Last Week’s Stem Cell Cloning News

Readers of this blog probably saw last week’s report, as the NPR headline put it, that “First Embryonic Stem Cells Cloned from a Man’s Skin.”  I was able to read the full text of the online publication, by Cell Stem Cell, here.

The stated goal of the work is to use somatic cell nuclear transfer (SCNT) to clone an embryo that can then be used to develop embryonic stem cells (ESCs) that are pluripotent—able to differentiate into any cell type in the human body—and coax them to differentiate as needed for use as a cell-based treatment for disorders where replacement cells might be helpful; e.g. heart failure, neurodenerative disease, or others.  In SCNT, an egg, donated by a healthy woman, is needed; its nucleus is removed and replaced with the nucleus from tissue (such as skin) from the person who would be treated.  With the necessary manipulations in the lab, an embryo is formed that can be used while it is still just a few days old to obtain the desired ESCs.  This technique has been successful in animals for a while now, but making human embryos this way has been successful only rarely, and then using tissue cells from fetuses or infants.  But the idea is to use cells derived from a patient, who would typically be an adult at the time of the needed treatment, so the current work is a technical advance by virtue of showing that embryos that can be used to give rise to ESCs can be made using cells from adults, even elderly ones.

In this case, the skin cell donors were two men, one age 35, the other age 75.  A total of 126 eggs were obtained from seven women.  The successfully cloned embryos—eight in total—came from using eggs from three of the seven donor women.  A couple of these embryos gave rise to ESCs, depending on the specific cloning procedures used.  The ESCs obtained as a result showed characteristics of true ESCs—including the ability to form tumors (teratomas).  (The potential to form tumors remains a safety issue for any stem cells—ESCs or induced pluripotent stem cells—used as therapy.)

No new ethical issues arise from this report; the well-described issues with cloning all apply.  First, human embryos were created specifically and solely for research, and for destruction in the process.  “Cells” alone were not cloned, but embryos.  The report itself calls them that.  Presumably, these embryos could develop into a full human.  That, the NPR report says, is something that “many people [find]… dangerous and repugnant, [but] it is not broadly illegal.”  Or, maybe the embryos couldn’t develop normally, which would make them, I suppose, severely impaired nascent humans created on purpose for research.  Induced pluripotent cells that do not create new embryos avoid the ethical issue, and might, in the end, be as safe as or safer than ESCs used for treatment.  Some would say “we need to do the experiment,” but if the experiment itself contains unethical features, why should those be carried forward in the experimental design?

And the ESCs created are intended to lead ultimately not just to treatment, but to profit.  The work, performed in South Korea with a government grant from that country, was conceived and executed in part by personnel from the biotech company Advanced Cell Technology.  They would argue, I believe, that the ability to “clone your own” cells for treatment will eventually be beneficial.  But the eggs, of course, are not “your own,” but come, rather inefficiently and potentially riskily (I didn’t see a discussion of the procedure used to induce hyperovulation), from young women “you” may not have heard of.    If ESCs using their cells are commercialized, presumably they retain no financial interest.

I wonder if any of them is named Henrietta…

Reflections on the Metaphors We Live–and Die–By

Images powerfully impact how we think and how we live. Metaphors, those images we use to describe the indescribable, to portray the unfamiliar and mysterious, are particularly so because of the identity relationships they create. In my last post, I commented on an article in the NYT entitled, “A Tumor: the Embryo’s Evil Twin,” which described the similarities between embryogenesis and the cellular behavior of malignancies. But the article alluded to more: to the metaphors we use to understand the two—to metaphors of life and death.

The article referenced Susan Sontag’s metaphorical description of her tumor as “alive,” as a “demonic pregnancy,” as a “fetus with a will.” Sontag used metaphorical images of life to portray the powers of death, but the tables turned quickly as others used images of death to portray life, making a mockery of the fetus by comparing it to an invading, parasitic tumor, images which gave rise to such movies as “Invasion of the Body Snatchers,” “The Blob,” “Alien,” and “Rosemary’s Baby.” No longer were death-producing forces described in terms of life, now a life-giving process was identified with death, supported by powerfully gruesome imagery, imagery that unfortunately remains semi-permanently burned into our minds’ eye.

Ironically, the use of these metaphors has the paradoxical effect of personifying tumors (“a fetus with a will”) while simultaneously depersonalizing the fetus (“a blob of cells). And if we can use warfare imagery located in such terms as “battle,” “fight against,” “survivor,” to depict our treatment of death-producing personified malignancies, how easy it is to carry those same metaphors over to the control of life-giving depersonalized ones (the meaning of the Greek root, metaphoro is, indeed, “to carry over” or “to carry between”). We utilize similar chemotherapeutic substances to control both. But control is the best we can accomplish: we can destroy life, but cannot give it. We can “win” some marginal “skirmishes” and postpone death, but cannot destroy it…

In truth, we are enslaved by our fear of death (Heb 2: 15), and we are not skilled in concealing our chains. Our lives are marked by our futile attempts to gain some measure of control over it by associating it in our minds with what we can control—and destroy. But in the process we create undesirable images of life, images that mock and devalue it.

The article emphasizes the genetic similarities between processes that lead to life and those that lead to death. Life, however, is not reducible to death; yet, life gone awry does lead to death. It is therefore not surprising that the same processes that are purposely designed for life can, in our fallen world, mindlessly destine death. For the processes of death are not a matter of an evil “will,” as Sontag states, but rather of our corporate fallen human will.

Yet ironically and hopefully, in God’s world life comes from death. For it is through the death and resurrection of Jesus of Nazareth, Jesus the Christ, that we humans have life, true life, life free from our enslavement to the fallen life-giving processes that now bring death.

This holy weekend when life and death hang in the balance, may we realize that death is not the final word; that the One who gives life has also brought life from death. He alone has destroyed death for us and offers us freedom from slavery to our greatest fear.

More on this week’s FDA meeting about “3-parent babies”

I choose the provocative title to mirror the sort of headlines that were written this week about the FDA’s two-day meeting of its Cellular, Tissue, and Gene Therapies Advisory Committee.  Steve Phillips addressed this meeting quite well in his post yesterday.  I would just expand on that a bit here.

As with all FDA Advisory Committee meetings, materials are made available to the general public, in this case, here.  The first day was dedicated to the topic Steve identified:  “oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease.”  Steve’s post provided a nice shorthand for what is intended: modifying the egg of a woman afflicted with a (rare, often serious or life threatening) disease attributable to mutations in mitochondrial DNA.  Said egg would receive “normal” mitochondria from a second woman’s egg cell.  The modified egg would then be fertilized by IVF.  At least, that is the most likely technique that appears to be in view.  Some approaches would take nuclei, or pro-nuclei, from a fertilized egg, constituting the deliberate destruction of an embryo.

A baby born of such a manipulation would indeed carry genes from three parents—two mothers and one father.  I doubt how much this would confuse the baby’s parentage; there are only 37 mitochondrial genes, and the bulk of the baby’s genetic endowment would come from two parents.  Still, any change would in principle be heritable—if the baby is a girl, that is.  Mitochondrial diseases are maternally inherited; fathers do not transmit mitochondria through their sperm.  Even so, this would be a momentous sort of step to take.

But, as Steve pointed out, the more immediate issues relate to risks to the child, and possibly to subsequent generations, and how one could meaningfully obtain informed consent.  A commenter pointed out that it is difficult to envision justifying these oocyte modifications as some sort of emergency therapy, so the necessary IRB meetings would be lively indeed.

Steve’s post barely covers the half of it.  I found the FDA briefing document on the subject harrowing indeed.  Although there are only a few mitochondrial genes, the mix of mutations is variable, as is the number of mitochondria that might be transferred, or that might be retained in cells of different types.  There appear on my read to be no good animal models.  There is no good way to predict the likelihood or severity of disease from analysis of the mutations of mitochondrial DNA, and preimplantation or prenatal diagnostic methods aren’t very good.   Potential risks to women undergoing the process seem relatively modest; they might not get pregnant.  Risks to the potential children are another matter:

“Potential risks to [the] children could include: 1) mitochondrial disease (particularly in women with mitochondrial disease), as a result of carryover of abnormal mitochondria and heteroplasmy; 2) disorders due to nuclear-mitochondrial incompatibility; 3) disorders related to aberrant epigenetic modifications; 4) birth defects and other disorders associated with the specific mitochondrial manipulation technology procedure; and 5) toxicities of reagents used in mitochondrial manipulation technologies. There may be additional risks that are difficult to predict because of limitations in current knowledge.”

And THAT still doesn’t do justice to the FDA’s briefing document, which makes it clear to me that they, at least, do not have a handle on what the risks are.  Keep in mind that, per the Belmont report, “relevant risks should be appropriately arrayed” in a research consent document.

(Oh, I almost forgot—one way to limit the risk of a child being born and passing mitochondrial disease to the NEXT generation is sex selection—bringing only boys, not girls, to term as a result of this oocyte manipulation.  Recall:  the diseases in question are maternally transmitted.)

This work is not ready for humans, even if it is regulated to limit its use to cases of known, severe mitochondrial disease.  Now, I am not schooled in the science, and I will watch for the meeting transcript from FDA to see if the Advisory Committee members were able to provide meaningful assessments of the risks.  But I’d want to see much more definition of the risks to consider human applications.  Even then, adoption would be a clearly preferable alternative from an ethical perspective.

But that of course gets at the issue of reproductive freedom, which is why we won’t see this subject go away.  Eventually someone will try it.  Such was the case with IVF in the 1970’s: Paul Ramsey objected on the grounds of risks to the children to be born, but then Louise Brown was born, and everything seemed OK, and many IVF babies, apparently healthy (pending long-term follow up; 1978 was only 36 years ago) have been born since.

It is noteworthy that the FDA’s briefing document contemplates oocyte mitochondrial manipulation not just for mitochondrial genetic disease, but also as a potential treatment for infertility.  That looks to be clearly beyond the pale here.  But the fact that it is included raises two further points:

  1. If this work proceeds for the purpose of allowing a seriously ill woman to conceive a genetically related, unaffected child, and that is perceived to be within the “therapeutic boundary,” it is probably only a matter of time before the boundaries are moved and the technique is used to support broad reproductive choice.  In that case, issues of heritable genetic changes will come much more to the fore than they may be at present.
  2. Oocyte manipulation becomes embroiled in the language of manufacturing; indeed, FDA’s briefing document discusses the need for “manufacturing controls.”  This is not all that surprising; the FDA is approaching oocyte manipulation as a form of gene therapy, about which it tends to apply drug development paradigms, ill-suited though they may be.  (See the separate topic of the second day of the FDA’s meeting—a guidance document addressing initial clinical trials of cellular or gene therapy.)

Similar work has been discussed in the U.K. recently; on April 23, 2013 I wrote about it on this blog, arguing that it too fundamentally alters core aspects of human nature and procreation that ought not be tampered with, whether because humans are in the image of God, or autonomous agents who at a basic level “ought not be disposed with,” or, at least, by virtue of a sort of “precautionary principle” that imposes a “presumption to forbear.”   The Nuffield Council in the UK was rather less concerned about the radical nature of what was being contemplated, endorsing oocyte manipulation as long as it’s safe.  Which is anything but clear at present.

But again, that was Ramsey’s other objection to IVF—that, like artificial insemination (donor), it fundamentally severed the procreative and unitive aspects of human sexuality.

The safety problems of human germline modification

Digital Journal has reported that the FDA is holding a public meeting this week to discuss “oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease”. Although the technique being discussed does not involve altering nuclear DNA it is a form of germline genetic modification because it is creating an oocyte that is a new genetic entity consisting of the nucleus of an oocyte from one woman who desires a genetically related child implanted in the enucleated oocyte of a woman free of the mitochondrial disorder that the first woman does not want to transmit to a child. The resulting combination of nuclear DNA from woman A and mitochondrial DNA from woman B would be genetically different from any possible child parented by either woman. This new genetic combination would be then transmitted to the child’s offspring so this would be a true germline genetic modification.

Although there are other ethical concerns about the use of such a technique, the clearest concern regarding such a procedure should be the safety of the children who would be its outcome. The problem with determining the safety of such a procedure is that the adverse effects of creating a genome that consists of nuclear and mitochondrial DNA from different individuals is that the adverse effects might not be evident until later in the child’s life or might not be evident until a generation or two later. By altering inherited characteristics all the descendents of the resulting child would be affected. How can you determine that a procedure is safe if it could take generations to determine its safety?

A related problem is the difficulty of obtaining consent for the studies needed to determine the safety of a procedure that alters the genetics of future descendants of the experimental subject. The initial consent would be obtained from the parents of the child being created, but to determine if the procedure is safe the child would need to be followed for his or her entire life and consent would need to be obtained again after the child reaches maturity. However the problem does not end there because further consent would be needed for each of the child’s offspring first from the parents of the next generation and then from the next generation as they reach maturity. (This problem has been discussed in detail by Rebecca Dresser. See her article “Designing Babies: Human Research Issues” in IRB: Ethics & Human Research 26.5 (2004): 1-8.)

It is difficult to conceive a way in which the safety of procedures that alter the genetics of succeeding generations could be established. If we are really concerned about the safety of human research subjects then this type of experimentation should not be allowed. Those who advocate this type of experimental intervention should be honest that it would have to be done without regard to the future safety of the human beings who are being experimented on and their future offspring.

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?

Erasing Inequality?

It is 2014 and, heaven help us, it is another election year in America. The talking points are already taking shape in our own political Yugoslavia, where dialogue was long ago supplanted by lecturing. On the right, one cannot hiccup without the word “Obamacare” coming out. Comparisons to the Hindenburg and Titanic are considered too tame; at least the former made it across the Atlantic and the latter had a few lovely days at sea. It has been intriguing to me that this blog, with contributors of strong opinion and willingness to express such, has left untouched commentary on the October 2013 rollout of the Affordable Care Act (ACA for short; “Obamacare “ as a term has gone from pejorative to badge of honor to pejorative again, and “ACA” is quicker to type, so thus it is…). I do wonder if, among its supporters and detractors alike, the difficult launch of the ACA has created some sense of grief, where the laudable aims of medicine to help all who suffer, and where there should be no affirmation that “everything is just fine the way it is,” should be considered acceptable. If this reform fails, perhaps we will never get any kind of reform. I won’t put words in the mouths of my blogging colleagues, but there has to be, at some humanitarian level, a bid of sadness at the initial difficulties of the ACA for those at the margins of society. On the right, I think it legitimate that there needs to be some expression of that, even within a firm critique of the legislation itself.

On the left, that all-American response to adversity—change the subject—has brought us to the “Message of 2014: Economic Inequality Must Not Stand.” This is, to some degree, laudable: recessions tend to ensure that winners win big and losers lose badly. Jesus told us that the poor would always be with us, but he didn’t seem especially happy about that whenever he encountered poverty. A sorrow about poverty is not the exclusive domain of a single political ideology, though how to deal with it varies greatly between the two American political parties. Solutions abound…just today came a piece by a former Bush Press Secretary, Ari Fleischer (can’t get the hyperlink to work, just Google it), about the social roots of economic inequality. At least we are all talking about it…

But is economic inequality sufficient as an ethical imperative? It seems there are lots of other kinds of inequality that should have principles of distributive justice applied as well. There is a thought that economic inequality is often a product of the “lucky versus the unlucky.” Some have advantages, things that allow them to win at life’s financial lottery. Others hold pieces of paper with losing lottery numbers and work on to beat the odds next time. I have not spent long periods of time studying economics, but it seems that there are a lot of lucky and unlucky people out there, too, beyond those who play the lottery for money.  My athletic prowess is revealed with many a “came in just before the guy with a heart attack” finishes in 5K races. Perhaps (and believably) I am not well-trained, but maybe I’m just not lucky to be gifted as an athlete.  But it would sure be great to be the top finisher in my age group!

Lots of other examples abound. Some seem to come down to the lottery of good fortune, or abundant blessing for the Calvinists out there. An advocate of the ACA, MIT’s Jonathan Gruber, sent the conservative blogosphere into hysterics this past fall when he declared that “genetic lottery winners” have paid “artificially low” insurance rates up until the advent of the ACA, where the playing field would now be leveled. There is more than a kernel of truth to that—it has genuinely paid to be healthy. But is that itself a form of inequality, a distributive injustice? Much can be said about what a social contract should include—what provides for the majority who didn’t “win the lottery,” and what means should exist to allow them to flourish. But is genetic fairness even a good thing?

Intellectually, economic injustice should mean that the many that are economically disadvantaged are not made “less poor” or the well-off made “less rich.” Each should make marked strides toward the middle, with the result that many get much richer and few get slightly poorer. In the perception of most, though, and with only a passing glance at the claims of the rich who are to be “soaked,” the standard becomes one that all should consider themselves rich. It is the mark of the human heart to find that no level of riches is completely satisfying, and so “good enough” is, alas, not good enough.

Does that perception apply to those who are not winners in the genetic lottery? If so, that means that there is an ethical imperative to be as close as possible to the best and brightest. Fortunately, we think, technology when applied to biology can do what economics cannot and even the playing field without the “genetic winners” giving up much more than their exclusivity. We all can be the best! Here there is more than a passing dalliance with eugenics, all in the name of equality.

I am an advocate of care for the poor, for helping those who are suffering economically, whether from mistakes they have made or through no fault of their own. Justice and grace are about that. But I know that humans have sought to be better than they are, to reach greater heights, and that life in a fallen world cannot erase the inequalities that arise as a natural phenomenon. So when we look at a more even playing field, in “economic inequality” or in human health and flourishing, have we really considered what most people find that to be, and whether erasing inequality in all its forms is a worthy objective for us to pursue?

The FDA’s Warning Letter to 23andMe

Recently, the Food and Drug Administration issued a warning letter to 23andMe (the name comes from the number of pairs of chromosomes—23—in human cells), the private company that sells genetic testing to individuals.   You place an order online, pay $99, and they send you a kit for collecting a sample of your saliva and mailing said sample to them for certain genetic testing.  There is a lot of your DNA (your genetic material) in your saliva, and it can be tested for certain information.

That is the start of it.  You don’t get information about ALL your genes; that still costs several thousand dollars and is not generally available.  What is provided is information about a number of “single nucleotide polymorphisms,” called “SNPs” (commonly pronounced as “snips”).  SNPs are normal variants, differences of a single building block of DNA, where different people may have different building blocks.  Some may be associated with certain disease states, but not all are, and they are far from the whole story when it comes to genetic testing.   In particular, SNPs are not, per se, mutations, but may be associated with important mutations.

For your $99, 23andMe will give you results without any interpretation, or information relevant to your ancestry.  Until recently, it had also been providing a service which coupled its testing results with information related to a number of potential health issues.  That’s where FDA comes in.  The FDA’s November 22, 2013 warning letter cited two specific health matters on which it claims 23andMe was providing medical guidance:  potential breast cancer risk related to the BRCA genes, and information about how a person might respond to doses of certain anticoagulants (blood thinners) used to treat people who have had serious blood clots.

But why would anyone object to providing people with information they want about their genetic makeup, as long as steps are being taken to protect privacy and prevent discrimination, as required by law?  Isn’t information empowering?

Well, in general, of course, it is.  But there are two problems.  First, people might take aspects of their medical care into their own hands (self-adjusting their medication doses) without a doctor’s supervision.  In the case of anticoagulants, that can be seriously dangerous.  Or the interpretation of results (e.g., with regard to the possible risk of getting cancer) could be more complicated than meets the eye, and false conclusions drawn—leading to unwise medical decisions or unnecessary anxiety, for example.  (Consider as a case in point the National Cancer Institute’s advice about BRCA testing for breast cancer susceptibility, too complex to go into in detail here.)  Paternalistic worries on my part?  Sure—but appropriately so, I think.

Second, the test result might itself be false.  On its website, 23andMe says its labs are CLIA-certified—like the blood test lab at your local hospital, for example.  In recent years, however, FDA has been moving to regulate certain diagnostic testing more closely than in the past.  To make a long story short, this means holding tests like those offered by 23andMe to more formal FDA approval processes than the routine day-to-day tests broadly used in medicine.  Central to that process is establishing to a high degree of certainty that the tests in question actually work.  (Along with that goes ensuring that the information given to a person about his or her results is accurate and complete.)  And, while it’s apparent from the FDA’s letter that there has been a long, ongoing exchange between it and 23andMe directed toward eventual approval of the company’s health-related testing (as opposed to the ancestry-related information), that process has not been completed yet.  I imagine that approval process will, eventually, be completed.

For now, however, FDA has blocked 23andMe from selling this testing to new customers.  A warning letter means the FDA is serious.  It contains demands that, if not promptly met, leave the FDA with legal authority to seize the product, seek court action, or impose monetary penalties.

More libertarian voices have condemned FDA for being too heavy-handed, but as someone who’s worked for a long time in regulated industry, I think there is a legitimate issue of protecting individuals in this case, and I’m in the FDA’s camp on this one.

The End of Amniocentesis? (and the Discontents Thereof)

This blog has carried posts about the development of non-invasive prenatal testing for chromosomal or genetic abnormalities.  Because some DNA of a fetus (unborn baby) circulates in the mother’s bloodstream, it is now possible to identify genetic abnormalities just by drawing a blood sample from a pregnant woman’s vein.  The more traditional techniques, done much later in pregnancy, are amniocentesis and the related procedure chorionic villus sampling.  Those techniques are invasive, requiring obtaining a sample directly from a pregnant woman’s womb (with some risk to the fetus).  Because diagnosis of conditions such as Down syndrome may lead to the decision to have an abortion, pro-life advocates such as the late Dr. C. Everett Koop called amniocentesis “a search-and-destroy mission.”  One does not have to be too prescient to see the day, fairly soon, when the mission moves much earlier in pregnancy, is done non-invasively, and covers a host of not only serious disorders that greatly shorten the life of a born child, or abnormalities like Down syndrome, but other genetic diseases or even variations that may or may not be desirable.  It is also a short but timely step to consider how this will affect the number and timing of abortions in the future.

Geneticists remind us that we should be careful not to let concerns run ahead of the state of the art.  They point out, for example, that:

  • The current non-invasive tests are mainly focused on chromosomal abnormalities—specifically, three trisomies:  Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13).
  • By professional guideline and, in some states, law, non-invasive testing should only be done in pregnant women who are at high risk for bearing babies with one of these syndromes.
  • The tests are not fully diagnostic, but only screening tests.  A positive result should still be confirmed with one of the more invasive tests.
  • The tests may be highly sensitive and specific for what they are assessing, but that is not the same as having a high predictive value.  The predictive value of positive or negative results may not be well-established, and depends critically on how prevalent, or common, the condition being tested for is in the population being tested.  For example, a positive result of a very accurate test for a rare disease still has a low likelihood of having actually detected the disease in an individual who tests positive.  This is an entirely trustworthy, if seemingly counterintuitive, fact—trust me.
  • Consequently, at the present, non-invasive prenatal genetic testing should not be done routinely, and should be done only with prior and ongoing careful medical counseling.  Also, care should be taken that women not rush into a decision to terminate a pregnancy based on one of these tests, out of a sense of feeling pressured not to wait too late into pregnancy.  This last point is likely to be apropos as legislative restrictions on abortions after 20 weeks—which I generally consider laudatory—gain some traction.

It seems to me that the basic ethical issues are the same, but one’s day to day approach should keep the current state of the art in mind.   This post was prompted by my morning email from Medscape, with more detailed discussions here and here, a brief visionary statement here, and a brief very top-level comment on the implications for abortion, by Dr. Arthur Caplan, here.

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.