Genomic Messages: How the Evolving Science of Genetics Affects Our Health, Families, and Future - George Annas, Sherman Elias (2015)
Chapter 5. Reprogenomics
In the baby trade, demand is too high and
desire too deep to be stopped. If parents want
children and nature doesn’t comply, then they are
likely to pursue these children through whatever means
possible. They will cross international boundaries and
undergo untested, unregulated treatments.
—Debora L. Spar, The Baby Business (2006)
No other area of genomics has fostered more debate and more attempts at regulation than the new reproductive technologies, also known as reprogenomics. This is not only because reprogenomics centers on babies and pregnancy, but also because it is fostered by the creation of extracorporeal embryos and the private recruitment of “surrogate mothers” to produce children genetically related to at least one member of the contracting couple. In the United States, the reproductive medicine industry has proven impossible to regulate at the federal level and formidable to regulate at the state level. Social media, including Facebook and Twitter, have broken national boundaries and enabled a thriving international trade that the Wall Street Journal has described as providing customers with a way to assemble a “global baby.” In their words, “With an international network of surrogate mothers and egg and sperm donors, a new industry is emerging to produce children on the cheap and outside the reach of restrictive laws.”
A front page article in the Styles section of the New York Times in early 2014 featured a half-page photo of a gay couple (David Sigal and Brad Hoylman) with their three-year-old daughter Silvia. The child had been gestated by a woman who used a donor egg and sperm mixed from both men. It is not unusual for a gay couple to contract with a woman to bear them a child. The story was about New York State reconsidering its law against paying women to bear children—“commercial surrogacy”—and perhaps adopting a law more similar to California, which permits payment. Hoylman, a new member of the New York Senate, has put this issue on its legislative agenda.
The New York law banning commercial surrogacy was passed in response to the memorable New Jersey Baby M case. Mary Beth Whitehead had agreed to have a baby for a childless couple but changed her mind after the child was born, deciding she wanted to keep the newborn. The New Jersey Supreme Court ultimately ruled that the contract the couple had signed with Mary Beth, in which she promised them her child, violated the state’s law against baby selling and was void. This transformed the dispute into a traditional custody case between parents. Custody was awarded to the sperm donor father because the judge thought it would be in the child’s best interest to be raised by his father instead of his mother, who was given visitation rights. Mary Beth Whitehead was what is now referred to as a “traditional surrogate”: she was artificially inseminated with the father’s sperm, and her own egg provided the other half of the child’s DNA. She was not only Baby M’s gestational (birth) mother, but she was also her genetic mother. Surrogate motherhood today almost always utilizes a donor egg so that the surrogate mother is not genetically related to the child. It was this change that convinced the California Supreme Court that the “real” mother of the child in such an arrangement was the “contracting mother,” the woman who hired the surrogate mother to gestate a child for her. In 2012 New Jersey Governor Chris Christie vetoed a bill that would have permitted some forms of payment to women who gestate children for others. Christie said he wanted more public discussion of “such a profound change in the traditional beginnings of a family.”
In this chapter we return to the same issues that were so prominent in state legislatures a quarter century ago. What should you consider when deciding whether to support additional regulation of the new reproductive technologies, and what should you consider when comparing adoption to assisted reproduction methods that permit you to have a child with a genetic relationship to you or your partner? The nature of the fertility industry also matters. It is, as Debora Spar chronicles in The Baby Business, a highly commercialized sphere of medicine. It is also unique in that its product is a genetically related child, and the price the would-be parents are willing to pay “is literally inestimable.” This is because if you seek a genetic tie to your child, “the possibility of substitution disappears.”
Relationships and Reprogenomics
Genomics and reproduction are inextricably connected, and the transmission of messages from our genome is the basis for creating most family relationships. It is a biological imperative, sometimes referred to as a natural instinct, for all species (including humans) to survive, and the means of species survival is reproduction. This is a fundamental feature of life. Moreover, because children possess a genome made up half from the mother and half from the father, children are genetically distinct from their parents. This difference matters and is the basis of evolution, a change in the gene pool of a population over time. All evolution is based on genetic change. The environment “selects” those organisms best adapted to reproduce themselves. If environmental conditions change, organisms that possess the most adaptive characteristics for those new conditions will come to dominate because of their increased reproductive success. It is the mutations in the genomic endowment of individuals that enable such adaptive changes. Another way of saying this on the species level is “mutate or die.”
Until relatively recently, human reproduction was almost exclusively based on sexual intercourse (the exception was the use of artificial insemination). With the advent, however, of what have come to be known as assisted reproductive technologies, or ARTs, it is now possible for humans to transmit their genes without sexual intercourse. ARTs are as remarkable as the sexual revolution brought about by effective contraception, which made sex without reproduction predictable. It should surprise no one that the social and ethical consequences of ARTs are every bit as revolutionary and remain the subject of intense public debate and speculation.
The birth of contemporary ARTs can be dated to the birth of Louise Brown in 1978. She is often inaccurately referred to as the world’s “first test-tube baby” (figure 5.1). This description is inaccurate not because she wasn’t the first (she was) but because there was no test tube involved. Her conception took place in a petri dish, and the embryo created (by combining her mother’s egg and father’s sperm) was transferred to her mother for gestation. The proper medical term for this procedure is in vitro fertilization, or IVF. Louise Brown’s healthy birth came after more than a decade-long collaboration between an embryologist, Robert Edwards, and an obstetrician, Patrick Steptoe. The pair encountered intense opposition from religious, social, and even medical groups, both because of the implications of creating a human embryo in the laboratory and because of the world’s overpopulation. As quoted in a Science article, people said, “Why would we help people having children when our main problem is how to prevent people from having children?” Others worried that the IVF procedure would create fetuses and infants with severe disabilities, and that there was no real science undergirding their “trial and error” methods. Criticism was silenced, however, with the birth of Louise Brown, who became an overnight international media sensation. Steptoe died in 1988. In 2010 Edwards was awarded the Nobel Prize in Medicine for his pioneering work, which opened the door to IVF and also to human embryo research and the derivation of embryonic stem cells. Had he survived, Steptoe would have shared the prize. By the time the prize was awarded, Louise Brown had given birth to her own child.
5.1 Robert Edwards with Louise Brown and her mother and son. Chris Radburn, “Professor Robert Edwards wins Nobel Prize,” Associated Press, October 4, 2010.
Nearly ten years after the birth of Louise Brown, in 1986, we published an article entitled “Social Policy Considerations in Noncoital Reproduction” in JAMA, the journal of the American Medical Association. We were so confident that it would quickly be recognized as the most scholarly and authoritative article on the subject that we purchased 1,000 reprints, anticipating requests for copies from around the globe (reprints are mostly a thing of the past, with PDF copies sent electronically today). A year later we still had about 950 reprints in our offices. “How could this be?” we asked ourselves. Maybe it was the timing, or maybe it was the title. The assisted reproductive technologies were still very novel and were known by a variety of terms, including “artificial reproduction” and “unnatural reproduction,” but no one favored adopting our overly clinical term, “noncoital reproduction.”
We believed it was prudent to reflect on the societal issues raised by these new techniques and arrangements, including IVF, use of embryos created in the laboratory, and surrogate motherhood. People magazine had just named Louise Brown one of the ten most prominent people of the decade, one who dominated it “by simply being.” In the context of clinical medical practice, we predicted that it would “often be critical to make distinctions, previously irrelevant, between the genetic, gestational, and rearing parents when sorting out individual rights and responsibilities.” A quarter of a century later, we can see that our predictions of confusion and conflict were, if anything, understated. A real-life experience from Sherman’s hospital illustrates some still unresolved disputes.
Joan (not her real name) was transferred from a community hospital to Northwestern while experiencing vaginal bleeding and carrying twins at twenty-one weeks of pregnancy. Joan was a “surrogate mother” and was accompanied by the gamete donor couple (who had provided the egg and sperm, hiring her to gestate the twin pregnancy that she was carrying following IVF). The twins were both alive, but she had begun to dilate, and the membranes were protruding (“hourglassing”) through the cervix into the vagina. A decision had to be made as to whether to try an emergency surgical procedure, called a circlage, in which the membranes would be pushed back into the uterus and a purse-string suture placed around the cervix to cinch it closed. It was explained to Joan and, at her request, to the gamete donor couple, that a circlage procedure carried risks to the fetuses, as well as to her. The likelihood of the procedure being successful in prolonging the pregnancy until the fetuses became viable was estimated to be low, in the range of 10–20 percent, but experience with cases like hers was very limited. Even if the pregnancy could be prolonged, there was a risk of delivering extremely premature infants who would require prolonged hospitalization in the newborn intensive care unit. The possibility of one or both infants suffering severe brain injury was very high. The risk to Joan was also high, particularly the risk of infection, which could lead to infertility or even a hysterectomy. The alternative approach was to induce labor with drugs and terminate the pregnancy.
Who should make the decision? Joan? The gamete donors (also the intended parents)? Joan’s physician? A judge? The hospital’s ethics committee? Basic principles of medical ethics and law give the authority to Joan because it is her body and she has the most at stake in the decision. When a medical intervention affects only the patient, the patient is afforded the legal right to make the decision. There is little room for dispute unless the patient is unable to understand the information necessary to make an informed choice. But what about this case, which involves not only the patient, Joan, but also two fetuses (to which she is genetically unrelated) and the genetic parents of the fetuses? It could be argued that since the entire purpose of the pregnancy was to provide the two gamete donors with genetic children, the architects of the “deal,” sometimes referred to as a “family project,” should be the primary decision makers.
It has been suggested that the gestational mother should have less to say about fetuses that she is carrying if they are not genetically related to her. The argument is that she should be considered not a pregnant woman at all but rather a type of container or vehicle, albeit a “viable vehicle,” to deliver the fetuses to their genetic parents. This, however, seems wrong, because Joan is pregnant, is very much biologically (if not genetically) connected to the fetuses she is carrying, and is taking all the physical risk, and much of the psychological risk, of the pregnancy. Whatever the relationship between the fetuses and the gamete donors, the relationship between the fetuses and Joan is much closer and more intimate. We also know that Joan’s body is the site of all decisions, and Joan is the only one who is guaranteed to be present at the time of birth to make decisions about the newborns’ care if necessary.
All these reasons, we think, suggest that Joan should make the treatment decision. Joan’s physician came to the same conclusion. The gamete (egg and sperm) donor couple fully supported Joan’s decision to terminate the pregnancy, although they were involved in the decision making only because Joan permitted them to be. Had they disagreed with Joan and demanded that the pregnancy be continued, their demand should have been ignored. Within a few hours of inducing labor, the twins were born. Because they were previable, no resuscitation efforts were made, and they died. Following the extremely premature delivery, Joan experienced excessive uterine bleeding, and an emergency removal of the placenta was performed under general anesthesia. The procedure was complicated because the placentas did not separate easily from the wall of the uterus. Joan was given twelve units of blood and required admission to the intensive care unit for thirty-six hours. She was discharged three days later.
Few surrogate mother arrangements go so horribly wrong medically. But all such arrangements require us to identify both the mother of the fetus and resulting child, as well as the person who has the right to make treatment decisions regarding the fetus during the pregnancy and the child after birth. Before IVF, we never questioned the identity of the child’s mother, even if the identity of the father was in doubt. Now both parental identities can be suspect, and it seems “natural” in our new genomic age to turn to DNA to define the mother-child relationship. This is often done, even though it seems simply wrong in a case like Joan’s, where the biological contribution, as well as risk of life, is overwhelmingly on the side of the gestational mother and her relationship to the child. To date, uniformity in laws has proven impossible, and people commonly pick the state in which to engage a surrogate mother based on its particular laws (for instance, California has been particularly inviting, since it recognizes the contracting couple or “intended parents” as the child’s legal parents). In the words of law professor Patricia Williams, “The [state] laws regarding surrogacy are a jumble of inconsistent public policies, free-market contract, civil interventions, and criminal sanctions.”
Whatever state you are in, we don’t think either genetics or contracts alone should determine parenthood and parental relationships. Rather we continue to believe, as we did at the dawn of the new reproductive technologies age in the 1980s, that the gestational mother (historically and accurately described simply as the “birth mother”) should continue to be considered the child’s legal mother for all purposes, with the rights and responsibilities to protect the child at birth. She can, should she choose so after birth, terminate her parental rights to the child. But termination of parental rights should always be her after-birth decision, not one imposed on her by contract or judicial decree prior to birth. Some commentators have suggested that the insistence that the birth mother continue to be legally considered the child’s mother, even though she has no genetic relationship to the child, represents a refusal to acknowledge the new genetics and the “new families” genetic technology can help create. We disagree, because, we think, it is a violation of the gestational mother’s human dignity to be treated as nothing more than an incubator. Moreover, we have noted that even as a matter of simple pragmatism in ART, the use of donor eggs (where the egg of a young woman is used to create an embryo for gestation by another woman—usually an older woman—who gestates and intends to raise the child) is much more common than the use of full surrogacy (where an egg from a donor—who could be the contracting woman—is used to create an embryo for gestation by a woman who intends to give up the child upon birth).
Applying the genetic model to donor eggs would mean that the woman who uses a donor egg to create an embryo that she gestates and gives birth to with the intention of rearing the child is not to be considered the child’s mother (the egg donor is). This, we think, is socially and ethically unacceptable, as it puts all births in question: just delivering a child would no longer be sufficient to be presumed to be the child’s mother. Instead, DNA samples would have to be taken and contracts examined to determine whose DNA was used, and therefore the child’s genetic (real?) mother. Only a social policy that was indifferent to the rights and welfare of both pregnant women and children could, we think, support such a counterintuitive and genomic-controlling result. The “California solution” of using contracts to designate the “intended parents” as the real parents is equally unsatisfactory, because while it does identify the parents, it does so at the expense of making the child a market commodity whose family relationships are determined entirely by a commercial transaction memorialized in a contract.
Social Policy Issues and Reprogenomics
In our JAMA article, we discussed various assisted reproductive technologies, not just the use of a gestational or “surrogate” mother but also artificial insemination by donor (AID), IVF, and embryo freezing. To help prioritize the need to develop policies for these methods, we constructed a table in which we assigned a value for an “Index of Relative Importance of Societal Issues.” The major issues considered were almost identical to the issues we continue to debate today: the potential of new methods to be put to uses other than infertility, ways to protect the human embryo, identification of the resulting child’s mother and father, screening of gamete donors, donor anonymity, and opportunities for commercialization.
Many of these issues are still being actively debated, and there have also been some notable surprises. The primary surprise to us is how central commercialization and the market have become to ARTs, and how globalized the fertility industry generally has become. We gave no thought to the rise of the Internet and the ability of couples, gamete sellers, and potential surrogate mothers to use the Internet to find each other and make deals that did not directly involve physicians (or lawyers) at all. Commercialization has taken many procedures out of the hands of physicians altogether and placed them in settings devoid of any meaningful regulation or oversight—most notably the Internet, which has facilitated the globalization of ARTs. Couples now have the entire world to choose from for reproductive services. India, for example, has become a “go-to country” for hiring a surrogate mother, and an entire new industry has grown up around this practice there. Today no meaningful discussion of reprogenomics can ignore either globalization or the use of the Internet. Canada prohibits the purchase and sale of gametes and payment of surrogate mothers. This law has been upheld by their Supreme Court. Nonetheless, citizens of Canada can, and do, make commercial deals with women from the United States and India on a regular basis. The ARTs simply cannot be effectively regulated globally on a country-by-country basis nor in the United States on a state-by-state basis.
Not only have opportunities for commercialization increased, but so have the number of ART methods and societal arrangements, including (but by no means limited to) egg freezing, “oncofertility” (preserving fertility of children and adults undergoing treatment for cancer and other life-threatening diseases), preimplantation genetic diagnosis, embryonic stem cell research, use of “savior siblings” (having a child to harvest umbilical cord blood stem cells in order to save the life of another child with a life-threatening disease), and the most socially controversial practice: asexual reproductive cloning. Because this remains impossible, we will hold off discussion of cloning until the final chapter of the book. For defining relationships based on genetics, however, it is worth noting that asexual genetic replication would destabilize family relationships. A woman who used her own egg and somatic (body) cell to create an embryo, then gestated and gave birth to the child, would be simultaneously the child’s mother and the child’s sister. Another reason for postponing the cloning discussion is that cloning has little, if anything, to do with assisted reproduction—since whatever else one can say about cloning, there is no “natural instinct” or urge for humans to reproduce asexually.
The rights and welfare of resulting children have become more important in the ART realm, and it is worth noting the paradox that the rights and welfare of children have historically been a secondary consideration in this field. When we first wrote on this subject twenty-five years ago, we had a great deal to say about protecting gamete donors, explicating parental rights and duties, defining the status of embryos, and even dealing with commercialization. But we devoted only one sentence to what we argued should be the undisputable “foundation” upon which ART guidelines should be built: “Primary consideration should always be given to the ‘best interests’ of the potential child, rather than to the donors, the infertile couple, or the physician or clinic.”
We continue to believe this, while acknowledging that this conclusion remains in some dispute and is not always easy to apply. It does answer the question of whether permanent records should be kept regarding the genetic parents (yes, because the child may want to know in the future) but does not so easily answer questions about whether the risks of specific procedures, like ICSI (intra-cytoplasmic sperm injection, injecting a single sperm into an egg, which could result in a child with the same genetic infertility problem as his father), are justifiable from the perspective of a child that would not have been born at all had ICSI (or any other ART with risks to the child) not been used. As Carl Djerassi has his character Frankenthaler note in his play about ICSI, An Immaculate Misconception (2000), “Before ICSI, men couldn’t inherit infertility . . . it was uninheritable! But now?” It is at least a paradox that the infertility industry, dedicated to treating infertility, also creates infertile males—for whom it can supply additional treatment. Of course, simply ignoring risks to the child because it would not exist without running those risks proves too much: it would justify complete indifference to the welfare of future children. But requiring would-be parents to avoid any and all risks to future children is also too exacting a standard. A parental obligation to avoid unreasonable and predictable risks may be as good as we can do for now, while studies of the children of ART continue.
Finally, and perhaps most importantly, we noted that these new technologies “not only change what we can do with regard to human reproduction, but they also threaten to change how we think about human reproduction, and perhaps how we think about humanness itself.” In the early days, for example, it was thought that the children of IVF, “test-tube babies,” might be looked at (and look at themselves) as freaks. This has obviously not turned out to be the case. Instead, more and more women are postponing attempts to have a child until late in their thirties, using the existence of ARTs as a rationale. Major corporations, led by Apple and Facebook, now offer their female employees the “benefit” of egg freezing—an offer that is likely to further spur the nascent egg-freezing industry but may ultimately do professional women more harm than good by encouraging them to postpone childbirth until they have fulfilled their “obligations” to their employers. This is because postponing pregnancy can mean having no child at all. Egg freezing is not the biological “insurance” it is often marketed as—it is more in the nature of a high-stakes gamble that your eggs can be successfully used to create embryos that you will be able to carry to term. It is too early for meaningful data on the usefulness and effectiveness of egg freezing to postpone childbearing.
Simply because IVF and childbearing later in life have been mainstreamed does not mean that other methods of ART, including use of frozen eggs, will be equally safe, effective, or accepted. In fact, as we observed in our JAMAarticle, IVF using the gametes of the married couple actually presents almost no new issues other than the creation of an extracorporeal embryo—that is, an embryo created outside the human body. This issue, however, is not a relationship one but rather a research one: the very existence of extracorporeal embryos has enticed scientists to manipulate and utilize the embryo for nonreproductive purposes, including the creation of embryonic stem cells.
Additional screening of extracorporeal embryos in IVF can also be seen as an integral part of IVF itself. Termed preimplantation genetic diagnosis, or PGD, the procedure combines IVF with manipulation of the embryo to remove a cell from it five to six days after fertilization. The cell’s genome is then examined to determine the presence or absence of specific genetic traits in the embryo. If the embryo is found genetically acceptable, it is used to attempt a pregnancy. PGD has been used primarily to select embryos that do not have conditions such as cystic fibrosis or myotonic dystrophy. By identifying embryos with aneuploidy and not using them to attempt a pregnancy, the success rate of IVF has been dramatically improved. The most controversial use of PGD is to use the technique to either screen for late-onset disease (diseases that won’t manifest until adulthood, if at all) or for specific traits, such as gender, or even hair or eye color. Looking for such characteristics has been labeled “designer babies,” and this seems a fair description of the goal. Screening for serious genetic diseases is one thing; screening for social reasons is another, and it should be discouraged if not outright condemned, because it directly commodifies children by valuing them not for themselves but for specific “desirable” characteristics.
PGD can also be used to prevent the use of an embryo with a serious genetic condition, and even keep the knowledge of the detrimental condition from the woman. Barbara Bailey (not her real name), for example, was worried that she might pass a gene (PSEN1) that caused early Alzheimer disease in her mother to her child but didn’t want to know whether she herself had the gene. Genomic practitioners were able to help her. Using in vitro fertilization (IVF), Barbara and her husband created embryos in a petri dish. In similar fashion to the technique used in the movie Gattaca, preimplantation genetic diagnosis was used to screen each embryo to see if it carried the PSEN1 gene. Two embryos that did not have the gene were then implanted into Barbara Bailey. Barbara herself was able to be certain her children would not have the PSEN1 gene without simultaneously learning if she had it herself. There are some genomic messages we want to hear, and some genomic messages we may not want to know about.
Related to PGD is a technique that conjures up even more anxiety about creating designer babies: so-called three-parent IVF, or mitochondrial manipulation techniques. Mitochondria are small specialized structures found in the cytoplasm that act as tiny power plants to provide energy essential for cellular function. Power-hungry cells in such tissues as brain, heart, muscle, liver, and kidneys contain the most mitochondria—up to several thousand per cell. Mitochondria have their own genomes separate from the genome present in the nucleus of the cell; mitochondrial DNA (mtDNA) are circular and contain only thirty-seven genes. Mitochondria are almost exclusively inherited from the mother; the egg usually destroys mitochondria in sperm during fertilization. About 4,000 children are born in the United States annually with a mitochondrial disease.
A technique has been developed that could allow women carrying mtDNA mutations to circumvent passing on a mitochondrial disease to their children by replacing mutant mtDNA with normal donor mitochondria in unfertilized eggs or at the single-cell-embryo stage. Another rationale for using the technique is to increase the likelihood that the egg from an older woman could be successfully used in IVF (by transferring the cytoplasm from the egg of a younger woman to the older woman’s eggs). The feasibility of treatment of mtDNA diseases has been demonstrated in animal models and in human eggs, and the FDA is currently deciding whether it is safe to permit research on humans with this technique (the FDA is not considering the ethical issues). The primary ethical arguments against using the technique are that it crosses the “bright line” of germ line genetic modifications—genetic modifications producing “designer babies” whose design genes will be passed down to future generations and could harm them—and that given the unknown risks of the procedure, alternatives (including use of a donor egg or PGD) should be pursued instead.
The designer baby argument is formidable, and we will return to it in chapter 10. A child could be considered genetically designed by modifying only one gene. The “three-parent baby” argument, on the other hand, is much weaker because supplying 37 genes out of 20,000 is hardly sufficient to be named a third parent, any more than supplying a single replacement gene—were this possible—makes the source of the replacement gene a parent. The central question then remains: do we have a compelling reason to cross the line into genetic engineering? The argument is a frail one, and there seems no reason at all to cross the line for anyone who supports the use of IVF with PGD or donor eggs. In early 2015 the House of Commons, by a vote of 382 to 128, approved the licensing of facilities to begin to use this procedure in England. Approval by a publicly-elected body, with oversight by a public agency, seems just right to us as a way to introduce extremely novel procedures into clinical trials. On the other hand, without any public debate, there are scientists who argue that this decision gives the green light to tinker “with the rest of our genome.” This is a serious misreading of the vote.
Extracorporeal Embryos and Stem Cell Research
Manipulating the human embryo for reproduction purposes is controversial because of its effect on both the resulting child and society’s views on parenthood. But any manipulation of human embryos remains highly controversial, even if the embryos are not destined to be used for reproduction. The use of human embryos for medical research, for example, has remained the most politically contentious medical research area since IVF was introduced. Debate over federal funding of such research continues to this day, with the only hope of compromise centered on using so-called leftover or spare embryos created for use in IVF clinics. This is because such embryos were created for a “legitimate” reproductive purpose (not to be used instrumentally, but simply as means to a research end), and when the couple no longer wishes to or needs to use these (now frozen) embryos for reproduction, it seems at least as legitimate to donate them for research as it does to destroy them or leave them frozen forever. One of the people we acknowledged in our 1986 JAMA article was peer reviewer Leon Kass. He did an exceptionally careful review of our submission, and we were grateful. Kass later became, we believe, overly fixated on human embryos. He was one of two ethicists who helped persuade President George Bush to limit federal funding to stem cells obtained from IVF embryos before his August 9, 2001, speech to the nation on this subject. In that speech, Kass was also named to head Bush’s Presidential Bioethics Commission.
It is a very minor footnote that George was asked to testify before this commission on ARTs in 2003. The major points George made were that the industry could not regulate itself (we had both concluded this on the basis of the more than five years we spent together on the Ethics Committee of the American Society of Reproductive Medicine), and the old “best interest of the sperm donor” model needed to be replaced with a child-centered, best interest of the child model. George also suggested that the commission had to make a fundamental decision about either concentrating their work on embryo research (an area in which consensus continued to seem unlikely) or broadening their agenda to suggest ways to regulate the ART industry. Unfortunately, we think, the commission chose the former. We were less kind to the commission and its agenda, which seemed to us and many others to have become overtly political, in a commentary we wrote for Nature that was published during the 2004 Democratic convention. We asked, “Can bioethics in the US rise above politics?” We didn’t think it likely, noting of the Bush/Kass bioethics commission: “Born with an embryo-centric, anti-abortion and anti-regulation political agenda, Bush’s President’s Council on Bioethics has repeatedly failed to transcend it.” We continued, with specific reference to ARTs, “In its report, Reproduction and Responsibility, the council attempts to come to grips with the ethics of assisted-reproduction technology, but ultimately reverts to embryo protection. A thoughtful national report on public oversight for the assisted-reproduction industry is long overdue in the United States.”
Federal funding for human embryonic stem cell research remained the exclusive ART-related issue debated at the federal level during the Bush administration, and this remains the exclusive issue in the Obama administration. Near the end of the Clinton administration, the National Institutes of Health (NIH) took the position that federal funding could be used to do research on stem cells derived from human embryos so long as no NIH funds were used to “destroy” the embryos, and the embryos themselves were not created for destruction but were “leftover” or surplus embryos created for reproductive purposes via IVF and were given for research purposes with the informed consent of the couple. Bush limited the application of this rule to stem cell lines created before his August 2001 speech on the subject. Obama reverted to the Clinton rules. His reversion was challenged in court, but the challenge was unimpressive and ultimately unsuccessful. Current NIH rules, which will remain in effect at least until Congress acts (an extremely unlikely prospect), are that federal funding can be used for research on human embryonic stem cell lines created by private funds. This makes no sense from an ethical point of view, but only from a pragmatic political perspective. The moral status of the human embryo no more depends on how it was created than the moral status of a child depends on how it was created, including whether it was the product of ART or even cloning.
Regulation of the Fertility Industry
The fertility industry is big business. There are more than 450 fertility clinics in the United States alone, and their ART procedures result in about 50,000 live birth deliveries and 62,000 infants a year. This is about 1.5 percent of all live births but 5.7 percent of all low-birth-weight babies. Of ART babies, 36 percent are born premature (compared to 12 percent non-ART babies). Most impressive (and a major downside of IVF) is the high percentage of multiple births, which can put both mother and babies at risk. Singletons account for about 55 percent of all ART infants, with 42 percent twins and 3 percent triplets or more. This compares to 97 percent of all non-ART births that are singletons. The incredible incidence of multiple births and premature infants in ART is a problem that has yet to be effectively addressed, although transferring single embryos seems likely to be the primary solution. A market approach would be to require ART clinics to pay for the neonatal ICU care of multiple births. This would discourage use of more than a single embryo per cycle.
The specialty of infertility medicine is based on, and often justifies itself by referring to, the deep desire of individuals to perpetuate themselves—and to most of us that means perpetuating our genes. It can be argued that genetic replication is the only way we (or at least our genes) can achieve immortality. This is also why fertility and genetics are inextricably linked, not only in a biological sense but also psychologically. It helps explain why many go to such great lengths in pursuing ART to achieve genetic parenting.
The intense desire for a genetically related child may also go a long way to explaining three of the most bizarre cases in the infertility industry: Cecil Jacobson, Ricardo Asch, and Michael Kamrava. We summarize these cases not because they are typical—thankfully they are not. They do, however, illustrate that in the absence of any effective regulation of reprogenetics, patients can be left at the mercy of the market and unscrupulous practitioners, and that the industry does not, and perhaps simply cannot, police itself. “Buyer beware” may be a good slogan at a department store, but it should have no place in the practice of medicine. The cases also suggest additional important issues in assisted reproduction, the kinds of regulation that might effectively protect infertile patients, and things you may want to consider in picking an infertility clinic. All three of these unusual cases are scandalous events in the infertility industry in general, and in the field of infertility medicine in particular. Patients were betrayed. Physicians went far beyond malpractice to engage in fraud. Their unethical actions affected not only the patients involved but also their genetic progeny.
We begin with Cecil Jacobson, a physician who misused the trust patients placed in him by artificially inseminating his infertile patients with his own sperm. In the 1960s, Cecil Jacobson received international notoriety as a pioneer in the development of genetic amniocentesis when he was on the faculty at George Washington University. He later established an infertility clinic in Fairfax, Virginia. In 1989, a former patient complained about his clinical practices. During an investigation, it was discovered that Jacobson had artificially inseminated dozens of patients with his own sperm, telling them that the sperm had come from anonymous donors. DNA tests linked Jacobson to at least fifteen children “fathered” by his sperm. He was sentenced to five years in prison for the federal crime of mail fraud, and his license to practice medicine was revoked (George was a consultant to the federal prosecutor). After he served his sentence, Jacobson moved to Provo, Utah, where he is said to be involved in agricultural research.
What is unusual about the Jacobson case, of course, is that it was the physician who was fixated on perpetuating his own genes, even at the expense of the rights and welfare of his patients. Taking unconscionable advantage of his patients and using his own sperm for artificial insemination (AI), he fathered perhaps one hundred children. We can ask what his social relationship is with the children (hopefully nonexistent), and perhaps more important, what their relationship should be to each other, since they are all half siblings. There was some concern that when the children grew up they might meet and marry each other, creating a higher risk of genetically compromised children. How should this be dealt with? And more generally, should there be a registry of all children conceived by donor sperm or donor egg so they can access their records when they turn eighteen to “discover” their genetic father or mother as well as any half-siblings? Developments in social networking and direct-to-consumer genetics companies have made it more feasible to identify genetic relatives. It is not possible to regulate contact via the Internet, and even if it was, who should set the rules for contact?
Sperm donors have been the model for policy making in ART (for example, “If men can sell their sperm, women should be able to sell their eggs,” and “Genes should determine parenthood”), but should the male model apply to egg donors? This question can be considered in the context of another exceptional case, that of Ricardo Asch. A native of Argentina, Asch came to the United States, where he developed a new reproductive technique called “gamete intrafallopian transfer,” or GIFT. GIFT is a variation on in vitro fertilization: eggs are removed from a woman’s ovaries and placed in one of her fallopian tubes, along with the man’s sperm, allowing fertilization to take place inside the woman’s body. The Pope John Center, in consultation with the head of the Pope Paul II Institute for the Family in Rome, approved the GIFT procedure in 1985, as long as the sperm are collected during sexual intercourse. In 1984 Asch was recruited to the University of California at Irvine, and in 1990 he was named director of the Center for Reproductive Health. In 1992, staff members of Asch’s fertility clinic began to suspect that embryos were being “misappropriated.” Ultimately Asch and two of his colleagues were accused of implanting “extra” eggs that were fertilized in vitro into as many as forty unknowing women, resulting in the birth of at least eight children who were genetically unrelated to the birth mother. In 1996, one of his colleagues was found guilty of mail fraud involving illegal billing. He was sentenced to three years probation and fired from the university. Another colleague fled to Chile, where he now practices medicine. The University of California paid more than $24 million for more than 130 incidents in which eggs or embryos were either implanted into nongenetically-related women or could not be accounted for. Asch fled the country to practice medicine in Buenos Aires. It was reported in 2014 that he was arrested in Mexico and later released after the Mexican authorities decided not to extradite him to face criminal charges in California.
Asch later further outraged his victims by dismissing the importance of genetics to reproduction. In an interview with Diane Sawyer on ABC’s Prime Time Live, Asch blamed Americans for being overly concerned about their genes: “I think it’s [a] much more materialistic society than other societies, the craziness about genes. . . . I think it’s entirely obsessed, this society, with genes.” He said genes “are, at least in my opinion, not that important. . . . I know they’re not important for IQ, for athletic ability.” This is a remarkably self-serving (and hypocritical) statement from an infertility physician who makes almost all his money by marketing precisely the opposite view of genes.
The final case is generally referred to by the name of the patient rather than her fertility physician, Michael Kamrava. Nadya Suleman is known around the world as the “octomom,” because she had eight babies in one IVF pregnancy (she reportedly insisted that her physician transfer all six embryos that had been created for IVF, two of which split). That really is all that has to be said about her case. Although some fertility experts, like Jamie Grifo, have argued that physicians should have nothing to say about how many babies women have, this position seems to us to be simply an abdication of responsibility. The fact that a patient can refuse any treatment does not mean that a patient, in the words a New Jersey court, can “demand mistreatment.” Nadya Suleman’s eight-baby IVF pregnancy was medical malpractice per se, an extraordinarily dangerous and unnecessary pregnancy not only for Ms. Suleman but also for her eight fetuses. It was appropriate that Kamrava lost his California medical license for this and other subpar care. It is also worth noting that although “infertile” by the industry’s definition (unable to become pregnant after a year of sexual intercourse), she already had six IVF babies and now has fourteen children. To her credit, we think, she became part of a PETA advertising campaign to encourage pet owners to spay or neuter their pets (figure 5.2).
5.2 Nadya Suleman endorsing PETA’s advertising campaign. Krista Kennell, “Octomom unveils PETA sign,” Associated Press, May 19, 2010.
Infertility medicine can rightfully be viewed as a subset of genomic medicine—here, not using your genes to help design a treatment or prevention program, but using your genes (as packaged in eggs and sperm) in a way that permits you to have genetically related children, your “personal” (genomic) children. Infertility medicine permits the combination of an individual’s genome with the genome of the other genetic parent. To enable one’s genome to survive is the goal of reproduction, making infertility medicine a subset of genomic medicine. Of course, if genomic reproduction were not the objective of infertility treatment, adoption would be the surest, safest, most cost-effective, and most socially responsible alternative.
Great strides have been made in ART over the past three decades, but we still have a long way to go. Most important, we think, is the development of consistent best practice guidelines by the infertility industry, backed up by consistent state laws that are designed primarily to protect children. Ultimately we will need international treaties to protect all parties involved in ARTs when people from outside the couple are engaged to help them create a genetically related child that they can rear. This is consistent with treaties for the protection of adopted children. Until such laws and practices are in place, couples looking to hire others to help them have children must proceed with extreme caution under a rubric usually not used in medicine: buyer beware.
Combining the fields of ART and genetics first led to preimplantation genetic diagnosis, which for couples at high risk allowed selection of embryos free of a specific disorder, such as Tay-Sachs disease or cystic fibrosis. In an editorial in the journal Fertility and Sterility, Richard S. Scott and Nathan R. Treff describe how rigorous evaluation will be needed as new genomic technologies change how embryos are screened to optimize the success of achieving a pregnancy and delivering a single healthy baby. Put another way, only those embryos with the greatest potential based on genomic testing will be selected for transfer. Presumably, this will allow the ideal of a single IVF embryo to be transferred without reducing pregnancy rates. (Twins could still occur, however, because a single transferred embryo can split.) The process of determining which embryo is “the most fit” for transfer is scientifically complicated and will require scientific research, including randomized trials, to assess both the safety and efficacy of any test.
At the beginning of this chapter, we noted that most family relationships are defined by genomic messages. We end with the acknowledgment that ARTs have made genomics much less determinative in defining relationships (think, for example, about egg donors). Nonetheless, even if not always determinative, genomics does provide an important way to view this question. Of course, genomics is inherently personal in reproduction that involves the transmission of our genome to our children. But genomes can also be viewed as universal—as geneticist Aravinda Chakravarti has put it, “All living humans are mosaics with ancestry from the many parts of the globe through which our ancestors trekked. In other words, each of us has around 6.7 billion relatives.” In this sense, the fertility industry’s crossing of international boundaries could help usher in not only a global business model for ARTs but also a better global understanding of universal human rights and human dignity. In the next chapter, we continue our discussion of the role of genomics in reproduction by shifting our focus to the human fetus.
WHEN THINKING ABOUT REPROGENOMICS,
CONSIDER THESE THOUGHTS
The interests of the one unrepresented party to ART,
the child, should be of primary concern to all parties.
“Surrogate” mothers are real mothers
and should be treated with dignity.
Sperm donor rules should not dictate egg donor
rules, because the risks are not the same.
Multiple IVF births can only be prevented by
limiting the number of embryos transferred.
Reprogenomics is a massive unregulated
commercial industry whose clients would benefit
from either enforceable best practice standards
set by physicians or federal or global regulation.
Reprogenomics is a global unregulated business
that makes it possible for you to bargain for
a genetically related baby, but you need to
follow basic “buyer beware” rules to protect
yourself and your child from exploitation.