A journal published by Lahey Health€¦ · A journal published by Lahey Health Fall 2015 Feature...

Lahey Health Journal of Medical Ethics FALL 2015 | 1

A j o u r n a l p u b l i s h e d b y L a h e y H e a l t hFall 2015

FeatureWhat was right about eugenics

2 | FALL 2015 Lahey Health Journal of Medical Ethics

“ The social function of morality is to get people to do things that they would not otherwise be disposed to do, or to strengthen dispositions that people already have but in weaker forms.”

— Elliott Sober and David Sloan Wilson


A j o u r n a l p u b l i s h e d b y L a h e y H e a l t hFall 2015

IN THIS ISSUE

4 Feature

What was right about eugenics

Nicholas Agar, Reader in Philosophy

6 Ask the ethicist

Should an IVF clinic honor a single man’s request for sex selection?

Judy E. Stern, PhD

7 The legal column

Balancing religious freedom and health care access

Holly Fernandez Lynch, JD, M. Bioethics I. Glenn Cohen, JD

8 Ethics and the humanities

The brave surgeon: A review of the film “The English Surgeon” and the book Do No Harm: Stories of Life, Death, and Brain Surgery, by Henry Marsh

Catherine Belling, PhD

10 Dialogue

Genomic newborn screening: Risks and benefits

Howard M. Saal, MD, FACMG Ronald M. Green, PhD

David Steinberg, MD, Editor Lahey Hospital & Medical Center 41 Mall Road, Burlington, MA 01805 [email protected]

James L. Bernat, MD, Associate Editor Dartmouth-Hitchcock Medical Center One Medical Center Dr., Lebanon, NH 03756 [email protected]

Deborah Sosin, Managing Editor

David M. Gould, Esq., Legal Editor

Susan M. Donovan, Circulation Manager

Editorial BoardDan W. Brock, PhD

Daniel Callahan, PhD

Muriel R. Gillick, MD

Ronald M. Green, PhD

Timothy Lahey, MD

Paul Reitemeier, PhD

James A. Russell, DO

Matthew Tilem, MD

Generous funding for Lahey Health Journal of Medical Ethics is contributed in memory of Harold Karp by the Karp Family Foundation.

The opinions expressed in Lahey Health Journal of Medical Ethics belong to the individual contributors and do not represent the institutional position of Lahey Health on any subject matters discussed.

ISSN NUMBER 1543-4672


What was right about eugenicsNicholas Agar, Reader in PhilosophyVictoria University of WellingtonWellington, New Zealand

The statement “But that would be eugenics!” is sometimes offered as a decisive rebuttal to proposals to use genetic information to decide what kinds of people should exist. I suggest that this rejection of eugenics is mistaken. Eugenics is an accepted and valuable part of medicine.

The word “eugenics” combines the Greek eu-, meaning “good” or “well,” with -genēs, meaning “born.” It was coined by Francis Galton and first appeared in his 1883 book Inquiries into Human Faculty and Its Development. Galton hoped to use the new evolutionary understanding introduced by his cousin, Charles Darwin, to not only better describe the human species but also to improve it. He defined eugenics as “the science of improving stock, which is by no means confined to questions of judicious mating, but which, especially in the case of man, takes cognizance of all influences that tend in however remote a degree to give to the more suitable races or strains of blood a better chance of prevailing speedily over the less suitable” (Galton, p. 17). Galton sought to apply to humans the methods used by farmers over millennia to improve the quality of their crops and livestock.

Galton’s proposal to improve human stock had two elements. There was negative eugenics. Galton was a critic of his age’s emerging social welfare systems, which he viewed as permitting the feckless, immoral and unintelligent to perpetuate their substandard hereditary material. Negative eugenic policies would prevent those with poor-quality hereditary material from having children. Positive eugenics would encourage those whose moral uprightness and diligence demonstrated that they had inherited the right stuff to have lots of children.

Galton’s proposal gained support from across the political spectrum. Today, however, it is remembered mainly for the many crimes committed in its name. The Nazi program of negative eugenics led to the murder of thousands of disabled people. The most widely discussed Nazi attempt at positive eugenics was the Lebensborn program, which encouraged members of the German armed forces to impregnate healthy Aryan women in Germany and its occupied territories. The Nazis were the most egregious practitioners of eugenics; but outside of Germany, negative eugenics led to forcible sterilizations and wrongful imprisonments.

We have learned the wrong lessons from eugenics’ objectionable history. The standard ethical analysis locates eugenics’ principal fault in its focus on inheritance. According to this view, eugenicists erred by seeking human improvement through the elimination of bad hereditary influences and the perpetuation of good ones. I suggest that the idea that we should seek to improve humanity by addressing hereditary influences is a morally valuable part of contemporary medicine. Eugenics shares with public health an interest in the well-being of populations. The focus of public health is on environmental causes of ill health, such as smoking tobacco and exposure to infectious disease. Eugenics involves a complementary focus on genetic causes of population ill health.

Galton made two mistakes. First, he seriously misunderstood human inheritance. Talk of more or less “suitable races or strains of blood” has no place in modern genetics. This factual error was exacerbated by a distinctively moral mistake. Galton thought we should improve the hereditary health of populations by managing human reproduction. He failed to appreciate the deep importance of procreative liberty — the freedom to make one’s own reasonable choices about reproduction. Today we reject the suggestion that improvements in population health justify curtailing procreative liberty. Fortunately, advances in genetic technologies show how we can improve the

genetic health of populations in a way that is consistent with respect for procreative liberty.

The factual errors of eugenicsGalton believed that the “more suitable strains of blood” tended to find themselves in classes and races that were perceived to be doing the best. The less suitable strains were found in people at the bottom of the social heap. Investigations of the human genome have revealed many genetic variants that increase our susceptibility to disease. But these show no preference for people located toward the bottom of social status hierarchies. Sequences of DNA that elevate the risk of disease are scattered across the genomes of those doing best in society and of those who suffer disadvantage. Some genetic diseases are more common in people belonging to certain ethnic groups. But it is simply false to assert that some ethnicities bear a greater burden of bad genes than others and therefore should be classified as worse in hereditary terms.

A second innovation in our understanding of heredity post-Galton is the rejection of genetic determinism. Genes do not typically causally fix traits. They affect them in concert with a diverse complexity of environmental causes. A few years ago, I purchased a genetic profile from a direct-to-consumer genetics company. That profile reveals the existence of many genes that increase my likelihood of getting certain diseases. I hope to reduce this likelihood, not by changing my genes but by living more healthily.

This picture of the relationship between inheritance and environment suggests a way to respond to genetic information. Genes and environments work together to make human beings. We should treat potential modifications of them similarly. We understand that the likelihood of melanoma increases with exposure to the sun. Practitioners of public health might, therefore, judge a sun-safety campaign to be a success if it reduces the reported rate of sunburn in the population. We might judge a eugenic


program to be a success if it reduces the incidence of genetic variants linked with melanoma in a given population.

Here we come to the moral error made by Galton. He hoped to manage human reproduction. Negative eugenics seeks to prevent or discourage people with bad hereditary factors from having children. Positive eugenics involves encouraging or requiring those with the hereditary right stuff to increase their reproductive work rate. We now view these as morally intolerable intrusions into the procreative choices of individuals. This kind of concession to individual liberties is apparent in our understanding of public health. It’s possible that laws dictating jail terms for parents who allow their children to get sunburned would lead to an overall increase in sun-safe behavior. But we would view this public-health measure as wrongly truncating a parental prerogative to decide how to raise children. Procreative freedom is such an important value that we are rightly wary of endangering it. We would not accept a law that imposed criminal penalties on people with Huntington’s disease, a serious neurodegenerative genetic disorder, who chose to procreate without taking precautions against passing on the condition to their children. We would reject the suggestion that women should be required to abort fetuses bearing the gene linked with Huntington’s disease.

Preimplantation genetic diagnosis as eugenicsThe new genetics furnishes the tools to realize Galton’s vision of improving the genetic health of populations in a way that does not wrongly restrict procreative liberty. Preimplantation genetic diagnosis (PGD) offers people who risk passing on a genetic disease to their children a way to avoid doing so. It involves the creation of a number of embryos by in vitro fertilization. After a few divisions, one or two cells are taken from the embryos and tested for the presence of a disease-linked gene. Embryos shown to be free of those genes are introduced into a woman’s body and pregnancy can proceed normally.

There are differences in the provision of PGD in different societies. But through these differences, we can identify the eugenic motive of increasing the genetic health of populations. Because PGD is not compulsory, the decision of prospective parents to use PGD is an expression of procreative liberty. It would be an unjustified intrusion on procreative freedom to make PGD compulsory. We can recognize a eugenic motive in society’s choices about which conditions PGD is made available for.

Were parents’ use of PGD to fall solely within the domain of procreative liberty, then they would be free to choose embryos that carry the tested-for disease gene. The idea that some parents might seek this option is not absurd. Perhaps they will expect to feel a closer bond with a child who shares their particular disease. It is wrong to permit people who have inherited the genetic cause of Huntington’s disease to use PGD to pass the disease-linked version of the gene on to their children on the grounds that it would strengthen the parent-child bond. It would be wrong because it uses PGD to reduce rather than to improve population health. In endorsing this limitation on procreative choices, we permit PGD to serve a eugenic end. It does not use beliefs about inheritance to either prohibit or mandate reproduction.

I do not mean to say that this appeal to the concept of disease is unproblematic. The question of where to place the boundary of the category of disease is fraught with philosophical difficulties but distinct from the issue that is the focus of this article. The category of disease contains many clear cases. We should use these to assess the suggestion that eugenics and public health share the goal of reducing the incidence of disease in a population. We should be consistent when dealing with environmental and genetic causes of disease.

Practitioners of public health and eugenics should be aware that efforts to address environmental or genetic causes of disease risk stigmatization. In many societies, public health campaigns exist whose purpose is to reduce the consumption of alcohol by

women who are aware that they are pregnant or acknowledge that there is some chance that they may be. Those who design such campaigns must exercise care not to devalue people who live with the effects of in utero alcohol consumption. Those practicing eugenics must also exercise caution not to devalue people who live with a genetic condition. A eugenic program that seeks to reduce the incidence in the population of mutations linked with fragile X must be pursued in ways that do not devalue people living with fragile X syndrome.

Techniques other than PGD have the potential to improve the genetic health of populations without wrongly infringing on procreative liberty. These include the donation of normal gametes to prevent the passing on of genetic disease and the technique of cytoplasmic transfer to prevent certain rare but serious mitochondrial diseases.

Concluding thoughtsI have suggested that, once purged of its factual and moral errors, the focus of Galton’s eugenics on heredity complements the focus of public health on the environmental causes of ill health. The term “eugenics” is tainted by its historical associations. We might prefer to avoid it. But we should be aware that a choice to not use the word is largely pragmatic. Those who seek to reduce the rate of cigarette smoking are not required to advertise Nazi Germany as the place where such programs were pioneered. Nor should modern advocates of improving population health by eliminating genetic variants linked with serious disease be required to highlight a connection with those who were gravely mistaken about how this should be done. n

Sources

Agar N. Humanity’s End: Why We Should Reject Radical Enhancement. Cambridge, Mass.: MIT Press, 2010.Galton F. Inquiries into Human Faculty and Its Development. London: Macmillan, 1883.Kevles D. In the Name of Eugenics: Genetics and the Uses of Human Heredity. Cambridge, Mass.: Harvard University Press, 1998. Kitcher P. The Lives to Come: The Genetic Revolution and Human Possibilities. New York: Simon & Schuster, 1996.Paul D. Controlling Human Heredity: 1865 to the Present. Atlantic Highlands, NJ: Humanity Books, 1995.


Ask the ethicistShould an IVF clinic honor a single man’s request for sex selection?

Judy E. Stern, PhDProfessor of Obstetrics and Gynecology;

Professor of PathologyGeisel School of Medicine at DartmouthHanover, New Hampshire

Question: A 49-year-old single man wants a genetically related child. He thinks it is unlikely he will ever marry. The man is a professional and is financially secure. He asks the reproductive endocrinologist at an in vitro fertilization (IVF) clinic to arrange for a donated egg from a “high-quality” donor to be fertilized with his sperm to create an embryo that would be implanted in a gestational carrier. He plans to request preimplantation genetic diagnosis (PGD) for sex selection because he wants a son. The necessary technology is available. Should the IVF clinic honor his request?

Response: Assisted reproductive technology (ART) provides critical fertility assistance for individuals unable to achieve pregnancy, but it can also be used to provide fertility assistance in a variety of social situations where there is no medical diagnosis. Given that there is no medical indication for such treatment and that it is not a medical emergency, providers have the right to deny treatment; decisions whether or not to offer treatment in these cases can be challenging. The case here invokes a number of complex ethical questions, including whether to provide services for a single man of advanced age making requests for a child with specific “special” characteristics.

ART is regularly used to treat single individuals. Often the single person is a woman seeking insemination with donor sperm. Frequently, these women are in their late 30s or early 40s, with a ticking biological clock and no partner on the horizon. Many are financially stable, with good careers and strong support systems of family and friends. The vast majority of ART

clinics in the U.S. offer treatment to such women.

Single men, as in this case, also make requests for fertility assistance, although in such cases the man provides only his sperm, and treatment requires the services of a woman to provide an egg and the capacity to carry a pregnancy. The Ethics Committee of the American Society for Reproductive Medicine (ASRM) supports this treatment,1 but whether clinics treat such individuals is dependent largely on the clinic’s familiarity and comfort with the use of surrogacy. There is no a priori reason to deny treatment to such an individual.

Age of a prospective parent can raise concerns about whether to provide treatment. For women using their own eggs, the likelihood of

of which would be possible for use. In traditional surrogacy, the woman who supplies the egg also carries the pregnancy. This form of surrogacy can be initiated through a medically simple insemination procedure. In gestational surrogacy, the egg and sperm of intended parents or donors are combined in vitro to form an embryo gestated in a different, surrogate carrier. Gestational surrogacy enables a couple to have a child that, though gestated in another, will have their DNA.

In the case under discussion, although a traditional surrogate could be used, the man is requesting that two women be involved — one to supply the egg and one to carry the pregnancy. This request could be for one of several purposes: his plan to use PGD for sex selection; his concerns that a woman who would be a surrogate might not be a “suitable” person to also provide the egg; or perhaps he is concerned about the legal implications of there being no identified mother for any resulting child. Regarding the first two items, it is notable that the man’s request requires the egg donor to undergo procedures of ovarian stimulation and egg retrieval and the carrier to undergo hormone treatments, both of which would be unnecessary were simple insemination of a surrogate undertaken. Regarding the latter, he might assume (not necessarily correctly) that he would have less legal risk if the egg provider and the carrier were different women. Consultation with a legal advisor and exploration of state law in his state of residence would be important in exploring this assumption.

Use of PGD for sex selection is recognized by the ASRM as controversial when used for nonmedical reasons.3 Because there is no pressing reason, such as family balancing, to use that technology in this case, I would not include it as a treatment option for this patient.

In summary, none of the above issues individually precludes treatment. However, there is another consideration recommended by ASRM — that of the prospective parent’s

Continued on page 9

“ The case here invokes a number of complex ethical questions, including whether to provide services for a single male of advanced age making requests for a child with specific ‘special’ characteristics.”

success often determines treatment. But women can also use donor eggs, and women of advanced age (past age 45) have made use of donor eggs.2 There has been frequent debate about the upper age limit for treatment with donor eggs; many clinics set the limit at around age 50. At 49, the man in this case is within this age limit, thus age itself does not pose a reason to deny treatment.

Since there is no egg provider for the case under discussion, some form of surrogacy is needed. There are two types of surrogacy: traditional and gestational, either


The legal columnBalancing religious freedom and health care access

Holly Fernandez Lynch, JD, M. Bioethics

Executive Director, Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics

Harvard Law School Cambridge, Massachusetts

I. Glenn Cohen, JD Professor, Harvard Law School; Faculty Director, Petrie-Flom

Center for Health Law Policy, Biotechnology, and Bioethics

Cambridge, Massachusetts

Whether employers providing health insurance to their employees should be required to cover free contraceptives in the face of a religious objection to doing so is a divisive question, potentially pitting religious and reproductive freedom against one another. What the law permits or demands in this scenario has been the source of more than 100 federal cases since the Department of Health and Human Services (HHS) promulgated the contraceptives coverage mandate in 2011, requiring certain employers to provide health insurance coverage of contraceptives without cost to their employees. This article will briefly recap the Supreme Court’s 2014 decision on the mandate in Burwell v. Hobby Lobby Stores, Inc.,1 discuss pending litigation and recent regulations, and comment on the implications of these cases for religious accommodation in U.S. health care.

Where we areThe Affordable Care Act (ACA) requires that most employers offer group health insurance that provides “minimum essential coverage,” including free “preventive care and screenings” for women. In its regulations, HHS determined that this should be interpreted to include all FDA-approved contraceptive methods and sterilization procedures.2

Recognizing the potential for religious conflict in this mandate, HHS offered an exemption for

those meeting the relatively narrow definition of “religious employer,” i.e., churches and other houses of worship.2 It also offered an “accommodation” for certain nonprofit religious organizations, such as religious hospitals and universities, allowing them to notify the government or their health insurer of their objection to the mandate in order to be relieved of the responsibility to contract, arrange, pay or refer for contraceptive coverage. Instead, their insurer must step in to provide free contraceptives to their employees, at no cost to and without the involvement of the employer.2 HHS has explained that this will ultimately be cost-neutral for insurers, as they are avoiding the costs associated with pregnancy and additional beneficiaries.2 Importantly, prior to Hobby Lobby, all other employers — including religious owners of secular, for-profit businesses — remained fully subject to the mandate, despite their potential religious objections.

Although religious freedom most often conjures images of the First Amendment, free exercise is more stringently protected by a 1993 statute called the Religious Freedom Restoration Act (RFRA). This statute provides that the government “may substantially burden a person’s exercise of religion only if it demonstrates that application of the burden to the person — (1) is in furtherance of a compelling governmental interest; and (2) is the least restrictive means of furthering that compelling governmental interest.”3

The Hobby Lobby case involved a successful challenge to the mandate as a violation of RFRA. The company in question is a large, but closely held, arts-and-crafts chain that was, at the time, neither exempted from the mandate nor eligible for accommodation, despite being owned by a religious family that objects to certain contraceptives and runs the chain, according to its website, “in a manner consistent with Biblical principles.”

The Supreme Court, over the dissent of four justices, concluded that a closely held, for-profit corporation like Hobby Lobby was a “person” within the meaning of RFRA, and was

also capable of exercising religion. Thus, RFRA applied, and the mandate could not meet its demanding test. The majority determined that the mandate clearly imposed a substantial burden because the religious objectors faced a choice between potentially massive fines for noncompliance and violating their religious beliefs; it was deemed irrelevant that the challengers would not directly have to buy or use contraceptives since they sincerely objected even to being complicit in helping pay, arrange or contract for those services.1

Although the majority conceded a compelling government interest in the mandate (i.e., helping to improve equal access to contraceptives), it found that there was a less restrictive alternative available to achieve that interest; namely, extending the accommodation that HHS had already offered to religious nonprofits also to closely held, for-profit corporations.1 Immediately after Hobby Lobby, HHS began work to extend the accommodation in precisely this way, and it now applies both to eligible nonprofits and certain for-profits.2

Where we should be goingThe public response to litigation over the contraceptives coverage mandate, and in particular the outcome in Hobby Lobby, has pitted liberals against conservatives and suggested that religious liberty is in a zero-sum game with women’s reproductive freedoms. We think that this perspective dangerously oversimplifies matters. It is possible to advance both religious liberty and reproductive autonomy simultaneously by insisting that religious freedom be infringed only when absolutely necessary. Indeed, we think that RFRA and the Hobby Lobby decision both recognize this equilibrium: we need not insist that for-profit corporations abide by the contraceptives coverage mandate despite their religious objections because there is a way to achieve the very same goal of free contraceptives access without doing so.

That said, the government’s “accommodation” compromise has not

Continued on page 9


Ethics and the humanitiesThe brave surgeonA review of the film “The English Surgeon” and the book Do No Harm: Stories of Life, Death, and Brain Surgery, by Henry Marsh

Catherine Belling, PhDAssociate Professor, Medical

Humanities & BioethicsNorthwestern University Feinberg

School of Medicine Chicago, Illinois

“It makes the operation safer because it makes the surgeon braver.”

—Henry Marsh, in “The English Surgeon”

In “The English Surgeon,” a 2007 documentary film about British neurosurgeon Henry Marsh’s philanthropic work in Ukraine, Marsh says these words to a patient he must keep awake throughout a brain tumor removal. In England, the patient would be anesthetized during the drilling of his skull, at least. In Ukraine, the technology is unavailable. Yet Marsh is optimistic — because the patient will be able to report any changes, the surgeon can be more securely aggressive. Marsh’s story is a brilliant, yet humble, exploration of the surgeon’s need for bravery in the face of a terrifying dual risk to the patient: that of operating, and also that of doing nothing; or, as Marsh says, “Russian roulette with two revolvers.”

Director Geoffrey Smith’s film focuses on Marsh’s work with Ukrainian patients. It centers on three stories: one successful, and rivetingly filmed, tumor removal; one diagnosis of inoperable glioma and the agony of not being able to act; and one decision to operate that went terribly wrong. This last story frames the film, and Marsh’s sadness frames his approach to his work, underpinning his book-length 2015 memoir, Do No Harm: Stories of Life, Death, and Brain Surgery.

In Do No Harm, Marsh conveys the perplexity of brain surgery. His instruments move “through thought

itself, through emotion and reason,” and “memories, dreams and reflections consist of jelly” (p. 1). It’s “simply too strange to understand,” but this conundrum does not dissuade Marsh; and his real contribution to our understanding of medical practice lies in an extraordinary tolerance for uncertainty and ambiguity, where tolerance is never denial. He must acknowledge his fallibility, then set to work. The book’s title reminds us that, despite one’s Hippocratic best intentions, the surgeon (like all physicians) will, sooner or later, do some harm to a patient. In a way, Marsh has written an account of his faith — in knowledge, technique and effort — in the face of blood-curdling suspense. The combination makes it a compelling read.

Marsh conveys the aesthetic and technical wonder of surgery while retaining humility about his own place, like a very small visitor lucky enough to be allowed to see marvels: “Above me, like the great arches of a cathedral roof, are the deep veins of the brain … [and] in the midline the Great Vein of Galen, dark blue and glittering in the light of the microscope” (p. 7). Yet he is a workman inside the bodies he visits. He describes elevating the brain, “creating a narrow crawl space … along which I now crawl towards the aneurysm” (p. 26). Wholly containing him, the procedure feels “akin to bomb disposal work, though the bravery required is of a different kind as it is the patient’s life that is at risk and not the surgeon’s” (p. 13). The surgeon, though, is the one who must act, and live with the responsibility for his actions when things go wrong. And when they do go wrong, he berates himself for his confidence — “I had been insufficiently fearful” (p. 4).

This focus on surgeons’ need for bravery (which is never foolhardy) allows Marsh to make valuable observations about the role of self-defense in clinical detachment. Acting in a state of uncertainty and anxiety can deform good intentions. Reflecting on his early career, he notes that he lost “the simple altruism I had had as a medical student” (p. 83). It is easy to be sympathetic when one is not responsible for bad outcomes, but “with

responsibility comes fear of failure” and patients themselves “become objects of fear as well as of sympathy” (p. 215). Encouragingly, now nearing the end of his career, Marsh shows maturity, allowing more room for empathy: “I am less frightened by failure — I have come to accept it. ... I can dare to be a little less detached” (p. 83).

One of his reasons for writing the book, it seems, is a determination to examine all the harm he has caused, almost as if the good he has done can be left to speak for itself. “I feel an increasing obligation to bear witness to past mistakes I have made,” he says, and he is mercilessly self-critical (p. 154).

It’s a good idea to watch the film, “The English Surgeon,” while reading the book. From outside Marsh’s perspective, we can see the good he does. We see what a contribution he has made in Ukraine, where surgical success has met with sanctions and threats of imprisonment if it appears to show the state in a bad light.

Marsh is deeply averse to bureaucracy, and the Soviet-style framework he encounters in Kiev also colors his attitude about practicing under the British National Health Service. Summoned to an NHS chief executive’s office, he compares: it is “like the offices, I thought a little sourly, of all the ex-communist apparatchiki [functionaries] … I have dealt with in the former Soviet Union” (p. 162). The implications of this comparison are thought-provoking from the perspective of health care in the U.S. in 2015.

Marsh’s surgical work happens amidst a frustrating clamor of paperwork and negotiations with administrators over things like “the European Working Time Directive” (p. 169). Rebelling against the dictates of “corporate outpatient management,” he still finds he can switch roles, “becoming a kind and polite surgeon, instead of an impotent and angry victim of government targets” (p. 266) — but he resents having to do so.

Finally, though, both the book and the film present the wonder of the brain and those who dare to tangle with it. The stakes, in terms of health

Continued on next page


Legal, continued from page 7

Ethicist, continued from page 6

childrearing ability.4 This consideration raises issues that may go beyond the specific aspects of a case. Assessments on these issues are often made during a psychological evaluation that can, at times, reveal a troubling history or patterns of behavior. I would want the assessment in this case to evaluate this man’s ability to form lasting relationships and to parent a child who might not attain his preferred levels of perfection with regard to “high-quality” characteristics or gender. I would want to know why he wants to become a parent at this stage of his life. With

no mother for this infant, I would also want to know that he has an external support system of family or friends and the ability to interact positively with infants and children. Only with approval of the psychologist and positive indicators of his ability to parent would I recommend acceding to the man’s request.

Outcome: The man was evaluated and clinic staff decided not to proceed with the requested IVF cycle. He was referred elsewhere. n

SourcesThe Ethics Committee of the American Society for Reproductive Medicine. Access to fertility treatment by gays, lesbians, and unmarried persons: A committee opinion. Fertil Steril 2009; 92: 1190–1193.

Ethics Committee of the American Society for Reproductive Medicine. Child-rearing ability and the provision of fertility services: A committee opinion. Fertil Steril 2009; 92: 864–867.

Ethics Committee of the American Society for Reproductive Medicine. Use of reproductive technology for sex selection for nonmedical reasons. Fertil Steril 2004; 82: S232–235.

Sauer MV. Reproduction at an advanced maternal age and maternal health. Fertil Steril 2015; 103: 1136–1143.

been a panacea and has itself been the subject of ongoing litigation by religious objectors seeking nothing short of complete exemption from the mandate. These employers argue that even when their insurers separately contract with their employees to cover contraception at no cost, contraception unacceptably remains part of the employer’s plan. Moreover, they maintain that the accommodation is insufficient to relieve them of complicity because the requirement to provide notice of their objection simply serves as a trigger for the provision of the objectionable insurance coverage by someone else.4

These arguments may be sincere, but we maintain that the current accommodation can stand up to the RFRA test, whereas the bare mandate at issue in Hobby Lobby could not. In fact, with the exception of the Eighth Circuit in September 2015, every Circuit Court of Appeals to decide a case challenging the accommodation since the Supreme Court’s Hobby Lobby

ruling (seven of them) has determined that it does not even substantially burden religious belief.4 Moreover, RFRA permits religious beliefs to be substantially burdened in furtherance of a compelling government interest so long as there is no less-restrictive alternative, as is the case here. The accommodation requires the absolute minimum from employers — notice and identification of the relevant insurer — while simultaneously promoting the critically important goal of free access to contraceptives.

The Court in Hobby Lobby did float the idea of having the government cover contraceptives directly when an employer objects,1 and as part of a universal government health care system, that could make sense. However, our country has repeatedly rejected such approaches and maintained an essential role for employers. Counting the possibility of government intervention as an available alternative would flout the RFRA test, allowing religious objectors

to win in every case. But it is critical to recognize that one way to minimize this sort of conflict in the first place would be to eliminate our current system of employer-based health insurance altogether. If employers had no role in health care, their religious objections would have no impact on their employees’ access to medical services, which is as it should be. n

1 Burwell v. Hobby Lobby Stores, Inc., 134 S. Ct. 2751 (2014).

2 The Center for Consumer Information & Insurance Oversight (CCIIO), Centers for Medicare and Medicaid Services: Fact sheet: Women’s preventive services coverage, non-profit religious organizations, and closely-held for-profit entities. http://www.cms.gov/CCIIO/Resources/Fact-Sheets-and-FAQs/womens-preven-02012013.html (CCIIO Fact Sheet).

3 RFRA, 42 U.S. Code § 2000bb (1993). https://www.law.cornell.edu/uscode/text/42/chapter-21B.

4 Sobel L, Salganicoff A. Round 2 on the legal challenges to contraceptives coverage: Are nonprofits “substantially burdened” by the “accommodation?” Henry J. Kaiser Family Foundation, Aug. 5, 2015. http://kff.org/womens-health-policy/issue-brief/round-2-on-the-legal-challenges-to-contraceptive-coverage-are-nonprofits-substantially-burdened-by-the-accommodation/.

Humanities, continued from page 8

and life, are profound for the patient, but Marsh’s reflections convey the existential stakes for the surgeon, too: “Are the thoughts that I am thinking as I look at this solid lump of fatty protein covered in blood vessels really made out of the same stuff?” (p. 27). Underlying both book and film is the

contradiction that we are formed of matter that can be manipulated, for good or harm; and Marsh’s last words in the film convey the reasoning that underpins all his bravery: “What are we if we don’t try to help others? We are nothing, nothing at all.” n

“The English Surgeon,” dir. Geoffrey Smith. 2007. Film.

Marsh H. Do No Harm: Stories of Life, Death, and Brain Surgery. New York: Thomas Dunne Books, 2015.


DialogueGenomic newborn screening: Risks and benefits

Howard M. Saal, MD, FACMGDirector of Clinical GeneticsCincinnati Children’s Hospital

Medical CenterProfessor of PediatricsUniversity of Cincinnati

College of MedicineCincinnati, Ohio

Professor Ronald M. Green does an admirable job of identifying and discussing many of the complex issues related to the current National Institute of Child Health and Human Development–funded research program intended to explore population-wide genomic screening of newborns (Lahey Health Journal of Medical Ethics, spring 2015). Newborn screening in the United States began with the work of Dr. Robert Guthrie, who, in 1961, developed the first inexpensive screening test for phenylketonuria; this was followed by the development of testing for T4 to diagnose congenital hypothyroidism, by Jean Dusseault in 1973.1 For a period of time, newborn screening was limited to testing for phenylketonuria, tyrosinemia, congenital hypothyroidism and galactosemia, all of which could be performed inexpensively on blood spots collected on filter paper. What made newborn screening for these disorders attractive was that treatment could be initiated in a timely manner, which could prevent death or severe morbidity. The development of tandem mass spectrometry has led to effective, cost-efficient screening for a large number of inborn errors in metabolism. The United States Department of Health and Human Services Advisory Committee on Heritable Disorders in Newborns and Children has recommended a uniform screening panel that screens for 32 core disorders and 26 secondary disorders.2

With the development of next-generation sequencing and the advancement of sequencing technologies, the cost of genome sequencing has dropped in price to about $1,000. However, it must be remembered that the current cost of newborn screening in Massachusetts for 53 inborn errors in metabolism is

just $68.79.1 Until the cost of genomic sequencing can approach this level, the practicality of genomic newborn screening will remain, at least economically, difficult to institute unless significant benefits can be demonstrated that will validate genomic sequencing.

Several technical issues exist that separate how a newborn genomic screening program would differ significantly from what is currently being used. The current technology offers rapid diagnosis, allowing for timely confirmation testing, followed by therapeutic intervention. With genomic sequencing, although the sequencing itself would take two to three days, interpretation of data from hundreds, perhaps thousands, of genomic variants could lead to delays in diagnosis and treatment. There are insufficient bioinformatics resources to support a large influx of new data from a nationwide genomic newborn screening program. Current data repositories of genomic variants must be expanded, and new databases need to be established to assist in the interpretation of variants of unknown significance. Inability to accurately interpret data generated by genome sequencing could result in missed diagnoses and misdiagnoses. Additionally, new strategies will need to be developed to store the overwhelming amount of data that will be generated.

Prior to the development of the newer technologies of comparative genome hybridization and genomic sequencing, approximately 50 percent of children with birth defects and genetic disorders went undiagnosed. The first step in major technology that increased our ability to diagnose rare genetic disorders was array comparative genome hybridization. This technology is used to diagnose submicroscopic chromosomal deletions and duplications and has increased the diagnostic yield of rare chromosome disorders by approximately 10 to 15 percent.4 Whole genome and whole exome sequencing have further increased diagnostic yield by approximately 30 percent.5 However, these tests have been designed as diagnostic tests, not as screening tests for large populations. The efficacy and interpretation of results from both of these testing modalities are dependent on comprehensive clinical analysis and careful phenotyping. It is difficult to envision using genomic

newborn screening prior to having more research and information regarding the phenotypes of many of the rare and ultra-rare diseases that are likely to be identified. In addition, even with knowledge of the phenotype of a child with a suspected genetic disorder, the interpretation of the sequence often takes weeks to months before a final diagnosis is confirmed.

One benefit of genomic sequencing as a screening test is the prospect of identifying mutations for most single-gene disorders. The number of single-gene disorders has risen dramatically, in no small part due to this technology. Over 6,000 single-gene disorders and 10,706 disease genes have been identified,6 and this number is increasing daily. However, most of these conditions are very rare and have no known treatments or interventions. Professor Green also points out that newborn genomic screening can obviate the need for the medical diagnostic odyssey when a child is born with a rare genetic disorder. However, since genomic sequencing and array comparative genome hybridization are becoming mainstream tests, these studies can be done postnatally, when a child presents with signs and symptoms suggestive of a genetic disorder.

With the looming possibility of being able to diagnose most Mendelian disorders by genomic sequencing, opinions will differ as to which diagnoses should be released to health care professionals and families. Should all possible diagnoses be released? In the absence of adequate natural histories and treatments for most of the rare disorders, one must be wary of this option. What if the diagnosis is for an adult-onset disorder or predisposition, such as the BRCA1 or BRCA2 mutation predisposing someone to breast or ovarian cancer? It is recommended that predictive genetic testing of minors be considered only if effective medical interventions exist.7

If such information exists, at what age should it be discussed with the child? If testing is done on the newborn, one no longer has the option to let the child, when older, decide for himself/herself as to whether he/she wishes to know about such a diagnosis, especially when faced with a de novo autosomal dominant disorder. The results will exist in the medical record to which the individual will have access at the age


of majority. How does one store this information safely and confidentially until age of majority? Also, with a diagnosis of an autosomal dominant adult-onset disorder in a child, one of the parents may also have the same mutation. The need for appropriate genetic counseling is paramount in such situations, both prior to and after testing.

One option may be to filter analyses to identify a limited number of disorders, perhaps only hundreds or a few thousand instead of more than 6,000. Several clinical laboratories are already using genomic sequencing for diagnosing groups of disorders with related signs and symptoms. By filtering the data, these laboratories have developed panels of a limited number of genes that are related to specific phenotypes, such as hearing loss and infantile seizures.

Given the reduced cost of genomic sequencing with improved bioinformatics, the American College of Medical Genetics Working Group recommended that, in addition to performing diagnostic testing, clinical laboratories should also analyze all samples for 57 genetic variants that are associated with serious disorders for which treatments, interventions and monitoring were available.8 This policy statement was met with a great deal of criticism because the recommendation was for mandatory reporting of results with no discussion of patient autonomy or informed consent.9 Genomic newborn screening could benefit the child’s family with regard to reproductive decision making. Although it should be important for each family to know if they have an elevated risk of having a child with a serious birth defect, for many families the decision would be limited to whether to become pregnant, since prenatal genetic diagnosis would limit decisions to terminate or continue a pregnancy. The option for preimplantation genetic diagnosis is limited to families that could manage the high cost of in vitro fertilization and blastocyst genetic testing.

Finally, there are already challenges to the medical management of the current number of children who are identified by newborn screening as having inborn errors in metabolism. Too few trained medical geneticists and genetic counselors are available to address current needs. If genomic newborn screening were to become the standard screening test, the number of children needing diagnostic confirmation, medical

treatment and management could easily overwhelm an already understaffed system. In addition, an inadequate number of trained genetic counselors are available to meet the demand of genetic counseling for the thousands of families that will be identified. There would have to be a dramatic increase in support of medical genetics residency programs and in training programs for genetic counselors. Also, there would need to be a significant paradigm shift in medical school, medical residency, nursing and other health care training that would place more emphasis on integrating patients’ genomic data into their health care management plans.

In conclusion, technology always moves forward; however, technological advances are often implemented before society is ready for the full impact of what they offer. Genomic newborn screening is one technology that is likely to become a reality someday. There will be great benefits, but there will also be many pitfalls. Clearly, there will be a need for a great deal of research to understand the technical aspects of testing, bioinformatics and broad public and professional discourse on the ethical, social and psychosocial impacts of genomic newborn screening.

Response: Dr. Saal is entirely right to observe that we are not yet ready for the widespread implementation of genomic screening of newborns. Among the challenges are imperfect knowledge of the relationship between genotype and phenotype; issues of cost; delays in diagnosis caused by the need to interpret data from hundreds, perhaps thousands, of genomic variants; and the paucity of genetic professionals to interpret such information. Nevertheless, I am convinced that as the cost of testing continues to drop, and as our understanding of the significance of genomic variants grows, genomic newborn screening will be in our future.

This expectation renders even more important early consideration of specific ethical issues associated with genomic screening. One major set of issues needing careful attention is predictive genetic testing of minors. As Dr. Saal observes, there has been a consensus that such testing should go forward only if effective medical interventions exist. There are also concerns about impinging on the child’s future autonomy in the case

of adult-onset conditions such as the BRCA1 or BRCA2 mutations. Nevertheless, there are also considerations on the other side of this debate. One is the difficulty of ensuring that relevant medical information is available when the grown child needs it. This might warrant early disclosure to parents of conditions of concern, and it suggests the need for greater research on the actual impact of such disclosure on both the child and the family. Another consideration is the relevance of such information to parental reproductive decision making, including parents’ possible need to employ genetic testing at any of several points in their future reproductive decisions.

The lead time that exists before the implementation of newborn genomic screening is an opportunity to encourage public discussion of the norms that should govern decisions made on behalf of those who are too young to make such decisions themselves. n

Ronald M. Green, PhDEmeritus Professor for the Study of

Ethics and Human Values Dartmouth CollegeHanover, New Hampshire

1 Association of Public Health Laboratories. The newborn screening story. http://www.aphl.org/AboutAPHL/publications/Documents/NBS_2013May_The-Newborn-Screening-Story_How-One-Simple-Test-Changed-Lives-Science-and-Health-in-America.pdf. Accessed June 12, 2015.

2 Health Resources and Services Administration. Newborn screening: Toward a uniform screening panel and system. http://www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/uniformscreening.pdf. Accessed June 12, 2015.

3 Baby’s first test. http://www.babysfirsttest.org/newborn-screening/states/Massachusetts. Accessed June 12, 2015.

4 Miller DT, Adam MP, Aradhya S, et al. Consensus statement: Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010, May 14; 86(5): 749–764.

5 Yang Y, Muzny DM, Reid JG, et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 2013, Oct 17; 369(16): 1502–1511.

6 GeneCards. Genes associated with diseases. http://www.genecards.org/cgi-bin/listdiseasecards.pl?type=full. Accessed June 5, 2015.

7 Ross LF, Saal HM, David KL, Anderson RR. American Academy of Pediatrics; American College of Medical Genetics and Genomics. Technical report: Ethical and policy issues in genetic testing and screening of children. Genet Med 2013, Mar; 15(3): 234–245.

8 Green RC, Berg JS, Grody WW, et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med 2013, July; 15: 565–574.

9 Burke W, Antommaria AHM, Bennett R, et al. Recommendations for returning genomic incidental findings? We need to talk! Genet Med 2013, Nov; 15(11): 854–859.

41 Mall Road, Burlington, MA 01805

Lahey Health Journal of Medical Ethics encourages reader participation. We welcome comments for our “Dialogue” column and invite submission of ethical dilemmas for “Ask the ethicist.” Send correspondence and requests for complimentary subscriptions to [email protected].

Lahey Health Journal of Medical Ethics can be found on the Lahey Hospital & Medical Center Medical Ethics website at Lahey.org/Ethics.

A journal published by Lahey Health€¦ · A journal published by Lahey Health Fall 2015 Feature...

Documents

Transcript of A journal published by Lahey Health€¦ · A journal published by Lahey Health Fall 2015 Feature...