Loyola University Chicago

Curtis R. Naser, Ph.D. 

Department of Philosophy & Program in Applied Ethics
Fairfield University
email: cnaser@funrsc.fairfield.edu

Introduction 

The Human Genome Project--a three billion dollar, fifteen year effort to map and sequence the human genome[1]--was begun in 1990 and is presently estimated to be ahead of schedule. The base-pair by base-pair sequencing of the entire three billion bases of the human genome is within reach within the next five years. The phenomenal success of the project in meeting and surpassing its goals is largely due to advances in sequencing technologies and informatics. Indeed, the standard genomic sequencing technologies[2] are largely automated and computer assisted. In addition, the analysis of raw genetic sequence, and its integration with maps of the various chromosomes is largely a project in informatics, the results of which are freely available over the World Wide Web[3]. The purposes of this massive, industrial strength science project, are manifold. Besides providing the building blocks for answering questions about the ontogeny of the human organism, how the human species has diverged both from its evolutionary precursors as well as how individual races and ethnic groups have diverged genetically[4], the Human Genome Project promises to revolutionize the practice of medicine and is already revolutionizing the strategies of biomedical research[5]. It is this latter promise that is probably the most compelling reason that the United States Congress was willing to invest $200 million a year in this project.

Even as the Human Genome Project enters the final phase of sequencing, having already produced high resolution maps of each human chromosome, the fruits of this project have begun to be applied to medical practice in the rapidly growing field of medical genetics. There already exist genetic tests for a number of human diseases, including Huntington's disease, breast cancer, and cystic fibrosis to name just a few of the more well known conditions. Mendelian Inheritance in Man, an online catalogue of human disease genes lists over 4000 gene locuses thought to be associated with human disease[6]. Although the Human Genome Project has yet to give rise to any new treatments of disease, early diagnosis of genetically related diseases has aided individuals in family planning, and the early management of their genetic diseases.

Genetic testing, however, is a double edged sword, offering both benefits and burdens. Some genetic diseases, such as Huntington's have no treatment, and while early genetic diagnosis may be an aid to family planning, knowledge of the disease may be a heavy burden to bear. Indeed, there is good evidence that a majority of individuals with a family history of Huntington's disease have opted not to seek the knowledge the genetic test offers[7]. Other conditions, such as the genetic predisposition to certain cancers may leave one with the unfortunate choice of prophylactic surgery such as double mastectomy for breast cancer or colostomy for colon cancer, or in either case, the anxiety of the vigil, waiting for the inevitable appearance of the cancer. Such testing is complicated in some cases by the incomplete penetrance of many disease genes, leaving patient and doctor to weigh probabilities rather than certainties. Prenatal testing also has the consequence that because treatments for genetic conditions are so rare, the only options when a genetic disease is detected in the fetus are abortion or carrying the fetus to term. In addition, there are social consequences of genetic testing, ranging from denial or discontinuation of health insurance, life insurance and employment, to social stigmatization and discrimination.

Because medical genetics is so loaded with risks, geneticists have been very careful to formulate exhaustive protocols for counseling prior to, during and after genetic testing. Patients need to be educated about each specific test: what the test can and cannot determine, the risks of the disease, the social implications of the genetic knowledge, the psychological burdens of the knowledge as well as possible treatment options.

Though these efforts are quite laudable, even if still controversial[8], the very technology which has given rise to the disciplines of medical genetics and genetic counseling, threatens to undermine them. Currently, most genetic tests are done at a central laboratory and can take several days to a week to complete. The tests are labor intensive and expensive. Until recently, most such testing laboratories would work only with certified genetics counselors in a medical genetics practice, thus guaranteeing that patients would be fully informed of all the risks and benefits of the test results as well as receive counseling after the test. But genetic testing is still a cottage industry which is now entering its adolescence. Just this past year, for instance, the Genetics and IVF Institute in Fairfax, Virginia broke ranks with two other testing labs which had agreed not to make the BRCA1 genetic test available directly to the public because of uncertainty about the risks posed by the gene. For $295 the Institute offered the test to anyone, arguing that it was any woman's right to have the test[9]. The industry's adolescence is now upon us.

This is just the tip of a very large iceberg, the hidden outlines and mass of which I hope to partially reveal in this essay. Genetic testing and sequencing technologies already exist which have the potential of putting a complete genetics testing laboratory in every physicians office, and maybe even in the local drugstore along side other over the counter medical testing. The stakes are quite high, not only because human genetics has rapidly become very big business[10], but also because the problems already associated with genetic testing will only get worse unless adequate solutions can be found. Let us take a look at one of these newer technologies which promises to transform the practice of medical genetics.

Sequencing and Typing Strategies 

Standard methods for genetic testing employ what is called the "polymerase chain reaction" or PCR. In order to test for the presence of a particular gene or allele's of a gene, a sample of DNA is isolated by means of two "probes"--each a 10 to 20 base long strand of DNA complimentary in sequence to DNA sequences at each end of the target gene. As the sample DNA is heated up, the two complimentary strands of DNA that form the double helix separate. When cooled again, the short probes are able to "hybridize" or bond to the target strands of DNA (one probe for each complimentary strand at opposite ends). Then as the sample is incubated at a moderate temperature, the polymerase enzyme initiates the formation of a complimentary strand of DNA starting at the probe. The cycle is repeated twenty to forty times and the result is that the target DNA has been amplified exponentially. The sample is then placed on an electrophoretic gel and even single base pair differences in length of the target gene can be resolved visually on the gel.

Sequencing of genes employees the same electrophoretic gel technique but the amplified DNA is first divided into four separate solutions and "digested" by enzymes that specifically cleave the DNA at one of the four base pairs that make up the molecule and a fluorescent tag is then added. The resulting solutions are then passed through an electrophoretic gel, and the sequence of the DNA is reconstructed by summation of the differing lengths of DNA. All standard sequencing machines employ computer assisted reading and analysis to reconstruct the sequence.[11] 

Gene Chips 

An alternative strategy has been developed by several companies, including Affymetrix of Santa Clara, CA, Hyseq of Sunnyvalle, CA and Synteni of Palo Alto, CA[12]. This strategy employs what are called "oligonucleotide probe arrays". The idea is that rather than using a single probe and applying it to a solution of DNA, a large number of probes are fixed at one end to the surface of a silicon chip approximately one centimeter square. A large number of different probes of predetermined sequence[13] can be so fixed in a predetermined spatial array or grid. Sample DNA is amplified and digested by enzymes into lengths equal to the probes' lengths (10 to 30 bases) and labeled with a fluorescent tag (sometimes the DNA is first converted into RNA). The resulting samples of DNA then hybridize to those probes whose sequences they match. A microscope is then able to read the resulting hot spots of fluorescence when illuminated by a laser of appropriate wave length. A computer is employed which has been programmed with the sequences and their positions on the chip. Thus a fluorescent mark on the chip indicates that a piece of the sample DNA has hybridized to those probes and therefore, the sequence of that particular sample is known[14]. The intensity of fluorescence can also be used as an indicator of the quantity of sample sequences present. This is important, for instance, it assessing total gene expression of cells by measuring which genes have be "switched on" and so have been expressed in the form of messenger RNA, and how much messenger RNA in each case has been produced[15].

Affymetrix is currently producing such chips for research purposes which have been divided into a grid of 40,000 squares, each 50 microns on a side. Consequently, a single such chip can contain approximately 40,000 different probes. In order to increase the accuracy of the chips, which they have demonstrated to be equivalent in accuracy to standard sequencing techniques, a great deal of redundancy is built into the probes. Presently, they are able to detect the expression of up to 6000 genes by analyzing expressed cellular RNA[16]. Affymetrix claims to be able to produce chips of 20 micron resolution giving the chip a total of 250,000 sites and they claim 10 micron chips are possible with a total of 1,000,000 sites[17]. Affymetrix anticipates commercial production of chips capable of monitoring the expression of 50,000 genes[18].

Such chips can be used to test for particular sets of genes, by using probes specific to those genes and their alleles. Alternatively, it is possible to employ such probes to do raw sequencing[19]. Reaction times vary from an hour to overnight depending upon the procedure and the necessity of amplifying the sample DNA prior to hybridization. Scanning time is quite short: fifteen minutes for a 20,000 probe array.

While Gene Chips presently remain tools for researchers, the long term goal will be to produce a fully automated system for clinical genotyping and sequencing. While this goal still remains on the horizon, it is being actively pursued by Affymetrix and other companies. Affymetrix and a consortium of other biotechnology companies and academic institutions is presently working under a $31 million grant with Stanford University from the U.S. Commerce Department to develop automated miniaturized genetics diagnostic systems for use in physicians offices [20].

Implications 

Though oligonucleotide probe arrays are not yet on the drug store counter top nor even in the doctor's office, we are not in the genetic Kansas anymore. The pace of genetic technologies is quickening rapidly, and we have not yet figured out how to handle the implications of the clinical genetics we already have available to us. Will we be able to use this technology for the good of all concerned? Or will the imperative "a technological can do implies a commercial must do," rule this new technology as it seems to rule so many others? Let us examine some of the benefits and risks of this new technology.

Benefits 

Genetic testing is presently labor intensive, time consuming and expensive. High speed testing, by whatever means, will bring genetic information to the physician and patient much more rapidly and at lower cost.

From a purely medical point of view, we should recognize that once the human genome project has completed the mapping and sequencing of the human genome and the characterization of all disease genes, high speed genetic testing and analysis will be an unparalleled diagnostic tool at the disposal of the physician. Such genetic information will form the basis of long term preventive recommendations and treatment. Further, as our understanding of the genetic bases of drug action increases, physicians will be able to tailor their treatments and prescriptions to the peculiar genetics of their patients. Likewise, as research progresses in infectious diseases, the genetic bases of susceptibility will become clearer. Thus immunizations and prophylactic treatments can be targeted to those who are susceptible. Speedy and efficient genetic diagnosis will be a necessary part of this process.

From the point of view of research, such technologies are already speeding up our ability to map, sequence and develop definitive diagnostic tests for disease genes. In addition, entire genomic RNA expression chips will become available to monitor the expression of genes in each type of cell as an organism develops from egg to adult. This research will ultimately prove invaluable in the study of developmental disorders as well as contribute profoundly to our basic understanding of ontogeny. And, as more and more genetic information winds its way into the medical record, such medical records will become invaluable sources for genetic epidemiology, containing both genetic information and medical history along with pertinent demographic data.

So researchers and clinicians alike are quite excited by the prospects of the increasing geneticization of medicine, which will only be accelerated as high speed genetic testing equipment becomes more available and inexpensive. But these benefits are not univocal. Let us now turn to how such a development both impacts on old problems and raises a host of new ones.

Old Problems Made Worse 

At its inception, the Human Genome Project was recognized to raise many profound ethical, legal and social issues. Detailed knowledge of genetics impacts upon our self understanding and our evolutionary history, the relationships between races and diverse ethnic groups, as well as our understanding of disease. Genetic testing has manifold implications, not just for how diseases are recognized, but also on how they will be treated, and just as important, how society responds to these diseases and the knowledge of them genetics affords. As a result, the architects of the Human Genome Project argued for and won a commitment of 5% of the overall budget to the study of the Ethical, Legal and Social Implications (ELSI) of the Human Genome Project [21].

Health Insurance: 

One of the first areas recognized to be impacted by increased understanding of genetics and the development of genetic testing techniques is health insurance. A 1993 subcommittee of the ELSI working group--Task Force on Genetic Information and Insurance--published a report entitled Genetic Information and Health Insurance [22]. This report analyzed the nature of insurance underwriting and the impact of genetic testing.

The basic problem is this: insurance companies have an interest in minimizing risk. They seek knowledge about the nature of the risks of the prospective insured in order to make a prudent judgment about whether that risk should be assumed and if so, at what cost. There are, of course, many limits to that knowledge, including the costs of gathering it. Insurance companies rely on a combination of actuarial tables, medical history and physical examination to make these judgments. On the other hand, individuals seeking insurance, have an interest in hiding their risks. In addition, individuals who are generally healthy may not seek health insurance coverage, whereas individuals who suffer from diseases or conditions have a clear interest in getting insurance coverage, leading to what insurers call "adverse selection" whereby the less healthy disproportionately seek more coverage. The predictable result is that those most in need of insurance will have the most difficulty obtaining. And when they are able to obtain it, the insurance company may exclude coverage for the very thing that presents the greatest risk to the insured--a preexisting condition or predisposition to disease.

Enter genetic testing. Genetic testing promises to provide highly specific information about present and future health problems, what George Annas has called a "coded future diary"[23]. Such information would obviously be a boon to insurance underwriters who could use this very detailed predictive information to minimize their risk by excluding some candidates from insurance coverage altogether, excluding specified genetic conditions from coverage for others, or increasing insurance premiums for specific risks on still others. Genetic information, however, can work against the interests of the insurance company, if an individual learns independently of specific genetic risks and seeks coverage on the basis of that knowledge. The result is the problem of adverse selection which works to overburden insurance pools with higher risks.

The conclusions of the ELSI task force on Genetics and Insurance was that because of these conflicting interests, a rational policy on insurance in an age of genetics was impossible. Unless there is fundamental reform of our health care system in the United States whereby everyone is guaranteed basic health coverage, the contradictions inherent in our system of health insurance will be radically exacerbated by genetic testing. Insurers will use this knowledge to exclude those of high risk, thus obviating the medical advantages of the testing in the first place. Likewise, individuals may seek genetic knowledge of themselves or their children, in order to make decisions about whether to carry insurance and how much to buy.

Presently insurers generally do not require the genetic testing of applicants for the simple reason that it is too expensive: the costs of testing large numbers of individuals exceed the money the insurance companies would save by excluding those of high genetic risk. If an individual, however, has undergone genetic testing, insurance companies will often demand that information, though if the testing has been done "off the record," the individual may be able to refuse that information, at the risk of lying to the insurance company[24].

High speed, inexpensive genetic testing, however, radically tips the precarious balance our society presently endures between the competing interests of insurors and insured. When genetic testing becomes cheap enough to be cost effective for insurors to demand, they no doubt will demand it, thus making what the task force recognized as an already irrational system worse. The insurance companies argue that they cannot selectively exclude themselves out of existence, and that an equilibrium will be achieved[25], but this may well be at the cost of a lack of coverage for a number of devastating genetic conditions which insurers will simply refuse to underwrite. The consequence will be that some of the medical benefits of genetic testing will be lost because individuals will not have the means to pay for the treatment of them because they already have been denied coverage.

This is a social disaster waiting to happen. Whether high speed genetic testing becomes a routine part of insurance underwriting and medical practice in five years or fifteen years, unless the underlying contradictions of health care financing and insurance are resolved, the inevitable result will be an economic boon to the insurers and a corresponding loss--often devastating--to the individual person.

Employment: 

The above nightmare is not confined only to those who must purchase individual insurance policies. Large group insurers and those who self-insure--employers--may also use genetic testing to exclude individuals of high risk. Employers may also have an incentive to exclude individuals of specific genetic risk if it is probable that they will lose that employee to health problems and disability in the foreseeable future[26]. Some businesses invest a great deal of resources in the training of their employees. If they are able to determine in advance who will be around long enough for them to recoup their investment, then employers will have an incentive to use genetic testing for that purpose, provided that the testing is cost effective. High speed genetic testing will eventually make such a practice cost effective. The result may be a class of the able bodied, but genetically future disabled, who may not be employable, or may not be able to find employment in their chosen profession.

Some employers may also seek to use cost effective genetic testing in order to minimize the risk of health problems which arise in certain work place conditions, such as exposure to toxins[27]. As the genetic basis of toxicology becomes better understood, it will be possible to discriminate between individuals who are more or less susceptible to particular toxins in the work place. It may be cheaper for the employers to weed out their susceptible employees (or future employees) than to clean up the work place of the toxins. Thus again, some individuals will find their ability to realize their professional goals thwarted by a form of genetic discrimination.

Another possibility exists that corporations involved in environmental pollution by human toxins may argue that the effects of those toxins are a result of the genetic predisposition of those who are affected, rather than the result of the toxin itself, thus seeking to absolve themselves of liability.

Prospects for Change: 

We presently have little or no effective public policy to deal with these problems, yet the development of genetic testing technology proceeds apace. Must it? Must we develop and then market these technologies before we solve the problems that they will inevitably create? Will we simply wait to see what happens and who gets hurt, before we, as a society, are willing to take action to solve these dilemmas? Considerations of social justice would lead us to proactively address these problems before they become worse. The ELSI Task Force on Genetics and Insurance, writing its report in 1993 at the height of the Clinton Health Care Reform effort, looked forward to its successful completion and felt confident that these problems could be headed off before they become worse. Unfortunately, their optimism was misguided.

The result presents an interesting lesson. Market forces have since penetrated heavily into health care in the form of managed care. It was recognized early on that the introduction of market forces to health care would lead to compromises in patient care. Managed care advocates argued otherwise, contending that managed care would make medicine more efficient. We have, in fact, seen both predictions come to pass. Health care costs have been at least temporarily held down and there is good evidence of compromise of patient care in a number of arenas[28]. As a result, society has responded piecemeal to these compromises, legislation being drafted to limit gag rules on physicians and force insurers to offer greater lengths of stay in hospital after certain procedures. But the underlying contradictions of our present system of health care financing continue to generate problems for patients and providers alike which compromise the goals of good medical care and treatment.

If the history of managed care is a guide, then we can only expect change in public policy when a sufficient number of individuals are sufficiently harmed to mobilize our representatives into action. The unfortunate consequence, however, is that not only are individuals sacrificed in the process but that the resulting policies are cobbled together piece meal. The result is an unsystematic morass of regulations.

In the area of genetic testing, it would be naive to expect that those who are contributing to the "progress" of the human genome project and the translation of its knowledge into practical and clinical applications, such as high speed genetic testing technologies, would be willing to slow down their efforts until society can be convinced of the need for proactive legislation. There simply is too much money at stake. Too many scientists have invested their careers and money in the commercialization of genetics and biotechnology, too many corporations are invested heavily in the same, for us to be able to slow the tide of genetics that is presently flooding our society. It will most likely be only in reaction to the injustices and harms that result from the application of genetics to social institutions such as insurance and employment that we will see any movement to ameliorate the most egregious harms that are to come.

New Problems 

While the impact of genetics upon insurance and employment have been recognized from the start of the rise of contemporary genetics, there are a number of areas just below the surface in which high speed genetics creates new problems. These areas include its impact upon genetic counseling and a host of difficulties raised by the convergence of this technology with the increasing computerization of the medical record.

Genetic Counseling: 

As noted above, the present process of genetic testing involves intensive counseling of patients and sometimes their families who may be impacted by the testing as well. The development, however, of high speed, comprehensive and inexpensive genetic testing, while a boon to the practice of medicine, may make it all but impossible to effectively counsel patients. Each genetic disease has its own unique set of circumstances, impacting the individual and family in very different ways. Strong social stigma may be attached to some genetic conditions, and the interpretation of genetic testing is complex and requires a great deal of knowledge and background. Patients need a great deal of education to be able to assess the need for and consequences of genetic testing.

Yet when we multiply the need for this education for each genetic condition several thousand fold in testing for multiple genes at a time, and when we place the testing apparatus if not in the hands of individual doctors and counselors, then in their ready reach, how will we be able to adequately educate and counsel patients about these tests. There is already evidence that many physicians ordering diagnostic genetic tests do not fully or even adequately understand the results, yet alone adequately prepare their patients for testing, even when the testing is restricted to conditions of their specialty[29].

The prospect of easily accessible genetic testing, perhaps even marketed directly to the consumer, that is fast and inexpensive may lead to too much information too fast. Without adequate counseling and interpretation by qualified physicians and counselors, individuals may be overburdened with information that they are simply not competent to understand. The possibility for misinterpretation without proper guidance is great, and could lead to imprudent decisions by patients and physicians who are not trained to interpret the results of genetic testing. While one can expect that along side of high speed genetic testing computerized interpretation of its results will develop, a consistent level of expertise amongst health care providers necessary to adequately interpret and act upon genetic testing results outside of the specialty of medical genetics will be long in coming. Genetic testing technology is rapidly outstripping the competence of health care providers to interpret it and high speed genetic technologies will radically exacerbate this problem.

Genetic Testing and the Computerized Medical Record 

This is perhaps the most disturbing result of the development of this new genetic testing technology. Because the gene chips produced by Affymetrix and others rely upon the computer to analyze the raw data coming from the reading of the chip itself, the results of the testing are presented in computer code of the sequences of the genetic probes which have matched. Depending upon the construction of the oligonucleotide probes on the chip, this code may be the entire sequence of a gene being tested, or it may indicate the specific allele(s) of perhaps a large number of specific genes being tested. Hence the computerized results will contain either raw sequence, or the specific sequences of small portions of a large number of genes, in addition to the immediate interpretation of these sequences in terms of the presence or absence of specific known alleles of the specified genes. While the results can be reviewed directly on screen using the software provided by the company, or printed out, it is unlikely that this computerized genetic information will then be discarded. Indeed, when such testing technology is finally approved for clinical use, whether in commercial testing laboratories, hospital cytogenetic laboratories or in the physician's office, the computerized code representing the specific genetic sequences tested will inevitably be ported into a computerized medical record.

There are a number advantages of this arrangement. First, it allows the physician or other specialist to access the raw sequence, thus enabling them to apply new knowledge to genetic information which has already been gathered. Specific alleles of a gene, for instance, may indicate how an individual will respond to different therapies developed in the future. Furthermore, by retaining genetic information in the computerized medical record, this information is more easily shared amongst consulting physicians, or transmitted to remote sites to which the patient may travel or relocate[30]. Furthermore, by including detailed genetic information in the medical record, it will be possible for researchers later to cull such vast and detailed records for associations between specific genes or alleles and the medical history and demographic information included therein. Such would be an exceedingly powerful database for a wide variety of genetic epidemiological research.

But the sword cuts in several directions. While a boost to the practice of medicine and the enterprise of research, inclusion of large quantities and highly specific genetic information in the medical record can also be a hazard to the patient in a variety of respects.

We have already discussed the impact of high speed genetic testing on insurance and employment. I will only point out here that the inclusion of this information in a computerized medical record further exacerbates these problems by making detailed genetic information readily available to insurers and employers, who already have a variety of ways of accessing the medical record. High speed genetic testing results coded in a computerized medical record simply hands insurers and employers genetic information on a silver platter, or rather an aluminum disc, as it were.

Equally troubling, however, are the issues of privacy and confidentiality. Medical records, and especially computerized medical records, have long been recognized as veritable sieves. Such records are routinely accessible to large numbers of individuals at hospitals, whether they have a need to know or not. In addition, patients are routinely required to authorize the release of their medical records to insurance companies as a condition of coverage, and these insurers in turn hand can sell or forward patient records to a variety of other agencies and businesses.

Aside from the use of these records by insurers and employers for purposes of minimizing their risks and costs, is there good reason to decry the openness of the medical record? There are two responses to this question. First, other harms may befall individuals whose medical records have been opened to other individuals, organizations or agencies. Secondly, there even if no "harms" per se result from these disclosures, still it may be argued that individuals rights have been violated. First, let us review some of the harms.

Embarrassment of Disclosure: 

Some medical and genetic information is highly personal and its disclosure may be an embarrassment to the individual and what is embarrassing or sensitive is itself a matter of personal feeling. Employees of a hospital, for instance, must bear the risk that their fellow employees with access to medical records may browse their records, simply out of curiosity. While some individuals may have the means to get their treatment elsewhere, many employees will be forced by their insurance to get treatment in specific hospitals, and perhaps in the very hospital in which they work.

This problem, however, is not limited simply to employees of a health care institution. The large numbers of individuals who work in health care and have access to medical records opens the general public who use these hospitals and facilities as well to the prying eyes and curiosity of electronic voyeurs.

While it is unpredictable what specific information an individual will find sensitive and thus rather not have disclosed to her neighbors, acquaintances or strangers there is some genetic information that will be more sensitive than others. Particularly sensitive will be that information pertaining to personality and intelligence. Though we presently know very little about the genetic bases of personality, intelligence and psychiatric disorders, this knowledge will come in time. And just as we do not routinely discuss or disclose our IQs because we feel that that is personal information, so we may anticipate that individuals will have a strong interest in maintaining the confidentiality of such genetic information.

Genetic Reductionism 

There is a danger that as we develop a more and more sophisticated understanding of genetics, that we will fail to recognize the limits of genetic knowledge. Dorothy Nelkin and Susan Lindee have already chronicled the penetrance of genetic ideology and metaphor into our popular culture[31]. As the advancement of genetics continues, we can only expect an increasingly genetic ideology to envelop us. While genetic scientists and physicians will admit that genes are not the complete story of the human being, the increasing reliance on genetics enforces this erroneous stereotype. The danger is that individuals may be categorized on the basis of the genes, rather than on the basis of who they are and what they have accomplished or can accomplish. The increasing reliance on genetics leads us to make all sorts of judgments on the basis of things that are completely out of the control of the individual--their genes--to the exclusion of what is in their control--namely, their capacity to adapt and overcome whatever limitations may have been placed upon them by their biology. Before high speed genetic testing becomes a routine part of our lives, we need to address societies tendency to oversimplify complex information and problems. What we need, in a word, is vastly better education of the public about the meaning and limits of genetics.

Patient Trust in the Health Care System 

It is perhaps a cliché that a physician has an obligation to maintain the strictest confidentiality in their relationships with patients. The wisdom of this principle, expressed first by Hippocrates[32] has never been seriously questioned. There are, however, a number of circumstances in which confidentiality must be overridden by higher needs. These include consultation with other providers about patient care. Thus these other providers enter into a similar relationship with the patient. While the circle of those who are privy to confidential information is thus widened, it remains within the scope of the principle. But in addition to provider access to medical records which is a necessary condition of care, insurance companies, billing personnel, hospital records and informatics personnel, QA personnel and sometimes government and accrediting agencies all have access to the medical record. Patients have simply had to accept this less than optimal state of affairs as a condition of getting the medical care they need. The addition of detailed genetic information to the medical record, however, raises the stakes for the patient, as such information can harm their economic and employment interests in other domains. Given the large number of individuals and agencies that have access to the medical record, and given the conflicting interests some of these may have vis-a-vis the patient's interests, it would be irresponsible to place such detailed genetic information in the electronic medical record until adequate safeguards to protect this information have been established. The fate of the model Genetic Privacy Act[33], which sought to do just that at the Federal level, does not leave one sanguine about the prospects of meaningful reform in this area. The openness of the medical record is already of concern to many patients. The addition of information that has the potential of working against their own interests in that record can only serve to undermine patient trust in the health care system.

Harms vs. Wrongs 

Even if the possible harms due to the disclosure of genetic information can be avoided by appropriate public policy, there remains the fact that patients expect that their records will remain confidential. Simply eliminating the possibility of harm due to disclosure does not eliminate the wrong or disservice to a patient whose records are open to perusal by so many individuals and agencies. Alexander Capron has elaborated on this distinction by arguing that a person who enters your house while nobody is home and neither takes nor disturbs any of your possessions, has not harmed you by removing or damaging any of your property, but has wronged you by both trespassing on your property and by violating your privacy[34].

The inclusion of detailed genetic information in the medical record leaves individuals open to such violations of their personal privacy, by exposing information which taken in its totality is unique to that individual and details a part of that person's past, present and future medical history. While genetic information is by no means the whole story of the individual human being, it is a significant enough part of the individual that the individual should expect that that information only be disclosed to those individuals who have a genuine need to know in advancing that individual's own interests. Such information is simply too sensitive to leave open to the perusal and use by as large of a cohort as presently has access to the medical record, whether or not such use constitutes an actual harm to the patient.

Commercial Interests in the Medical Record 

The introduction of managed care has increased the level of bureaucratic access to the medical record, not only to review individual patient care, but also for the purposes of reviewing provider practices which the managed care organization (MCO) may want to encourage or discourage. For instance, MCOs regularly review the patient records of treating physicians in order to assess the frequency with which physicians order various tests, treatments and prescriptions. While the MCO may argue that this activity is no different that standard quality assurance (QA) reviews, the purposes of the MCO review are at least two fold: 1) to indeed assess the quality of care delivered, but 2) to evaluate the practices of the provider in light of predetermined economic goals. Physicians who routinely order more diagnostic tests than average are encouraged to limit such orders. If they fail to, their future participation in the plan and consequently ability to treat current patients, may be threatened and ultimately terminated. Although patients have of necessity (some might say, by coercion) signed over to the MCO the right to review their medical records, few patients actually understand that their records are being used for a purpose other than their own medical interests, namely, the advancement of the MCOs own economic interests.

There are other purposes as well to which a computerized medical record may contribute, particularly one which contains so much detailed genetic information as high speed testing will make possible. The Consumer Advocate for the City of New York, Mark Green, published a report in 1996 detailing the practices of pharmaceutical benefits managers (PBMs) in the development of formularies and their use of patient records to modify physician prescribing habits to conform to the set of drugs the PBM and MCO have decided to cover[35]. Unfortunately, the choice of preferred drugs is in many cases based upon the amount of money a pharmaceutical manufacturer is willing to pay the PBM, or in some cases whether such manufacturer owns a controlling interest in the PBM. The report details several cases in which the pharmaceutical manufacturer has been given access to patient records for these purposes[36]. One can only imagine to what other ends our medical records are put as well, once these corporations have a copy of our medical records. As more detailed genetic information becomes a part of these records, they will increasingly become more and more valuable as a research tool. Will PBMs and their manufacturer partners limit the use of these records to just their marketing potential--an activity that is already questionable enough--or will they not go on to further exploit our records and the genetic information they hold to further advance their commercial interests through basic biomedical research? For instance, a detailed genetic profile of patients taking a particular drug would serve a pharmaceutical manufacturer in discovering which genetic types are more or less susceptible to that drug's specific action, as well as side effects. While such information may also be of use to the patient, should patients not have some say in whether their records and genotypes are used for this purpose?

Unfortunately, the situation is worse than that. It is routine for MCOs, pharmaceutical corporations and data management firms such as Equifax and IMS America to sell medical records back and forth[37]. The inclusion of detailed genetic information will not only make these records more valuable as a research tool, but they also obviate any pretense at the protection of individual confidentiality, even if the records have been stripped of personal identifiers. This is because the amount of genetic information anticipated to be placed in the medical record is already specific enough to uniquely identify an individual. Indeed, it has even been proposed that a person's social security number be replaced by a unique profile of their DNA as a personal identifier[38]. Thus, in principle, anybody into whose hands such records fall, may be able to identify the individual person simply by matching detailed genetic information back to the original medical record which includes the name and address.

There is another domain in which "anonymity" becomes highly problematic: the use of "anonymous" tissues and cells in research. As soon as a sufficient amount of genetic information is incorporated into the medical record, the idea of an "anonymous" tissue sample will become an oxymoron, since one need only test the genotype of the specimen to and then search the medical records databases[39] for the corresponding unique sequence or genotype. Since a great deal of genetic research is conducted on anonymous tissue samples precisely because it is believed that the source of those tissues cannot be harmed because they are anonymous, the impending loss of anonymity will suddenly create a host of human research subjects suddenly "at risk" but for whom no institutional protections exist since the research is often conducted outside the purview of the institutional review boards whose charge it is to protect such subjects. The research is outside of their purview precisely because the Federal Regulations[40] exempt such research from IRB review and consequently from any process of informed consent on the part of the sources of those tissues.

Research Interests in the Medical Record 

It is nowadays difficult to discuss the conduct of biomedical research outside of the context of commercial interests[41]. The above scenario raises deep problems about individuals' right to privacy, who "owns" the medical record and hence who can profit from it, and what obligations are owed to patients. High speed genetic testing, as I have argued will make these records even more valuable and we can expect large numbers of interests to line up at the electronic feeding trough in the future. It is difficult any more to distinguish between pure "research" interest in these electronic medical records and the resultant commercial interests since scientists themselves have discovered their own financial interests in exploiting the knowledge they produce, even if at public expense.

Nevertheless, if we can abstract for a moment from these commercial interests, we find behind them a genuine interest on the part of biomedical research to exploit for the public good the value of genetics and the wealth of information genetic testing will produce in the electronic medical record. After all, if knowledge is commercially valuable, it is ultimately so because that knowledge will contribute to the practice of medical and/or public health. Thus researchers claim that apart from the commercial exploitation of medical records, they should have access for the purpose of generating generalizable knowledge of benefit to all. Thus if we clear away the obfuscation of market interests, we find at bottom a fundamental conflict between an individual patients expectation of, if not right to, the privacy of their medical record against society's interest in exploiting the information contained therein for the benefit of all. It is fundamentally a value judgment how we settle this conflict.

This raises one of the more interesting questions in how we evaluate problems raised by complex new technologies. Typically, the ones who best understand these technologies are the ones who seek to exploit them, for whatever purposes. The individual patients, however, who have an interest--whether as a matter of right or a matter of protection from harms--generally have neither the background, experience nor knowledge to fully appreciate the possibilities of such technologies and how they may be exploited. Thus, who is going to speak for those who essentially have no representation in such decisions? Is it sufficient for the managers of managed care, the scientists and the CEOs of various biotechnology firms to set their own standards for protection of patient confidentiality and privacy, or is this tantamount to simply letting the fox guard the chicken coop?

The Darker Side 

On August 21, 1996, the New York Times carried a story reporting that New Jersey law enforcement officials arrested 12 alleged members of the Genovese crime family on charges of racketeering and conspiracy for infiltrating Tri-Con Associates, a health care corporation which "arranged and managed group medical, dental and optical programs for employers and unions with networks of health-care providers"[42]. In addition to submitting false claims, inflating fees and laundering money--usual mob activities--prosecutors were very worried that because Tri-Con had access to patient records, that these records might be used for the purpose of blackmail and extortion. Robert Buccino, of the Organized Crime Bureau of New Jersey was quoted, saying "They did have access to medical records, and it could be used for extortion and other criminal purposes." To my knowledge, they found no further evidence of such activities, but if not at Tri-Con, we will see other examples of this in the future.

The possibility of individuals gaining access to medical records, and particularly medical records replete with detailed genetic information, for the purpose of exploiting that information for personal gain and against the interests of the patient is a scary prospect. For here, not only are the patient's rights to privacy and confidentiality violated, but their interests may be directly harmed in a variety of ways. We do not need a take over of an MCO by the mob for this to happen. We need only individuals who have access to medical records and the willingness to exploit this access.

Conclusion 

High speed genetic testing, in whatever form it eventually comes to our doctors' offices, promises to radically transform the practice of medicine. It can be used to great medical benefit of all persons. At the same time, however, the social conditions in which we presently live are not ripe for exploiting this technology without causing as much if not more harm to the very individuals we seek to medically benefit. Until we can resolve the underlying contradictions in health care financing and access to medical care; until we can come to some consensus about the limits of using genetic information in employment; until we can establish a national policy on the privacy and confidentiality of electronic medical records; until we can empower individual patients to control the uses of their medical records; and until we can safeguard electronic medical records from their unscrupulous use by criminal interests; the volumes of genetic information that will be liberated by these technologies promises to harm as much as to help.

Can we responsibly develop and use these genetic technologies before we solve these underlying problems, or will we only be forced to solve them when wide spread genetic testing hits the fan of commercial exploitation? It is difficult to be optimistic. In spite of commitment of 5% of the Human Genome Project to the study of the Ethical, Legal and Social Implications (ELSI) of genetics, the problems genetics raises are still with us. Has ELSI simply been ethical window dressing--a bold but in some areas ultimately futile attempt to harness this technology for the good of the patients themselves? Does our collective failure to so far to address the problems of insurance, employment and privacy in a systematic way absolve the researchers, physicians and corporations who develop this technology of further responsibility for the harms that will inevitably result from its wide spread dissemination and use? If we cannot translate even the basic recommendations of the ELSI Task Force on Genetics and Insurance into a coherent policy, then what purpose does this ethical reflection serve in advance, if we will only wait until a large enough number of persons are harmed by the introduction of genetic technology to routine medical practice?

In establishing ELSI, scientists and policy makers sought the advice of a broad range of disciplines to help formulate policy in advance of what was foreseen to be the revolutionary impact of genetics on all of our lives. That advice has been forthcoming in spades. Much remains controversial, but the road ahead is fairly clearly charted, if we have the will to address these issues now. But if we fail to have the will to make the changes necessary to make genetic technologies safe for society, what then? What responsibility do the scientists and physicians who have profited enormously from this three billion dollar project have to the public who has paid for it and yet stands equally to be harmed as well as helped by it at the same time? But alas, so many of the scientists have lost their impartiality, have they not, by investing in development of the technology their work has made possible? It would be unrealistic for us to hope that the scientists who have so invested in these projects would, as a matter of principle, refuse to complete them until our social conditions have been transformed sufficiently to make these technologies genuinely safe for the public. Technology appears to have an inevitability about it that seems to drive itself into our lives and transform our society and self understanding. But is it really the technology that is the driving force, or is not just the thirst for profits really fueling the engine of technological change?

Footnotes: 

[1] See for instance R. Cook-Deegan, The gene wars: Science, politics, and the human genome project (New York: W. W. Norton, 1994); Walter Gilbert, "A vision of the grail," in Daniel J. Kevles and Leroy Hood, eds., The code of codes: Scientific and social issues in the Human Genome Project (Cambridge: Harvard University Press, 1992), pp. 83-97; Daniel Koshland, "Sequences and consequences of the human genome," Science 246 (October 13, 1989): 189; James D. Watson, "The Human Genome Project--past, present, and future," Science 248 (April 6, 1990): 44-49.

[2] See Richard A. Gibbs, "Pressing ahead with human genome sequencing," Nature Genetics 11 (October, 1995): 121-125.

[3] Genebank is a database which includes a constantly updated list of known genetic sequences of human both human and non human genes. Genebank may be accessed at the following URL: http://www.ncbi.nlm.nih.gov/Web/Genbank/index.html. The National Center for Biotechnology Information also maintains a search engine that gives access to a wide variety of genetic information and can be accessed at URL: http://www.ncbi.nlm.nih.gov/.

[4] This is largely the subject of the Human Genome Diversity Project, an international effort to collect DNA samples from every ethnic population around the globe. See L. Roberts, "A genetic survey of vanishing peoples," Science 252 (1991): 1614-1617; and The North American Committee of the Human Genome Diversity Project. Answers to frequently asked questions about the Human Genome Diversity Project. The HGDP has engendered a great deal of controversy, see for instance Rural Advancement Foundation International. Indigenous people protest U.S. Secretary of Commerce patent claim on Guaymi cell line. Press release; October 26, 1993.; B.-J. Crigger, "The 'vampire project'," Hastings Center Report (January-February, 1995): 2; Rural Advancement Foundation International - USA, "Gene hunters in search of "disease genes" collect human DNA from remote island populations," RAFI Action (Fall, 1995): 1-4; C. Macilwain, "Tribal groups attack ethics of genome diversity project," Nature 383 (September 19, 1996): 208.

[5] See James D. Watson, "A personal view of the project," in Daniel J. Kevles and Leroy Hood, eds., The code of codes: Scientific and social issues in the Human Genome Project (Cambridge: Harvard University Press, 1992), pp. 164-176. The social, scientific and even moral worth of the project has also been called into question on a number of fronts. See, for instance, Ruth Hubbard and Elijah Wald, Exploding the gene myth (Boston: Beacon Press, 1993); and R. C. Lewontin, "The dream of the human genome," New York Review of Books (November 19, 1992): 31-40.

[6] Online Mendelian Inheritance in Man, OMIM (TM). Center for Medical Genetics, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD), 1996. World Wide Web URL: http://www3.ncbi.nlm.nih.gov/omim/.

[7] See Marleen Decruyenaere, Gerry Evers-Kiebooms, and Herman Van den Berghe, "Perception of predictive testing for Huntington's disease by young women: preferring uncertainty to certainty?," Journal of Medical Genetics 30 (1993): 557-561. For a discussion of the ethical implications of pre symptomatic testing, see Marlene Huggins, Maurice Bloch, Shelin Kanani, Oliver W. J. Quarrell, Jane Theilman, Amy Hedrick, Bernard Dickens, Abbyan Lynch, and Michael Hayden, "Ethical and legal dilemmas arising during predictive testing for adult-onset disease: The experience of Huntington disease," American Journal of Human Genetics 47 (1990): 4-12.

[8] See Angus Clarke, "Is non-directive genetic counseling possible?," Lancet 338 (October 19, 1991): 998-1001.

[9] See Gina Kolata, "Breaking ranks, lab offers test assessing cancer risk," New York Times (April 1, 1996): A1. See also Paul H. Silverman, "Commerce and genetic diagnostics," Hastings Center Report 25 Suppl. (1995): S15-S18.

[10] C. Anderson, "Genome project goes commercial. [News]," Science 259 (Jan 15, 1993): 300-302; Anonymous, "Capitalizing on the genome [editorial]," Nature Genetics 13 (May, 1996): 1-5; Henry T. Greely, "Conflicts in the biotechnology industry," Journal of Law, Medicine and Ethics 23 (Winter, 1995): 354-359; ; Richard Stone, "Biotech sails into heavy financial seas," Science 260 (1993): 908.

[11] For a good introduction to the methods of genetic analysis see Mapping the genome. Los Alamos Science, Number 20 (1992), which has individual chapters on gene mapping, PCR, and gene sequencing.

[12] See Nicholas Wade, "Where Computers and Biology Meet: Making a DNA Chip," New York times (April 8, 1997).

[13] For a complete description of the process by which the probes are constructed see Stephen P. A. Fodor, J. Leighton Read, Michael C. Pirrung, Lubert Stryer, Amy Tsai Lu, and Dennis Solas, "Light-directed, spatially addressable parallel chemical synthesis," Science 251 (February 15, 1991): 767-773; and A. C. Pease, D. Solas, E. J. Sullivan, M. T. Cronin, C. P. Holmes, and S. P. A. Fodor, "Light generated oligonucleotide arrays for rapid DNA sequence analysis," Proceedings of the National Academy of Sciences 91 (1993): 5022-5026. For a good "layman's" explanation see Sandeep Junnarkar, "'GeneChip encodes DNA on silicon," New York Times (March 15, 1997). See especially the diagrams in the sidebar which provide a helpful illustration of the how oligonucliotide probes work.

[14] For a good overall explanation of the process, see Michael J. Kozal, Nila Shah, Naiping Shen, Robert Yang, Raymond Fucini, Thomas C. Merigan, Douglas D. Richman, Don Morris, Earl Hubbell, Mark Chee, and Thomas R. Gingeras, "Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays," Nature Medicine 2 (July, 1996): 753-759.

[15] See D. J. Lockhart, H. Dong, M. C. Byrne, M. T. Follettie, M. V. Gallo, M. S. Chee, M. Mittmann, C. Wang, M. Kobayashi, H. Horton, and E. L. Brown, "Expression monitoring by hybridization to high-density oligonucleotide arrays," Nature Biotechnology 14 (December, 1996): 1675-1680.

[16] ibid.

[17] See R. J. Lipshutz, D. Morris, M. Chee, E. Hubbell, M. J. Kozal, N. Shah, N. Shen, R. Yang, and S. P. A. Fodor, "Using oligonucleotide probe arrays to access genetic diversity," Biotechniques 19 (September, 1995): 442-447.

[18] Wade supra note 12.

[19] See Radoje Drmanac, Ivan Labat, Ivan Brukner, and Radomir Crkvenjakov, "Sequencing a megabase plus DNA by hybridization: theory of the method," Genomics 4 (1989): 114-128.

[20] See the Affymetrix press release of October 24, 1994.

[21] For a source of materials on the Ethical, Legal and Social Implications of the Human Genome Project, see E. T. Juengst, "The human genome project and bioethics," Kennedy Institute of Ethics Journal. 1 (Mar, 1991): 71-74; E. T. Juengst and J. D. Watson, "Human genome research and the responsible use of new genetic knowledge," International Journal of Bioethics 2 (Apr-Jun, 1991): 99-102. ELSI resources are also available at the ELSI page; see also the Genetics and Public Issues page maintained by the National Center for Human Genome Research; see also the National Human Genome Research Institute.

[22] Task Force on Genetic Information and Insurance, Genetic information and health insurance: Report of the task force on genetic information and health insurance. (Washington, D.C.: National Institutes of Health, 1993).

[23] George J. Annas, "Privacy rules for DNA databanks: Protecting coded 'future diaries'," Journal of the American Medical Association 270 (November 17, 1993): 2346-2350.

[24] This leads to the unfortunate consequence in genetic testing and counseling that many individuals will seek testing "off the record," traveling to distant clinics and paying cash for the testing and counseling in order to insure that the results of the tests do not become a part of their medical record. Counselors typically inform prospective clients that they may be required to provide the results of any genetic tests to insurers and employers, if asked. The purpose of seeking the testing "off the record," however, is to precisely avoid getting caught if they choose not to divulge the results of genetic tests. This places those who perform genetic tests and counselors in the position of at least aiding in consumer fraud.

[25] For a defense of the insurance industry's practices of underwriting in light of genetic testing, see R. Pokorski, "Use of genetic information by private insurers," in T. Murphy and M. Lappe, eds., Justice and the human genome project. (Berkeley: University of California Press, 1994), pp. 91-109. For a defense of reforming health insurance policy see Kathy L. Hudson, Karen H. Rothenberg, Lori B. Andrews, Mary Jo Ellis Kahn, and Francis S. Collins, "Genetic discrimination and health insurance: An urgent need for reform," Science 270 (October 20, 1995): 391-393.

[26] See L. Gostin, "Genetic discrimination: the use of genetically based diagnostic and prognostic tests by employers and insurers," American Journal of Law & Medicine 17 (1991): 109-144.

[27]See Karen Rothenberg, Barbara Fuller, et al., "Genetic information and the workplace: Legislative approaches and policy challenges," Science 275 (March 21, 1997): 1755-1758; American Medical Association Council on Ethical and Judicial Affairs, "Use of genetic testing by employers. [Council report]," Journal of the American Medical Association 266 (Oct 2, 1991): 1827-1830.

[28]The conflicts of interest and resultant compromise of medical care in the managed care industry is well documented. See for instance Mark Green, What ails HMOs. (A report by the Public Advocate for the City of New York, January 1996); Linda Emanuel, "Bringing market medicine to professional account," Journal of the American Medical Association 277 (March 26, 1997): 1004-1005; Martin Gottlieb, Kurt Eichenwald, and Josh Barbanel, "For biggest hospital operator, a debate over ties that bind," New York Times (April 6, 1997); John H. McArthur and Francis D. Moore, "The two cultures and the health care revolution," Journal of the American Medical Association 277 (March 26, 1997): 985-989; Elisabeth Rosenthal, "The HMO catch: when healthier isn't cheaper," New York Times (March 16, 1997)

[29] See Francis M. Giardiello, Jill D. Brensinger, et al., "The use and interpretation of commercial APC gene testing for familial adenomatous polyposis," The New England Journal of Medicine 336 (March 20, 1997): 823-827.

[30] See, for instance, Sheri Alpert, "Smart cards, smarter policy: medical records, privacy, and health care reform," Hastings Center Report 23 (Nov-Dec, 1993): 13-23.

[31] Dorothy Nelkin and M. Susan Lindee, The DNA mystique: The gene as a cultural icon (New York: W. H. Freeman and Company, 1995); see also the critique offered by Ruth Hubbard and Elijah Wald, Exploding the gene myth (Boston: Beacon Press, 1993).

[32] "What I may see or hear in the course of the treatment or even outside of the treatment in regard to the life of men, which on no account one must spread abroad, I will keep to myself holding such things shameful to be spoken about." From Hippocrates, "Oath of Hippocrates," in Warren T. Reich, eds., Encyclopedia of bioethics (New York: Simon & Schuster MacMillan, 1995), p. 2632.

[33] George J. Annas, Leonard H. Glantz, and Patricia A. Roche, The genetic privacy act and commentary (Boston: Boston University School of Public Health, 1995).

[34] See Alexander M. Capron, "Protection of research subjects: Do special rules apply in epidemiology?," Journal of Clinical Epidemiology 44 Suppl. I (1991): 81s-89s. For a more detailed discussion of the ethical aspects of privacy and the medical record, see Sheri Alpert, op cite note 25.

[35] See Mark Green, Compromising your drug of choice: How HMOs are dictating your next prescription. (A report by the Public Advocate for the City of New York, December 1996).

[36] Pharmaceutical firms may also seek to use patient records for various marketing purposes as well. See for instance Michael W. Miller, "Patients' records are treasure trove for budding industry," Wall Street Journal (February 27, 1992); Elyse Tanouye, "Merck to exploit Medco's database," Wall Street Journal (August 4, 1993).

[37] See Gina Kolata, "When patients' records are commodities for sale," New York Times (November 15, 1995): A1, C14.

[38] See Lisa L. Dahm, "Using the DNA profile as the unique patient identifier in the community health information network: legal implications," The John Marshall Journal of Computer & Information Law 15 (Winter, 1997): 227-275, who recommends using "RFLP" profiles as the unique patient identifier.

[39] It is presently anticipated that because of the problems associated with increasing cooperation among various health care organizations, including hospitals, MCOs, and other providers, that medical records will soon be organized into large electronic databases, or Community Health Information Networks (CHIN) as they are called, accessible across individual places of health care delivery. Such large integrated databases while eliminating the fragmentation of data on individual patients amongst a number of offices and institutions, will make it correspondingly easier for others, both legitimate and illegitimate to access patient records by centralizing them. See Francoise Gilbert, "Selected legal issues in the use of community health information networks," Healthcare Information & Management Systems Sociology 9 (1995): 43-52.

[40] See the Code of Federal Regulations: 45CFR Part 46.101(b)(4) and 46.102(f).

[41] For a small sampling of the problem, see Lawrence M. Fisher, "Cancer-research venture announced," New York Times (August 21, 1996): C6; M. Wadman, "Drug company 'suppressed' publication of research [news]," Nature 381 (May 2, 1996): 4; Anonymous, "Gene donors' rights at risk," Nature 381 (May 2, 1996): 1; Anonymous, "Capitalizing on the genome [editorial]," Nature Genetics 13 (May, 1996): 1-5; Philip J. Hilts, "Researcher profited after study by investing in cold treatment," New York Times (February 1, 1997); R. S. Fersko and M. J. Connolly, "Intellectual property issues in a clinical trial: A corporate perspective," Quality Assurance 1 (June, 1992): 237-248; G. J. Annas, "Outrageous fortune: selling other people's cells," Hastings Center Report 20 (1990): 36-39; Ruth McNally and Peter Wheale, "Biopatenting and biodiversity," The Ecologist 26 (1996): 222-228; C. Anderson, "Genome project goes commercial. [News]," Science 259 (Jan 15, 1993): 300-302; Richard Stone, "Biotech sails into heavy financial seas," Science 260 (1993): 908.

[42] See Selwyn Raab, "N.J. officials say mob ring infiltrated health care," New York Times (August 21, 1996): A1, C19.