A Bit More on Futility

In his Nov. 15th post, Joe Gibes warned of how pay-for-performance—the coming standard for paying doctors and hospitals—creates an incentive for doctors unethically to refuse to treat the sickest patients.  The week before, he rightly challenged my Nov. 8th post about futile care, warning that being too strict about a patient’s autonomy to dictate his end-of-life care could easily create a situation whereby his physicians could be considered obligated to provide ineffective treatments, essentially reducing the physician to the role of technician.  I think Joe is right on both counts.  But a bit more to say about this…

A neighbor of mine just lost his uncle to a long illness.  I am told there was some tension among family members, because one in particular “wanted everything done” and had resorted to diagnosing the gravely ill uncle’s medical problems by applying her native intelligence to what she could find on the Internet.  A debate about hospice referral was brewing, but the patient foreclosed the debate by passing from this life to the next.

Clearly, patients or surrogates acting as amateur physicians is uncalled for, and the physician’s calling requires affirming his knowledge and judgment, and educating patients and surrogates about proper medical standards.  But these cases should not distract us from the possibility that pay-for-performance or some other construal of physician authority and/or resource constraints would create the sort of unethical incentive Joe worried about, when it comes to end-of-life decisions.  This is what Wesley Smith has been writing about for years—“futile care theory” masquerading as cover for a “culture of death” in which patients’ ends are hastened by willful denial of indicated care.  That denial can come in the form of a physician’s refusal to honor a patient’s wishes, or the fiat of a hospital ethics committee, or the insistence that the patient’s surrogates, not the physician or hospital, bear the burden of seeking a relevant court order.  Smith writes, for example, about cases in which life support is removed against the wishes of a patient with capacity, in the name of “futility” and legal protocols that call for a patient desiring continued care, when physicians disagree, to seek transfer to another facility willing to provide the treatment, and possibly sticking the patient with the bill for the transfer.

Of course, such a scenario could arise under “pay for performance,” or other circumstances.  Smith at times writes as if he thinks that any criteria of medical futility necessarily create this problem, and I’ve seen writings on the internet that seem to paint Dr. Pellegrino, of all people, with a similar brush.  That, it seems to me, would be taking it too far.  Some treatments are indeed ineffective.  Even then, cost-effectiveness analysis will tend to broaden the definition of ineffective treatment.  Against that, it seems to me the physician must start with a bias toward defending not only the patient’s best interests, but also the patient’s perspective.  And the decisions whether a treatment is non-beneficial or disproportionately burdensome to the patient are made by the patient or his surrogate, from the patient’s perspective—not the doctor’s or the hospital’s or the “provider’s” or the health care budget invoked in the name of “society.”  These matters call not just for wisdom, sensitivity, and communication, but also for vigilance, I think.  We don’t want “autonomy gone wild,” but neither should we welcome “paternalism gone wild.”

[Note to readers:  I will take next Thursday, Thanksgiving Day, off.  Thank you for reading this blog, including my posts.  I hope you will participate actively, by commenting (with civility, of course) as you see fit.]

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.

On Futile Treatments

This past September 9, the journal JAMA Internal Medicine (formerly the Archives of Internal Medicine to oldsters like me) published a report (Huynh et.al.) that intensive care physicians at five academic hospitals perceived that up to 20% of the care they provide is futile, at an estimated “futile cost,” if you will, of about $2.6 million.  Yipes.

In an invited commentary, Drs. Robert Truog and Douglas White took issue with the study, for two reasons.  First, it focused only on the individual opinions of intensivists, excluding the views of patients, their families, other physicians potentially involved in the patient’s care, and other members of the medical care team.   Second, they argued, it probably overestimated the “potential savings” of not providing the “futile” treatments.  Intensive care unit costs are largely fixed, they wrote, meaning that incremental, or marginal, costs of the next treatment administered are relatively small in the grand scheme of things.  Perhaps better to focus on excessive testing and drug prescribing in general, they suggest, to “bend the cost curve.”  (I’ve blogged on a similar point in the past.)

(Regrettably, over at the Hastings Center’s “Over 65 blog,” Dr. James Sabin seems to endorse the findings of the Huynh study, in the context of reporting that, by a 3-to-1 ratio in one poll, the public believes that provision of unnecessary care is a bigger problem in Medicare than lack of access to care.  This seems to miss the criticisms of Truog and White, and to conflate “unnecessary” and “futile” care.)

Drs. Truog and White offered four suggestions to physicians when responding to requests for treatment they judge futile (I’ve rearranged their order here for my convenience):

  • Respond not with a unilateral refusal to provide the treatment, but by increasing communication with the patient or the patient’s surrogate—attempt to define a mutually acceptable treatment plan, and involve other expert consultants (e.g., formal ethics consultations) early on;
  • Recognize that the issues are complicated, and that patients unable to speak for themselves may not have a physician advocate—ready to articulate and support their preferences—near at hand in the moment;
  • Distinguish between truly futile treatment and “potentially inappropriate” treatment, that may prompt disagreements by, for example, posing such a high cost that the intensivist might be convinced that limited resources are better provided elsewhere; and
  • In the case of intractable conflicts, pursue a fair process of dispute resolution, which could include ethics committee review, obtaining second opinions, arranging transfer to another hospital, or “informing surrogates of their right to seek judicial intervention.”

Over at his “Human Exceptionalism” blog, Wesley Smith was not so sure about these last two points.  A shift of emphasis to “potentially inappropriate” (and costly) treatment sounds, he said, like “ad hoc death panels,” and any conflict resolution process should be one of mediation rather than decision-making.  The hospitals tend to have the power in these discussions, he said, and as such, should bear the burden of proof and of initiative in seeking any court orders.  And cost-containment pressures, including the changes that everyone seems to agree must be made in how physicians are paid, will increase the incentive to withhold or stop treatment earlier than might otherwise be the case, he suggests (albeit more colorfully than I have here).

So, some points:

  • Certainly communication with the patient or the patient’s surrogate, with input from consultants and the care team, is essential;
  • Unilateral decisions should certainly not be made by an intensivist;
  • Certainly the patient’s regular doctor, or a physician who takes the patient’s view and can advocate for the patient’s wishes, should be involved, rather than care decisions being devolved in the critical episode solely to the people running the ICU;
  • Certainly we should beware the potential for cost-containment pressures to stunt the decision-making process away from the proper care of the individual patient;
  • I would agree we should resist the creep implied by Truog and White’s “potentially inappropriate” category;
  • In an “intractable” conflict, the patient’s wishes should control;
  • And certainly we should not forget that futility in medicine—if we must use the term—applies, as Dr. Pellegrino said, to interventions that meet all of the following criteria:
    • They are “ineffective; i.e., unable to change the natural history of a disease or its trajectory toward death;”
    • They are “non-beneficial; i.e. unable to satisfy any good or value perceived by the patient or his or her surrogate;” and
    • disproportionately burdensome to the patient physically, psychologically, or financially.”

“Reduce the Excess Population?”

One hears this sort of argument from some environmentalist quarters:

(1)    The ecosystem (global temperature, number of species becoming extinct, supplies of essential nutrients) is under extreme and increasing pressure.

(2)    Human activity is the principal cause of (1).

(3)    The earth’s population of humans is growing.

(4)    This growth will exacerbate (1), perhaps very soon, to the point of unsustainability if not catastrophe.

(5)    Therefore, we have to do something to stop the growth in—or even reduce—the number of people on the earth.  Oh, and it might need to be really radical.

I have encountered this argument personally in recent weeks.  My response was not to assert “the Malthusian fallacy” (if you will), but to angrily appeal to respect for human life and human dignity.  In essence, “Is that so, Ebenezer?”  Just how should we manage the population, and its effects?  Restrict living standards in parts of the world—and, by extension, not just resource utilization but also, quite probably, public health?   Institute a worldwide “one child” policy?  Identify one or more groups of people for “culling?”  (Any volunteers to go first?)  Or what?  And who are the wise, progressive philosopher-kings who will promulgate and enforce the necessary edicts?

Of course, assertions that overpopulation is a, or perhaps the, fundamental temporal problem facing the human race raise questions of stewardship and creation care (which I can’t delve into here), or, more broadly, a moral philosophy of nature (about which I know little of recent development but am beginning to encounter in a new book—to be reviewed in a future post—addressing the ethics of synthetic biology).  I raise the matter here because I’m reminded of the importance of resisting an attitude that does not just blame human sin, but human existence itself, when it comes to resource management.

I know about the tragedy of the commons, but I’m talking about something—an insidious misanthropy—that I think runs deeper.  Consider the response of a friend of mine to this:  on September 14, one Erle Ellis took the “anti-Mathusian” line in the New York Times; to wit, human technological innovation has repeatedly enhanced the earth’s carrying capacity, and we should aim, and can expect, to repeat this feat in the future.  We are limited only by “our imaginations and our social systems.”

Well.  How 19th century.  But I do tend to prefer some level of optimism over the line I complained about at the outset here.   My less-optimistic friend wrote to the Times (looks like they did not run it) that, after all, the earth is not infinite, and that our technological cleverness is what has created the current environmental straits.  (I do not intend to weigh in here on just how severe those straits are.)  Things bite back, after all.

Fair enough, I suppose, but we had an animated conversation over his last implication to the Times:  that human population growth is akin to cancer.  After all, that is what we call uncontrolled growth.   The poverty of the analogy aside, I submit that the underlying impulse behind it is pernicious.  Perhaps that impulse is nothing more than the contemporary cry of “speciesism.”  When I try to appeal to stewardship, my friend responds that the very word is arrogant.  (I note in passing the “arrogance” of the Presidential Commission for the Study of Bioethical Issues, which appealed to “responsible stewardship” as a fundamental principle in responding to synthetic biology and emerging technologies.)

For sure, responsible stewardship requires humility.  As we seek that, maybe this is an example:  Michael Shermer, publisher of Skeptic magazine and no member of the Religious Right, reviewing two recent books on population for the Wall Street Journal:  “[W]e would all do well to note the circumspect prediction made by population biologist Joel Cohen in his definitive 1995 book, ‘How Many People Can the Earth Support?’  Mr. Cohen’s answer: anywhere from four to 16 billion!”   And, by the way, global birth rates are falling, which may be a good thing or a bad thing (another topic for another time).

For my part, I’ll try to be circumspect about this subject, but I won’t compromise human moral status in the process.

The Declaration of Helsinki At 50

For the seventh time since its initial promulgation in 1964, the World Medical Association (WMA) has revised the Declaration of Helsinki.  It remains a foundational statement addressing the protection of human research subjects, although it lacks the detail of laws and regulations governing human subject research in the United States and the European Union, at least.  As such, by itself the Declaration is an insufficient guide to standards for clinical trials and other research involving humans.  Although the Declaration addresses itself primarily to physicians, it is proper for anyone involved in human subject research to attend to it—and, indeed, it contains statements addressing non-physicians, governments, sponsors (including, notably, the pharmaceutical industry), and other bodies.

Revisions to the Declaration include reformatting, to highlight specific issues addressed; and new provisions speaking to compensation for subjects who suffer harm as a result of the research; the importance of publishing results (including negative results); post-trial access in poorer countries to potentially effective treatments used in a trial; inclusion of women, minorities, and other groups historically under-represented in clinical trials; the makeup and need for prior study review by a properly constituted ethics committee; and improvements in informed consent.   These are all improvements over the prior revision.  Indeed, an accompanying editorial in JAMA, the Journal of the American Medical Association, points out that there have been past attempts to skirt some of the Declaration’s assertions by referring to a prior version.  Anyone involved in human subject research should keep in mind that the October 2013 version is the relevant version; others are for historical interest only.

Still, the WMA seems to me to be playing catch-up, not only with existing regulations, but also with current practice of and discussions about human subject research.  For example, people wrestling with issues in the process and documentation of informed consent have carried the inquiry and advanced practice well beyond the Declaration’s eight brief paragraphs on the subject, appropriately stated though they are.  And a further review by Drs. Millum, Wendler, and Emanuel in JAMA points out areas where the Declaration still seems to come up short, for example:

  • Criteria under which informed consent may be waived are not addressed;
  • Research involving net risks to subjects—which may, under some circumstances, be warranted—receives conflicting guidance under the Declaration;
  • The acceptability of certain research combined with medical care seems to be restricted too severely;
  • The discussion of vulnerable populations overemphasizes access to care, not the risks of being at increased risk of harm in the course of the research itself, and protections for vulnerable populations gets short shrift;
  • The use of placebos seems too strict, potentially condemning research that may offer real improvement of care to some subjects even when the most advanced standard of care is not used—research into reducing perinatal transmission of HIV in underserved areas is offered as an example.

Important as the Declaration may be, it is not the best or most complete guide to the protection of human subjects.

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.

The Dead Donor Rule—Under Siege But Not Dead Yet

Last week, two “Perspective” articles in the New England Journal of Medicine addressed the “Dead Donor Rule” (DDR—everything has an acronym), the principle that the donor of a vital organ, for transplantation, must be dead before that organ is removed from the donor.  This prompts the question of how to know when a person is dead.  Historically, a cardiac or cardiopulmonary standard—irreversible cessation of all cardiac and pulmonary function—predominated.  Then, with the advent of modern intensive care and artificial ventilation, a neurologic standard—complete cessation of all brain activity, including the brain stem—was developed.  This standard, “brain death,” has been dominant since about 1970.  Other standards have been proposed, but these two are by far the most prominent and most viable.  Still, they are imperfect and imprecise, and while we can tell that someone has died we cannot say exactly when he has died.  And that is critical for transplantation medicine, because an organ for transplantation is more likely to be useful if it is obtained as close to the point of death as is acceptable; the consequences of death begin quickly, reducing the chance that a transplanted organ will work well in the recipient.  To deal with this, formal protocols for “controlled donation after cardiac death,” or CDCD (those acronyms again) have been developed.  Their use has prompted unease:  are we waiting long enough?  Are we sure the donor is dead?

For several years now, Robert Truog, M.D. and bioethicist Franklin Miller, Ph.D., have argued that the DDR itself ought to be abandoned.  In their recent NEJM piece, they propose that “certain living patients, such as those who are near death but on life support, should…be allowed to donate their organs, if doing so would benefit others and be consistent with their own interests.”  They suggest that the DDR be replaced by applying the principles of autonomy (honoring a prospective donor’s clearly articulated and/or documented choice) and nonmaleficience (doing no harm to a donor who is nearly dead anyway).  They appeal to the altruism of donors and their families, and to the need for more organs to meet a growing demand for transplantation.  They cite two cases, including one in which the DDR was invoked to prevent premortem donation of even non-vital organs (a kidney and one liver lobe).   Nine other M.D.s joined me in responding, often in horror, in favor of the DDR on the NEJM website.  (The comment period ended October 9.)  A relatively anodyne opposing piece in the journal argued for retaining the DDR as “an indispensable ethical protection for dying patients who plan to donate organs and one that strengthens public trust and confidence in our voluntary system of organ donation,” the emphasis being on public trust.  (One might be forgiven for imagining that if public confidence were less at issue it might be allowed that we reconsider the DDR.)

As I indicated, Truog and Miller have been at this for a while.  The late Dr. Edmund Pellegrino brought them up in a piece I recommend to readers of this blog:  his personal statement appended to the 2008 report on “Controversies in the Determination of Death” by the past President’s Council on Bioethics.  At that time, Dr. Pellegrino rejected Truog and Miller’s reasoning as “a utilitarian device.” Perhaps their present appeal to nonmaleficience is in response to that, but if so, it seems cruelly ironic at best, because to remove one’s heart before one has died is most certainly to do harm, despite one’s stated wishes about organ donation.  Or, perhaps, Truog and Miller would accept putting their approach under the umbrella of [supposedly acceptable] physician-assisted suicide.

In any event, while agreeing that current definitions of death are problematic, tending to favor a cardiopulmonary definition of death, allowing that “ethically sensitive” protocols for controlled donation after cardiac death were being developed, and calling for prudence in decision-making, Dr. Pellegrino also argued that “[r]elaxation of the DDR is a morally unacceptable and logically specious way to deal with the uncertainties of the criteria for death of the donor.  It leaves the choice of the criteria for death to individual preference, amounting to eventual abolition of any stable criteria for death.  Some additional dangers are:  the use of assisted suicide to facilitate organ donation; legitimizing the use of patients in permanent vegetative states or of ‘less-than-perfect’ infants as donors.  It exposes ‘undeclared’ patients to ‘presumed’ consent to donation.  Given the expanding cultural and ethical pluralism of the U.S. about all aspects of life and death, eliminating the DDR promises a future of moral and legal chaos.  Above all, it exposes the vulnerable or gullible patient to an increased danger of exploitation for the benefit of others. ”

Further, organ donations at the end of life can often raise the question of whether continued treatment is clinically futile.  Dr. Pellegrino reminded the reader of the three criteria for clinical futility: it is ineffective (inability to change the natural history of a disease); non-beneficial (unable to satisfy any good perceived by the patient or his or her surrogate); and disproportionally burdensome to the patient.  We do well, I think, to keep in mind that clinical futility must be attested by a physician committed to the care and interests of the donor, not just the transplant surgeons.

He concluded:  “If we grant, as I do, that [Hans] Jonas’s judgment about the imprecisions of decisions at the life-death interface is cogent, then his advice to ‘lean’ in the direction of protecting life is ethically sound and grounded in a valid precautionary principle.  Within these ethical constraints, the dignity of the donor and recipient, and the benefits of organ transplantation, can be protected.  The act of organ donation could retain its moral credibility without compromising care of the donor.”

Read the whole thing.

Corey’s Apology

My July 25 post included a reference to the controversy over a Biola University student’s attempt to display graphic images of abortion on campus, the university’s rather aggressive response to stop her from doing that, and the reaction of the Center for Bio-Ethical Reform (CBR).

About a month later (August 20), Biola’s president, Dr. Barry Corey, published an open letter addressing the matter.  In it, he apologized to the student and to “anyone of interest” in the public for actions that “were perceived to be heavy-handed and retaliatory.”  Strongly affirming Biola’s pro-life commitments, Dr. Corey outlined five types of steps the university is taking:

  • Communication—restatement by the University, starting with its president, of Biola’s “current and historic position on the sanctity of life” in various venues.
  • Instruction—through sponsoring a pro-life chapel service with invited presenters who will “demonstrate the use of images compassionately, ethically and effectively.”
  • Policy—This term, the University is developing “a clear policy supporting the ethical and compassionate use of graphic images in places trafficked by students.”
  • Leadership—in the “academic team” (the dean’s office, I presume) to ensure that pro-life commitments are reflected in the curriculum, learning objectives, and outcomes measures.
  • Continuing [Biola’s] Commitment—advocating for life in the universities activities “and through our legal action.”

I think that this letter is a model for how to address a sensitive controversy.  My understanding is that it has generally been warmly received in the pro-life community, but that the Center for Bio-Ethical Reform may not be entirely satisfied.  But I think we should be.

On the Threshold of the “Great Collision”

Of course, we all know about the common characterization of “Obamacare” as an impending “train wreck,” and it’s impossible to avoid bad theater like Sen. Cruz’s legislatively futile launch of fundraising for his 2016 presidential campaign.  (That is the most charitable way I can think of to describe it, if that is indeed charitable.  Otherwise, it’s like he’s leading the lads at the barricades in Les Miserables.)

And of course, I cannot suggest that I can predict the outcome of all this.  But it seems that:

  • To consider the Affordable Care Act (ACA) a step on an inevitable march to government single-payer is progressive wishful-thinking;
  • To think that the ACA will be defunded, or fully delayed, much less repealed, is conservative wishful-thinking (even if the executive has, indeed, effectively suspended big chunks of the act solely on its initiative);
  • The government has effectively created a restricted-choice insurance system, that may keep premium costs unnecessarily high;
  • That said, the premium subsidies are poorly constructed, as subsidies tend to be.  According to the Kaiser online subsidy calculator, my family (my wife, our two sons age 21 and 23 [remember we can cover them to age 26], and I) could get a subsidy of over $11,000 per year if we earned $94,000 (399% of the poverty level).  If we made $95,000, the subsidy would be $0.  I leave it to you to judge the justice of this.  Recall that, at least at the outset, claimed income levels are subject to the honor system.  Presumably there will be a “clawback” mechanism in future years;
  • But, because “affordable” is based on individual coverage, not family coverage, and one’s employer provides the former but not the latter, one’s family could suffer an enormous cost hit in the exchanges.  This ought to be readily fixable, but it is terribly sloppy that it’s a problem to begin with;
  • In general, young adults subsidize oldsters like me, but if my sons’ incomes are low starting out, maybe they do OK;
  • A much better approach would have been to subsidize the insurance purchases of some, allow more breadth in coverages and pricing, and create an incentive by saying that once insured, and continuously insured, one could not be re-rated or have coverage dropped.  (This from Dr. Scott Gottlieb.)
  • Perhaps the greatest ethical worry about the ACA is that in it, the government exempted itself from the Privacy Act, leaving the risk that people’s individual health information may be rather less protected than it ought to be;
  • Doctors, hospitals, and, probably eventually, drug companies, will make less money.  That may not be so bad, or it may be.  As I’ve mused before on this blog, what the compensatory responses will be, I will not try to guess;
  • It is, of course, good for more people to have access to health insurance.  One hopes they will be able to find doctors;
  • If the public exchanges struggle, they will be eclipsed by the private exchanges being set up by industry in general and, in some cases, health insurers.  (I read Aetna has its own.)  This would not surprise me.  I used to work for the government.  It does some things well, but I would venture, not something like this;
  • Finally, as Holman Jenkins commented this weekin the Wall Street Journal, a number of other effects may have been set in motion:
    • A decline in importance of Medicare, as more people seek private alternatives and payments to doctors are reduced;
    • A longer-term decoupling of health insurance from one’s job may take place—something that a lot of people of different political convictions have argued for, for some time.  (I for one do not mourn the demise of the useless “mini-med” policies.)
    • In that case, what is left?  “A schedule of declining subsidies…that phase out with income”—which sounds like something the Republicans have pushed.

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.