The Changing Moral Focus of Newborn Screening: An Ethical Analysis by the President's Council on Bioethics

Chapter Three: The Future of Newborn Screening

In the previous chapter, we considered certain urgent ethical dilemmas that confront us today as the states proceed to expand their mandatory newborn screening programs. In this chapter, we lift our eyes from the present scene and contemplate how newborn screening may continue to evolve as the age of genomic medicine advances. Over the next years and decades, anticipated developments in the technology and the practice of medicine are likely to alter the landscape of newborn screening entirely, ushering in a potentially vast increase in the kinds and amounts of genetic data that can be routinely collected upon the birth of a child.1 It is quite possible that today’s debates over whether to add this or that rare disorder to a uniform screening panel will be swamped, in the context of genomic medicine, by a radically more expansive approach to genetic screening. It is the burden of this chapter to sketch some of the possible consequences for newborn screening and to outline the serious ethical dilemmas that we are likely to face in the future.

This chapter has three parts, addressing the following topics: first, newborn screening in the age of genomic medicine; second, the case for newborn profiling; and third, the case for caution.

I. Newborn Screening at the Dawn of the Genomic Era

The completion of the Human Genome Project in 2003 signaled the beginning of the age of genomic medicine. With the full mapping of the human genome, researchers are increasingly able to pinpoint errors in genes that cause or contribute to a multitude of conditions, from rare genetic disorders to common illnesses. On the basis of comprehensive genomic knowledge, it is believed that physicians of the future will be able to tailor diagnosis and treatment to the unique genetic profile of the individual patient, thereby eliminating much of the guesswork of traditional “one size fits all” medical practice.

To achieve its full potential, personalized medicine will require physicians to gather large amounts of genetic information from their patients. The National Human Genome Research Institute (NHGRI) has announced the goal of reducing the cost of sequencing an individual human genome first to $100,000 and then to $1,000. At this last price point, thought to be reachable by 2014, an individual’s full genome could be added to his or her medical file as part of routine medical care—to supplement and in some ways to supersede the patient’s family medical history. The $1,000 genome may arrive sooner than even this optimistic projection would suggest. In 2007, the complete genome of geneticist and co-discoverer of the double helix James D. Watson was sequenced at a cost of about $2 million;2 in the fall of 2008, a company in California announced plans to begin offering complete human genome sequences for $5,000, starting in the spring of 2009.3

In the meantime, it is already feasible, using “gene chips,” microbeads, and other state-of-the-art multiplex technologies, to test an individual’s DNA for the presence of hundreds of thousands of distinct single nucleotide polymorphisms (SNPs), which are minute variations in the DNA sequence that can affect how (or correlate with other DNA variations that affect how) the individual develops diseases and responds to pathogens, drugs, vaccines, and so forth.4 Already, a handful of private companies are offering, for as little as $399, to check your genome for known variations believed to correlate with particular traits, conditions, and susceptibilities.5 Clearly, the genomic era is already upon us.

Rapid medical and technological progress aided by the Human Genome Project is challenging both the practice and the principles of newborn screening. As mentioned, most babies born today in the United States are screened at birth for between thirty and fifty genetic disorders, primarily by using MS/MS to detect abnormal levels of metabolites in the infant’s blood. At the same time, the National Institute of Child Health and Human Development (NICHD) is spearheading efforts to move beyond such limited, phenotypic methods of newborn screening toward DNA-based platforms that can “offer enormous opportunities to identify staggering numbers of potentially pathogenic mutations in a very large number of disease-associated genes.”6 Many competent observers expect that, in the not too distant future, simple and inexpensive DNA-based multiplex platforms will be the standard instruments of newborn screening in most states (supplemented with phenotypic testing for conditions that require it).7

In 2006, Duane Alexander, Director of the NICHD for more than two decades and thus one of the nation’s leading voices in pediatric medicine, coauthored an article with his colleague Peter van Dyck offering their “vision of the future of newborn screening.”8 In that article, Alexander and van Dyck refer to the principle that “it is appropriate to screen only for conditions for which effective treatment already exists” as a dogma that “dooms us to continued ignorance and unavailability of treatment because affected individuals are not identified until they exhibit symptoms, too late for effective preventive interventions to be tested or applied.”9 They call for the development and implementation of DNA-based multiplex platforms that can be used to screen newborns for “virtually all target conditions with one test system.”10 More fundamentally, in their view every medically significant genetic marker should be assumed to be screenable except those specifically excluded on a case-by-case basis.11 Assuming that in a matter of years or at most decades the Human Genome Project will bear fruit in the form of affordable whole-genome sequencing or at least affordable multiplex SNP genotyping, this vision seems a plausible picture of a not-too-distant future in which infants are routinely screened at birth for almost all medically significant genetic markers (with a few conditions deliberately excluded), to be treated immediately when possible, and otherwise to be enrolled in registries to await trials of experimental therapies. Personalized genomic medicine will then start from the moment of birth, as the pediatrician will be in possession of a complete map of each young patient’s known genetic defects, vulnerabilities, and susceptibilities. In what follows, we shall denote this vision of a vastly expanded screening program by the phrase “newborn profiling.”12

Thus, in contemplating the future of newborn screening, Alexander and van Dyck are calling for the old “dogma”—“screen only if you can effectively treat”—to be superseded by a new principle—“screen unless there is a compelling reason not to screen.” Such a radical change in the ethical framework of newborn screening might seem far-fetched today, but in some ways the ground for it has already been prepared by the ACMG in its 2005 report. As described in the preceding chapter, the ACMG report’s recommended expansion in newborn screening quietly incorporates the principle that all conditions that can be detected by multiplex assay should be included in the mandatory screening panel, regardless of whether or not they meet the traditional Wilson-Jungner criteria. The fact that, in the ACMG report, this principle led to the inclusion of only a handful of rare disorders detectable by MS/MS should not obscure the fact that the stage has been set for a truly vast expansion in multiplex newborn screening, once DNA-based assays become widely available and affordable. Therefore, in the face of a possible future where full-scale newborn profiling is routine, it is essential that we consider both the promise and the peril of that prospect. In the remainder of this chapter we look at each in turn.

II. The Case for Newborn Profiling

Given that the current debate is mostly about whether to add this or that disorder to the limited panel of conditions for which newborns are routinely screened, why should we believe that in the future the default practice could be to screen all newborns for every known genetic abnormality? The short answer is this: because the logic of personalized medicine and of technological progress will inexorably demand it.

A.  The Logic of Personalized Medicine and Technological Progress

In 2001, Francis Collins, who led the Human Genome Project from 1993 to 2008, described what genomic medicine would look like in its earliest stage:

By the year 2010, it is expected that predictive genetic tests will be available for as many as a dozen common conditions, allowing individuals who wish to know this information to learn their individual susceptibilities and to take steps to reduce those risks for which interventions are or will be available. Such interventions could take the form of medical surveillance, lifestyle modifications, diet, or drug therapy. Identification of persons at highest risk for colon cancer, for example, could lead to targeted efforts to provide colonoscopic screening to those individuals, with the likelihood of preventing many premature deaths.13

Collins’ example illustrates the powerful intuitive appeal of personalized genomic medicine. Colonoscopy is normally recommended to begin at age fifty, but with a family history of colon cancer it is recommended to begin at forty years or earlier. But as geneticists discover correlations between particular combinations of SNPs and elevated risk of colon cancer, it will increasingly be possible to adjust the time at which colonoscopy should commence to the specific genome of the patient, thereby catching many cancers at an earlier, treatable stage. In principle, the same sort of adjustment of routine screening schedules will be possible when screening for other cancers, tremendously improving the odds of detecting and eliminating those cancers before they turn deadly. As renowned obstetrician-gynecologist Alan Guttmacher and colleagues put it, “genomics-based knowledge and tools promise the ability to approach each patient as the biological individual he or she is, thereby radically changing our paradigms and improving efficacy.”14

The drive toward unlimited expansion of newborn screening will also be fueled by technological progress, which has given us—in MS/MS—a method of screening for dozens of metabolic disorders at once, and which will soon deliver—in the form of DNA-based multi-array platforms—the ability to screen whole genomes for tens or hundreds of thousands of medically significant markers. Some observers believe that a “technological imperative” in modern society (combining a desire for commercial profit with a belief that “knowledge is power” and that “if we can do it, we should”) makes it inevitable that maximal use of genomic information will become part of the medical practice of the future.15

Once personalized genomic medicine becomes standard medical practice for adults, the logic of providing physicians with this powerful tool earlier and earlier in the patient’s life may prove inescapable. Even if cancers, for example, are relatively rare in children and adolescents, why wait until adulthood to uncover susceptibilities and vulnerabilities that could well be countered by changes in diet and life habits (to say nothing of prophylactic therapies) at an early age?16 As Collins suggests, “with increasing genetic information about common illnesses, this kind of risk assessment will become more generally available, and many primary care clinicians will become practitioners of genomic medicine…”17 Because so many of our habits are formed in childhood, there will be compelling reasons for pediatricians to become genomic practitioners as well. To fulfill its promise of predictive and preventive as well as personalized care, genomic medicine will push the point of data collection to the moment of birth—if not earlier.

B.  The Benefits of Biobanking

Biobanks, which are huge repositories of tissue samples or health information that interlink human genotypes with lifelong medical histories, could help us make use of the large quantities of genetic data collected from newborns.18 Biobanks at present are typically considered to be research enterprises, but, under the rubric of genomic medicine, it seems likely that in the future they will more and more become a tool for the clinician, a sort of “family history” writ large. It will be crucial not only to collect genotypic data from a large number of patients, but to correlate these data with exact medical histories recorded over many years.19 Most genetic determinants of disease are likely to be complex and polygenic, and the more these cross-linked databases are mined for significant correlations, the more we will learn about each patient’s differential risks and susceptibilities.20

Here, too, the logic of personalized medicine dictates that the collection of genotypic data and its correlation with individual medical, environmental, and lifestyle histories should cover the whole human lifespan, not excluding adolescence, childhood, birth, and even gestation in the womb.21 Moreover, the day of their birth is arguably the most convenient opportunity to enroll children, with the cooperation of their parents, in the comprehensive data-gathering system on which their personalized medical care will be predicated. In fact, pediatric biobanks are already being established in this country, and it stands to reason that the most powerful and useful form of such databases would include comprehensive genotypic data and medical histories collected from infants starting at birth or even in utero.22

The hope of finding a cure for rare and as yet untreatable genetic disorders will provide a powerful incentive for comprehensive newborn profiling. Disorders that afflict only a handful of persons each year are more difficult to study than more common diseases whose victims are easy to locate and study. An obscure illness for which there is as yet no treatment is more likely to be elucidated and ameliorated or cured if newborn screening gives the medical community an accurate picture of the prevalence of the disorder as well as early access to as many of its sufferers as possible. Genomic medicine offers a compellingly systematic approach to the search for treatment of such illnesses, including the following methodical steps: comprehensive genetic profiling at birth, followed by enrollment of all afflicted patients in a biobank of genotypic data; careful study of the course of the illness in each patient, with all significant medical histories entered in the biobank; and finally, when innovative therapies become available, easy access to pools of potential research subjects, to be contacted and enrolled in experimental trials if they are willing. Surely it will be seen to be in the patients’ interests, broadly understood, to push their incurable genetic ailments into the column of treatable illnesses, even if no actual treatment is available at the time of their diagnosis.

C.    The Psychosocial Consequences of Testing Positive: A Silver Lining?

With comprehensive screening, there is hope that the psychosocial consequences of testing positive for a genetic ailment will be less severe. When knowledge of genetic abnormalities is rare, the news that one carries a dangerous and defective gene is potentially devastating. It can entail debilitating anxiety, depression, and despair, not to mention stigmatization and discrimination by others. This is one of the strongest reasons for protecting the individual’s right of informed consent with respect to genetic testing, a right that is admittedly compromised when parents (or state governments) make the decision to have children genetically screened.23

But a case can be made that, with the full flourishing of genomic medicine and the routine gathering of thousands of data points from every human genome, the stigma attached to most genetic defects will largely dissipate, and along with it some of the most severe psychological sequelae. It will be better understood then that every one of us, without exception, carries a multitude of minute genetic variations, some of them favorable to health and happiness, others less auspicious. The sense that we are all in the genetic lottery together, and no one is simply a winner or a loser, may well provide the best foundation for a healthy and realistic attitude toward the vicissitudes of inheritance. This is not to say that the discovery that one carries a fatal or incapacitating gene defect, like the trinucleotide repeats that cause Huntington’s, will be easy to bear, but it does suggest that a comprehensive transformation of American medicine in the genomic direction will render genetic disease as a whole less horrifying and isolating.

D.  The Support of Parents and Advocacy Groups

Finally, one can anticipate growing pressure from parents and advocacy groups to embrace rapid expansion of newborn screening.24 As Alexander and van Dyck noted in their response to a critical colleague, there is an “almost unanimous preference of parents for knowing the diagnosis in the newborn period.”25 And indeed, studies have consistently shown strong (and growing) public support for genetic screening, especially among parents of children with genetic disorders.26 Parents in the latter group seem to believe that they have a right to know whether their child has a genetic disorder, even if it is untreatable, and they believe that such knowledge is good.27 Notwithstanding the traditional principle that we should screen only for conditions that can be effectively treated, many American parents seem increasingly willing, if not eager, to learn whatever they can about their children’s health, including any genetic abnormalities that can be detected at birth.28

Such parents may be exhibiting a tendency that the French writer Alexis de Tocqueville noticed in Americans as long ago as 1831: He found that Americans are unwitting followers of the French rationalist philosopher, Descartes, in that they tend “to take tradition only as information, and current facts only as a useful study for doing otherwise and better; to seek the reason for things by themselves, and in themselves alone, [and] to strive for a result without letting themselves to be chained to the means.”29 In short, if their child has a problem, American parents simply want to know everything they can about it. That tendency may help to explain why the American public today, when surveyed, often shows more enthusiasm for expanded newborn screening than pediatricians do.30 Whether it is indeed the parents’ right to decide on behalf of their young child that every genetic abnormality should be brought to light, is another question.

It would be difficult to exaggerate the role of patient advocacy groups in pressing for the expansion of newborn screening.31 As March of Dimes Foundation president Jennifer Howse and colleagues put it, “Expansion of [newborn screening] has been driven primarily by a combination of advances in technology and medical treatment, and the sustained advocacy efforts of consumers and voluntary health organizations.”32 University of North Carolina pediatrician Donald Bailey and colleagues noted that, during public commentary on the ACMG’s report, every advocacy group that commented endorsed the uniform screening panel and noted a range of benefits that would result from expanded screening. Moreover, “there was no mention of any risks or burdens of screening other than to discount arguments that conditions for which there is no proven medical treatment for the child should not be included in newborn screening.”33 Parents who discover that their newborn child suffers from a rare genetic illness are quite likely to add their support to groups calling both for universal screening and for increased funding of research to find a cure. Undoubtedly, such vigorous advocacy of newborn profiling makes a good deal of sense under the paradigm of genomic medicine. But it also means that those promoting the agenda of personalized genomic medicine and newborn profiling have a strong and energetic natural ally in the parents of genetically afflicted children and the groups that represent them.

III.  The Case for Caution

We have seen that there are powerful arguments—and potent technological and social forces—favoring the eventual realization of the vision of universal DNA-based profiling of newborns, with all genetic markers of medical interest included by default, and perhaps only a handful of disorders excluded on a case-by-case basis. We now turn to some of the reasons for doubting whether this vision is likely to be realized, and whether—even if it is attainable—the benefits would outweigh the costs. In the long run, it may, in fact, prove impossible to hinder the logic of genomic medicine from assimilating the currently limited practice of newborn screening to its all-embracing paradigm. Nonetheless, even if these future developments turn out to be unstoppable, it would be prudent to remind ourselves of some of the reasons for doubting whether the new regime of maximal screening will be altogether benign. We can at least approach the future with our eyes open, alert for signs of peril amidst the progress.

A. “Personalized Medicine” in the Traditional and Increasingly Rare Sense

As we have seen, there is some plausibility to the view that “the logic of personalized medicine” will inevitably push us in the direction of sequencing everyone’s genome as early as possible, and that lifetime clinical care will eventually consist of personalized prevention and treatment strategies based on a detailed analysis of the patient’s genetic predispositions and susceptibilities. And yet, there is an older and perhaps deeper notion of personalized medicine that is likely to push back against the assumption that genome-based health care will necessarily be better and more personal. In this sense, the personalized medicine that is most meaningful to patients is based on the physician’s knowledge of the patient’s medical and life circumstances and on the trusting relationship between patient and physician.34 Only a crude genetic determinism could lead us to expect that an individual’s decoded genome would ever be an adequate substitute for the physician’s understanding of the whole person entrusted to his or her care. Adding a complete sequence of the genome to everyone’s medical file from birth onward is not likely to replace a significant portion of medical care with algorithmic diagnosis and treatment.

Of course, this is not to say that genomic information will not play a valuable part in future medical care. In some cases, genomic analysis will certainly alert the physician to health risks that might not otherwise be evident from an examination of the patient and from knowledge of the family history. A realistic expectation might be that, for any given health condition, a small minority of patients will benefit from knowledge about genomic risk—and that, with the breadth of information likely to be available, everyone will likely benefit from genomic risk information at some point—but that much of health care will continue to proceed independently of genomic risk profiling.35 On the whole, then, the goal of providing personalized medical care in the older and perhaps more fundamental sense of the term will continue to depend on the character, commitment, and skill of the physician in developing an understanding of the patient as a whole person. In the words of Wylie Burke and Bruce M. Psaty,

[G]enuinely personal health care, as practiced by physicians for centuries, is based on the relationship between patient and physician rather than on any particular technology. Even in the genomic era, the focus on individual patient needs and concerns will remain at the core of health care; and if genetic testing diverts physicians’ attentions away from the specific concerns of the patient, it may interfere with the practice of personalized medicine.36

B.  Doubts About the Power of Genomic Medicine

Although many scientists and policymakers are confident that studies of the human genome will provide a wealth of valuable information about health status and health risk in the near future, not all competent observers agree. In particular, doubts have been expressed about the potential of genomic studies to find markers for susceptibility to the most common diseases afflicting mankind, as opposed to the rare metabolic disorders that are the primary target of newborn screening today.

For example, the population geneticist David B. Goldstein has publicly dissented from the idea that unlocking the human genome will lead to the discovery of common variants that predispose people to various forms of cancer, heart disease, Alzheimer’s, and other common major illnesses. This idea, known as the Common Disease/Common Variant hypothesis, suggests that genome-wide association studies will contribute powerfully to the development of personalized medicine and to the precise tailoring of medical treatment to the patient’s individual susceptibilities to serious illness.37 According to Goldstein, the enormous labor of cataloging all the common genetic variations in the human population as part of the HapMap project has led to the discovery of only a handful of genes that account for a disappointingly small portion of the genetic risk for disease. Goldstein said recently:
 
There is absolutely no question, that for the whole hope of personalized medicine, the news has been just about as bleak as it could be… For schizophrenia and bipolar disorder, we get almost nothing; for Type 2 diabetes, 20 variants, but they explain only 2 to 3 percent of familial clustering, and so on… It’s an astounding thing that we have cracked open the human genome and can look at the entire complement of common genetic variants, and what do we find? Almost nothing. That is absolutely beyond belief.38

In a review of the recent achievements of genome-wide association studies, Goldstein and colleagues wrote the following:

Despite understandable celebration of these achievements, sober reflection reveals many challenges ahead… [F]or most of the traits studied, known variants explain only a fraction of observed familial aggregation, limiting the potential for early application to determine individual disease risk… The ultimate objectives—full descriptions of the susceptibility architecture of major biomedical traits and translation of the findings into clinical practice—remain distant.39

Neil Holtzmann and Theresa Marteau, prominent experts on genetic testing, agree:

It would be revolutionary if we could determine the genotypes of the majority of people who will get common diseases. The complexity of the genetics of common diseases casts doubt on whether accurate prediction will ever be possible... Although we do not contend that the genetic mantle is as imperceptible as the emperor’s new clothes were, it is not made of the silks and ermines that some claim it to be. Those who make medical and science policies in the next decade would do well to see beyond the hype.40

Other experts remain optimistic, while acknowledging that the full benefit of the human genome project will take time to realize.41 Yet it may well be that, for quite some time, detailed knowledge of the human genome will remain primarily useful for the diagnosing of rare genetic disorders rather than for ascertaining a given individual’s susceptibilities to a large number of serious common illnesses.

C.    Newborn Profiling and the Problem of Risks and Benefits

Many of the same concerns that have been expressed in regard to limited expansion of the newborn screening panel would a fortiori be applicable in the case of newborn profiling. Norman Fost’s judgment42 that every genetic disorder is different, and that every screening is an experiment with potentially bad as well as good consequences, would be all the more pertinent in the event of a greatly expanded screening panel. At the very least, we would need to plan for an immensely expanded infrastructure for testing and confirming, sorting out false-positives, counseling families, and assessing the outcomes for the affected children.

In clarifying the possible harms of gathering genetic information pre-symptomatically, it is important to distinguish the different components of the problem:
 

1. First, such information may be clinically valid but not practically useful. Detected genetic variations in the genome may suggest an elevated risk for a condition that never actually develops, and to initiate treatment pre-symptomatically may do the patient more harm than good.43
2. Second, genomic risk information that is assumed to be valid may sometimes turn out to be unreliable—if, for example, it is based on population studies that were too small or that failed to take into account critical non-genetic variables.44
3. Third, there are the psychosocial effects of false positive results and, in the case of true positive results, of adversely labeling the individual as suffering from disease from the moment of birth.45
4. Fourth, there is the danger that screening will lead to a cascade effect—in which genetic risk information of perhaps uncertain validity leads to additional tests and interventions, causing anxiety, extra costs, and even some risk of medical harm.46

If genomic data come to play a large role in the health care of the future, health care systems will have to learn how to manage such data prudently, so as to reveal the information that can potentially benefit the patient while suppressing the information that is likely to lead to net harm.

One example will suffice to show just how complex and elusive are the benefits and harms involved in each component of genetic screening. The case of Duchenne muscular dystrophy (DMD) has been examined with great sensitivity by pediatrician-ethicist Lainie Friedman Ross, whose review of the case we draw on here.47 Newborn screening for DMD is currently being offered to parents at certain hospitals in Ohio as part of a pilot project funded by the CDC.48 DMD is an X-linked degenerative disease of the muscles that affects about one in 3,500 boys. Symptoms usually begin before the age of six and lead to braces, wheelchair dependence, and death before the age of thirty. There is considerable support for newborn screening of DMD even though it does not meet the Wilson-Jungner criteria of having an accepted treatment and an agreed policy on whom to treat. DMD is more common than PKU and its natural history is well understood. But, as Ross writes, “the main concern is whether early diagnosis improves prognosis.”49

One problem is that the standard treatment for DMD with corticosteroids has deleterious side effects and may be inappropriate for younger boys. If treatment is to be delayed until later in childhood, screening at birth may not be justified; some would argue, however, that “avoiding the diagnostic odyssey” is reason enough to screen at birth. Perhaps it would be better to improve pediatricians’ abilities to recognize early symptoms of DMD, for pre-symptomatic identification of a genetic disease might subject the child to stigmatization, discrimination, and unnecessary psychological harm. On the other hand, there are data indicating that early screening is the only effective way to diagnose DMD without considerable delay.

Some experts argue for DMD screening as a way to assist “reproductive decision-making” and “life planning”; but these alleged benefits to the family must be weighed against the potential harms of diagnosing the child months or years before he or she becomes symptomatic, harms that include needless anxiety, disruption of the parent-child bond,50 and the possibility that parents will misuse the information51 or seek out dangerous alternative treatments,52 not to mention the ill effects of false-positives.53 To further complicate the issue, a study by nursing investigator Evelyn Parsons and colleagues found that early diagnosis of DMD caused transient increases in parental distress but no long-term disruption of the parent-child bond.54

Despite the uncertain benefits of screening for DMD at birth, voluntary screening is offered in some countries, usually requiring explicit consent from the parents. In Wales, where informed consent is required, as many as ninety-four percent of parents agree to the screening at birth. In Germany, on the other hand, where voluntary screening is offered between one and twelve months of age, only five percent of parents elect to participate; these differences in parental acceptance of voluntary DMD screening may simply reflect the different circumstances in which the screening is offered.

All in all, it is difficult to judge whether the benefits of newborn screening for DMD outweigh the risks. All we can safely say is that a thorough informed consent process may help parents understand the advantages and disadvantages and make a more thoughtful choice for their infant. Yet multiply this example a hundred or a thousand fold and it is easy to see just how difficult it would be to ask parents to weigh the benefits and harms of a greatly expanded newborn screening panel. Already, when states are screening newborns for at most dozens of heritable disorders, it is impracticable to explain to parents the peculiar risks and benefits of screening for each condition. This task would be all the more daunting if newborn screening for thousands of genetic markers were to become widely available.

D.   Ownership of Genetic Information and the Challenge of Informed Consent

Another problem concerns the ownership of the information gathered by newborn screening and, perhaps in the future, by genomic profiling. To whom does this information properly belong?55 Does it belong to the child alone, to use or to disregard as he or she sees fit once he or she becomes an adult? Or do parents (as some of them seem to believe) have an unlimited right to know the genetic abnormalities of their children? Do physicians have a claim on such information once it exists? Should the state in which the child is born, in the interest of building ever more useful genomic databases, have a presumptive right to “biobank” the child’s genotypic data? If newborn screening detected a range of unfavorable predispositions in the child’s genome, would they amount to “pre-existing conditions” that insurers or even potential employers would be entitled to consult before offering the patient health insurance or employment?56

These questions point to the inevitable tension between newborn screening and the principle of informed consent. Ideally, we would want a momentous decision such as whether to be tested for a serious genetic disorder to be made by the patient, with full understanding of the implications of a positive result. With newborn screening (or with testing later in childhood) we allow the parent (or the state, if the screening is mandatory) to make that decision on the infant’s behalf, but such a transfer of responsibility raises serious ethical questions. The case of Huntington’s disease is instructive here. As noted above, Huntington’s is a late-onset neurological disorder, always fatal, and at present untreatable. It is a dominant and fully penetrant Mendelian disorder, which means that children of a parent who has been diagnosed with Huntington’s have a fifty percent chance of having the gene and the disease themselves. The defective gene has been identified, and there is a definitive DNA-based test for its presence. Nancy Wexler has written with passion and eloquence on the tremendous complexity of the question of whether or not someone at risk for Huntington’s should choose to be tested.57 In the end she concludes that there is no right decision for everyone, and that each person at risk must be allowed to make that decision for him or herself after reaching young adulthood. Although Huntington’s is far from typical of most genetic disorders, Wexler draws some general conclusions: above all, that truly informed consent, including a full psychological appreciation of the ramifications of the information, must be the principle upon which testing programs are designed. Information should not be foisted on someone without permission.58

As there is currently no treatment and no medical benefit from early detection, and a positive diagnosis is so potentially devastating, there has been widespread agreement that Huntington’s is one of the genetic disorders least suitable for routine screening, especially at birth or in early childhood. Alexander and van Dyck, for example, mention it as a prime candidate for exclusion from a greatly expanded newborn screening panel. It is reasonable, in fact, to try to range genetic disorders on a continuum, with those like PKU that unquestionably merit newborn screening (and where the patient’s right of informed consent is properly waived) at one end, and those like Huntington’s that should be left up to the individual at the other end. Yet it is quite likely that the psychological complexity of the personal decision whether to be tested for Huntington’s would also be present in the case of other genetic disorders, even if they are not fully penetrant and invariably fatal. Deciding to screen for a multitude of conditions means taking from children the right to decide these questions for themselves when they have reached an age of sufficient maturity and thoughtfulness. Although nominally exercised for the benefit of the child, routine newborn screening is inevitably in some measure a violation of the child’s right “not to know,” if that were his or her choice. This may be a price worth paying, but it ought to be paid in full awareness of its meaning.59

E.  Genetic Disease and Human Difference

There is also a danger that, with genomic medicine and universal genetic profiling, there will be a blurring of the distinction between genuine disease and mere difference. Only a small proportion of the abnormal gene variants uncovered by newborn profiling will lead directly and inexorably to serious illness. Typically, medically important SNPs will merely correlate (often in combination with other SNPs) with elevated susceptibilities for various medical conditions, and even these correlations will be unpredictable and highly variable, depending on a host of unknown factors. The important discipline of epigenetics teaches that an individual’s actual health will be a complex result of genetic and environmental factors and will not be determined simply by his or her genes.

Yet some people, ignorant of these subtleties, may have an exaggerated idea of the degree to which “bad” genes doom us to dreadful outcomes. Thus, with expanded newborn screening, significant decisions may often be made by parents in light of the identification of genetic “abnormalities” in their children that might end up having no clinical expression at all. Accordingly, it remains an open question whether all this information about the children’s possible medical future will be used for their benefit and will not shape in adverse ways the parents’ view of their children, their worth, and their prospects for happiness. Furthermore, what will it be like for children to grow up in possession of this vast storehouse of genetic information? Will they see it as an entirely beneficial resource, to be used throughout life to improve their health, adjust their habits and lifestyle, and assist their physicians when diagnosis proves elusive? Or will it instead be a burden, weighing them down with a fatalistic sense of limitations and lost possibilities?

F.   Newborn Screening, Genomic Medicine, and Eugenics

Advocates of a broadened notion of “benefit” often extol the utility of newborn screening for helping parents make future reproductive decisions (e.g., adoption, egg or sperm donation, IVF and PGD, amniocentesis and abortion, etc.).60 But this notion of “benefit to the family” is not unproblematic. First, if the putative benefit to the family is to be realized by preventing the birth of siblings with the detected genetic defect, then it would make more sense to screen for the defect prenatally, so that the family is not burdened with even one defective child.61 Putting it so callously highlights the morally problematic character of screening for family planning. If we test an infant, not in the hope of providing treatment for his or her condition, but with a view to making sure that no further children come into the family with the same defect, are we not in effect telling the child that he or she was, in some ways, a regrettable mistake—that, had we known his or her genetic makeup in advance, we would have tried to prevent his or her birth? To the affected child, family planning in this sense means not “limiting the incidence of a defective gene” but “preventing the birth of any more kids like me.” Here the laudable goal of reducing the incidence of genetic disease comes into collision with the wish and the obligation to treat every family member as a being with inherent and equal worth. Moreover, should the uniform panel of conditions be greatly expanded, the propriety of its use for family planning purposes would become even more questionable. Suppose that expanded screening of an infant reveals not a fatal and incurable disease but instead a host of genetic variants, each of which merely confers elevated risk for some condition or other? Who is to say at what point an uncovered defect becomes serious enough to warrant preventing the birth of other children who might carry it? At what point have we crossed the line from legitimate family planning to capricious and morally dubious eugenics?

Indeed, the expansion of newborn screening, however reasonable it may be in itself, seems symptomatic of a broader phenomenon, a sort of Faustian imperative driving the search for genetic knowledge back to earlier and earlier points along life’s path. Neither PGD nor amniocentesis is new, but it seems likely that as time goes on these procedures will come to seem more and more like routine options for prospective parents. Should the information gleaned from these tests seem sufficiently “negative,” some parents will be tempted to discard the “defective” embryo or abort the “defective” fetus, and that choice will no doubt be justified as “good” for someone: for the unborn child, for the unimplanted embryo, for the parents themselves, for the future siblings, or for society at large. In this way, the blameless intention to diagnose and treat our children’s illnesses will have drifted into the rather more sinister project of purifying future generations of their undesirable members. The specter of “eugenicide” hovers over the eagerly anticipated marriage of newborn screening with genomic medicine.

Of course, prenatal genetic testing has been underway for several decades and preimplantation genetic diagnosis for the last decade or more. The development and spread of these techniques can hardly be attributed to the emergence and proliferation of newborn screening.62 Nor can we say that expanded newborn screening (or even full newborn profiling) will necessarily lead to more prenatal or preimplantation testing or that, with the growing acceptance of genomic medicine, parents will be more likely to resort to IVF and PGD (or to amniocentesis and selective abortion) to prevent the birth of genetically inferior offspring—although there are, in this regard, relevant lessons to be learned from the declining incidence of Down syndrome due to selective abortion.63 Genomics could teach us to accept that all of us are born with an assortment of disease susceptibilities, that genetic perfection is therefore unattainable, and hence that prenatal “weeding out” of undesirable genomes is impractical and therefore unnecessary, at least in many instances. Certainly there are today many advocates of expanded newborn screening whose chief concern is with the health and well-being of our born children and who are not advocates of expanded prenatal screening and selective abortion.64 Nonetheless, it is prudent to consider now the possibility that, if genomic profiling of infants at birth were to become standard practice, people might begin to wonder: why wait until birth to make use of such a powerful tool?65

Indeed, the use of multiplex platforms to screen for genetic abnormalities prenatally is not merely a distant promise, it is a reality. Already, a private company and an academic medical center are offering to the public a cutting-edge DNA-based procedure for prenatal identification of dozens or even hundreds of genetic abnormalities while the fetus is gestating.66 The technique, called “microarray-based comparative genomic hybridization,” or “array CGH” for short, examines the DNA of the fetus for minute deletions and insertions that have been linked to disease or deformities.67 The private company, Signature Genomic Laboratories of Spokane, Washington, charges $1,850 for the use of its “Signature PrenatalChip,” and already (as of November 2008) 380 mothers have had their physicians send in DNA samples from their fetuses so that they could be analyzed for the presence of more than seventy genetic syndromes associated with mental retardation, physical malformation, and health and behavioral problems.68 The medical center, Baylor College of Medicine in Houston, offers a similar service at a cost of $1,600 and has already analyzed more than 300 samples of fetal DNA collected from mothers undergoing amniocentesis or chorionic villus sampling. In addition, a federally-funded study is currently evaluating prenatal genetic screening by array CGH in 4,000 pregnancies.69 Should that study be deemed a success, multiplex prenatal screening might soon become a commonplace practice.

It is not at all clear what parents are supposed to do with the information gleaned from such prenatal testing, especially if the identified abnormalities are of questionable or variable clinical significance, as many of them certainly will be. Some couples will presumably consider terminating the pregnancy if the results of DNA testing are sufficiently “bad” (otherwise why pay for such an expensive procedure?). But how bad does the news have to be to tempt the parents to prevent the birth of a “defective” child? Substantial numbers of parents are prepared to terminate a pregnancy if the chromosomal abnormality that causes Down syndrome is revealed by amniocentesis. But what will they do when platforms like the Signature PrenatalChip reveal that their baby might suffer from such varied conditions as Marfan syndrome (a disorder of the connective tissue believed by some physicians to have afflicted Abraham Lincoln), brachydactyly (causing shortness of the fingers and toes), nail-patella syndrome (which may cause poorly developed nails and other deformities), or X-linked short stature (affecting only boys)? What are parents to do when told—as the Signature chip can tell them—that their unborn child has certain DNA deletions believed to confer a slightly elevated risk of schizophrenia? How such information will be used, and whether gathering it can truly be said to benefit the child who undergoes testing, are questions very much worth pondering as genomic medicine progresses. It is hard to judge how widespread prenatal testing for multiple genetic abnormalities will become as these techniques become cheaper, more powerful, and more widely available. But, as the genomic age advances, it would be foolhardy to assume that multiplex DNA screening will modestly confine itself to the period after the baby’s birth.

G.   Genetic Information and the Problem of Self-Knowledge

We presented in the preceding part of this chapter the argument that, with newborn profiling, a sense that everyone has his or her own share of genetic imperfections and that “we are all in this together” might soften the impact of any bad news. The psychosocial burdens, to children as well as to parents, of living with an identified genetic abnormality, would certainly be more widely felt if every couple were to go home from the hospital with a virtual avalanche of information about the genetic defects and susceptibilities of their newborn child. But we then would be in uncharted territory, and it is not at all clear how human beings would adapt to such a massive increase in genetic self-knowledge. More precisely, we are speaking here of a massive increase of self-information, which does not automatically translate into wisdom or genuine self-knowledge.

Such reflections lead, finally, to the deeper and more troubling question of the value of knowledge itself for human happiness. As Nancy Wexler wrote,

The blind seer Tiresias confronted Oedipus with the quintessential dilemma of modern genetics: “It is but sorrow to be wise when wisdom profits not.”70

The presumption of modern science, including medical genetics, has always been that knowledge is fundamentally good for human beings, and that the more we know about ourselves the better we will be able to live the kind of lives we want to live. Yet the truth of this supposition remains in doubt as we lift the lid of the Pandora’s box of our genomic inheritance. Surely there is much information there that, used wisely, will improve our lives and help free us from illness, infirmity, and uncertainty. Yet there is also the possibility that such knowledge will be misused or misinterpreted, that it will tempt us to stigmatize and to discriminate against the genetically unfortunate, and that under its weight some of us will incline toward fatalism and despair.

IV.  On the Necessity and the Limits of Speculation

In the preceding two sections, we have sought to describe the essential elements of the cases for and against newborn profiling. We have marshaled arguments suggesting that the logic of personalized medicine and of technological progress will, in time, yield unequivocal benefits for infants and their parents, for pediatricians and biomedical scientists, and for society at large. But we have also assembled reasons to doubt whether the convergence of genomic medicine and newborn screening will be either as impressive or ultimately as desirable as some of its proponents may believe. We have sought to tether these prognoses to certain known facts about the present: for example, to the plummeting cost of whole-genome sequencing; to the growing number of companies offering affordable gene chips and other DNA-based screening platforms; to surveys that have revealed keen parental interest in genetic information about offspring; and to the impact of amniocentesis on the declining incidence of children born with Down syndrome. Nonetheless, our analysis of the case for and the case against newborn profiling has been an exercise in speculation—one that is both necessary to attempt but also limited in its usefulness for purposes of ethical analysis and policymaking. It is limited insofar as the only definitive test of our prognoses—about both the benefits and the harms of newborn profiling—will be the day to day unfolding of this imagined future. But such speculation is also necessary if our ethical analysis and policymaking are to be well informed and anticipatory. Just as patients need to consider prospectively the possible risks and benefits of a course of treatment or of participation in a clinical trial—risks and benefits that may or may not materialize for any given patient—society at large must consider the long-term potential, for good and for ill, of an expansionist vision of newborn screening. Speculation is always doubtful, but if we do not try to think imaginatively about what the convergence of newborn screening and genomic medicine will bring, we may find ourselves overtaken by a future for which we are ill-prepared. Rather than approach the future blindly, we should—bearing in mind the limited range and sharpness of our prospective vision—opt for awareness and transparency.

Our concern for awareness and transparency has only been heightened by the ACMG report and its aftermath, for it appears that the implications of the report’s recommendations—amounting to a fundamental change in the moral focus of newborn screening—were certainly not brought out in transparent ways for the purposes of public discussion and optimally informed policymaking. Thus, at both the federal and the state levels, we are confronted with the question: What should we do now?

_______________________

EndNOTES

1. And not only genetic data: the medically relevant information that will be collected is likely to embrace both “epigenetics,” the systematic study of heritable but non-genetic factors that influence an organism’s development, and “proteomics,” the systematic study of the full complement of an organism’s proteins (“proteome” being a word formed by analogy with “genome”).

2. The company that sequenced Watson’s DNA is called “454.” See Emily Singer, “The $2 Million Genome,” Technology Review, June 1, 2007.

3. The company is called Complete Genomics, and its website is www.completeg
enomicsinc.com/. See Emily Singer, “Five Thousand Bucks for Your Genome: A New Sequencing Service Could Change the Face of Human Genomics,” Technology Review, October 6, 2008; and Erica Check Hayden, “$5,000 Genome Next Year, Company Promises,” Nature News, October 6, 2008.

4. Gene chips are glass or silicon chips to which are bonded thousands of microscopic spots containing short DNA sequences called oligonucleotides. Each spot serves as a probe to detect the presence of a particular SNP in the target DNA sample. The leading developer of gene chips is a company called Affymetrix. Another approach is to bond the oligonucleotide probes to thousands of microscopic silica beads, which are then randomly deposited onto a glass substrate. The resulting array is then used to check the target DNA sample for particular SNPs. A company called Illumina has pioneered the use of microbeads.

5. See, for example, the websites www.23andme.com and www.decodeme.com, each of which offers to test a client’s DNA for several hundred thousand known SNPs. See Robert F. Service, “Gene Sequencing. The Race for the $1000 Genome,” Science 311 (2006): 1544-1546; and Sarah E. Gollust, et al., “Direct-to-Consumer Sales of Genetic Services on the Internet,” Genetics in Medicine 5 (2006): 332-337. For a thoughtful discussion of some ethical and legal implications of the $1,000 genome, see John A. Robertson, “The $1000 Genome: Ethical and Legal Issues in Whole Genome Sequencing of Individuals,” American Journal of Bioethics 3 (2003): W35-W43.

6. Duane Alexander and James W. Hanson, “NICHD Research Initiative in Newborn Screening,” Mental Retardation and Developmental Disabilities Research Reviews 12 (2006): 301-304, p. 302.

7. Nancy S. Green and Kenneth A. Pass, “Neonatal Screening by DNA Microarray: Spots and Chips,” Nature Reviews Genetics 6 (2005): 147-151.

8. Duane Alexander and Peter C. van Dyck, “A Vision of the Future of Newborn Screening,” Pediatrics 117 Supplement (2006): S350-S354.

9. Ibid., pp. S351, S352.

10. Ibid., p. S351. In his presentation before this Council on June 23, 2006, Dr. Alexander elaborated: “[Tandem mass spectrometry] still doesn’t go as far as we need it to go. And so we’re looking at potential DNA-based systems. If we could have this, we could screen for basically anything we have the gene for… The numbers go into the hundreds. And each time we discover a new gene or a new abnormality of a gene the number of conditions would go up.

        “…[T]hese are things that are coming along and that we are investing in, trying to develop an enhanced capability to screen, and to have a test that is so attractive, so simple, and not too expensive, so that every state will want to use this in their screening program, and no longer will there be this state-to-state variability, so that what you get screened for depends on the state in which you’re born.” (For an online transcript of Dr. Alexander’s remarks, see www.bioethics. gov/transcripts/june06/session5.html.)

11. In their article, Alexander and van Dyck mention only Huntington’s disease (an invariably fatal, as yet untreatable, adult-onset, Mendelian dominant, neurological disorder) as a possible candidate for exclusion. (“A Vision of the Future of Newborn Screening,” p. S353.) It is not clear what other disorders they would put in the same category. At Duane Alexander’s June 23, 2006, appearance before the Council, Council Member Floyd Bloom pointed out that Huntington’s would seem to fulfill “all of the criteria by which you listed the tests that you want to include, even though we can’t treat them.” (See www.bioethics.gov/transcripts/
june06/session5.html.) If a new treatment were developed that, when started early in life, produced even a modest decrease in the morbidity or mortality of Huntington’s disease, it is reasonable to suppose that Alexander and van Dyck would move Huntington’s into the “screen” column.

12. We borrow this informative phrase from the 2005 report, Profiling the Newborn: A Prospective Gene Technology?, published by the Human Genetics Commission of the United Kingdom, available online at www.hgc.gov.uk/.

13. Francis S. Collins, “Implications of the Human Genome Project for Medical Science,” Journal of the American Medical Association 285 (2001): 540-544, pp. 543-544.

14. Alan E. Guttmacher, et al., “Educating Health-Care Professionals about Genetics and Genomics,” Nature Reviews Genetics 8 (2007): 151-157.

15. On the “technological imperative” in modern medicine, see Evan Willis, “The ‘New’ Genetics and the Sociology of Medical Technology,” Journal of Sociology 34 (1998): 170-183; Daniel Callahan, What Price Better Health Care? Hazards of the Research Imperative (Berkeley: University of California Press, 2003);and Arnold Pacey, The Culture of Technology (Cambridge, Massachusetts: MIT Press, 1985).

16. On the other hand, there is some evidence that DNA risk information may be less likely to achieve behavior change than other types of health risk information. See Theresa M. Marteau and John Weinman, “Self-Regulation and the Behavioural Response to DNA Risk Information: A Theoretical Analysis and Framework for Future Research,” Social Science and Medicine 62 (2006): 1360-1368.

17. Francis S. Collins, “Implications of the Human Genome Project for Medical Science,” p. 544.

18. See Dan M. Roden, et al., “Development of a Large-Scale De-Identified DNA Biobank to Enable Personalized Medicine,” Clinical Pharmacology and Therapeutics 84 (2008): 362-369. Some countries are or will soon experiment with large-scale biobanks. One example is the UK Biobank, whose database will cover 500,000 volunteers and will interlink their health, lifestyle, and environmental histories with gene maps of DNA extracted from their blood. See their website at www.ukbiobank.ac.uk. An even more ambitious genomic biobank, intended to include the entire population of Iceland, was inaugurated by an act of the Icelandic parliament in 1998, but has subsequently been scaled back considerably in the face of legal and ethical controversy. See Henry T. Greely, “Iceland’s Plan for Genomics Research: Facts and Implications,” Jurimetrics 40 (2000): 153-191.

19. In the United States, the “Genomics and Personalized Medicine Act of 2007,” sponsored in the 110th Congress by then Senator (and now President-Elect) Barack Obama in order “to secure the promise of personalized medicine for all Americans by expanding and accelerating genomics research and initiatives to improve the accuracy of disease diagnosis, increase the safety of drugs, and identify novel treatments,” calls for the establishment of “a national biobanking distributed database for the collection and integration of genomic data, and associated environmental and clinical health information, which shall facilitate synthesis and pooled analysis of such data.” The text of the proposed legislation may be found online at www.govtrack.us/congress/billtext.xpd?bill=s110-976.

        On the prospects for a large-scale U.S. biobank, see also the March 2007 report of the Secretary’s Advisory Committee on Genetics, Health, and Society, Policy Issues Associated with Undertaking a New Large U.S. Population Cohort Study of Genes, Environment, and Disease (Bethesda, Maryland: U.S. Department of Health and Human Services, 2007), available online at www4.od.nih.gov/oba/sacghs/
reports/SACGHS_LPS_report.pdf.

20. See Kaare Christensen and Jeffrey C. Murray, “What Genome-Wide Association Studies Can Do for Medicine,” New England Journal of Medicine 356 (2007): 1094-1097.

21. However, for a study of the legal and ethical problems posed by the establishment of genotypic databases, see Henry T. Greely, “The Uneasy Ethical and Legal Underpinnings of Large-Scale Genomic Biobanks,” Annual Review of Genomics and Human Genetics 8 (2007): 343-364.

22. See Jocelyn Kaiser, “U.S. Hospital Launches Large Biobank of Children’s DNA” (News of the Week: Genetics), Science 312 (2006): 1584-1585. According to Kaiser, Children’s Hospital of Philadelphia plans “to analyze DNA from 100,000 children and begin searching for links to childhood diseases such as asthma, diabetes, and obesity.” See also Alon B. Neidich, et al., “Empirical Data About Women’s Attitudes Towards a Hypothetical Pediatric Biobank,” American Journal of Medical Genetics Part A 146A (2008): 297-304; and David Kaufman, et al., “Ethical Implications of Including Children in a Large Biobank for Genetic-Epidemiologic Research: A Qualitative Study of Public Opinion,” American Journal of Medical Genetics Part C: Seminars in Medical Genetics 148C (2008): 31-39.

23. See Rony E. Duncan, et al., “‘You’re One of Us Now’: Young People Describe Their Experiences of Predictive Genetic Testing for Huntington Disease (HD) and Familial Adenomatous Polyposis (FAP),” American Journal of Medical Genetics Part C: Seminars in Medical Genetics 148 (2008): 47-55.

24. On psychosocial risks and of comprehensive genomic testing of children compared to genetic testing, see Benjamin Wilfond and Lainie Friedman Ross, “From Genetics to Genomics: Ethics, Policy, and Parental Decision-making,” Journal of Pediatric Psychology, July 22, 2008 (epublication ahead of print), pp. 1-9; and Morris W. Foster and Richard R. Sharp, “Ethical Issues in Medical-Sequencing Research: Implications of Genotype–Phenotype Studies for Individuals and Populations,” Human Molecular Genetics 15 (2006): R45-R49.

25. Some of the same social pressures are at work in driving the states to offer the maximal panel of conditions for newborn screening. As Jeffrey Botkin put it in remarks to the Council on February 3, 2006, “I think there’s a strong social attitude that screening is a good thing, and I see it in the paper every morning with the body scanners. You know, spend 600 bucks. Detect disease early and save your life. Well, there’s no data to support any of that, but it’s part of the social consciousness now, and I think how that’s translated into newborn screening is the strong sense that if you’ve got five tests, that’s good. If you’ve got 20 tests, that’s really terrific, and any self-respecting state, you know, should not have less than 40 tests on its panel.” (Remarks available online at www.bioethics.gov/trans- cripts/feb06/session6.html.)

26. Duane Alexander and Peter C. van Dyck, “Neonatal Screening: Old Dogma or Sound Principle?” (in reply), Pediatrics 119 (2007): 407.

27. For example, Fragile X syndrome, the most common inherited form of mental retardation, does not meet the criteria for routine newborn screening, as there is currently no cure or medical treatment. But in a recent survey of parents of children with Fragile X, large majorities (over ninety percent) favored screening newborns both for the genetic disorder and for carrier status. See Debra Skinner, et al., “Screening for Fragile X Syndrome: Parent Attitudes and Perspectives,” Genetics in Medicine 5 (2003): 378-384.

        Another example: Although professional guidelines recommend against testing minors for adult-onset genetic conditions, medical oncologist and family risk assessment expert Angela Bradbury and colleagues found that, among parents who are carriers of the BRCA mutations (which correlate with increased risk for breast cancer) and their adult children, as many as forty percent supported genetic testing of minors for the mutations. In fact, the adult children viewed such testing even more favorably than their parents, suggesting that succeeding generations are growing more and more comfortable with the idea of routine genetic screening. See Angela R. Bradbury, et al., “Should Genetic Testing for BRCA1/2 Be Permitted for Minors? Opinions of BRCA Mutation Carriers and Their Adult Offspring,” American Journal of Medical Genetics Part C: Seminars in Medical Genetics 148C (2008): 70-77.

28. In a 1998 survey, North American parents (mostly mothers) of children with diagnosed or unconfirmed genetic conditions were asked, “Some conditions can be found at birth through a simple blood test. Sometimes there is no treatment for the child. In these cases, the main purposes of testing the newborn child are to find out if this child has a genetic condition and to let the parents know that they could have another child with the same condition. If you were a parent, would you want your newborn child tested right away so that you could find out if your next child would have a genetic condition?” Seventy-one percent said “yes,” eleven percent said “no,” and eighteen percent said “I don’t know.” See Dorothy C. Wertz and John C. Fletcher, Genetics and Ethics in Global Perspective (Dordrecht, The Netherlands: Kluwer Academic Publishers, 2004), p. 72, and Dorothy C. Wertz, “Ethical Issues in Pediatric Genetics: Views of Geneticists, Parents and Primary Care Physicians,” Health Law Journal 6 (1998): 3-42. The conductors of the survey report that, “in write-in comments, parents said they had a right to know, that the information would help them relate to their child, and that they wanted the information so they could decide about having another child.” (Wertz and Fletcher, Genetics and Ethics in Global Perspective, p. 72)

29. Surveying the general public on these questions, a 2007 report released by the University of Michigan C. S. Mott Children’s Hospital National Poll on Children’s Health found that fifty-four percent of adults endorsed genetic testing of children even if no effective treatment is available, and thirty-eight percent of parents were willing to have their children’s DNA stored in a government DNA biobank. (Report available online at www.med.umich.edu/opm/newspage/2007/
NPCH_4.pdf.)

30. Alexis de Tocqueville, Democracy in America, trans. Harvey C. Mansfield and Delba Winthrop (Chicago: University of Chicago Press, 2000), Volume 2 (1840), Part 1, Chapter 1, “On the Philosophic Method of the Americans,” p. 403.

31. Pediatrician Kruti Acharya and colleagues found that “most physicians support diagnostic genetic testing of high-risk children but are less supportive of expanding newborn screening, particularly for conditions that do not meet the Wilson and Jungner criteria.” See Kruti Acharya, et al., “Pediatricians’ Attitudes Toward Expanding Newborn Screening,” Pediatrics 116 (2005): e476-e484, p. e476.

32. Diane B. Paul, “Patient Advocacy in Newborn Screening: Continuities and Discontinuities,” American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 148C (2008): 8-14.

33. Jennifer L. Howse, et al., “Critical Role of the March of Dimes in the Expansion of Newborn Screening,” Mental Retardation and Developmental Disabilities Research Reviews 12 (2006): 280-287.

34. Donald B. Bailey, Jr., et al., “Changing Perspectives,” p. 275.

35. See Edmund D. Pellegrino and David C. Thomasma, For the Patient’s Good: The Restoration of Beneficence in Health Care (New York: Oxford, 1988); and David C. Thomasma and Judith Lee Kissell, eds., The Health Care Professional As Friend and Healer: Building on the Work of Edmund D. Pellegrino (Washington, D.C.: Georgetown University Press, 2000).

36. On the other hand, the reality of medical practice in the current era is one in which the physician’s time with patients is seriously compromised by various demands, including the intrusive burdens of documentation and paperwork and the financial imperative to “process” as many patients as possible in increasingly abbreviated periods of time. Some argue that genomic medicine and information technology will combine forces to alleviate this often distressing reality: information technologies will simplify and speed the acquisition and processing of clinically relevant information, including genetic information, while the application of genomic medicine itself will involve the use of genetic counselors as aids to the physician and will thereby ease the challenges of today’s one-on-one patient-physician encounters. See Kenneth M. Ludmerer, Time to Heal: American Medical Education from the Turn of the Century to the Era of Managed Care (New York: Oxford University Press, 1999); and Ralph Snyderman and R. Sanders Williams, “Prospective Medicine: The Next Health Care Transformation,” Academic Medicine 78 (2003): 1079-1084.

37. Wylie Burke and Bruce M. Psaty, “Personalized Medicine in the Genomic Era,” Journal of the American Medical Association 298 (2007): 1682-1684, p. 1684. Burke and Psaty continue, “Personalized medicine has always been a component of good medical practice. Genetic tests may provide new tools, but they do not change the fundamental goal of clinicians to adapt available medical tests and technologies to the individual circumstance of their patients. As genetic tests become widely available, personalized medicine will include assisting patients to make wise use of genetic risk assessment, taking into account the cautions discussed in this article. When genetic testing is used, the personalized nature of the care will extend well beyond the patient’s base pair sequences.”

38. On the Common Disease/Common Variant hypothesis, see David E. Reich and Eric S. Lander, “On the Allelic Spectrum of Human Disease,” Trends in Genetics 17 (2001): 502-510; and Neil Risch and Kathleen R. Merikangas, “The Future of Genetic Studies of Complex Human Diseases,” Science 273 (1996): 1516-1517.

39. See Nicholas Wade, “A Dissenting Voice as the Genome Is Sifted to Fight Disease,” The New York Times, September 15, 2008.

40. Mark I. McCarthy, et al., “Genome-Wide Association Studies for Complex Traits: Consensus, Uncertainty and Challenges,” Nature Reviews Genetics 9 (2008): 356-369.
See also James H. Ware, “The Limitations of Risk Factors as Prognostic Tools,” New England Journal of Medicine 355 (2006): 2615-2617.

41. Neil A. Holtzman and Theresa M. Marteau, “Will Genetics Revolutionize Medicine?” New England Journal of Medicine 343 (2000): 141-144.

42. See Alan E. Guttmacher and Francis S. Collins, “Welcome to the Genomic Era,” New England Journal of Medicine 349 (2003): 996-998.

43. Norman Fost, “Ethical Implications of Screening Asymptomatic Individuals,” p. 2814.

44. Mary Ann Baily and Thomas H. Murray, “Ethics, Evidence, and Cost in Newborn Screening.”

45. Neil A. Holtzman and Theresa M. Marteau, “Will Genetics Revolutionize Medicine?”

46. Robert T. Croyle, Psychosocial Effects of Screening for Disease Prevention and Detection (New York: Oxford, 1995).

47. James W. Mold and Howard F. Stein, “The Cascade Effect in the Clinical Care of Patients,” New England Journal of Medicine 314 (1986): 512-514; and Richard A. Deyo, “Cascade Effects of Medical Technology,” Annual Review of Public Health 23 (2002): 23-44.

48. Lainie Friedman Ross, “Screening for Conditions that Do Not Meet the Wilson and Jungner Criteria: The Case of Duchenne Muscular Dystrophy,” American Journal of Medical Genetics Part A 140A (2006): 914-922.

49. See www.cdc.gov/ncbddd/duchenne/screening.htm. CDC is also funding a pilot DMD screening program in Georgia for boys ages six through fifteen months.

50. Lainie Friedman Ross, “Screening for Conditions that Do Not Meet the Wilson and Jungner Criteria: The Case of Duchenne Muscular Dystrophy,” p. 915.

51. If the diagnosis is made later in life, then a strong bond is allowed to form early, and the parents’ love for the child will lead them to do what is in the child’s best interest. If the diagnosis is made too early, there is a risk that a parent will see the child from the beginning as a “defective” being and not simply as “my” child.

52. When a child has been identified early as genetically “abnormal,” the parents may be inclined to treat him or her as a second-class member of the family. Nancy Wexler tells of a woman whose two young children were at risk for Huntington’s disease and who wanted to have them tested early because “she only had enough money to send one to Harvard.” See Nancy S. Wexler, “Clairvoyance and Caution: Repercussions from the Human Genome Project,” in The Code of Codes: Scientific and Social Issues in the Human Genome Project, eds. Daniel J. Kevles and Leroy Hood (Cambridge, Massachusetts: Harvard University Press, 1992), pp. 211-243.

53. Elizabeth Campbell and Lainie Friedman Ross, “Parental Attitudes Regarding Newborn Screening of PKU and DMD,” American Journal of Medical Genetics 120A (2003): 209-214.

54. Even false-positive newborn screening results (quickly corrected) have been found, in some cases, to cause lasting harm to the early bonding of parent and child. See Elizabeth A. Gurian, et al., “Expanded Newborn Screening for Biochemical Disorders: The Effect of a False-Positive Result,” Pediatrics 117 (2006): 1915-1921; and Josephine M. Green, et al., “Psychosocial Aspects of Genetic Screening of Pregnant Women and Newborns: A Systematic Review,” Health Technology Assessment 8 (2004): 1-109. For the impact of false positives in screening for particular diseases, see Michael B. Rothenberg and Edward M. Sills, “Iatrogenesis: The PKU Anxiety Syndrome,” Journal of the American Academy of Child Psychiatry 7 (1968): 689-692; Audrey Tluczek, et al., “Psychological Impact of False-Positive Results When Screening for Cystic Fibrosis,” Pediatric Pulmonology Supplement 7 (1991): 29-37; and Göran Bodegård, et al., “Psychological Reactions in 102 Families With a Newborn Who Has a Falsely Positive Screening Test for Congenital Hypothyroidism,” Acta Paediatrica Scandinavica Supplement 304 (1983): 2-21.

55. The authors conclude that, “Concerns about the negative effect of newborn screening on the early mother-baby relationship have not been substantiated.” Evelyn P. Parsons, et al., “Newborn Screening for Duchenne Muscular Dystrophy: A Psychosocial Study,” Archives of Disease in Childhood Fetal and Neonatal Edition 86 (2002): F91–F95.

56. The question of what should be done with the dried blood specimens left over from newborn screening is resolved differently in different states. Some states store the samples indefinitely; others discard them after a few months. Some states have policies permitting the use of residual blood spots outside of the newborn screening context, for forensic, clinical, evaluative, or epidemiological investigations. Very few states inform the parents that their child’s blood might be retained. When used for such research purposes, the blood samples are “anonymized,” but some observers are concerned that they could be re-identified through database linkage or genomic fingerprinting. See Richard S. Olney, et al., “Storage and Use of Residual Dried Blood Spots from State Newborn Screening Programs,” Journal of Pediatrics 148 (2006): 618-622.

57. The fear that genetic information, once gathered, might subject the individual to insurance or employment discrimination led Congress to pass (and President Bush to sign into law) the Genetic Information Nondiscrimination Act (GINA) of 2008. The Act “prohibits group health plans and health insurers from denying coverage to a healthy individual or charging that person higher premiums based solely on a genetic predisposition to developing a disease in the future. The legislation also would bar employers from using individuals’ genetic information when making hiring, firing, job placement, or promotion decisions.” See Statement of Administration Policy, April 25, 2007, online at www.genome.gov/
Pages/PolicyEthics/GeneticDiscrimination/SAPonHR493.pdf. Only time will tell whether GINA will prove successful in preventing insurance and employment discrimination based on the results of genetic screening and testing.

58. Nancy S. Wexler, “The Tiresias Complex: Huntington’s Disease As a Paradigm of Testing for Late-Onset Disorders,” FASEB (Federation of American Societies for Experimental Biology) Journal 6 (1992): 2820-2825. See also Wexler’s presentation before this Council on September 8, 2006, available online at www.bioethics.gov/
transcripts/sept06/session6.html.

59. Nancy S. Wexler, “The Tiresias Complex: Huntington’s Disease As a Paradigm of Testing for Late-Onset Disorders,” p. 2824.

60. See Dena S. Davis, “Genetic Dilemmas and the Child’s Right to an Open Future,” The Hastings Center Report 27 (1997): 7-15. We shall return to the issue of informed consent in our discussion of state-mandated newborn screening in Chapter Four.

61. See, for example, Alexander and van Dyck, “A Vision of the Future of Newborn Screening,” p. S352.

62. In a response to Alexander and van Dyck, the noted British epidemiologist Nicholas Wald made the following argument: “Neonatal screening is, in general, a poor method of alerting couples to a disorder before the birth of an affected child, because it cannot detect the first affected pregnancy in any family. Prenatal screening would often be more effective, identifying most affected pregnancies, including the first one in any family. The argument that neonatal screening is useful in influencing “prenatal diagnosis and family planning” is more an argument in favor of prenatal screening than a reason for neonatal screening.” See Nicholas Wald, “Neonatal Screening: Old Dogma or Sound Principle?” (letter to the editor), Pediatrics 119 (2007): 406-407, p. 406.

63. Moreover, limiting the expansion of newborn screening would not affect the existing cases in which parents seek prenatal testing based on their desire to avoid the birth of another child with a genetic disorder.

64. See Ralph L. Kramer, et al., “Determinants of Parental Decisions After the Prenatal Diagnosis of Down Syndrome,” American Journal of Medical Genetics Part A 79 (1998): 172-174; and Darrin P. Dixon, “Informed Consent or Institutionalized Eugenics? How the Medical Profession Encourages Abortion of Fetuses with Down Syndrome,” Issues in Law & Medicine 24 (2008): 3-59.

65. For example, the Cystic Fibrosis Foundation (www.cff.org) places all its emphasis on newborn screening rather than on prenatal diagnosis. On the other hand, their website does explain that carrier testing is available to expectant parents (or to those who are considering having a child) to “determine if a person might have a child that may have certain diseases or health care needs, such as cystic fibrosis (CF).” The website continues, “Your decision to be genetically tested to learn if you carry a mutation or mutations of the CF gene may be difficult and is a personal choice. You may wish to talk with your medical or religious advisors to help you decide. The American College of Obstetricians and Gynecologists (ACOG) suggests that all couples who are considering having a child—or those who are already pregnant—should have genetic carrier testing for CF.”
        For its part, the ACOG website explains, “The purpose of having this information about your developing baby is so you can prepare yourself to care for a child with special health care needs or so you can terminate the pregnancy.” (See www.acog.org/from_home/wellness/cf001.htm.)

66. Again, this is not to suggest that the expansion of newborn screening should be held responsible for any future increase in the use of prenatal and preimplantation testing. The availability of less invasive testing methods, such as blood tests for pregnant women, will be a more likely cause of significant growth in the practice of prenatal testing. See Ainsley J. Newson, “Ethical Aspects Arising from Non-Invasive Fetal Diagnosis,” Seminars in Fetal and Neonatal Medicine 13 (2008): 103-108.

67. See Bridget M. Kuehn, “Prenatal Genome Testing Sparks Debate,” Journal of the American Medical Association 300 (2008): 1637-1639.

68. See Trilochan Satoo, et al., “Prenatal Diagnosis of Chromosomal Abnormalities Using Array-Based Comparative Genomic Hybridization,” Genetics in Medicine 8 (2006): 719-727; Lisa G. Shaffer, et al., “Comparison of Microarray-Based Detection Rates for Cytogenetic Abnormalities in Prenatal and Neonatal Specimens,” Prenatal Diagnosis 28 (2008): 789-795; and Catherine D. Kashork, et al., “Prenatal Diagnosis Using Array CGH,” Methods in Molecular Biology 444 (2008): 59-70.

69. Kuehn, “Prenatal Genome Testing Sparks Debate,” p. 1637; Rob Stein, “Fresh Hopes and Concerns as Fetal DNA Tests Advance,” The Washington Post, October 26, 2008. Signature Genomics Laboratories (www.signaturegenomics.com/Prena
talchip.html) assures potential users of its PrenatalChip that, when scanning the fetus’ DNA, “specific loci have been excluded which are associated with adult-onset conditions.”

70. Rob Stein, “Fresh Hopes and Concerns as Fetal DNA Tests Advance.”

71. Nancy S. Wexler, “The Tiresias Complex: Huntington’s Disease As a Paradigm of Testing for Late-Onset Disorders,” p. 2820, quoting Sophocles, Oedipus Tyrannos, lines 316-317.

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