Leonard M. Fleck: Opening Argument in the Affirmative

It took 10 years (1993–2003) and $3 billion to complete the first map of the human genome. What was the point? A short answer would be to fulfill the hope of better understanding the genetic roots of many diseases and then to develop the therapeutic interventions that would disrupt or manage those disease processes. In 2003, that hope would have been seen to be extremely remote and unaffordable. In 2021, that hope has been realized to a significant extent. It has been realized because the cost of doing Whole Genome Sequencing (WGS) has been reduced to less than $1,000, although the cost of analyzing, interpreting, and counseling a patient who has had WGS would add another $2,000. Less than 50 percent of Americans could afford this as an out-of-pocket cost. Health insurers will only cover these costs in very limited circumstances. This is what prompts my question: Are there considerations of healthcare justice which would require public funding for WGS?

What do we see as the medical value of WGS? Is WGS a medical need? If so, what circumstances would be included? Many individuals would see WGS as a preventive measure. It would reveal an individual’s potential health vulnerabilities before those vulnerabilities might manifest themselves as symptoms, sometimes indicative of advanced (incurable) disease. That is, WGS would provide an individual with opportunities to prevent or forestall those disease vulnerabilities with behavioral changes and clinical attentiveness.Footnote ¹

WGS would also allow couples to determine whether they posed any serious genetic risks to future possible children so that they could alter their reproductive plans for the good of their future possible children. Along these same lines, if they were to choose preimplantation genetic diagnosis, they could choose to have WGS of the eight-cell embryos they would have produced. In an established pregnancy, WGS could be used to do prenatal testing, looking primarily for serious genetic disorders that might adversely affect the length of life or quality of life of that child as a child. After birth, WGS could be used to do a complete neonatal screening in place of the limited screening now done at birth. Again, the focus of the screening would be health risks posed for that child as a child, matters over which parents had legitimate decisional authority.

Next, for both children and adults who might be faced with puzzling clinical circumstances WGS might be of great help in identifying a rare or ultra-rare genetically rooted health disorder that would be outside the knowledge ken of most physicians. This would save the costs and suffering associated with a long and painful diagnostic odyssey, even if the result were bad news. Finally, WGS is essential in a therapeutic context for patients with metastatic cancer. WGS would be necessary to sequence tumor genomes, as well as the patient’s genome, in order to see if that cancer is driven by a targetable genetic mutation for which at least one of a hundred or more of these targeted cancer drugs or immunotherapies might be beneficial. None of those drugs are curative. All are extraordinarily expensive. Some portion of those patients will gain at least extra months of life, sometimes an extra year or two.

Not everything listed above would be judged to be “medically necessary,” which would more readily trigger concerns about healthcare justice. However, it is also true that none of those suggested uses of WGS would be justifiably regarded as being medically frivolous. Something else to keep in mind is that WGS can have consequences for first-degree relatives. For example, the Geisinger Clinic accepted 174,500 genetic samples and found 1181 “genetic variants that could lead to health conditions.” Those researchers estimated that five close relatives per person would have that same variant.Footnote ² It might be very important for those relatives to have access to WGS. However, as noted above, fewer than 50% of Americans could afford to pay that cost. Should we, citizens of a just and caring society, accept that as unfortunate, but not unjust?

I will argue that a “just” and “caring” society with limited resources to meet unlimited healthcare needs should, as a matter of justice, provide publicly funded access to WGS for some limited range of medical purposes, whether diagnostic, preventative, therapeutic, reproductive, or a matter of public health.Footnote ³ We can start with a broad argument in support of this claim. WGS provides valuable health-related information for diagnostic, preventive, therapeutic, or reproductive purposes. This is information that is otherwise not easily available, not available at all, or only available by more intrusive and expensive means. Individuals who are financially well off can afford the current out-of-pocket costs for WGS. The financially less well-off risk avoidable health harms, which is one reason why this is a matter of healthcare justice.

Consider the family of P450 genes that regulate drug metabolism. Most of us are in the normal range. Others will be either fast or slow metabolizers of prescription drugs. If our status is unknown to us and we are slow metabolizers, then a normal dose of a drug will accumulate in our system with potentially disastrous consequences. Knowing that before the fact would allow a proper drug adjustment. Furthermore, 7 percent of 1,200 Food and Drug Administration approved medications are affected by actionable germline inherited pharmacogenes. Even more importantly, 18 percent of outpatient U.S. prescriptions (more than 4 billion per year) are affected by actionable germline pharmacogenomics.Footnote ⁴ This should make clear we are talking about significant numbers of patients.

Consider another example. A wealthy individual receives information from WGS that suggests the need for additional testing and a timely therapeutic intervention to cure or manage a genetically instigated health problem. Their health insurance will pay for all that medically necessary follow-up care. Joe Plumber has equally good health insurance as our wealthy individual, which would pay for comparable care, except he does not have the ability to pay for WGS out-of-pocket. One possible result is that what would have been a curable disease becomes incurable once it is clinically manifest. That is unjust.

That last judgment is an egalitarian judgment, that is, equal treatment for all who have equal medical need. I take it that everyone who does not have a heart of stone and a brain of mush would agree that if an uninsured individual showed up at the emergency room with an appendix about to burst, it would be outrageously indecent to put that individual in the hospital parking lot to die without treatment. My example with Joe Plumber would be less dramatic and would likely occasion no moral outrage because it would appear to be merely unfortunate. Nevertheless, it does parallel the appendix example. In neither case are we talking about extraordinarily costly, marginally beneficial healthcare that might be “beyond justice.” In both cases, the care needed to save a life is very effective and societally affordable. This is one reason why there should not be financial barriers to medically helpful WGS. This is why WGS should be publicly funded in at least some limited range of circumstances.

To the extent that WGS can be helpful in situations such as I described above, it is a matter of protecting fair equality of opportunity for all and effective liberty for all.Footnote ⁵ Individuals might suffer a lifelong disability for lack of timely access to WGS and the medical therapy that would have prevented that disability. To the extent that WGS could have prevented that disability in an individual who could not afford it, this would represent an unjust failure to protect fair equality of opportunity. This is another justice-relevant consideration for public funding of WGS. What might be unclear at this point is when WGS would be an option. Individuals could be offered this option when they first reach adulthood. I stress that it is an option, not an obligation. There might be many individuals who would reasonably prefer to be ignorant of the details of their genetic endowment, especially if some of those details would yield persistent stress.

Prioritarian considerations of healthcare justice would also seem to support public financing of access to WGS. This would be especially true for those individuals who might be identified as being among the genetically least well off. Family history might provide the strongest clues regarding who might be among the genetically least well off. These are individuals with family histories of breast cancer, or Lynch syndrome (a type of colon cancer), or some early forms of dementia, or various types of heart disease, and so forth. Some of these medical problems may be manageable or postponable, but not curable. These are all serious medical problems that potentially threaten length of life or quality of life. If earlier attention to these vulnerabilities would represent a net health benefit for these individuals, then this is a justice-relevant consideration for public funding of WGS.

I should add that sufficientarians would likely endorse this last conclusion as well. That is, in some range of circumstances, WGS would be seen as part of a basic healthcare package that ought to be guaranteed to all as a matter of justice and decency. In other words, WGS is not the kind of medical care that is “more than enough,” more than what a reasonably just and decent society would guarantee to all its members. Consider in this regard what we struggle with as a society when we are trying to define what ought to be included in a basic health benefit package guaranteed to all. We struggle with medical interventions that are very costly, that are often used for life-prolonging purposes in the late stages of life, that treat chronic degenerative conditions in ways that yield only marginal benefits, such as a $250,000 left ventricular assist device for patients who are in late-stage heart failure. By way of contrast, if WGS is used wisely in the early stages of life (children and young adults), it can prevent or forestall many chronic degenerative conditions (assuming individuals are willing to make needed [difficult] behavioral changes). WGS is relatively inexpensive compared to the type of care that characterizes much end-of-life care for patients with cancer or heart disease or chronic obstructive pulmonary disease (COPD) or diabetes, and so forth. WGS, used judiciously by future possible parents, can protect the best interests of future possible children in a very fundamental sense. All of this suggests that WGS ought to be part of a basic benefit package guaranteed to all in our society.

Utilitarian considerations will often support WGS as a technology that ought to be available to all who would take advantage of it, especially for preventive purposes. If what is learned from WGS is used by adults to alter behavior with otherwise costly health consequences, then that saves money for the healthcare system as a whole. If what is learned by any individual from WGS in terms of their own health vulnerabilities results in sharing that information with other family members who would take advantage of that information, that too has beneficial financial consequences for society, including a healthy workforce and related productivity gains. If WGS is used by future possible parents to alter their reproductive choices because they discover they are at risk for having a child with a serious genetic disorder, such as cystic fibrosis, and the result is the birth of a child without that disorder, that too is a public benefit that can be more readily assured with public funding of WGS. For these same reasons, replacing our current limited forms of neonatal screening with broader screening (maybe some sort of mini-WGS) would result in earlier and better treatment of rare and ultra-rare genetic disorders in these infants. This is especially critical if the disorder is one that has produced irreversible (potentially lethal) damage in an infant if parents need to wait for clinically ascertainable symptoms to manifest themselves.

Finally, I have for a long time been an advocate for the role of rational democratic deliberation in addressing problems of healthcare justice (rationing and priority-setting) in a resource-constrained society.Footnote ⁶ So it is reasonable to ask whether public funding for WGS in some limited range of circumstances would be endorsed through a fair and inclusive process of rational democratic deliberation. The reasons given above would all seem to yield a likely affirmative endorsement through the deliberative process. To use Rawls’ language, the fact that all these different healthcare justice perspectives would converge in endorsing public funding for WGS means that we would have an overlapping consensus in this matter, that this proposal is not one that would only be favored by one or another comprehensive sense of healthcare justice. Rawls would say that what is endorsed here is a product of a public sense of healthcare justice, as opposed to some more narrow conception of healthcare justice.Footnote ⁷

Some other considerations that would flow into the deliberative process would be the following. First, the broad introduction of WGS into the clinical context would prevent a significant range of medical harms related to genetic ignorance among health professionals (now being corrected among younger physicians). Second, WGS being used more often would yield significant diagnostic benefits in those cases that are otherwise very difficult to diagnose, that is, any of those rare or ultra-rare genetic disorders. Third, WGS essential to precision medicine and its therapeutic hopes. This is especially true in the case of metastatic cancer when that cancer is driven by more than 100 possible genetic mutations that are advancing that cancer. WGS is necessary for identifying those genetic drivers by mapping those tumors so that an appropriate targeted therapy or immunotherapy can be used to manage the progression of that cancer. One thing that our deliberators need to keep in mind is that only 10 percent of cancers are hereditary; the vast majority of cancers arise from spontaneous mutations in cancer suppressor cells. This is genetic information that can only be culled in a clinical treatment context, not at any earlier point in life. Consequently, I would see our democratic deliberators agreeing that WGS ought to be publicly funded in a somewhat limited way as a matter of healthcare justice, as a matter that is in the public interest, and as a matter that is economically rational.

Leslie Francis: Opening Argument in the Negative

In this response, I raise two lines of questions about Professor Fleck’s general defense of WGS: (1) What benefits does WGS provide that other, currently available technologies do not, and what risks does it have, that other currently available technologies do not have? (2) If WGS is to be funded through shared resources, should any conditions be attached to that funding?

Professor Fleck’s argument is premised on justice in access to healthcare. This is its greatest strength. I agree wholeheartedly with Fleck about the importance of health justice (even though we might disagree about some of the details). We also agree that if WGS were important in preventing serious illness or disability, it should be considered as part of a basic minimum of healthcare. In this respect, there is nothing special about WGS; it should be considered for inclusion on the same basis as other diagnostic interventions. Where we disagree is over the present-day benefits of WGS. As I outline below, the benefits Fleck envisions do not require WGS for the most part today. Someday, WGS might prove more beneficial and—if it does—I would agree that it should be paid for from shared funds. In fact, my second point—that a condition of the funding should be appropriate information sharing—can be viewed as helping to bring forward the day when the benefits of WGS are more apparent.

To introduce my approach, I am what in today’s discussions about justice would be called a “nonideal” theorist. Problems of justice, such as problems of healthcare funding, must be addressed in the context of existing institutions that are at best imperfectly just.Footnote ⁸ I address these problems from the perspective of how today’s world might become more just, not from the perspective of a model of ideal justice. My analysis, therefore, considers what form payment for WGS should take in the context of contemporary healthcare systems. In the United States, which means in the context of a mix of institutions paying for healthcare, the question of payment might better be framed as payment from shared resources rather than as a special program funded by the public.

So, what are the added benefits and risks of WGS? Fleck begins with the costs: the actual sequence costs about $1,000 to perform. Performing sequencing once has a potential advantage of efficiency; once available, the sequence can be accessed as needed over a lifetime. However, a sequence by itself is uninformative; analysis of the sequence must be paid for separately and is not a one-off event. We are continuing to learn more about the significance of different variants even of genes that have been well studied such as BRCA-1 and BRCA-2 genes implicated in breast and ovarian cancers.Footnote ⁹

Many of Fleck’s examples of the advantages of WGS involve single genes or combinations of genes that are known to have deleterious variants. These can be tested for without WGS. The family of P450 genes regulating drug metabolism can be tested for directly; the significance of many variations is known and currently available tests identify targeted variations.Footnote ¹⁰ Breast cancer testing involves BRCA-1 and BRCA-2; Lynch syndrome is currently identified with alterations in the genes of MLH1, MSH2, MSH6, PMS2, and EPCAMFootnote ¹¹ ; early forms of dementia are associated with the APOE-e4 variantFootnote ¹² ; and various forms of cardiomyopathy, hypercholesterolemia, arrhythmia, vascular disorders, and heart failure are associated with known genetic variants.Footnote ¹³ Finally, Fleck points to the clinical relevance of sequencing tumor genomes—a process that sequences the tumor genome rather than the individual’s genome.Footnote ¹⁴ These methodologies are all currently available, and do not require WGS.

Other claims that Fleck makes for WGS are more difficult to evaluate because they are quite speculative. For example, he claims that it might alert people to “their potential health vulnerabilities,” allow couples “to determine whether they posed any serious genetic risks to future possible children,” allow “a very complete neonatal screening in place of the limited screening now done at birth,” or identify “a rare or ultra-rare genetically rooted health disorder.” Support for each of these claims depends on currently available knowledge. This knowledge might be identification of variants of known concern, the patient’s clinical presentation, the patient’s family history, or our growing understanding of the significance of polygenic risk scoring. For identification of variants of known concern, WGS is not necessary, although having a sequenced genome already available for analysis might be more efficient and cheaper in the long run if a number of tests are to be run at different points in time. Family histories may provide a clue that such genetic testing is warranted. Patients with rare conditions for which the cause is unknown may benefit from WGS, but this is a small subset of individuals. The most likely of these possibilities that could support additional benefits from WGS is polygenic risk scoring.

Polygenic risk scoring (PRS) compares an individual’s genome to the genomes of others known to have or lack the condition in question.Footnote ¹⁵ PRS identifies an individual’s relative risk in comparison with information about a population. To date, because the most information about genomic variants has been obtained from individuals of European ancestry, PRS is most informative about individuals in this population. PRS may be misleading for other individuals.

What, then, are the potential risks of WGS? Fleck elides an initial problem, WGS in children. He observes that the focus of the screening would be health risks that are posed for the child during childhood over which the parents have legitimate decisionmaking authority. Many of these risks are currently included in newborn screening panels. Fleck criticizes these panels as “limited” and indicates that WGS could be used to “do a very complete neonatal screening.” However, current panels are constructed based on a complex set of factors, including the sensitivity and specificity of the test, its reliability and predictive value, and the availability and success of treatment.Footnote ¹⁶ Although WGS may eventually be useful in this context, its present utility depends on the state of knowledge with respect to identifiable conditions of concern that require clinical management during childhood. To avoid parental misunderstanding of the significance of identified variations, genetic counseling may be needed. Moreover, providing parents with information beyond what is relevant to their children’s clinical management raises ethical questions about whether their attitudes and behavior towards their children may be altered or whether they have information that their children would later prefer not to have be available to anyone other than themselves or perhaps even to be available at all. The American Medical Association ethics opinion on genetic testing of children emphasizes the importance of likely benefits to the patient during childhood and respect for the patient’s future autonomy.Footnote ¹⁷

Risks and benefits of PRS are more complex. One clear risk is that a score will be understood for more than it can deliver. People may be given scores from a database that is not informative for them and thus be misled. Or people may confuse elevations of relative risk with absolute risk; a 5 percent increase in relative risk in comparison with a population may represent a very low risk whereas a 5 percent absolute risk may be of at least some importance for the person in deciding how to manage her preventive health.

Recent work in which I have been involved about PRS for suicidality presents a case study of some possible advantages and disadvantages of this information.Footnote ¹⁸ In a pilot study of focus groups made up of survivors of suicide attempts and family members of people who had successful suicide attempts, we found concerns that people would view results as deterministic of their fates. We also found relief that suicidality had not been their fault and perceptions that information could be helpful in guiding behavior such as whether to keep guns in the home. Finally, we found the need for greater understanding of the significance of elevated risk scores on the part of both patients and their family members. To the extent that WGS is used in evaluating PRS for serious and stigmatizing medical conditions such as suicide risk, we concluded, it must be coupled with efforts to enhance understanding of the meaning and significance of this information. The costs of the training, personnel, and time involved in this understanding are left aside in Fleck’s discussion. One recent estimate is that there are about 7,000 trained genetic counselors in the world today.Footnote ¹⁹ One current listing of programs identifies 22 colleges and universities in the United States offering genetic counseling programs, at an average cost of over $11,000 for in state students and over $36,000 for out of state students; annual wages for genetic counselors average about $84,000.Footnote ²⁰

Let me now turn to arguing that payment for WGS from shared resources should be conditioned on the willingness of people receiving this service to allow access to their genetic and relevant clinical information. For the benefits of WGS to increase and to be available to more diverse populations, and especially to move beyond knowledge of the significance of disorders associated with single genes or limited sets of genes to PRS, more information is clearly needed.

People who receive WGS from shared resources are getting a benefit that depends on information already provided by others. This may be the information that led to classification of the significance of variants. For example, Myriad Genetics relies on its database of information about the association between identified variants and disease in its analyses of the clinical significance of the results of a genetic test. In the aftermath of its loss of patent protections for breast cancer genes, Myriad has continued to assert trade secret protection for these data.Footnote ²¹ Polygenic risk scoring, as described above, depends on databases from populations that are representative of the patient seeking the assessment. It, thus, may be particularly important in the contemporary context to obtain access to information from persons who are not of European ancestry.

Patient confidentiality about genetic information presents an obvious objection to this requirement. However, data access may be subject to protections that reduce these risks. One important protection is to have access be by distributed queries rather than by actual transfer of any information, the model used by the U.S. Sentinel program for the detection of unusual side effects or interactions from drugs.Footnote ²² The ability to query can also be limited. One limitation method would be to require clinicians and researchers to submit queries to a trusted third party, so that no patient information is ever accessible by anyone other than the trusted third party.

Both reciprocity and justice support this condition. Individuals who receive WGS from shared funds are receiving a benefit that might not otherwise be available to them. But the benefit is not only payment for the sequence and its analysis from shared funds. The benefit derived from WGS depends on information obtained from or provided by others. Without information about associations between genotypes and phenotypes, we would not have the understanding we do about even the significance of single gene variations. PRS depends on large databases drawn from relevant populations for particular patients. On Lawrence Becker’s classic view of reciprocity (1986), reciprocity in the sense of returning good for good is a virtue core to human social life.Footnote ²³ Arguably, allowing information drawn from oneself to be part of the information stream contributing to the utility of WGS is an example of this kind of reciprocity in action.

Moreover, increasing the richness of the data available for interpreting the significance of WGS is critical to just distribution of its benefits. On the approaches to justice that he favors, Fleck argues, it is unjust for some to have access to the benefits of WGS when others do not. The injustice is particularly severe when it tracks otherwise disadvantaged groups. But the inability to pay for WGS is only a part of why its benefits might not be equitably available for all. Genetic databases that are currently available in the healthcare context skew impressively toward those of European ancestry.Footnote ²⁴ Parenthetically, databases available for law enforcement skew disproportionately toward people of color and people in poverty, at least in the United States.Footnote ²⁵ These distributions suggest that, as things currently stand, people of European ancestry are more likely to benefit from WGS and that it is concomitantly more important to increase the supply of data from other groups who are less likely to benefit from WGS.

The current distribution of the benefits of WGS thus does present a significant problem of nonideal justice. The burdens of increasing access to the benefits of WGS fall disproportionately on groups already burdened by injustice. These groups have historically been subject to stigmatization and injustice in access to healthcare. In the United States, they are also groups that have been disproportionately subjected to injustice in the use of genetic information. Examples include the racist efforts to link intelligence to inheritanceFootnote ²⁶ and contemporary interest in ancestry testing on the part of white nationalists.Footnote ²⁷ They also include the decision by researchers to repurpose genetic samples originally drawn from the Havasupai tribe, a people whose ancestral lands were the base of the Grand Canyon. The samples had originally been drawn with permission for a study of the genetics of diabetes, a serious health problem among the tribe, and then were used for the study of schizophrenia and an analysis of tribal origins, both highly offensive to the tribe.Footnote ²⁸

These disproportionate burdens, combined with histories of injustice and justified mistrust, are in my judgment the strongest argument against requiring people to allow access to information as a condition of receiving WGS from shared resources. This situation presents a common dilemma in nonideal justice: the burdens of improving justice may themselves be borne in ways that are unjust. In such a dilemma, my approach would not be to forestall improvements that come with unequal burdens, but instead to consider how the injustice of the burdens can be lessened and especially whether the injustice of the burdens is likely to contribute to worsening injustice in other ways. The concept of “corrosive disadvantage” developed by Wolff and de-ShalitFootnote ²⁹ —disadvantages that interact so as to make each a deeper disadvantage, such as the interrelationship between poverty and poor health—is helpful here. If the disadvantage of sharing information compounds other unjust disadvantages, such as discrimination in employment or access to healthcare, that would be a particularly serious concern from the perspective of nonideal justice. On the other hand, as genetic information becomes increasingly part of clinical practice, the lack of relevant information for groups disadvantaged in other ways may also become corrosive.

My conclusions must thus be contextualized. At present, the case for the additional advantages of shared funding for WGS is relatively weak and lies primarily in the existence of a complete sequence at the ready for later use. WGS is likely to be more informative about the significance of complex traits in persons of European ancestry, to the extent that it is informative at all. Guarding against risks of misunderstanding may require resources that are not currently available for genetic counseling. The added benefits of WGS require not only payment for the sequencing process, but also access to information drawn from associations between phenotype and genotype in populations. Reciprocity thus presents a reason for conditioning payment for WGS on the willingness to share information. Increasing justice in access to benefits of WGS will require increased diversity in the information available about populations but the burdens of this increased diversity will be borne by those in populations for whom WGS is disproportionately less beneficial. Addressing this situation as a dilemma in nonideal theory requires balancing the interactions between injustice in access to clinical benefits of WGS and other disadvantages, with the risks that allowing access to information will contribute to stigmatization and discrimination of those in otherwise already-disadvantaged groups.

Leonard M. Fleck’s Rebuttal: WGS as a Public Interest

Let me begin my response to Professor Francis by noting that I too regard myself as a nonideal theorist of justice. Tradeoffs among competing considerations of justice are inevitable. However, tradeoffs that would make disadvantaged social groups even worse off are never warranted under the rubric of nonideal justice. To clarify my own view, I do not endorse the idea of publicly funding WGS for all 330 million Americans. The cost per WGS would be $3,000 for the testing, analysis, interpretation, and counseling, or $990 billion. We have only limited resources to meet virtually unlimited healthcare needs. Doing WGS for all Americans might represent a desire for most Americans but it is not a medical need. Consequently, public funding for such an effort would be neither a just nor wise use of limited healthcare resources.

What I do argue for is limited public funding for WGS judged to be medically necessary. For example, a recent article in the New England Journal of Medicine concluded that “whole genome sequencing provided rapid and accurate genomic profiling in patients with AML and MDS,” what was described as “better diagnostic yield” than conventional testing methods.Footnote ³⁰ This represents medical necessity and should not be denied to patients whose private insurance (or lack of insurance) would result in denial of this technology. The same will be true more broadly with respect to the mapping of tumors. WGS will yield a more accurate map of those tumors than current technologies, that is, identify correctly more often the primary genetic driver of that tumor progression so that the correct targeted cancer drug can be administered.

I will readily concede that if we imagine using WGS for preventive purposes in adults, this will likely be a waste of money, especially if what is learned requires a significant change in behavior. Likewise, I will concede that WGS at present would have minimal utility in the context of preimplantation genetic diagnosis or prenatal screening. The result in those cases would be parental information overload, that is, parental confusion regarding practical implications, and perhaps unwarranted poor decisionmaking by parents. If we can create what I will call a “skinny version” of WGS for purposes of neonatal screening, I would argue that would have greater clinical utility than current neonatal screening efforts and would not burden parents with information overload. I should add that such a “skinny version” of WGS would require shared decisionmaking with parents, as opposed to current public health obligations without consent. Again, cost should not be a barrier, which is why I contend this should be publicly financed.

I agree with Professor Francis that reciprocity should be part of our civic conception of healthcare justice. If the cost of WGS is publicly funded, then that genetic information should be included in a public research database. Any individual data used would be anonymized so as to protect individual privacy rights. This would be one way of gradually building a non-European genetic database that would yield useful medical-genetic information of roughly equal value for all racial/ethnic population groups. As Professor Francis notes, the U.S. system for financing access to needed healthcare is extremely fragmented, which is a major reason why achieving justly the benefits of WGS in a limited range of circumstances will require public funding. However, if the clinical knowledge gained through WGS cannot be implemented for the benefit of individual patients who lack the health insurance needed to finance relevant subsequent care, then we will have come up against an injustice that itself needs correction, most especially in the case of marginalized social groups.

Finally, we need to see WGS as a work in progress. Much remains unknown regarding the human genome and its links to various diseases and disorders. One of the biggest practical ethical challenges we will face is linking emerging knowledge regarding the human genome to those individual genomes stored all over the country where it might have clinical relevance. Solving problems such as that should be regarded as a public interest requiring public financing.

Leslie Francis’s Rebuttal: Toward Realizing the Promise of WGS

We agree on much more than it seemed at the outset of this discussion: (1) Problems of healthcare funding in the United States today are problems of nonideal justice. (2) Where clearly medically necessary, WGS should be paid for out of shared resources, just as other medically necessary testing should be paid for. WGS is not a special form of medical testing; it should be judged by the same standards of clinical validity and utility as other forms of testing. (3) When people receive costly healthcare from shared resources, there is an argument from reciprocity for allowing information gained in that care to be used in improving knowledge about care for others, provided there are adequate protections against information misuse. (4) This argument is especially strong for genetic information, where more is available about some population subgroups than others. However, it is particularly important to guard against information uses that worsen injustice to those who already are being treated unjustly or are experiencing the ongoing consequences of historical injustice.

Where, then, do we disagree? A simple characterization might be that Fleck is the optimist and Francis is the pessimist. Fleck reads the facts about what WGS can do today far more generously than Francis does. Francis emphasizes inequality in the information available and hence the utility of WGS for many and worries about risks of stigma and discrimination more than Fleck does. This said, I think there’s a lot more to our differences than glass half full or glass half empty. Perhaps most importantly, I think it is very important not to put more weight on genetic information than it can bear. Particularly as we enter a realm beyond the identification of single genes responsible for causing diseases and the mechanisms by which they operate, caution is critical. We need to be alert to risks of over-confidence, misinterpretation, and misalignment between available data and individual patients. To be sure, as we do develop knowledge about the health significance of genome variations through WGS, we should use that in healthcare just as we use other clinically relevant information. Our use of WGS should then continue forward through knowledge sharing that can help others (although beyond the scope of this discussion, I would make the same reciprocity argument for other healthcare paid for from shared resources). But we should not conclude that the general case has been made today for widespread payment for WGS from shared funds. Fleck appears to concede this last point; his surrebuttal is careful to limit the case for WGS to situations in which it has demonstrated benefit.