almost inevitable. Genetic technologies were developed initially with public tax dollars, through federal research programs. We must work to impose more democratic control over biotech corporations and the academic scientists who work with them, to insure that the public interest is paramount over private greed.


WENDY MCGOODWIN
Executive director, Council for Responsible Genetics, Cambridge, Mass.

As the director of a non-profit watchdog group that monitors the biotechnology industry, I am most concerned about the increasing "geneticization" of our society. More and more, our society looks to genes to explain a vast array of medical conditions -- and even complex social behaviors. Genes certainly play a role in our lives and in our health. However, we are vastly more than the sum of our genes.

This overemphasis on genes has negative social consequences, because it shapes the way that we establish research priorities and social policies. For example, as we pour resources into the search for genes that predispose people to various types of cancer, we obscure the fact that the majority of cancer cases are caused by exposure to environmental carcinogens, not by inherited genetic mutations.

Overemphasizing genes creates a blame-the-victim mindset, and diverts attention and money from research into environmental clean-up measures that could, in fact, reduce the incidence of cancer. To the extent that proposed genetic "solutions" divert resources from the social and environmental roots of ill health, they will exacerbate rather than solve our health problems.


SUZANNE TOMLINSON
Bioethics counsel, Biotechnology Industry Organization, Washington

Many biotechnology companies are using genetic information to develop diagnostic and predictive tests, as well as new medicines to treat and cure diseases. These and other products undoubtedly have already helped millions of people and hold tremendous promise for patients with unmet medical needs.

The information provided by genetic tests thus is extremely valuable. But all test results must be interpreted by trained counselors, including physicians. And we must be sensitive to the fact that these tests may present complicated emotional messages or dilemmas for patients, their families, and their physicians.

The Biotechnology Industry Organization also recognizes the need for confidentiality of all individually identifiable medical information. However, laws that inappropriately restrict the use of such information could slow the development of new drugs and dash the hopes of people whose lives depend on access to innovative treatments. We must establish standards that protect the confidentiality of identifiable individual medical information without unduly hampering its use.

Because it is difficult to distinguish genetic from medical information, legislation to guarantee confidentiality of medical information should not address genetic information separately. Such information cannot be scientifically or practically separated from other medical information. Even a simple fact like gender is genetic information.

We fully embrace the regulations already put in place by the Food and Drug Administration and the National Institutes of Health to protect the safety of participants in medical research and the confidentiality of information that researchers gather about them. We believe that additional efforts to protect the confidentiality of medical information and to promote research are best served by a national standard, which can guarantee strong, uniform federal protections.


OLUFUNMILAYO OLOPADE
Assistant professor of medicine and director, Cancer Risk Clinic, Pritzker School of Medicine, University of Chicago

Over the past two decades, our understanding of cancer has improved as our knowledge of the genetic alterations that characterize cancer has increased. It is now widely accepted that cancer is a genetic disease, and that an accumulation of genetic defects can cause normal cells to become cancerous. Much of this knowledge came through studies of the genetic alterations occurring in tumor cells and studies of families with inherited susceptibility to cancer.

The most effective approach to preventing, diagnosing, and treating cancer is to identify individuals who are at risk. Genetic testing for cancer susceptibility can identify these individuals and provide unique opportunities to develop new strategies for early detection and prevention. While public debate has focused almost exclusively on the risks and benefits of genetic testing for healthy people, 5 to 10 per cent of cancer survivors are at risk of other malignancies because of inherited susceptibility. Genetic counseling and testing should be incorporated into clinical cancer care and should be available to family members at risk of developing the disease.

But genetic testing has inherent limitations because not every person shown to be genetically susceptible to a disease will develop it.


JEREMY RIFKIN
Author, The Biotech Century: Harnessing the Gene and Remaking the World (Jeremy P. Tarcher/Putnam, 1998)

We are in the early stages of a great transition from the industrial age to the "biotech century." Genetic technology is already being used in a variety of businesses. The biotech century promises a cornucopia of genetically engineered plants and animals to feed a hungry population, genetically derived sources of energy and fiber to build a "renewable" society, and wonder drugs and genetic therapies to produce healthier babies, eliminate human suffering, and extend the human life span. But with every step we take into this brave new world, we face the nagging question: At what cost?

Will the release of thousands of genetically engineered life forms into the environment cause genetic pollution and irreversible damage to the biosphere? What are the consequences of reducing the world's gene pool to patented intellectual property, controlled by a handful of life-science corporations? What are the risks we take in attempting to design more "perfect" human beings? What will it mean to live in a world where people are increasingly defined and discriminated against on the basis of their genes?

The biotech revolution will force each of us to hold a mirror up to our most deeply held values, making us ponder the meaning and purpose of existence. This may turn out to be its most important contribution.


Copyright (c) 1998 by The Chronicle of Higher Education
http://chronicle.com
Date: 07/03/98
Section: Opinion
Page: B6