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New tools, new dilemmas: genetic frontiers.

New Tools, New Dilemmas: Genetic Frontiers

Under the aegis of "the new genetics" direct exploration of the human genome has exploded the boundaries of an earlier genetics. Already the new DNA technologies have brought us screening tests for Huntington disease and cystic fibrosis, as well as claims to the first complete (although admittedly low resolution) map of the human genome. The use of restriction enzymes and probes for mapping and sequencing human genes evokes visions of a genetics no longer limited to making statistical predictions for groups or populations, but instead able to detect with great accuracy the presence of disease in a given individual.

The powerful new methods, expansive scope, and accelerated pace of human molecular genetics combine to catapult us into ethically unfamiliar territory. The molecular method generates not simply diagnoses but presymptomatic and contingent diagnoses. Its scope potentially includes not only serious genetic disease but also mild conditions and bothersome or unusual traits and characteristics. And its pace threatens to outstrip our capacity to react sensibly to its implications.

To use these new genetic screening capabilities wisely thus requires anticipating novel stresses and preparing strategies responsive to both the opportunities and dangers afforded by enhanced diagnostic powers. It also requires understanding our tools and individual and societal options for shaping them to our purposes.

New Tools, New Powers?

The term "molecular" reveals the basic methodologic novelty of human molecular genetics. Traditional genetic inquiry proceeds from recognition of diseased states or abnormal gene products to inferences about genetic inheritance based on analysis of patterns of transmission. Its central diagnostic tools are assessments of symptoms and signs (at individual or social levels), pathology (at organ, tissue, and cellular levels), and assays of gene products, such as structural proteins or enzymes (at subcellular levels). [1] In human molecular genetics, however, the structure of a gene at the molecular level is often discovered before anything is known about the gene product it encodes.

The most basic molecular tools for studying genes are enzymes that generate strips of genetic material called restriction fragment length polymorphisms (RFLPs). Restriction enzymes generate DNA fragments of differing lengths that form patterns of lines in a special gel; skilled geneticists read these patterns in the same way that a scanning device at a supermarket checkout counter reads a "bar" or price code on the bottom of a box of cereal.

A marker becomes useful diagnostically if the RFLP pattern it generates is statistically associated with the occurrence of a particular condition. In most cases, interpreting a given individual's pattern requires comparing it with those of his or her affected and unaffected family members, a process called linkage analysis. Probes that generate these types of patterns are called "linkage markers," while markers that can establish a diagnosis without reference to family members are called "direct" markers. Linkage analysis generally requires the skills of a trained geneticist and is very costly and time-consuming, while direct tests theoretically can be conducted more cheaply and rapidly, and made more easily available. Currently, most molecular diagnosis is conducted via linkage analysis.

Whether direct testing becomes common depends partly on biologic realities, and partly on priorities and support for new research. Linkage analysis may be required because the gene for a given condition has not yet been isolated, or because the condition is marked by considerable genetic heterogeneity (that is, it has a large variety of genetic causes, making diagnosis on the basis of a small number of patterns difficult or impossible). Developing an assortment of new markers (as part of a coordinated national project to map the human genome, for example) increases the chances not only of identifying markers for specific genes but also of having multiple markers to compensate for problems of heterogeneity.

Sensible geneticists disagree about the likelihood of discovering a substantial number of direct markers. Until recently, many believed that direct testing would remain unavailable for the vast majority of inherited diseases, but findings in several newly investigated diseases, such as cystic fibrosis and classic hemophilia, have altered this opinion. [2] The amount of heterogeneity in genes for relatively common disorders may turn out to be surprisingly small, making a handful of markers coupled with advances in technology all that is necessary for rapid diagnosis of many conditions.

The scope of human molecular diagnosis, in terms of number and kind of possible conditions identified, continues to expand exponentially. For example, gene probes can identify or specify certain diseases manifested by nondiagnostic clinical or biochemical abnormalities. Probes of this sort have already found application in characterizing certain hemoglobinopathies, such as beta thalassemia. [3] Other genetic markers indicate the malignancy or metastatic potential of tumors such as neuroblastoma and small-cell carcinoma of the lung. [4] For another tumor, retinoblastoma, new markers can sometimes determine whether the condition is inherited versus acquired when family history is inconclusive, allowing affected individuals to determine their risk of transmitting genes for it to their children. [5]

Another advance is to use probes to diagnose carrier states in certain recessively inherited disorders, where the individual is not at risk of developing the condition but "carries" genes that can be transmitted to offspring. These new markers are particularly valuable for diagnosing diseases previously silent in carriers. Markers for both cystic fibrosis and Duchenne muscular dystrophy have been developed for this purpose. [6]

The most dramatic new diagnostic powers, however, arise in forecasting the later development of a condition in the individual tested. For a few of these "late-onset disorders," predictions have astonishing accuracy. Individuals who carry genes for conditions such as Huntington disease and adult-onset polycystic kidney disease will develop the disorder, if only they live long enough ....

More commonly, however, probes that predict illness for adults reveal less determinative genes, which confer "susceptibility" or "vulnerability" to conditions like Alzheimer disease, abnormal cholesterol levels and heart disease, or bipolar (manic depressive) illness. These genes may cause disease as much as five or six decades after detection, but only if unknown genetic or environmental factors conspire. Hence, they might best be termed "contingency genes."

Markers that identify contingent conditions will not be rare. Not only are many traits and disorders coded for by more than a single gene, but environmental factors--biological, psychological, and social--almost universally affect gene expression. Common disorders often have a genetic base characterized by decreased or uncertain penetrance (the gene is fairly likely to give no evidence of its expression despite being present in sufficient "dose") or wide variability in expressivity (the gene causes a very severe condition in one individual but a virtually unnoticeable condition in another).

The pace of development for all these kinds of markers has been astounding. In little more than a decade, markers for over three hundred genetic disorders have been identified, and technical advances promise further acceleration. DNA storage, or "banking," allows genetic material to be kept frozen for generations, perhaps indefinitely. Amplification techniques speed identification and characterization of new markers, and special denaturing gels augment capacities to identify small mutations. [7] Aspects of mapping (deducing the correct order of markers and genes on chromosomes) and sequencing (discovering the precise series of bases in given stretches of DNA) have been automated, and storage of data in computer banks makes possible nearly instantaneous analysis and sharing of information. [8]

Unfortunately, the development of new tools for molecular diagnosis currently outpaces advances in therapy, genetic or otherwise. Molecular diagnosis usually leaves therapeutic intervention dependent upon subsequent identification of the types and levels of dysfunction actually involved in generating disease. Searching for better markers eventually may lead to isolating a given gene, investigating its DNA sequence and products and, finally (but only potentially), securing meaningful therapy. [9]

New molecular techniques thus hold promise for heightened understanding, earlier diagnosis, and possible interventions. Yet, like more traditional approaches, molecular genetics merely gives us tools for developing information. Nothing more than sequences or associations are given by the probes and markers--leaving us responsible for fashioning new knowledge and deciding what to do with it.

New Dilemmas

In the early 1970s, controversies attending attempts to introduce carrier detection programs for sickle cell anemia and Tay-Sachs disease spurred research groups to articulate standards for evaluating the ethical acceptability of proposed genetic screening efforts. [10] A consensus emerged that programs should at minimum fulfill four major criteria: 1) the condition must be serious; 2) diagnostic tests must be accurate; 3) therapy or other meaningful intervention must be available; and 4) screening goals must be achievable at reasonable cost, or alternatively, at an acceptable cost-benefit ratio.

Proposals designed for a prior era of genetic screening, however, may at times mislead us in dealing with the consequences of new and rapidly accumulating genetic information. Social "progress" and the expansive methods, scope, and pace of human molecular genetics have combined to strain earlier unifying concepts. How does one evaluate the seriousness of a contigent condition? Is the accuracy of a molecular test to be measured against the actual presence of identified DNA sequences or against the eventual development of a predicted condition? Should presymptomatic and nonmedical interventions such as changes in occupation and life style be considered therapy? And against what standards are costs and benefits to be measured?

In addition, the most recalcitrant of previous dilemmas will inevitably insinuate themselves into any new analysis: definitions of disease and normalcy, priorities for eliminating as opposed to treating genetic disease, questions about mandatory testing and the proper role of the state, arguments about nondirective counseling and the limits of beneficence, and issues of genetic discrimination and the proper locus of control for genetic information.

We can expect the novel features of molecular genetics to lend special urgency to the subtle and difficult problems posed even by wholly beneficently motivated uses of genetic technology. The need for access to DNA samples will predictably heighten earlier concerns about genetic ownership and privacy, and raise troubling questions about storage of genetic information. The ability to detect relatively unburdensome traits and conditions reopens inquiry into our ability to distinguish disease and normalcy, and diagnosis of late-onset and contingent conditions necessarily challenges concepts of genetic identity and determinism. Identifying presymptomatic conditions via the molecular method will undoubtedly intensify debate about what constitutes a sufficient warrant for intervention.

The implications of rapid progress in molecular diagnosis are less certain. More than any other feature of molecular diagnosis, the pace at which we proceed is under our direct control. In addition, we can at least theoretically distinguish the speed with which we acquire new information from the speed with which we use it. If genetic discrimination relates in part to ignorance of shared genetic vulnerabilities, then learning more about ourselves at the genetic level may turn out to have surprisingly beneficial consequences.

Genetic Privacy

Special concerns about genetic privacy emerge from new abilities to score not only information extracted from DNA but now also the basic genetic material itself. Extended family histories and DNA samples from multiple generations contain genetic data limited only by our ability to probe it. Yet few guidelines exist to aid DNA banks in handling such information. [11] Must DNA that is no longer needed be destroyed? Can relatives who contributed DNA for an initial diagnosis insist on reciprocal sharing of the collected genetic material, even if for unrelated purposes? Can DNA stored in plastic vials be sold...or "inherited"? [12]

As genetic diagnosis gains increasing credence, individuals may wish to have access to genetic information preserved for future use by forward-looking predecessors. One can envision a heightened societal attention to heritage, with DNA stored in banks becoming a new type of ancestral shrine. An emphasis on exploring genetic roots might promise a renewed commitment to intergenerational relatedness. Yet, the impossibility of protecting confidentiality argues instead for maintaining only information than can be shared publicly.

Formerly, genetic counselors agonized over conflicts between their duty of confidentiality to their clients versus a felt duty to share genetic information with potentially afflicted relatives. Currently, the need to collect blood or tissue samples for linkage analysis means that involved relatives can, at least theoretically, decide for themselves how much information they want. Nonetheless, family pressures toward participation of even distant relatives can result in harms to individuals and to family relationships. Otherwise unsolicited, and often unwelcome findings (including nonpaternity), can confront relatives volunteering to assist in genetic diagnosis. Even with prior consent, disclosure in these circumstances is especially painful.

Genetic Identity, Normalcy, and Disease

The clinical and ethical acceptability of using genetic markers generally springs implicitly from a sense that some good comes out of early or enhanced diagnosis--someone benefits. Since in most cases an individual or family complains of disease (a tumor of unknown malignant potential, a previous child with Tay-Sachs disease), providing information or initiating treatment after diagnosis constitutes the rationale for pursuing testing.

Probes for late-onset and contingent conditions call this relatively simple model into question. For example, are asymptomatic young adults who carry genes associated with the later development of bipolar disease "diseased," even though not ill? One reason for substituting the language of "contingency" for that of "susceptibility" is that the latter tends to impute passivity and illness to those "cursed" with genes linked with the potential emergence of disease. Contingency implies malleability and a certain amount of independence from nature's dictates. A contingent condition may simply not occur, or may be prevented through early intervention. Hence, the contingent aspect of many common disorders may eventually inform our public imagination about genetic identity and determinism. We have always known that nurturing ourselves and each other could prevent the onset of certain conditions, but this power may be far greater than expected.

We may also have much to learn about genetic normalcy. Advancing knowledge may reveal us all to be in some sense weak and unusual. The fact that all humans carry approximately five recessive genes for lethal disorders was used to neutralize misplaced eugenic efforts in the 1970s. Similarly, we may discover that all of us carry a large number of genes for contingency disorders, dissipating much of the impetus for identifying as "abnormal" those who carry such genes.

Still, just as eugenics flourished under the banner of social responsibility and new "understandings" of the genetic basis of disease, so too may euphenics (the nongenetic improving of individuals through environmental changes) flourish in medical and social settings rife with pressures to acquire information and implicit mandates to act on it. While issues of exclusion of the genetically unfit will of course still arise, they will likely be joined by issues of selective inclusion: a social welcome for all, as long as you protect yourself from your genes.

Warrants for Intervention

A credo of medical care has been that the earliest diagnosis of a condition is the most desirable. And early diagnosis is already demonstrating benefits in one contingent condition: establishing genetic predisposition to an unusual syndrome of multiple endocrine tumors now allows major changes in clinical management, permitting invasive diagnostic and therapeutic procedures to be reversed for those children at highest risk. [13] Presymptomatic diagnosis of Huntington disease and other highly penetrant, devastating, late-onset diseases also seems rightly to provoke research and trials of promising agents.

Early diagnosis has its dark side, however. The ability to identify and treat many common conditions risks establishing a populace of "diseased" individuals and increasing medicalization of daily life. Failure to adhere to a suggested therapeutic regimen may then result in individual guilt and self-recrimination, or worse, a "blaming of the victim" by others through effects on insurance premiums or more subtle forms of stigmatization.

More importantly, turning all forms of contingency into illness is both premature and personally and socially undesirable. Can we be sure that a contingent condition is necessarily something to be circumvented? Conceivably, many genes predisposing to "undesirable" traits may also have as yet undiscovered beneficial effects, like the protection afforded by sickle cell trait against malaria. [14]

A central question therefore concerns how we are to assess the benefits of intervention for contingent disorders. Unfortunately, "diagnosis" (through identification of an underlying genetic substrate) often tends to legitimize interventions prior to rigorous evaluation of their potential benefits and harms. Yet most currently available therapies for genetically based conditions require long-term lifestyle changes. These may be highly burdensome but have little effect on ultimate morbidity and mortality, or they may reduce life's overall benefits as perceived by the individuals being treated. [15]

If interventions in childhood are possible, they may be difficult and create a potential for intra-familial conflicts and family disruption. Since markers exist to detect genes predisposing familial hypercholesterolemia and other lipid disorders, a zealous clinician might be tempted to argue that failure to maintain an identified child on a low cholesterol diet constitutes a new category for parental medical neglect. [16]

Early intervention for behavioral or psychological conditions will create particularly difficult problems. Markers exist for bipolar disorder (in some lineages) and are being sought for schizophrenia and other cognitive, affective, behavioral, and learning disorders. [17] Despite compellingly beneficent motivations for presymptomatic intervention, successful treatments may prove elusive. Routine symptomatic approaches may seem unduly harsh for presymptomatic use, and new interventions will be very difficult to evaluate in some of these disorders.

Providing effective therapy, and determining that its benefits outweigh its harms--two crucial elements for justifying new diagnostic interventions--may thus prove as difficult as establishing minimum criteria for seriousness and predictability of late-onset and contingent disorders. If human molecular genetics is to function well in improving medical care, complex judgments about appropriate use will be unavoidable.

Incentives and Arenas for Choice

Is there any a priori ground for supposing that the new tools of human molecular genetic will be used poorly rather than well? Perhaps not. But neither are there clear grounds for optimism. Present incentive structures predominantly support uncritical incorporation of new diagnostic technologies, and there is no obviously satisfactory locus for complex judgments that would differentiate helpful from unnecessary or harmful pursuits.

At first glance, health professionals might appear to be capable and desirable intermediaries between potential patients and the biotechnology industry. The professional genetics community has mobilized rapidly to insure that extensive counseling services are available for anyone being tested for Huntington disease or polycystic kidney disease. But we can expect these resources to be badly overstrained as markers for diseases that are more prevalent in society--like Alzheimers, diabetes, abnormal blood lipids, and bipolar disorder--emerge from research laboratories into clinical practice.

Moreover, beneficent clinical drives to diagnose and treat, powerfully reinforced in the United States by the threat of malpractice, could operate to bring molecular genetics indiscriminately into medical practice. Rather than risk "missing" a diagnosis that will later prove relevant, clinicians may feel compelled to request whatever tests are available, especially if the tests are relatively simple and cheap. [18] Fears of malpractice litigation or of liability under theories of "wrongful birth" or "wrongful life" are no doubt partly responsible, and nt entirely unfounded. [19]

Patients generate other pressures to use genetic testing. Some prospective parents demand assurances of fetal well-being that require otherwise unnecessary testing. While sophisticated genetic scrutiny does seem a natural response to heightened parental hopes for and expectations of "perfect" babies, inquiries into genetic normalcy, contingency, and their relation to therapy become particularly vexing when one is previewing the fetal genome. [20]

Guidelines for genetic screening rely on "nondirective counseling," where an individual or family determines the level of burden associated with a given condition, based on information conveyed in as nearly "value-neutral" a fashion as possible. However well this framework may have functioned when the occurrence of serious disease propelled an individual or family into genetic counseling, it is inadequate alone to handle questions about appropriate applications of newly developed genetic diagnostic tests in general medical practice.

Guidance from regulatory agencies will be of only limited value. Oversight by the Food and Drug Administration under the Medical Device Amendment of 1976 could insure that markers are reliable for diagnosing a given condition. But if one of the markers now available in research settings were offered commercially, FDA approval alone would indicate nothing about whether it would actually help an individual or family. [21]

Cost containment efforts may also motivate increased testing. Both prenatal and postnatal presymptomatic diagnosis and intervention may prove to be cost effective, generating increased societal interest in their utilization. The expression of this type of interest has in the past ranged from subtle social disapproval to actual coercion of individuals unwilling to submit to screening.

In particular, current pressures to curtail spiraling employee healthcare costs could tempt employers to rely on genetic "predictors" to guide hiring decisions. Although most genetic screening tests will be less predictive than direct examinations for expressed conditions, a history of forced workplace screening in the early 1970s provides painful testimony to employers' inabilities to resist the urge to exclude potentially costly employees. [22] Legislation designed to protect the handicapped may discourage such abuses, but it is less certain how courts (and others) would respond to discrimination claims if screening led not to exclusion from employment, but to coercion of affected workers into "wellness plans" or the establishment of sliding-scale contributions to insurance pools.

The Research Paradigm and Clinical Restraint

The possibility that multiple incentives will encourage injudicious introduction of new markers, coupled with the lack of readily available mechanisms to control the novel diagnostic options on the near horizon, suggests an agenda in meeting these challenges. Since three novel features of human molecular genetics not only explain but generate most of these pressures, these must be addressed directly.

The methods of molecular diagnosis raise one overarching consideration: therapies will be largely unavailable or of uncertain efficacy at the time tools for screening are developed. This means that few markers will be able to satisfy traditional criteria for widespread use, and that clinicians who choose to test individual patients will have no firm basis for counseling or making recommendations about "therapy." Under these circumstances, well-designed pilot studies and comprehensive clinical trials offer substantial scientific and ethical advantages over ad hoc decisionmaking by clinicians. [23] These studies should address not only the accuracy of proposed tests, but their clinical worth. [24] That is, protocols should incorporate evaluations of the need for as well as efficacy of treatment for detected conditions. If studies demonstrate that patients diagnosed by genetic testing fare worse than those never identified, both marker and proposed therapy are indicted.

Consistently introducing new markers under explicit research paradigms also yields a structure for approaching the conceptual and practical challenges posed by the vastly expanded scope of human molecular genetics. In practical terms, we need to know which tests to offer in which settings, and who is to make these decisions. If we are not to offer testing for every available marker, then we must have workable concepts of "disease" and "seriousness," for assessing genetic "oddities." We must also decide whether we can commit ourselves to intuitive distinctions, such as those that separate prenatal from neonatal and other types of screening.

The research paradigm helps by temporarily forestalling certain liability concerns, such as "wrongful birth," "wrongful life," and preventable injury, so that clinicians are relieved of the supposed (and feared) responsibility of having to identify all potentially diagnosable conditions. The burden of proof shifts to those who would claim that a condition causes serious disease. If it is not the standard of care to offer prenatal screening for stuttering, for example, then clinicians must be able to trust that the courts can know this. Having a marker under study concretely demonstrates its unproven character.

We can and should reject any form of mandatory prenatal screening for genetic indications, but whether we should limit access to certain kinds of testing is far less certain. Since a woman's elective abortion requires no legitimating legal reason, we tend not to talk about legitimating moral reasons either. Yet most geneticists still resist participating in efforts at sex selection. [25] Similar dilemmas will soon face us as markers for other not clearly undesirable "conditions" become available.

We need now to initiate debate about whether there are limits on the types of information that geneticists are obligated to provide. In terms of prenatal testing, for example, this might mean renegotiating the limits of nondirective counseling or encouraging open decisions by professional groups to refuse requests for certain forms of testing.

Genetics and Public Understanding

Finally, we need as a society to face these issues as they play out in the public arena. The complexity of the new genetic technology, the magnitude of its implications, and the pace of its development combine to make a thorough societal understanding seem almost unattainable. The rapidity of gains in information makes assimilation difficult, and the acquisition of new information in a piecemeal, incremental fashion serves only to encourage stigmatization of those found to have newly diagnosable conditions.

Perhaps obtaining a relatively full understanding of human genetic potentials in one fell swoop might more easily lead to recognition of vulnerabilities in each individual and thereby foster tolerance. Paradoxically, the project to map the human genome may achieve this as a largely unintended consequence--the realization that in every individual, sequences of DNA occur that could make the individual in some sense "unfit," if viewed in isolation. Perhaps only the happenstance of fate and current research priorities conspire to permit the discrimination of individuals demonstrably vulnerable to biological, personal, and social contingencies.

Moreover, despite our advances a vast impenetrability cloaks almost all prognostication about human traits and conditions. In fact, the language of "contingency" itself reveals a wobble in the lofty trajectory of the new human molecular genetics: for diseases of low or uncertain penetrance or for which expression is determined in part by other factors, genetic forecasts remain statistical, predictions not predeterminations. Peering into a given individual's future to predict the development of some currently undetectable condition represents a heretofore unheard-of capability, but the power of probes to forecast the future is forever limited by the power of genes to cause it.

Perhaps we should actively encourage greater public acceptance of variation and vulnerability. We may not yet be either willing or able to adopt an ethic of genetic screening and intervention that is responsive to the desire to promote individual and societal wellbeing while not destructive of the richness of expression inherent in nature and human society. We can never escape differences, even if doing so were desirable. Diseases and disabilities will inevitably result from our interactions with an environment harsh if not actively hostile. Despite all efforts at improving diet and insuring adequate exercise, individuals will become ill, grow old, and die.

Therefore, as we seek wisdom in the use of our humanmade tools, reaching beyond what is given, we must always be keenly aware of our inescapable frailties...especially those that arise--not from any defect in our genes--but from a failure in our vision.

References

Preparation and publication of this work was supported in part by a grant from the Charles A. Dana Foundation. The authors gratefully acknowledge comments and criticisms on an early draft by members of The Hastings Center's project "Ethical and Policy Issues in Genetic Screening," conducted through the generous assistance of the Dana Foundation. We owe special thanks to Jessica Davis, Stan Rose, Peter Rowley, Greg Grabowski, and Charles Hartman, and we appreciate the editorial assistance of our colleagues Bruce Jennings and Varun Gauri.

[1] ERic T. Juengst, "The Dynamics of Progress in Medical Genetics," in Eric T. Juengst, guest ed., Historical and Philosophical Problems in Medical Genetics (Boston: Kluwer Academic Publishers, in press).

[2] C. Thomas Caskey, "Summry: A Milestone in Human Genetics, "Cold Spring Harbor Symposia on Quantitative Biology 51 (1986), 1115-19.

[3] S.H. Orkin, and Haig H. Kazazian, Jr., "The Mutation and Polymorphism of the Human Beta-Globin Gene and its Surrounding DNA," Annual Review of Genetics 18 (1984), 131-71.

[4] Robert C. Seeger, et al., "Association of Multiple Copies of the N-myc Oncogene with Rapid Progression of Neuroblastoma," New England Journal of Medicine 313:18 (October 31, 1985), 1111-16; Hiltrud Brauch et al., "Molecular Analysis of the Short Arm of Chromosome 3 in Small-Cell and Non-Small-Cell Carcinoma of the Lung," New England journal of Medicine 317:18 (October 29, 1987), 1109-13.

[5] Janey Wiggs et al., "Prediction of the Risk of Hereditary Retinoblastoma, Using DNA Polymorphisms within the Retinoblastoma Gene," New England Journal of Medicine 318:3 (January 21, 1988), 151-57.

[6] Harry Ostrer and J. Fielding Hejtmancik, "Prenatal Diagnosis and Carrier Detection of Genetic Diseases by Analysis of Deoxyribonucleic Acid," Journal of Pediatrics 112:5 (May 1988), 679-87.

[7] Randall K. Saiki et al., "Analysis of Enzymatically Amplified Beta-Globin and HLA-DQ Alpha DNA with Allele-Specific Oligonucleotide Probes," Nature 324 (November 13, 1986), 163-66.

[8] U.S. Congress Office of Technology Assessment, Mapping Our Genes: Genome Projects: How Big, How Fast? (Baltimore, MD: Johns Hopkins University Press, 1988).

[9] Eric P. Hoffman et al., "Characterization of Dystrophin in Muscle-Biopsy Specimens from Patients with Duchenne's or Becker's Musculr Dystrophy," New England Journal of Medicine 318:21 (May 26, 1988), 1363-68.

[10] Research Group on Ethical, Social, and Legal Issues in Genetic Counseling and Genetic Engineering of the Institute of Society, ethics and the Life Sciences, "Ethical and Social Issues in Screening for Genetic Disease," New England Journal of Medicine 286:21 (May 25, 1972), 1129-32.

[11] American Society of Human Genetics, "Guidelines for DNA Banking and DNA Analysis," American Journal of Human Genetics 42:5 (May 1988), 781-83.

[12] The California Court of Appeals recently ruled that explicit consent for the use of human individuals' tissues and cells is required prior to commercial exploitation, defining an emerging standard that such tissues are property. John Moore v. The Regents of the University of California, et al., 1988 Cal. App. 666 (July 21, 1988).

[13] Shirley Myers et al., "Progress Towards Identification of the Genotype for Multiple Endocrine Neoplasia 2A (MEN2A)." Paper presented at the annual meeting of the American Society of Human Genetics, New orleans, LA, October 12-15, 1988.

[14] Jerome I. Rotter and Jared M. Diamond, "What Maintains the Frequencies of Human Genetic Diseases?" Nature 329 (1987), 289-90.

[15] Gerry Oster and ARnold M. Epstein, "Cost-Effectiveness of Antihyperlipemic Therapy in the Prevention of Coronary Heart Disease," Journal of the American Medical Association 258:17 (Novembr 6, 1987), 2381-87.

[16] Constance Holden, "NIH Moves to Debar Cholesterol Researcher," Science 237 (August 14, 1987), 718-19.

[17] Janice A. Egeland et al., "Bipolar Affective Disorders Linked to DNA Markers on Chromosome II," Nature 325 (February 26, 1987), 783-87; Nancy J. Cox, "Molecular Genetics: The Key to the Puzzle of Stuttering?" Amerian Speech-Hearing-Language Association (1988), 36-40.

[18] See Sherman Elias and George J. Annas, "Routine Genetic Screening," New England Journal of Medicine 317:22 (November 26, 1987,) 1407-08.

[19] Lynn D. fleisher, "Wrongful Births: When is There Liability for Prenatal Injury?" American Journal of Diseases of Children 141 (1987), 1260-65.

[20] Anne McLaren, "Can We Diagnose Genetic Disease in Pre-Embryos? New Scientist 16 (December 10, 1987), 42-47.

[21] Frank E. Young, "DNA ProbesA: Fruits of the New Biotechnology," Journal of the American Medical Association 258:17 (November 6, 1987), 2404-2406.

[22] President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, Screening and Counseling for Genetic Conditions (Washington, DC: Government Printing Office, 1983).

[23] Thomas C. Chalmers, Jerome B. Block, and Stephanie Lee, "Controlled Studies in Clinical Cancer Research," New England Journal of Medicine 287:2 (July 13, 1972), 75-78.

[24] For example see Peter T. Rowley, Starlene Loader, and Margaret Walden, "Response of Pregnant Women to Hemoglobinopathy Carrier Identification," in Genetics Diseases: Screening and Management, Thomas P. Carter and Ann Willey, eds. (New York: Alan R. Liss, Inc., 1986), 151-72.

[25] John C. Fletcher and Dorothy C. Wertz, "Ethics nad Human Genetics: A Cross-Cultural Perspective," Seminars in Perinatology 11 (1987), 224-28.

Kathleen Nolan is associate for medicine at The Hastings Center in Briarcliff Manor. NY. Sara Swenson was a research assistant at The Hastings Center before entering Yale Univesity School of Medicine, New Haven, CT, where she is currently a first-year medical student.
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Title Annotation:effect of medical genetics on medical ethics
Author:Nolan, Kathleen; Swenson, Sara
Publication:The Hastings Center Report
Date:Oct 1, 1988
Words:5339
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