Toward human-animal hybrids

To be published tomorrow in the Federal Register, the massive, Byzantine thousands-upon-thousands of pages repository for all of the rules and regulations that constitute so much of de facto law in the contemporary United States: a Request for Public Comment on the Proposed Changes to the NIH Guidelines for Human Stem Cell Research and the Proposed Scope of an NIH Steering Committee’s Consideration of Certain Human-Animal Chimera Research.  

As always, the technical issues are complex.  But, briefly, some scientists are working on putting human “pluripotent” stem cells—like embryonic stem cells, the kind that can produce many different organs or tissues or even a full human being—into early embryos of other mammals, such as mice or pigs.  Why?  To try to understand a disease better, or, in the case of some of the pig work, event to “grow” a human organ in an animal for future transplantation.

The National Institutes of Health (NIH) limits the scope of what it will pay for, because, frankly, we don’t know what we will get.  Concerns include having an animal with a more “human-like” brain, or one that can make human sperm and egg cells, or one that could breed to “spawn,” if you will, a part-animal, part human or even a human baby in a female animal.  More generally, what percentage of human cells does it take for a living being to be considered human, and how far might we experiment with adding human cells to animal embryos and animal cells to humans?

Farfetched?  Some scientists have reportedly looked at human stem cells in mice to see if brain function is affected in a way that can help understand psychiatric conditions.  See this discussion from the New York Times.

The proposed revisions to the NIH rules purport to make restrictions tighter by prohibiting government funding of experiments in which any pluripotent cells, not just the specific ones in the current guidelines, are inserted into early embryos from non-human primates (monkeys, apes) or breeding animals when the work may have contributed to human sperm or egg cells having been produced. 

But they would open introduction of human cells into other mammals’ embryos, or in non-breeding situations, as long as a committee determines that there could not be “a substantial contribution or a substantial functional modification to the animal brain by the human cells.”  Even here, they exclude rodents, presumably to permit such work in mice or rats to proceed.

The NIH wants to claim that this work can be carefully monitored and regulated to keep it from getting out of hand.  But non-government funded research would not be affected, and intrepid actors will invariably try to stretch the boundaries.  And some are concerned that even in the specific case, much less the “field” as a whole, we can’t predict where it will all lead.

If the society could, it should slow much more of this work down, if not call a halt entirely.  But legal bans are likely to be circumvented, and appeals to potential benefits generate continual pressure to move ethical boundaries further.   I think that ultimately it will not do to argue that eventual risks outweigh benefits.  Rather, we would have to convince our fellow humans that ethics require that we just forego some opportunities.  And that’s a hard sell.

Some California Physicians are trying to fight back against Doctor-Assisted Suicide

The Wall Street Journal op-ed page this week carried an offering (subscription required) from one Dr. Philip Driesbach, a cancer doctor in California who is one of six plaintiffs on a lawsuit attempting to block California’s new “End of Life Options Act,” which went into effect July 9.  Dr. Driesbach’s article covers several key points:

  • ·       By allowing such individuals as potential heirs and the owners of caregiving facilities to be formal witnesses to a request for aid in dying—something the law prohibits them from doing if the document in question is a will—the law removes protections from vulnerable people.
  • ·       The law does not require psychological referral—and hence screening for coercion or easily treatable conditions—unless there are clear signs of mental illness. 
  • ·       “Killing is never medical care,” and doctor-assisted suicide is “fundamentally incompatible with the physician’s role as healer,” a position still affirmed by the American Medical Association.
  • ·       There is no compelling reason to compel doctors, as opposed to others, to take on the role of “agent of death.”
  • ·       There is something contradictory about asking the medical community, which has objected to participating in capital punishment, to become the agents of hastening peoples’ deaths.  (Dr. Driesbach actually said, “killing the innocent” here—I’m sanitizing, perhaps unnecessarily.)
  • ·       He cited the 2015 testimony of Dr. William Toffler of Oregon, who stated that doctor-assisted suicide in Oregon operates under “a shroud of secrecy” under which getting accurate data about the practice is “impossible” unless one works for the Oregon Health Division.

Rather, Dr. Driesbach charges that the push for doctor-assisted suicide is part of a social campaign, a “necro-political” movement, funded by rich donors who are quick to invoke equal protection under the law in other contexts but ignore it here.  I think he’s right.

A similar lawsuit has been filed in Vermont against that state’s law. Not everyone in the medical profession is supine before the doctor-assisted suicide juggernaut.

The Strange (Future) Case of Doctors & Mr. Hyde

On 28 June 2016, the Supreme Court declined to hear an appeal of a Ninth Circuit decision that forced a small pharmacy in Washington to dispense Plan B (a “morning after pill” that terminates a pregnancy via abortion) despite the religious objections of the pharmacist owners. In other words, the lower court ruled that the pharmacists must violate their conscience by prescribing Plan B or terminate their pharmacy business. Only three Supreme Court Justices agreed to hear the case; four are required. It can be argued that if Justice Scalia were still on the Court, The Court would have heard the case. As such, the Ninth Circuit’s ruling stands but is limited to the Ninth Circuit. Justice Alito’s dissent is worth the 15 page read. Doctors of Pharmacy no longer have religious/conscience protections in the United States within the Ninth Circuit.

Read that last sentence again.

Conscience protection for other health care providers may be more tenuous than is generally granted. Previously, multiple federal amendments provided health care workers conscience protections (Church Amendment, Public Health Service Act 245 & Weldon Amendment) A separate rider to annual omnibus bills called the Hyde Amendment actually prohibited federal Medicare and Medicaid funding of abortion specifically. The PPACA (Obamacare) changed the funding rules and arguably some of the previous conscience protections to the point where President Obama had to issue Executive Order 13535 specifically guaranteeing continuation of those protections in order to secure passage of the PPACA. The alleged tenuousness of current conscience protections mentioned above is the fact that an Executive Order can be easily be rescinded by this or any future president while overturning, even in part, the PPACA is no easy task. Additionally, efforts by those pro-abortion to eliminate amendments like the Hyde Amendment in its current form are vigorous and ongoing. (The link is presented as evidence not endorsement)

Regarding the title, the late Congressman Mr. Henry Hyde, author of the Hyde Amendment, is the antithetical homonym of the fictional Mr. Edward Hyde, the evil sociopathic alter ego of the philanthropic Dr. Henry Jekyll. Ironically, the present day Hyde (along with the other amendments listed) may be one of health care’s last protections against future violations of moral integrity by continuing to allow the unobstructed practice of medicine with one’s conscience intact.

On the “Moral Era” of Medicine

A colleague shared a recent JAMA article titled “Era 3 for Medicine and Health Care.” The author, Dr. Don Berwick, quickly surveys Era 1 — the “era of professional dominance”– and Era 2 — the “era of accountability and market theory”– before introducing what he hopes to see in “Era 3,” the “moral era.”

Berwick identifies nine changes that need to take place in order to accommodate this new era which has seen the implementation of ACA, the extensive use of electronic medical records, and the consolidation of hospitals and health plans. Several of the suggested changes are already taking place in health care systems across the country. Others are a bit more idealistic. I would like to use this space to mention two of the more idealistic changes.

Change number 8 is “hear the voices of the people served,” a noble goal indeed. While many health care organizations have moved in the direction of ‘patient-centered care,’ fewer embrace “paying special attention to the needs of the poor, the disadvantaged, and the marginalized, and firmly defending healthcare as a universal human right.” Seeing each patient as a human being, possessing great worth and dignity, is fundamental to all areas of bioethics, from the research lab to the bed of the dying patient. Humans need to be treated with humanity.

Change number 9 is even more idealistic: “Reject greed.” Berwick writes:

“Health care has slipped into tolerance of greed and it has to stop, through volunteerism when possible, through strong regulation when not. Rapacious pharmaceutical pricing, hospitals’ exploiting market leverage to increase prices, profiteering physicians, and billing processes that deteriorate into games with consultants coaching on how to squeeze out more profit all hurt patients and impair trust.”

Idealistic, right? But we know that one devastating medical emergency can bankrupt an insured middle class family and that many others are finding it impossible to make ends meet while undergoing expensive medical treatment. Bioethics should continue to address the staggering financial impact that medicine has on our society. As Berwick suggests, blindly ignoring these factors will lead to even greater regulation.

Bioethics has much to say if “Era 3” is truly to be the “moral era.”

Organ Harvesting in China

On June 13, 2016 the House of Representatives passed HR 343, “Expressing concern regarding persistent and credible reports of systematic, state-sanctioned organ harvesting from non-consenting prisoners of conscience in the People’s Republic of China, including from large numbers of Falun Gong practitioners and members of other religious and ethnic minority groups.” )  In part, the bill “calls on the United States Department of State to conduct a more detailed analysis on state-sanctioned organ harvesting from non-consenting prisoners of conscience in the annual Human Rights Report.”  This is a welcome response to a horrific practice.

Newsweek  reports that according to The Falun Dafa Association, “[I]n China patients aren’t waiting for organs. Rather, organs are waiting for patients.”    This is because executed prisoners provide a constant supply of organs.  The international community must continue to voice its strong disapproval of this practice.  We look forward to the June 22nd report of David Kilgour, former Canadian Secretary of State, investigative journalist Ethan Gutmann, and Canadian human rights attorney David Matas on China’s organ transplantation industry.  It is to their great credit that they are shining a bright light on this troubling issue.

Organ donation is a scientific marvel and a great blessing to those who have received life-saving organs.  Executing  prisoners of conscience and harvesting their organs is beyond the pale of ethical conduct.  It defies human dignity and scandalizes the international community.  It needs to stop.

Gender Indiscrimination

Steve Phillips has recently written in this blog about gender dysphoria and our culture’s struggle to respond consistently to it. Please see here for that discussion. North Carolina recently passed a law requiring individuals to use the bathroom of their biologic sex rather than their self-identified gender. This has resulted in claims of gender discrimination and gender phobia against those who do not wish to be in the same shower or bathroom with someone of the opposite biological sex, regardless of how that someone chooses to self-identify his or her gender.

In early June, a young high school student in Alaska, whose biological sex is male but who identifies as a female, recently placed 5th and 3rd place in the girls 100 meter and 200 meter state high school track meet. Interestingly, the cries of discrimination focused almost exclusively on the claim that this was unfair to the other women running in the same race. Said differently, there have been extremely few claims of gender discrimination or gender phobia against those who do not want to be in the same sporting event with someone of the opposite sex, regardless of how that someone chooses to self-identify his sex.

Why is there a difference?

Notice that in both cases, opposing sides agree that males and females are different, deserving different bathrooms and different sporting competitions, the latter a successful result of Title IX federal regulations beginning in the 1970’s. Both sides seem to agree that the issue is how to discriminate who belongs in which group. In both examples, one side argues that subjective self-identification is a sufficient claim to gender group membership while the other side demands objective biological criteria. So who is right?

And why is the girl who finished 6th in the 100 meter Alaska High School Track meet less likely to be called bigoted if she complains about having to race against the boy who identifies as a girl as when she complains about having to share the shower with him after the race? If the difference is one of fairness/justice in public sports competition, it is unclear why we should elevate public sports competition above private social interpersonal contact in terms of our bigotry tolerance.

But let’s say we do. Both the IOC and the Women’s Sports Foundation have position statements that effectively argue that the issue comes down to objective biological criteria, namely testosterone levels. At least in competitive sports, subjective self-indentification is not a sufficient claim to gender group membership.

But what about public bathrooms? Curiously, the Justice Department is using Title IX, that landmark federal regulation banning sex discrimination by schools that receive federal funds, to effectively require schools to be rather gender indiscriminate. Effectively, they are requiring schools to allow students to use sex-segregated bathrooms based on their self-identified gender or move away from sex segregated bathrooms altogether. As Jeannie Suk recently stated in The New Yorker: “The discomfort that some people, some sexual-assault survivors, in particular, feel at the idea of being in rest rooms with people with male sex organs, whatever their gender, is not easy to brush aside as bigotry. But having, in the past several years, directed the public toward heightened anxiety about campus sexual assault, the federal government now says that to carry that discomfort into bathrooms is illegitimate because it is discrimination. [emphasis mine]”

It seems that our culture’s response to this issue remains incoherent.

Mitochondrial replacement boosterism

A new Viewpoint article (available for free, without a prescription) from the Journal of the American Medical Association (JAMA) asserts that the United States is acting too slowly to advance mitochondrial replacement techniques (MRTs), the so-called “3-parent baby” approach that would seek to prevent mitochondrial DNA disease, which is transmitted maternally.  The authors approve of the recent recommendations by the afore-named Institute of Medicine (IOM), but are dismayed that, for now, recent federal legislation blocks FDA from further consideration of MRT applications.  This runs counter to the principle of beneficence, they argue, by foreclosing the possibility of reproductive relief for the estimated 800 US women affected each year.  This is their number, not mine, and presumably refers to 800 attempted births per year by women affected with these mitochondrial diseases, which are inherited and so present in an affected individual for life.  Again, the goal would be to allow these women to conceive and, one hopes, give birth to an unaffected offspring. 

In any event, the authors of the article in question find the IOM’s recommendations thoughtful, but the aforementioned legislation thoroughly unreasonable.  Besides blocking the advance of science in the U.S., we are ceding ground to the U.K., where it’s full speed ahead for clinical applications of MRTs.

Now, the IOM recommendations were anything but slapdash, reflecting careful thought leading to conclusions with which one may yet disagree.  What troubles me about the JAMA piece is how cavalier the authors are in embracing MRTs as the camel under the tent for doing anything and everything to the human genome.  They write (emphases are mine, not theirs):

“[The recent] developments [regarding MRTs] are nothing short of historic and their significance multifaceted. First, mitochondrial replacement therapy represents the sole example of state-approved germline gene therapy in the human. Second, it comprises the only known intervention with the potential to reduce the burden of mitochondrial DNA diseases. Third, it constitutes the first case in which organelle and, indeed, whole cytoplasmic cellular replacement are being contemplated. Fourth, it irrevocably alters assisted reproduction by placing it at the center of future genome editing efforts. Fifth, it acts as a test case for the regulatory adjudication of other emerging reproductive innovations. Examples include but are not limited to editing the genome of the human embryo and the prospect of using somatic (eg, skin) cells to generate eggs and sperm in a laboratory dish.”

I encourage readers to let this paragraph sink in.  The thinly-veiled argument is that putting breaks on these technologies is illegitimate not only because it violates the principle of beneficence, but more importantly because it could delay the day when humans are fully engineered.  The authors and their apologists will object that I am putting words into their mouths, but I think their enthusiasms are showing.

Read the whole thing.

Fabricating Man

It has been reported that last week, a group of scientists met in a closed-door session at Harvard Medical School to discuss concrete steps and industry involvement to achieve the goal of synthesizing—creating in the laboratory—an entire human genome, and putting it into a cell, within 10 years.  Reportedly led by Harvard’s George Church, a leader and chief enthusiast of the technical prospects of genetic engineering, the meeting reportedly was aimed not at creating whole people, just human cells.  How reassuring.  This paragraph uses “reportedly” several times because media coverage—traditional or social—was shunned by the participants.

This would be a huge jump from the work in recent years to synthesize the whole, and then the “minimal,” genome of one species of bacteria.  But one can readily imagine the undertaking becoming feasible within the next generation or so.

Could such an effort be ethical?  Well, IF the only conceivable—not technically feasible, but conceivable, or able-to-be-intended—use was to create a specialized cell for cellular therapy, then one could do some level of mental gymnastics to argue that the effort was sufficiently circumscribed to warrant proceeding.

But of course the real goal would be to alter whole individuals—or “create” them—for some purpose, ostensibly good, but possibly mischievous.  As such, the laboratory synthesis of an entire human genome has unethical ends to begin with, so ought never be attempted.

Others closer to the work may not be so categorical but nonetheless think this is a place that we ought not charge to.  Specifically, Stanford bioengineer Drew Endy and Northwestern University bioethicist Laurie Zoloth have written an open letter criticizing the attempt.  Endy, who is on the cutting edge himself, and who offered thoughtful testimony to the Presidential Commission for the Study of Bioethical Issues a few years ago about synthetic biology, was invited to the “invitation-only” meeting, but declined to attend. 

Read their entire letter here.  It is very well stated.

Endy and Zoloth worry that an effort to make an entire human genome could get diverted to evil ends—like figuring out how to create super-viruses—or to gain an advantage in the “competitive marketplace” of human reproduction.  “Would it be OK to make Einstein’s genome” and put it into cells, they ask?  If so, how many, and who controls them?

More critically, they suggest that just because something can be done does not mean that it is ethical to proceed, and they ask, how should we decide whether it is ethical.  They write, “[T]he narrative of creation of the human is the central narrative for many religious communities. To create a human genome from scratch would be an enormous moral gesture whose consequences should not be framed initially on the advice of lawyers and regulators alone. The perspectives of others including self-identified theologians, philosophers, and ethicists from a variety of traditions should be sought out from the very beginning. Critical voices representing civil society, who have long been skeptical of synthetic biology’s claims, should also be included.  The creation of new human life is one of the last human-associated processes that has not yet been industrialized or fully commodified. It remains an act of faith, joy, and hope.  Discussions to synthesize, for the first time, a human genome should not occur in closed rooms.”

The time has come for a massive public outcry to slow down our biotechnologists.  They are arrogating fundamental decisions onto themselves and attempting to declare, unilaterally, that they alone can create the means for declaring their work ethical and then make the decisions, in what is frankly a closed loop.  To quote a wiser man than I, it is time to “stand athwart the world and yell, ‘stop’!”

“Throw the main switch, Igor!”    

Doctors Push the PAS Envelope

Over at his “Human Exceptionalism” blog, Wesley Smith has had a steady stream of recent posts about physician-assisted suicide (PAS), also called “physician-aid-in-dying” or “medical-aid-in-dying” (MAID).  “Hat tip” to Mr. Smith for the story that introduced me to the “MAID” acronym.  It is reported that Ontario’s College of Physicians and Surgeons think that the proposed law being considered by the Canadian federal government to allow PAS has too many precautions, and would make it too hard for people to avail themselves of PAS, or “MAID.”  (I guess “PAID” was too obviously unfortunate.)

The Ontario doctors reportedly object to the following:

  • ·       A proposed requirement that each request for aid in taking one’s own life be approved by two physicians who are independent of each other and have no business relationship.  What could be wrong with that?  In parts of Canada, the doctors are all part of the same group, making it hard to find two who are not linked by a business relationship.  Were the object ethical, I would sympathize.  But I don’t find PAS ethical, and would counter that the structure of Canadian medicine might foster a kind of “groupthink” that would make truly separate, independent assessments—the apparent goal of the restriction—elusive.

Then again, maybe this is just a consequence of medicine’s ceasing to be an independent, learned profession, but rather an employment arrangement.

  • ·       A proposed requirement that two independent witnesses sign each request for assisted death.  What could be wrong with that?  The witnesses would not be allowed to be people who might materially benefit from the requester’s death, or who are family members or caregivers of the requester.  So “complete strangers” would have to be involved in a difficult discussion and decision.   One may sympathize with the objection.  The people most likely to know a dying person’s wishes are likely to be close to that person.  Forcing the person to broaden the conversation would arguably be an affront to dignity in itself.  Further, one would not want to create an incentive for outside parties to promote themselves as “suicide certifiers,” an arrangement that would just magnify potential mischief.  And one would not want to create an incentive to pressure third parties into complicity with the evil that I argue PAS constitutes.  But the aim of the proposed restriction appears to be to prevent people close to a dying person—prospective heirs, burnt-out loved ones—from giving the person a “push,” so to speak.  And, as requests broaden—as they have in Europe—from terminally ill to depressed people, it would be good to have a way for someone to step up and block the “push,” and urge life, not death.

In my view, the discomfort with this proposed restriction simply illuminates the fact that PAS is not a step that civilized, humane society—or the profession supposedly devoted to proper care—should be willing to take.  Dragging the decision into the light merely exposes just how questionable the practice is.  The Ontario doctors might say, “a request for PAS is rather more momentous than getting a document notarized.”  To that, I guess I’d say, “precisely.”

  • ·       The proposal to limit PAS in Canada to people in advanced decline from severe illness that makes natural death “reasonably foreseeable.”  What could be wrong with that?  The Ontario doctors say it’s too imprecise.  It’s impossible to predict when someone will die.  So doctors won’t know how to interpret it, will interpret it differently, or might shy away from granting requests because of the uncertainty.

Again:  precisely.  The inability to predict the time of death is one reason why medicine should be (remain?) about caring for sick and suffering people, including with proper palliative care, and helping make what remains of life as humane as possible.  We should not step over into the active hastening of death.  Not sure how to implement PAS guidelines?  Don’t participate in PAS!

Unless one advocates complete “autonomy” in PAS, and would have doctors rubber-stamp every request—assuming, all the while, that every request is freely and knowingly offered.

The Canadian provision was proposed in response to a mandate last year by Canada’s Supreme Court that the government must recognize a right to PAS by June 6, 2016, or the Court will just impose it, according to less restrictive terms than in the proposed law, meaning that even if the law is enacted, it will probably be struck down by Canada’s high court. 

Medical errors and more medical errors

Last week the BMJ reported that annually, there are 251,000 hospital deaths due to preventable medical errors in the US. There’s some debate about the calculations that they used to arrive at that number, and about what exactly constitutes a medical error. However, rather than quibble over the fine points, let’s acknowledge that medical errors are an ethical problem that must be addressed. In this post I would like to widen the conversation beyond the hospital walls. Below is a sample of some deaths due to preventable medical errors that weren’t included in the BMJ calculations (most of these ones happen outside of hospitals); nevertheless, they too affect thousands of people annually. I will also attempt to provide a taxonomy of the relevant errors.

Deaths due to the inability of the patient to obtain medical care because they couldn’t afford the care or the insurance — unknown number. The medical error here is a systemic one, the rationing of health care on the basis of who can pay for it.

Deaths of patients due to their being the subjects of human research — unknown number. This is peculiarly prevalent among embryonic patients (as Jon Holmlund wrote about last week). The medical errors include the failure to extend to embryonic research subjects the protections enumerated in the Declaration of Helsinki. There is also a category error: classifying embryonic patients as something other than human beings.

Deaths of embryonic or fetal patients through elective induced abortion — 977,000 (2014 data). The same category error as previous comes into play here: the failure to recognize the humanity of the unborn human.

Deaths of patients from drugs prescribed by their physician for the purpose of suicide — the numbers data is incomplete. The number is relatively low but projected to grow as more jurisdictions legalize physician-assisted suicide. The errors here include a professionalism lapse (forgetting that the professional status of medicine was established, among other things, on the dictum that doctors do not give deadly drugs, even if asked to do so). There is also the error of hubris: the belief that doctors can decide that someone should be allowed to kill themselves.

Preventable medical errors, all.