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?)

 

 

Euthanasia, pediatric and adult, and the underlying concept of a life not worth living

Jon Holmlund’s recent post about pediatric euthanasia in Belgium made me think about what I had posted a couple of weeks ago about PGD and lives not worth living. There is a way in which the concept of a life not worth living underlies a whole spectrum of ethical issues from PGD and selective abortion to pediatric and adult euthanasia. There is a basic conflict between those who take different ethical positions on these issues over whether there are certain quality of life issues that can allow one person to decide that another person’s life not worth living.

For those who take the position that it is permissible for couples who are at risk to have a child with a serious genetic disorder to use PGD or prenatal diagnosis with selective abortion to try to insure that any child that is born is free from the genetic disorder, a part of the argument for their position is that it is permissible to discard the embryos found to have the disorder or abort the fetuses found to have the disorder due to the poor quality of life that would be experienced by those children if they were born. That is saying that the lives of those children would not be worth living. That decision is being made by the parents for their children and being confirmed by the physicians and others who participate in the process.

Those who support the permissibility of active infant euthanasia as practiced in the Netherlands under the Groningen protocol are also saying that the infants whose lives are being ended have lives that are not worth living. Again this decision is being made by the parents and confirmed by the physicians involved that the infant’s life is not worth living.

The situation with voluntary euthanasia of children as it has recently been allowed in Belgium is more complex. If the child does not actually have full decision making capacity or is being overtly or covertly coerced, it is again someone other than the child who is making the decision that the child’s life is not worth living and the situation is similar to infant euthanasia. If the child has full decision making capacity then it could be reasonable to consider the situation to be the same as adult voluntary euthanasia.

With adult voluntary euthanasia some would argue that the concern about one person deciding that another person’s life is not worth living is not an issue because it is the one whose life is being ended who is making that decision. However, whether what is being done is voluntary active euthanasia in which a physician is administering a lethal drug or physician assisted suicide in which the physician prescribes the drug with the intent that the patient will self-administer it, the physician who is involved must make the decision that the act of ending that patient’s life is warranted. Few would be willing to take respect for autonomy so far as to say that anyone who requested assistance to end his or her life should be provided the means to do so without a judgment by the physician that the decision to do so was an appropriate one. Assisting someone to commit suicide who is despondent over a break-up of a relationship is irresponsible. Thus physician participation in voluntary active euthanasia or assisted suicide requires an independent decision by the physician that the decision to request assistance in ending life is reasonable. The only way a physician can make the decision to participate is to decide independently that the patient’s life is not worth living.

The only situation in which ending a life to avoid a poor quality of life could be done without one person deciding that another person’s life is not worth living would be unassisted suicide. There are Christian and Kantian arguments for why that is not morally permissible, but that lies outside the realm of these thoughts.

Since all of these actions, from PGD to adult voluntary assisted suicide involve one person making a decision that another person’s life is not worth living, a crucial issue is whether it is morally permissible for us to make such a decision about another person’s life. For those of us who have an understanding that every human life has value simply because of being human, we must answer that it is not permissible to make that decision. We understand that no matter how difficult a life may be that person still has value and our response to those whose quality of life is poor and who are having to endure more suffering than it would seem that they ought to is to affirm the value of that person’s life by caring for the person’s needs. We cannot say that another’s life is not worth living.

At what cost experimentation…?

A new opportunity in reproductive technology has recently appeared in the news: uterine transplantation—referred to in the lay press as “womb transplants.” The experimental procedure was performed on 9 Swedish women in 2012 using live donors; they will soon be trying to conceive. The UK is preparing to follow suit using cadaveric donors. And not to be outdone, the Cleveland Clinic recently announced in a physician newsletter that one of their transplant surgeons is hoping to do the same, if the “ethical, procedural, and financial hurdles can be overcome.”

The accepted indications for uterine transplantation are loss of a uterus due to cervical cancer or Mayer-Rokitansky-Kuster-Hauser syndrome. MRKH is a congenital condition in which the uterus, cervix, and/or vagina are congenitally absent or underdeveloped and is commonly associated with renal abnormalities. It affects approximately 1 in 4500 female infants in the US who have a normal 46XX chromosomal complement and, as adults, have normally functioning ovaries. No definitive genetic cause has been identified.

On the surface, uterine transplantation appears to be a beneficial and hopeful procedure, one that would allow women to bear children who could not do so otherwise; and it would do so without the depersonalized use of artificial wombs (still on the drawing board) or the legal conundrum of surrogacy. It has, no doubt, raised the hopes of many women. But there are ethical concerns surrounding the current experimental risks of the procedure as well as looming issues with regard to costs and resource allocation.

Of primary concern is the ethic of human experimentation for a non-life-threatening condition (Jon Holmlund may have to weigh in here). Despite years of animal experimentation, to date there have been no successful pregnancies in primate models. In light of this fact, the first human uterine transplant was attempted in Saudi Arabia in 2000, but ended in a hysterectomy within 3 months due to thrombosis of the anastomosis. Turkey has also attempted one cadaveric transplant; the woman later conceived but miscarried. As one surgeon from Sweden stated, “This is a new kind of surgery. We have no text books to look at.” The transplant surgeon from the Cleveland Clinic concurred noting that they are “patching” together information from each animal trial in order to proceed with human clinical trials. Is such human experimentation legitimate? While human experimentation may be a necessary evil when life-threatening conditions are involved, it seems difficult to justify when the issue being addressed is not a “life-threatening” but a “life-enhancing” one.

According to the U.S. Dept. of Health and Human Services, in order to approve research on human subjects, Institutional Review Boards that oversee research protocols must determine that “risks to subjects are minimized by using procedures already being performed for diagnostic or therapeutic purposes,” and that “risks are reasonable in relations to the anticipated benefits.” But the question remains: who decides?

For the risks are not insignificant. Unlike most transplantation cases which involve sterile organs, this is a “clean-contaminated” case involving an elevated risk of infection due to the need to reconnect the uterus to the vagina. Using an organ from a live donor where the cervix and vagina cannot be sterilized exacerbates this risk of infection, as does required immunosuppression. The risk of clot formation in the anastomosis is real—as evidenced in the Saudi case–necessitating additional surgery to remove the transplanted organ. And even if the transplant is successful, further surgery is required to later remove the transplanted uterus, for this is considered a “new” kind of transplant—an “ephemeral transplant:” it is not intended to be permanent. After 2 pregnancies the uterus would be removed so that the need for immunosuppression would be eliminated.

But calculation of risk cannot stop with the recipient, for it involves two other lives: the donor and the fetus. The procedure needed to remove the uterus for transplantation is much more complicated than a normal hysterectomy entailing a laparotomy and greater risk to the donor’s renal system.

Finally, there are the significant risks to the fetus, whose survival is speculative at best. In order for these women to bear children of their own, in-vitro fertilization, with its attendant risks to the embryos, would be required since the fallopian tubes would not be anastomosed in the transplantation. It appears that the endometrium in these transplants is responding normally to the hormonal milieu, since some of the women have had menses, but what about the myometrium—the muscle wall: will it function properly, expanding and contracting, if a pregnancy occurs? Will there be greater risk for uterine rupture due to damaged myometrium—a life-threatening situation for mother and baby?

There is the additional risk of immunosuppressive drugs on the fetus. A British physician stated that the data from renal transplants “didn’t suggest” that the babies are at increased risk from the drugs. It is curious that in all other circumstances we are to practice only according to valid and reliable evidence, not suggestions. Human research should not be exempt; the risks of immunosuppression should rightly be proven before intentionally subjecting a fetus to those risks for the sake of another.

The greatest concern, however, is that of uterine circulation. The uterus has tremendous collateral circulation that is required for placentation and nourishment of the fetus; yet during transplantation, only the major uterine artery and vein are anastomosed. Will collateral circulation develop, and if so, how long will it take? Is one year adequate? How will one know—only when it fails? Abnormal placentation or vascular abnormalities place the fetus at great risk for miscarriage or growth retardation—essentially, intrauterine starvation. This is the greatest concern of the British researchers: yet having no answers, they move ahead, driven by the technological imperative—and competition.

Given the significant attendant risks, are there some hurdles that should not be attempted? Prudence would require that some level of success be achieved in animal or primate models before forging ahead in human clinical trials. In our obsession to attain one more technological milestone—an ephemeral uterine transplant–we have minimized or ignored the risks to all involved, and especially to the fetus who has become a disposable pawn in the desire for another’s self-fulfillment—an issue to be continued…

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?

Weighing Autonomy and Justice in the Balance

The monthly on-line AMA Journal of Ethics, “Virtual Mentor,” (virtualmentor.org), arrived in my inbox the other day. It is a topical forum in which medical students under the mentorship of faculty members test their ethical wings by addressing aspects of a particular ethical issue. The topic for January was “Ethics and Assisted Reproductive Technology.”

Two “bookend” articles caught my eye: “Assisted Reproduction for Postmenopausal Women” and “Who Pays? Mandated Insurance Coverage for Assisted Reproductive Technology.“ The first article in the forum presented the case of a 53 year old menopausal woman (a corporate CEO whose work had always seemed to “get in the way” of childbearing) who decided that it was time to have a child “before it was too late.” She would, of course, require donor eggs and IVF to achieve her goal. The social, economic, and medical reasons (not principles) for and against such assistance were listed in the article before concluding that out of respect for personal autonomy, this woman should be offered the desired treatment. Also implied in their remarks was that such decisions should be based solely on the patient’s good, not that of society–in other words, autonomy trumps justice.

The final article in the forum, ironically, evaluated arguments for and against mandated insurance coverage for assisted reproductive technology and concluded that “parenthood should be available to all, but the particular route to parenthood is not.” Furthermore, since adoption is a viable option that fulfills the desire for parenthood, the need to mandate insurance coverage for assisted reproductive technology is eliminated.

In any discussion of ART a thorny issue raises its ugly head: is infertility a disease or a social construct? Apparently both the World Health Organization and ASRM have declared infertility a disease—the operative word being “declared.” Undoubtedly, the declaration, like the recent declaration by the AMA that obesity is a disease, was motivated by concerns for reimbursement—to force insurance companies to pay for testing and treatment. Curiously, the US Supreme Court has also ruled that the inability to reproduce is a disability that warrants protection under the ADA.

More accurately, however, infertility is not a disease but a symptom or condition resulting from other factors, some of which may be disease processes (pelvic inflammatory disease, endometriosis), but others not (menopause, anovulation). As we move toward a single-payer system of health care, questions about what qualifies for coverage increasingly arise, forcing us to look seriously at issues of autonomy and responsibility. The primacy of the patient good, referenced in the first article, is an appropriate response when medicine is holistically understood to be an encounter between one who is ill and vulnerable and one who professes to be able to help, heal, cure, and care. But such was not the context in the first article where evaluation was based purely on patient autonomy, not on a relational encounter. Moreover, in a paradigm where autonomy reigns, as illustrated by this case, there is no room for consideration of the consequences of the choices being made or for the consistency between the choices and stated life plans. Such considerations belong only to a relational encounter. Yet can we allow individuals, in the name of autonomy, to make irresponsible choices, if we as a society are then obligated to come to the rescue, not of their lives, but of their life plans?

Treatment of infertility is not a matter of life and death, but of perceived self-fulfillment. Neither life nor fullness of life, however, is contingent upon childbearing. Strangely, the second article made a reference to the “stigma of barrenness” a concept that is anachronistic at best. In the past, when opportunities for fulfillment outside of childbearing did not abound and a woman’s worth was determined by her reproductive fruitfulness, a “barren woman” did experience stigmatization. But that is no longer true; certainly today barrenness does not equate with fruitlessness. This is not to deny that there is sadness, grief, and anxiety associated with the inability to bear children. But grief and suffering are not absolute evils to be eradicated at all costs; they are often means that God uses to help us grow, if we are only willing to learn from them.

I regularly encounter older women in my practice who are childless. When questioned about the circumstances, they invariably state, “it just didn’t happen.” They demonstrate a level of acceptance that is not found among those struggling to reproduce today, where expectation, rather than acceptance, is found—expectation of the effectiveness of technological resources. Have we in fact created this dilemma through the technological imperative? Nowhere in either of these two articles was mention made of a child as gift but only of a “child as means to self-fulfillment” or perhaps “child as post-script to one’s resume.” But even the idea of “gift” in our culture has become corrupted: it is no longer something unexpected to be received but the fulfillment of a request. Sometimes our expectations are our greatest source of suffering.

Are we, as a society, obligated to provide for the self-fulfillment of each of our members? Where do we draw the line? How do we balance the technological imperative with limited resources–autonomy with justice? These are vital questions that require consideration before implementation.

In my next post, womb transplants…

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.

Some Data on Egg Donation—But None on Risks to Egg Donors

Assisted reproductive technologies (ARTs)—notably in vitro fertilization—are becoming commonplace, yet one often hears the complaint that outcomes data about them are lacking.  Today, JAMA (the Journal of the American Medical Association) published some data online.  The article and an accompanying editorial are available for free online.  I will touch on only some of the interesting findings of this report here.

But I note that medicine and bioethics seemingly remain uninterested in the risks to egg donors, about which more at the end of this.

The authors report that fertility clinics (of which there are 443 in the U.S.) are required to provide data to the National ART Surveillance System (NASS) of the Centers for Disease Control and Prevention (CDC).  A 1992 law requires fertility clinics to report all ART cycles to the CDC.  For this report, the authors reviewed summary data between 2000 and 2010.  They used information from all or most of that time to analyze trends in donor oocyte cycles—where one woman donates eggs to be used for ART for a different woman seeking infertility treatment.  They also used the most recent data, from 2010, to make some assessments of factors that predict certain outcomes.

Again, just some of the findings that struck me:

  • The number of annual donor oocyte cycles increased from 10,801 in 2000 to 18,306 in 2010.  (There were 82,563 “autologous” cycles—women having induced ovulation in an attempt to conceive with IVF using their own eggs—in 2010.)
  • The percentage of ART cycles using frozen (as opposed to fresh) embryos increased from 26.7% to 40.3%.
  • The mean (average) age of donors was the same throughout (28); ditto for recipients (41).
  • In 2010, almost all donors were younger than 35.
  • In 2010, about 25% of recipients were OVER 45 years old.
  • Also in 2010, in the “autologous” (own egg) situation, the woman was over 40 only about 13% of the time.
  • “Good perinatal outcomes”—defined as a singleton birth at 37 weeks or later, with the baby weighing at least 2500 grams (about 5 pounds, 8 ounces)—increased from 18.5% to 24.4%.  Still a lot of small babies and preemies.
  • The rate of elective transfer of just one embryo increased from almost none (0.8%) to 14.5%).  Still, in 2010, 74% of the time, 2 embryos were transferred to the recipient.  Three or more embryos were transferred less than 10% of the time.  Compare that (again in 2010) with the “autologous” (own egg) situation:  a single embryo  was transferred in about 15% of the cases, two in about 50%, three in about 20%, and four or more in about 10%.
  • Five in eight (62.5%) of pregnancies were single pregnancies in 2010, and 44% of these ended in a good perinatal outcome, compared with 36.7% being twin pregnancies with good outcome in 25% of those, and 0.8% of pregnancies being triplet or more, with only one birth (also 0.8% of the total) 37 weeks or later and weighing over 2500 grams.
  • Interestingly, neither donor nor recipient age was related to pregnancy outcome.

No other information about infant health was included, nor were there any statements about whether “reductive” abortions were used.

The authors commented that it appears that the American Society of Reproductive Medicine’s recommendation that donor ART be done with single embryo transfer from a donor younger than 35 years was not being followed.

Also, and critically, the authors pointed out that they had no data on health outcomes for the donors.  At the end of their paper, they write, “given the increasing trend of oocyte donations, the inclusion of more detailed information about donor risks, such as ovarian hyperstimulation syndrome, in the NASS will be useful for monitoring the safety of donor cycles.”

The writer of the editorial pressed this last point further:  “[T]he current NASS data regarding outcomes of donor oocyte cycles have an important limitation—no data on health outcomes in donors.  Donors are at risk for all of the complications associated with ovulation induction, including the potentially life-threatening ovarian hyperstimulation syndrome.  In addition, there is uncertainty about longer-term issues such as effects on the donor’s own fertility or the need to inform recipients about the discovery of health issues not known at the time of donation…More complete data…are needed so donors can make truly informed choices and, once those data are available, mechanisms can be put in place to ensure that the donor recruitment and consent process at clinics is conducted according to the highest ethical standards.”

The editorialist’s comments are simply mainstream medical and bioethics.  It is scandalous that this does not get more attention in the bioethics community.  For example, I searched for “oocyte” or “egg” on the website of PRIM&R (Public Responsibility in Medicine and Research) and I got bupkus.  Amazing.  They should be all over this.  Anyone who would like to point me to something I’m missing from the bioethics community, please feel free to comment.

Thoughts on varied subjects: commercial surrogacy, professionalism, and Obamacare

A potpourri of stories from this week that prompted bioethical musings, in no particular order . . .

The BBC News website ran a fascinating, heartbreaking story this week about women in India who are paid to gestate other women’s babies: commercial surrogacy, a billion-dollar-a-year industry in India. The main figures in the story — a woman named Vasanti living in a dormitory for commercial surrogates, who is carrying a baby for a Japanese couple; and the doctor who runs the IVF clinic and dormitory — spend much of the story talking about how positive the practice of surrogacy is. Thus it is jarring — and revealing —  to get to the last sentence in the story, where Vasanti says, “. . .we want a good future. That’s why we [did] this, and not in my entire life do I want my daughter to be a surrogate mother.” (Italics mine)

***

Last week’s JAMA ran a narrative by Gordon Schiff, MD, which begins,

It’s 5 PM on a Friday afternoon. After 2 hours on the telephone trying (and failing) to get her insurance plan to pay for her medication refill, I reached into my pocket and handed the patient $30 so she could fill the prescription. It seemed both kinder and more honest than sending her away saying, “I’m sorry I can’t help you.” While I hardly expected a commendation for such a simple act of kindness, I was completely surprised to find myself being reprimanded for my “unprofessional boundary-crossing behavior” after the resident I was supervising shared this incident with the clinic directors.

(If you have a JAMA subscription you can read the whole thing here, otherwise it has been reposted for free  here.) Dr. Schiff’s reflections on this incident are eloquent and worth reading and pondering. From the perspective of a Christian physician who also works with the underserved, I am saddened at how far our profession strays from its moral foundations when  a detached, medicine-as-business model replaces the self-giving care that Christ modeled.

***

You may have missed it, but new provisions of the enormous law affectionately known as “Obamacare” went into effect this week with the beginning of open enrollment and the opening of online insurance marketplaces. The new law is extremely complex and promises to raise health insurance costs for many, including myself, at least in the short term. Lots of people are complaining about it, some more savagely than others. Many of my colleagues and patients have bemoaned it, and with good reason. But there is one group who have not complained to me about it at all: my patients who do not have, and until now have not been able to afford, health insurance.

On forced procreation and the right not to be a father

Wednesday’s Chicago Tribune ran a story on the top of the front page: “Couple battle over frozen embryos.” It is a tale that has been told many times in many places, with slight variations in the details: woman finds she has cancer; chemotherapy will end her fertility; boyfriend donates “genetic material” and, using her eggs and IVF, they make embryos; boyfriend and girlfriend split up; now she wants to implant embryos, but he wants embryos destroyed; Illinois Supreme Court to weigh in.

The boyfriend claims that “he never agreed to give up a say in whether he becomes a parent, that forced procreation would violate his constitutional rights” (italics mine). The Tribune story quotes him as saying, “I have the right not to be a father.”

Whoa, wait a minute. Forced procreation? The way I read the story, nobody was holding a gun to his head when he made his donation.

Nobody is denying that he has a right not to be a father. But it seems to me that he relinquished that right the moment his “genetic material” met her egg, and made a third party, a separate embryonic human. In other words, it’s too late — He already is a father.

If there is a “right” not be a father, it is the right to avoid fatherhood by avoiding going around fertilizing ova, not the right to avoid fatherhood by killing one’s offspring.

 

Stem cell programming inside the body

On August 29, I wrote about research into developing germ cells (sperm and eggs) from induced pleuripotent stem cells (iPSCs) that were developed in the laboratory and injected into mice.  I mused about some potential implications for assisted reproductive technologies and the like.

A broader area of stem cell and regenerative research seeks to use drugs or other approaches to reprogram cells within the body, without having to remove them and manipulate them or culture them in the laboratory.  One application would be to develop a drug that would induce certain stem cells in the body to develop into cells that had been damaged or lost in a disease process.

Last week, Nature published a paper online from a group in Spain that had succeeded in reprogramming cells in adult mice.   A brief, free summary is here; the full article is available to subscribers or for purchase online.

Now, at present, iPSCs can be induced by treating mature cells to express four genes that, when expressed, cause the mature cell to “de-differentiate” into an immature, pleuripotent state.  A pleuripotent cell is capable of developing into any type of cell found in a given, fully formed organism; i.e., a pleuripotent human cell is capable of becoming any kind of human tissue.  But pleuripotent cells can’t become a whole new individual.  For that, a “totipotent” cell is required.  A zygote—a fertilized egg cell—is a totipotent cell.  Early on in embryonic development, cells lose totipotency, but retain pleuripotency.   In fact, embryonic stem cells obtained by destroying a human embryo generally are not able to develop into a new embryo.   (Apparently, iPSCs generated in vitro have been said to be transiently totipotent, but generally iPSCs are not totipotent.)

What is remarkable about last week’s Nature report is that it looks like the researchers obtained not just iPSCs, but totipotent cells, by a technique designed to give rise to iPSCs in an intact mouse.  They derived “transgenic” mice—mice that have extra genes—that express the four genes needed to induce a mature cell to become an iPSC.  The mice were engineered so that their extra genes—their “transgenes”—were under the control of a genetic switch that turned on the transgenes if an antibiotic, doxycycline, were given to the mice.  That’s easy:  just put the antibiotic in the drinking water.  No antibiotic, the genes were off, and the mice were healthy, for at least 2 years, as if they had not been engineered.  Too much antibiotic, and the extra genes were “on,” full blast, and the mice lost weight and died.  But give an intermediate dose, and the genes were switched on just the right amount that the mice were riddled with “teratomas.”

A teratoma (from the Greek “teras,” or “monster,” and the suffix oma, meaning “tumor”) is an uncommon human tumor that usually does not metastasize, like cancer, although it can.  It arises from pleuripotent cells—germ cells and embryonal cells.  It is one of those oddities that pathologists routinely show to medical students, and they’re wild, because they can contain, chaotically,a mix of mature tissues—bone, kidney, muscle, hair, the occasional tooth, or whatever.

In the experiment in question, the transgenic, sufficiently switched-on mice had teratomas in all sorts of tissue, arising from different organs.  In other words, they had iPSCs crop up, and grow into tumors, in various organs inside their bodies.  The researchers were able to obtain these iPSCs from blood samples obtained from the mice—so they were circulating.

But now it gets wild.  First, these in vivo iPSCs were genetically more similar to embryonic stem (ES) cells—obtained from an actual embryo—than to iPSCs derived in vitro.  Moreover, like ES cells but unlike in vitro iPSCs, these in vivo iPSCs were able to form placenta cells.  And—get this—when injected into the abdomens of normal, non-transgenic, “wild type” mice, the in vivo iPSCs, unlike the ES cells or in vitro iPSCs, developed early embryos.

So, the in vivo iPSCs are much more versatile than ES cells or the iPSCs we may have become used to referring to.  As with any early research, translation into a medical application is some way off, but one can in theory envision a future treatment to induce these cells in a sick person, harvest the cells from the blood stream, and use them to treat a disease.  (There’s a sweeping statement for you, and admittedly so.)  But the apparent totipotency of these cells suggests a new wrinkle on cloning, for one.