Prenatal Genetic Testing, and Down Syndrome

Lots of people don’t understand prenatal genetic testing, including both patients and doctors. For instance, many people think that the BUN genetic ultrasound or the “Quad screen” or the prenatal AFP tests can tell whether or not a baby has a genetic anomaly (they can’t; they can only indicate whether a fetus has an increased risk for a genetic anomaly), or that the tests are accurate in predicting whether or not babies have Down Syndrome (they’re not; only about 5% of mothers who test positive with standard methods actually have a baby with Down Syndrome, and even with the latest cell-free DNA method the proportion only goes up to 45%. An invasive procedure such as amniocentesis or CVS is necessary to confirm the accuracy of such testing).

A study in last week’s JAMA attempted to find what would happen if women were given a “decision support guide” to help them understand prenatal genetic testing. I doubt very much that the guide was slanted against genetic screening; yet when women were given more complete information than what is given in “usual care per current guidelines,” less women opted for genetic screening or invasive testing.

This study implies, of course, that “usual care” means that doctors are usually not fully informing women about these tests. And that is understandable, if not excusable, within the confines of a busy clinic schedule. It is much easier and quicker to say, “Do you want testing to see if your baby has any genetic defects?” — or, worse yet, “You need to get genetic testing because you’re over age 35″ — than to try to explain what is meant by “risk,” and that a positive result means almost nothing more than “You will need another test to interpret the result of this test.”

But if doctors don’t have enough time, or are not trained well enough or whatever, to give informed consent for testing that can have life or death consequences, if our usual and customary care is to do this testing without informed consent, then why is this testing considered standard of care?

***

On a separate but not unrelated topic,in a commentary published in Wednesday’s Chicago Tribune, a mother of a girl with Down Syndrome writes of the lessons she hopes her son will learn because he is growing up with a sister who has Down Syndrome. Here is an excerpt:

He will have a broader perspective of what “normal” is than most of his peers. Hearing his own sister being referred to as the “R-word” will enable him to teach those around him that it is wrong to dehumanize others with such offensive language. He will remind people that his sister has the right to be valued, respected and accepted — just like anyone else. He will be courageous and strong and will not allow bullying to be tolerated.

He will recognize that the diagnosis, condition or illness does not define the individual. It is simply a part of what makes him or her unique.

I hope this snippet will encourage you to read the entire article.

PGD, BRCA, and the difference between Diseases and Risk Factors: “The lamps are going out . . .”

It is currently estimated that up to 65% of women with the BRCA gene mutation will develop breast cancer. Monday’s Wall Street Journal (WSJ) reported on the growing number of women with the BRCA gene mutation who are undergoing in-vitro fertilization, having the resultant embryos tested for the presence of the mutation via preimplantation genetic diagnosis (PGD), and choosing to implant only those free of the mutation.

PGD has been used for years, typically for parents to selectively implant embryos free of certain genetic diseases — the kind where if you have the gene, you have the disease. It has been occasionally used to select embryos of a certain sex, or embryos with a characteristic such as deafness to match parental characteristics. In other words, it has been used to select out embryos who actually have a disease or characteristic.

The use of PGD mentioned in the WSJ article is something subtly but altogether different. Whereas other uses of PGD select out embryos with a certain disease, screening based on the BRCA gene is used to select out healthy embryos. These are embryos who do not have a particular disease, but who have risk factors for a particular disease.

This is a fundamental distinction. People who have the BRCA mutation are not sick! They don’t have any disease! If they develop cancer, then they will have a disease. But “Having the BRCA mutation” is not a disease! Approximately 35% of people with the mutation will never have the disease associated with the mutation. For the others, preventive measures and treatments are available. (I am not here pretending that the preventive measures and treatments are fun and easy. But they available and mainstream, not experimental.)

The rationale of one person in the article is, “I thought, if I could have a healthy baby who doesn’t have to worry about the same thing I did, why wouldn’t I?” And, “. . . doing PGD to avoid passing on the BRCA mutation seemed like an obvious precaution.” In other words, the decision was a no-brainer.

But if it’s a no-brainer to select out embryos with the BRCA mutation, then it’s equally a no-brainer to select out embryos with genetic predispositions to all kinds of things: heart disease, diabetes, social anxiety disorder, baldness, ingrown toenails, erectile dysfunction . . .

It was at the moment that it became acceptable to profile embryos and weed out those who didn’t meet our arbitrary criteria that we started down this road. I am afraid we will not be able to stop before it reaches its inevitable, logical conclusion. (Seen Gattaca lately?)

 

 

PGD and lives not worth living

A colleague just e-mailed me about an article in Monday’s New York Times titled “Ethics Questions Arise as Genetic Testing of Embryos Increases”. The article focused on the decision of Amanda Kalinsky and her husband to use preimplantation genetic diagnosis (PGD) to have unaffected children after a genetic test at age 26 showed that she had the gene for Gerstmann-Straussler-Scheinker disease, a rare form of transmissible spongiform encephalopathy. The disease is a neurodegenerative disorder that usually has its onset of symptoms between age 35 and 55 and progresses to death within 2 to 10 years. Ms. Kalinsky has multiple family members who have suffered from the disease including her father. The article pointed out that the use of PGD is growing rapidly to allow potential parents with genetic disorders in their families to screen for the disorders and only implant embryos free of the disease. The center that did the PGD for the Kalinskys has tested embryos from over 2500 couples.

The article presented opinions from several ethicists on the morality of using PGD to select unaffected embryos, particularly for disorders that do not become evident until adulthood. They range from Janet Malek from Brody School of Medicine who said that “people who carry a gene like GSS have a moral duty to use preimplantation diagnosis — if they can afford it — to spare the next generation” to David Wasserman from Yeshiva University who pointed out that “eliminating embryos with such genes is essentially saying someone like Ms. Kalinsky should never have been born.”

The most disturbing were the statements made by Ilan Tur-Kaspa the founder of the fertility clinic used by the Kalinskys. He said that couples like the Kalinskys have three choices: do no testing and hope for the best, conceive naturally and have prenatal testing and then choose whether to abort, or do IVF with PGD. He fails to include the fourth option which Ms. Kalinsky originally had considered which is to choose not to have children at all. While several of the ethicists quoted in the article mentioned concerns about doing PGD for diseases that appear in adulthood or for genes that only increase the risk of diseases late in life, Tur-Kaspa was reported to have said that “after having done the procedure a thousand times, he cannot think of a gene he would not test for if a patient requested it.” He also said that in the majority of his patients PGD is done without testing the potential carrier first who does not want to know his or her own genetic status. The embryos are simply tested for the disorder that runs in the family and only unaffected embryos are implanted. He said that “if all the embryos carry the faulty gene, the couple is told that none of their embryos was viable, which can happen with or without a mutated gene.”

The problem with IVF and PGD, particularly when done for diseases that manifest themselves in adulthood or for genes that only confer an increased risk of a disease such as breast cancer, is that the embryos that are discarded are viable. They are just like Ms. Kalinsky was when she was an embryo. As Wasserman pointed out the destruction of such embryos with an unwanted gene is saying that people who have genetic disorders have lives that are not worthy of being lived. The selection of embryos free from a genetic disorder involves the rejection of the embryos who have the disorder. It says to people currently living with genetic disorders and disabilities that it would have been better if their disorder had been found when they were embryos so their lives could have been ended before they were born. Those who practice IVF with PGD need to be honest about what they are doing. They are not discarding nonviable embryos. They are discarding embryos who are expected to grow up into people who have disabilities and not allowing them to live. We should never say that having a disability means that a person’s life is not worth living. None of us is without our flaws. If some lives are not worth living, how can we say that our lives are worth living and theirs are not?

A Genetic “Fix” for Down’s Syndrome?

A couple of weeks ago I mentioned some of the thoughts presented at the July Summer Conference hosted by the Center for Bioethics and Human Dignity—thoughts I am still processing in the afterglow of an enjoyable and stimulating few days. Much has re-shaped my thinking on a host of issues, to which I alluded previously. But there was one nugget that remains with me, nagging at me, even as it was presented as a rather small bit of fresh information in a larger context of bioethical analysis of prenatal diagnosis. In a workshop session led by the estimable David Prentice, formerly a faculty member at Indiana State University and now a Senior Fellow with the Family Research Council, it was mentioned that American scientists have been successful in experiments to eliminate the “third gene” that is found in various “trisomy” disorders. This, of course, is most commonly seen in Trisomy 21, the genetic abnormality responsible for Down’s syndrome. The process, perhaps best described in an article in The Guardian, essentially inactivates the third chromosome, the one that makes a crowd out of an otherwise happy pair, in a process that is similar to what happens in normal meiosis, where the female gametes are formed and a non-functioning Barr body is produced. In typical British style, and in reality, the science is described as “elegant,” and is worth a look.

My first impulse on hearing this news was joyous relief. For as long as amniocentesis has been commonplace, the default position of genetic counselors when guiding those with a diagnosis of Down’s has been one of pregnancy termination, of abortion of the fetus that would suffer the mental and physical tolls of Down’s. Now that we can fix it, I thought, these babies can live. If we view genetic disorders as the fallout from a world where brokenness pervades all of creation as the result of sin, then a “fix” is a manifestation of God’s grace to make straight what has been made crooked by the Fall. It is a good thing, and I can view it as such. But what if we find a way to “eradicate” trisomy 21 and Down’s syndrome, even as the technology is still quite nascent and the fix quite tentative? Is that an altogether good thing, to see a future free of people who suffer Down’s?

I used the word “suffer” when describing someone with Down’s because it is a descriptor that is common, provocative, and almost entirely wrong. Certainly the medical issues associated with Down’s are real, the cardiac and gastrointestinal problems, the increased risks of cancer and dementia. Yes, Down’s syndrome is linked with numerous medical maladies—ones that made a thirty-year old adult with Down’s a rarity just a generation ago. Individuals certainly live longer today, blessed by improved medical technology. But do they flourish? I think of my prayers for my children when they were infants: protect them, of course, but most of all, keep them devoted to God through their lives, let their eternity be inextricably linked with their Savior. I would rather their earthly lives be significant than they be happy, to be completely honest. And I reflect on my experiences with those who have Down’s syndrome. I have yet to meet one who seems to typify “suffering.”

So we may someday, perhaps sooner than we can imagine, be able to eliminate trisomy 21 with a genetic “zap.” Will the child whose chromosome count has been normalized be a very different one from the one who has not had genetic intervention? I think of an 18-month old I met this week, who sat in his stroller as I examined the new puppy his parents just adopted. They looked like many parents of children with a mental disability, who have learned to accept the modification of their dreams for a child and who, so sadly, must somehow justify their decision to even bring this child into a judging world, given the options. But as I do the checkup on this bundle of puppy energy, they could see the same smile I could see, one that is more manifestly beautiful than that from a “normal” child in how it processes the unfolding scene. I can’t quite describe its wonder and delight. This smile was a mark of grace in a seemingly graceless world, one that God has supplied to a youngster created in His image and whom He has declared will someday judge the angels. I would have missed that if this little boy had been “fixed” by a genetic repair.

I think of my cousin, now in his mid-thirties, who has faced so many medical issues, and who has so challenged the lives of his parents. I have, sadly, struggled to connect with him over the years, because I cannot relate to his experiences and cognitive abilities easily. It is only in recent years that I see what I’ve missed. The middle of three brothers, he is the one who has been best able to find a true sense of pure worship toward God, one that has become clouded by cynicism (at least for now) in his high-functioning, articulate siblings. Would I wish an easier ride for my aunt and uncle, and for anyone with a special needs child in a society that values the capabilities of an individual above all else? Of course. But how serious have I been in my prayers that my children develop a deep spiritual devotion—would I exchange their future college and career and social success for it? If they were never to inculcate this devotion, would I sacrifice all the “normal” stuff and hope for a child with a lower IQ, a host of medical challenges, and a heart that embraces God?

None of us will ever know what would have happened spiritually, or in the degree of happiness and earthly success, if those with mental disabilities like Down’s had been rendered “normal.” I initially rejoiced at the happy thought that Down’s syndrome and similar issues would be cured someday. In the weeks that have passed, I have found new ways to grieve the potential loss of these individuals in our world, individuals who have made it a richer place for being here. Is it ethically wrong to wish an end to genetic aberrations? I think not. Is it ethically wrong to appreciate the diversity of God’s blessings that transcend a fallen world? Increasingly, I find it isn’t.

On Myriad Genetics and Withholding Information

Mutations in the BRCA1 and BRCA2 genes confer an increased risk of many types of cancer. In 1995, Myriad Genetics patented the BRCA1 and BRCA2 genes which it had successfully sequenced and isolated, giving the company an effective monopoly on testing for mutations in these genes. However, Myriad’s achievement rested on many other shoulders: in 1990, US researchers first began to zero in on the BRCA1 gene, and in 1994 UK researchers first located the BRCA2 gene. Last year, Myriad made $500 million; most of its profits came from the BRCA test,which typically costs $3,000 to $4,000, putting it well out of the financial reach of many women. In June of this year, the US Supreme Court ruled that naturally-occurring genes cannot be patented; almost immediately, another company announced that it would offer the BRCA test for $995.

After the Supreme Court ruling, Myriad’s president and CEO stated that “we remain focused on saving and improving peoples’ lives and lowering overall health care costs.”

In the meantime, Myriad maintains a database of the information it gained from nearly two decades of testing millions of women. Until 2005, Myriad shared that data with the National Human Genomics Research Institute’s Breast Cancer Information Core, an open-access database of information that helps researchers understand breast cancer genetics. However, since 2006, Myriad has withheld its BRCA data — data that it generated by charging 250,000 women annually thousands of dollars a test.

Dr. Robert Cook-Deegan, a research professor at Duke University’s Institute for Genome Science and Policy, is cited in an article in this week’s JAMA arguing that the data Myriad is withholding might help improve cancer care of prevention. “The easy thing to do would be to behave like most other laboratories and share the information,” he said.

Not just the easy thing, but the ethical thing. In another article in the same issue of JAMA, Dr. Harlan Krumholz of Yale University School of Medicine is quoted as saying, “Science cannot be self-correcting if only some of the data are available to only some of the people.” Just as naturally-occurring genes cannot be considered proprietary per the Supreme Court, so population data that is potentially important for human health should not be considered proprietary. It is not clear why Myriad is withholding its information; some speculate that it hopes to leverage the data for profit. Maybe such a strategy makes good corporate business sense; it is not consonant with ethical scientific practice, and does not square with Myriad’s stated focus on “saving and improving peoples’ lives and lowering overall health care costs.” If Myriad is really interested in “saving and improving lives,” even if it doesn’t bring in lots of money for the company coffers, it should make available the data it has gathered from millions of patients. As Cook-Degan said, “Women paid for those tests — and paid premium dollars.”

 

The information for much of this post came from the article “Supreme Court Tules Agains Gene Patents,” published in the July 24/31 issue of JAMA, p 357 (Vol 310 No 4), available for free here.

On (Being) Better than Human, Part 3A

As I noted in Part 1 of this series (see my 03/25/13 post), in Better than Human Allen Buchanan considers four major lines of objection to the “enhancement enterprise.” As Buchanan summarizes them, each of these objections claims that biomedical enhancement is “different” in morally significant ways from other kinds of (nonbiomedical) enhancement. Specifically, these objections assert that:

(1) biomedical enhancements are different because they change our biology; (2) biomedical enhancements are different because (some of them) change the human gene pool; (3) biomedical enhancements are different because they could change or destroy human nature; [and] (4) biomedical enhancements are different because they amount to playing God (p. 12).

In Chapter 2, Buchanan takes on the second and third of these objections—that is, the “changing the human gene pool” and “changing human nature” objections, respectively.

The heart of Buchanan’s discussion in this chapter is a consideration of two competing analogies in terms of which one might understand evolutionary biology—or, alternatively, “nature” (p. 29)—and its processes: the “master engineer” and the “grim tinkerer” analogies, respectively. On the former analogy, “organisms are like engineering masterpieces: beautifully designed, harmonious, finished products that are stable and durable (if we leave them alone)” (p. 29). On the latter, evolution is “morally blind,” “fickle,” and “tightly shackled” (p. 49)—it produces “cobbled-together, unstable works in progress, and then discards them” (p. 28).

Evolution is disanalogous to a master engineer, Buchanan says, in two key respects. First, “natural selection never gets the job done” (p. 28). Environments are constantly changing, and organisms are constantly adapting both to their environments and to each other, in “a ceaseless round of adaptation and counteradaptation” (p. 28)—resulting in further changes both to organisms and their environment, in a process that never arrives at a terminus. So rather than being “the end points of a process whereby they climb a ladder to perfect adaptation to their environment,” organisms instead exist in a state of perpetual instability, one that belies the “finely balanced” nature implied by the master engineer analogy (pp. 28-29). Second,

unlike a master engineer, evolution doesn’t design what it produces according to a plan that it draws up in advance. Instead, it modifies organisms in response to short-term problems, with no thought of long-term effects. Evolution has no overall game plan for any species, and the results show it. What’s useful for solving today’s problems can cause new problems—and even extinction—down the line (p. 29).

In the final analysis, Buchanan contends, “evolution is more like a morally blind, fickle, tightly shackled tinkerer” than a master engineer. The burden of the rest of the chapter is to provide reasons why (on Buchanan’s view) we ought to accept this analogy over against the master engineer analogy.

In order to adjudicate between these two analogies, Buchanan says, we need to grasp certain key aspects of the mechanisms of evolution (p. 29). The first thing to notice in this regard is that nature is replete with instances of “suboptimal design” (pp. 30-31), which Buchanan takes to be prima facie evidence that the master engineer analogy is problematic at best. Examples of such “design flaws” include, inter alia, the fact that in male mammals the urinary tract “passes through (rather than being routed around) the prostate gland, which can swell and block urinary function,” and the “hasty shift from quadruped to biped, which resulted in back and knee problems and a birth canal that passes through the pelvis, resulting in greatly increased risks to both mother and child in the birthing process” (p. 30). Numerous additional examples could be cited (and Buchanan cites several other illustrative examples here).[1] “Design flaws” such as these led Darwin to develop his theory of natural selection, with which, Buchanan informs us, “Darwin debunked the argument from intelligent design, one of the traditional arguments for the existence of God, by cataloguing the ‘clumsy, blundering, wasteful’ works of nature” (p. 30).

To show more clearly why nature is not best thought of as a “master engineer,” Buchanan introduces at this point a distinction between what he terms “Unintentional Genetic Modification” (UGM) and “Intentional Genetic Modification” (IGM). UGM is “evolution as usual, what Darwin called ‘descent with modification,’ where a driving force of the modification is natural selection”—in other words, “evolution without intentional modification of human genes by human beings” (p. 31). IGM, then, in the context relevant to our discussion, is intentional modification of human genes by human beings.

Buchanan’s aim here is actually two-fold: first, he wants to provide reasons why we ought to reject the “master engineer” analogy in favor of the “grim tinkerer” analogy, and second, he wants to give us reasons for considering the possibility that it may be preferable, in at least some circumstances, to actively pursue IGM rather than simply leaving the development of the human species entirely to UGM. His subsequent discussion in the remainder of this chapter is designed to accomplish both of these aims simultaneously. To that end, he begins by enumerating some of the built-in limitations of UGM, and then goes on to describe some ways in which IGM might be employed to overcome those limitations.

In the next post in this series, we’ll finish up our explication of Buchanan’s argument, and then develop some critical observations regarding that argument. By way of preview, three major limitations of UGM to which Buchanan draws our attention are the facts that (1) UGM is “insensitive” to post-reproductive quality of life (pp. 32-37); (2) in UGM, beneficial mutations spread only by way of a “nasty, brutish, and long” process (37-45); and (3) UGM selects only for “reproductive fitness, not human good” (pp. 45-48). Critical remarks will focus, in turn, on several epistemological, ontological, and moral issues raised by the way Buchanan frames and develops his argument in this chapter.

 


[1] A bonus for the philosophy buffs out there: In the context of this discussion of “design flaws,” Buchanan offers an arresting image in answer to Nagel’s famous query regarding what it’s like to be a bat. As Buchanan explains, “bats spend a good deal of their time hanging upside down, closely packed together, with their feces pouring down over their bodies to their heads. (Imagine yourself holding a toothpaste tube upright and squeezing it until the contents cover your hands. That’s what it’s like to be a bat.)” (p. 31).

Journeys of Transformation

In my last post, “A Preview of Coming Attractions” (02-11-13), I signaled the start of a multi-part series of review essays covering three recently published books addressing ethical issues surrounding enhancement technologies and practices. I had intended to launch that series with today’s post. Before starting that series, however, I want to go on a brief discursus, one that will, I believe, turn out to be relevant to the themes to be touched on in the forthcoming series.

Last week, I attended the annual “Christ and Culture” lecture at California Baptist University in Riverside, California. This year’s speaker was Ralph Winter, producer of the first three X-Men films and numerous other successful film projects. Using such recent films as Les Miserables, Toy Story, Avatar, and others as illustrative examples, Winter set out, in the broadest sense, to show “how the gospel is often displayed in… contemporary film.” The unifying theme in all these stories is what Winter referred to as a “journey of transformation.” In each of these stories, the main character/hero grows through experiencing some form of adversity, learns something important about him or herself, and is transformed positively in some way.

One of Winter’s central concerns in his lecture was to explore the general question of how Christians engage with the broader culture, and particularly with how they communicate their messages to that culture. Here, Winter contends that “Christian stories often fail because we’re afraid of the journey,” by which he means that “our stories often hide from pain”—they avoid addressing the painful, the difficult, the ugly, the uncomfortable aspects of life—and place an emphasis on propositional assent over against an embrace of the “transformational journey” that is the life of faith. That is to say, there is a tendency to focus on the destination (heaven) to the exclusion of the journey that we take along the way.

What does all of this have to do with bioethics? There are at least two central lessons to be learned here.

First, in the context of genetic enhancement technologies and practices, it is worth asking the question: to what extent is the “enhancement enterprise” (broadly speaking, the attempt to “improve” human capacities by way of genetic or other interventions and/or technologies, as well as the cultural push toward embracing that agenda) in fact driven by a deep-seated, underlying “fear of the journey”—that is, a fear of those aspects of the aging process that are ugly, uncomfortable, painful, and so forth? Put more simply, to what extent is the drive toward “enhancement” really a flight from the inevitable realities of our lives as embodied creatures? (I do not propose to answer this question here; I pose it, however, as an important background issue to be kept in mind when considering specific arguments regarding the enhancement enterprise.)

Second, and more generally, our bioethical reflections—whether on beginning of life issues, end of life issues, or whatever—must always be attentive to the lived reality of embodied human existence. In particular, we must be willing to face the sometimes harsh realities of pain, suffering, indignity, and so forth, that can accompany the experience of various medical and other conditions. This is especially pertinent at the end of life, where the dying process can (but does not necessarily) involve significant levels of pain, discomfort, and distress. In a word, our bioethical reflections must tell “stories” that are true to the lived realities of human existence. If we are not willing to face these sometimes difficult realities, our pronouncements on bioethical issues are likely to seem shallow, insensitive, or even irrelevant.

This is not to say, of course, that our arguments and other reflections on bioethical issues should be overly-negative or fatalistic. Indeed, a focus on truth mandates that we tell “the truth, the whole truth, and nothing but.” This means being attentive to the fact (for example) that while the aging and dying processes can be characterized by pain, discomfort, and suffering, they are not always so characterized (indeed, with the skillful use of pain management techniques, they rarely need to be—but that is a different post altogether). The aging and dying processes can also be characterized by peace, joy, personal growth and development, and a sense of fulfillment. In a phrase: these processes can themselves be “journeys of transformation.” From the perspective of Christian theology, of course, the entire human lifespan can be understood in this way as well. The key point for present purposes is simply this: our bioethical reflections and arguments must attend to the potentially transformational aspects of the experience of pain, suffering, and the like, in addition to other considerations having to do with rights, obligations, principles, and so on.

Human life, in other words, is as much about the journey as it is about the destination. And that fact can make all the difference when it comes to bioethics.

The myth of non-directive genetic counseling

An article and its accompanying editorial in this month’s American Journal of Obstetrics & Gynecology report on a study comparing the practices and attitudes of two types of specialists regarding prenatally diagnosed fetal abnormalities: maternal-fetal medicine (MFM) specialists, who are obstetricians; and fetal care pediatric (FCP) specialists, who are (as the name suggests) pediatricians. The article is titled, “Prenatally diagnosed fetal conditions in the age of fetal care: does who counsels matter?”

The answer to the question posed in the title is decidedly yes. For instance, compared to the pediatricians, the MFM obstetricians reported  more than twice the pregnancy termination rate among patients carrying a fetus with Downs Syndrome. They were more likely than the pediatricians to “somewhat or strongly support” a decision to abort a fetus with Downs Syndrome. The discussion section of the article notes that pediatric and obstetrician specialists may “hold contrasting perceptions of life with disabilities . . . We cannot explain why, after multivariate analysis, our reported termination rates differed between specialties for Downs Syndrome.”

Two observations: First, those who deny that prenatal genetic testing is eugenic claim that the counseling given around such testing is non-directive, that is, that it does not influence a woman whose fetus tests positive for some condition to have an abortion. They say that the counseling gives just the facts: “Your fetus has Downs Syndrome,” not,”You should abort this fetus because it has Downs Syndrome.” If the results of this study are true, it exposes that claim for the wishful thinking — or insidious deception —  that it is. As the study authors write, ” …our study supports concerns that prenatal decisions and outcomes may sometimes reflect provider attitudes.”

Second, isn’t it interesting that between obstetricians (who typically do not care for Downs Syndrome patients) and pediatricians, it is the specialists who actually care for patients who have Downs Syndrome, who actually know something about how the syndrome affects people and families, and who are far more familiar with the details of living with the syndrome, who are the ones less likely to recommend that a woman abort a fetus who is suspected of having it?

The state of PGD—an update from ASH

At the 53rd meeting of the American Society of Hematology (ASH), held from December 10-13 in San Diego, there was an “education spotlight” session entitled, “Preimplantation Genetics: The Science, The Medicine, The Bioethics.” The speakers were Joyce Harper, PhD, from the University College London Centre for Preimplantation Genetics and Diagnosis (PGD), and Mark Hughes, MD, PhD, from Genesis Genetics Institute in Detroit. I’m hardly a PGD expert, so I attended to hear perspectives from people who are practicing it. The session was long on science and medicine but too short on the discussion of ethics. This was a shame because the speakers clearly have ethical worries, even though they are clearly not congruent with the concerns of most TIU bioethicists. Still, I found the session thoughtful and informative.
There was far too much for a brief blog post, but here are some highlights, first on the medical/scientific side:
1) PGD can be made on a single cell (typically 1-5), taken at any of several stages of early embryonic development. Dr. Hughes showed how he takes a single cell at the blastocyst stage (5-6 days after fertilization). Results in 24 hours, with a stated diagnostic error rate of 0.7%, and an attendant 1% post-PGD risk of a genetic-recessive disease (compared with 25% by standard Mendelian genetics).
2) PGD is most commonly used by fertile couples to try to avoid a severe genetic disease after a first affected birth or known risk based on parental genetics.
3) Genetic analysis is moving toward genome-wide arrays that can read the entire genome quickly, and at ever lower cost (currently about $2500 per genome). Dr. Hughes: “The technology now has no limitations [diagnostically]…so the question is not ‘can we?’ but ‘should we?’” [diagnose].
4) Biopsied embryos generally—but not always—do well, so the success rate of the (necessary) IVF pregnancies is reduced. The number of implantations is also reduced—e.g., 12 eggs to get 10 fertilizations, 8 embryos biopsied, 7 successfully diagnosed, 5 abnormal and 2 normal, one of those two judged viable for implantation.
5) Dr. Hughes said there were 47,164 PGD babies in the US in 2010. I thought he said born in 2010 but that number sounds high for a single year. Still, it’s a lot.
6) The most prominent “savior sibling” examples are for a disease that is curable with bone marrow transplant (BMT), e.g., sickle cell anemia (SCA). The PGD baby’s umbilical cord blood (UCB) becomes the donor blood. An example is sickle cell anemia (SCA). Dr. Hughes told the story of the family of NBA player Carlos Boozer, whose first child was cured of SCA after receiving a UCB transplant after the birth of his baby brother. Dr. Hughes is working to take this approach to SCA to West Africa at low cost.
7) For a Mendelian-recessive disease, one needs an unaffected embryo that is also an HLA (immunologic) match, with the probabilities being ¾ x ¼=3/16. In other words, 16 embryos to get 3 genetically appropriate “saviors.”
As I said, the ethical discussion was compressed, and must also be here. Clearly one worries about all the other embryos created in this process—and at least one questioner at ASH raised this by mentioning the value of all people despite disease or disability. As someone who considers himself a strong pro-lifer, I do find PGD for the most severe genetic disorders a “hard case,” and I have to admit that I am reluctant to condemn the Boozers. The speakers were most concerned about how to limit the use of PGD, medically. They are clearly uncomfortable with drawing premature conclusions or taking action on the often-uninterpretable results of a genome-wide analysis. They also raised hard cases of using PGD for otherwise treatable disease (e.g., polycystic kidney, or to obtain UCB to transplant a sibling with leukemia), using PGD to get an Rh-negative baby when mom has sensitized to Rh in a prior pregnancy, or using PGD to eliminate a cancer-susceptibility gene like BRCA-1 from the family tree (Dr. Hughes would accept, but he had debated Francis Collins, who would not permit this). Bottom line: these two professionals do seem to agree that defending the “therapeutic boundary” is important. If I read that correctly, I find it at least a bit reassuring and perhaps a contact point for engagement.
Space does not permit more here. I’m happy to try to field questions or carry on discussion through comments.

Knowing too little about too much

 

With the ability to map the human genome, we find ourselves in the bewildering position of knowing too much and knowing too little at the same time.

Consider this scenario: The year is 2015. You, being the modern that you are, want to know your future, so that you can have some degree of control over it. You’re pretty sure astrology isn’t very helpful; but you’ve been keeping up with Time and Newsweek, and you’re thinking from what you’ve read there that genetic testing offers the scientific equivalent of what astrology promises. So you go down to the local Genetics-R-Us and for a mere $99 have your entire genome analyzed in 15 minutes. You then sit down with one of their genetic consultants, who reveals that you have a 64% likelihood of developing diabetes and a 43% chance of developing colon cancer. You go on a vegan diet, exercise three hours a day, and start a regular regimen of bowel cleansing and weekly colonoscopies. You have your genome analysis results sent to your primary care provider (PCP) to be part of your medical record.

Fast forward to 2025, when you are diagnosed with a rare cancer of the nose. After a little research, you discover that this particular type of cancer can be predicted by genetic testing. Genetics-R-Us went out of business, so you go to your PCP and demand to know why she didn’t warn you about the possibility of this cancer. She steps out to do a little research and comes back into the room:

“It turns out that the gene that predisposes you to this kind of cancer wasn’t discovered until 2019, and you had this test done in 2015.”

“But when that information became available, why didn’t you go back and recheck my genome?” you reply.

“That’s the responsibility of the company that tested you,” she says, as she gets her defense lawyer on the phone.

“But Genetics-R-Us went bankrupt! You’re the only one who has the data!”

“We have thousands of these genome maps in our records, each consisting of six billion base-pairs. They are encoded in various formats, none of which are compatible with each other, and some of which are so outdated we can’t access them anymore. Plus, a 200-page update of the latest new gene dicoveries is published every month. We simply don’t have the resources to go back through everybody’s individual genome and check for all of these genetic abnormalities that are constantly being discovered.”

***

With the capability to map an individual’s genome, we can gather lots of data, but we do not yet have the knowledge of how to apply that data (much less the wisdom with which to use it!). We know too little about all that we know. As genome testing becomes more affordable and widely available, some of the ethical questions that arise are, Is there an ethical obligation to go back an re-analyze data in light of new findings? If so, whose is the responsibility?