Still further on heritable human gene editing

I want to spend a little time—several consecutive posts—on the subject of heritable gene editing in humans, and on the recent report by the National Academies of Science, Engineering, and Medicine on it.  The topic bears more attention than a single blog post, written in a bit of a rush, based on only the initial release of the report, pending a deeper dive.  That is where I have been until now.

At the link above, one can download for free a pre-publication pdf of the full, book-length report.  (Last week I had found a 4-page summary that I can’t seem to locate again this week.)

Less than 15 months ago, in early December 2015, the Washington Post was reporting that “experts” were saying “It’s too early for gene-editing of human reproductive cells.”   Some, like Nobel laureate David Baltimore of Caltech, drew the line at attempting to establish a human pregnancy with an implanted embryo that had been gene-edited.  Others working in the field were writing that even a moratorium on laboratory studies of editing human sperm or egg cells was wise.  Then, as now, these experts (and they truly are experts, providing careful reflection for public benefit and guidance) were calling for more public input before pushing ahead.

Still, in a separate brief summary of the new report’s key points, the committee that prepared it says, first, that laboratory studies of editing human egg or sperm cells, the cells that produce them, or early human embryos “is essential to the advancement of science and should continue with[in] existing regulatory structures.

What has changed in less than 15 months?  May I suggest, nothing?  Last week, I used the words “runaway train.”  To be sure, I hear something of the same worry behind the experts’ just-released report.  In the 4-page summary I have, they write, that developing policies around human genome editing is “pressing, in large part, because of the…growing use of the CRISPR/Cas9 system.”  Growing use, as in, exploding.  I think we can concur with the committee about the urgency of the matter.

But, again, the experts seem to have moved from “don’t proceed with any pregnancies from this” to “clinical research trials could be permitted” only under a set of circumstances that are carefully controlled, at least to the extent possible.  In my post last week I copy-pasted their full list, the shorter form of which includes the following critera:

  • Absence of reasonable alternatives
  • Restriction to editing genes that have been convincingly demonstrated to cause or to strongly predispose to a serious disease or disabling condition
  • Availability of credible pre-clinical and/or clinical data on risks and potential health benefits of the procedures
  • Ongoing, rigorous oversight during clinical trials of the effects of the procedure on the health and safety of the research participants
  • Comprehensive plans for long-term, multigenerational follow-up while still respecting personal autonomy
  • Continued reassessment of both health and societal benefits and risks, with broad on-going participation and input by the public

IF one were going to allow attempts to, for example, prevent or “genetically cure” sickle-cell anemia prenatally, one would want to meet these criteria.  But suppose we could meet them all, except for of course the multigenerational follow-up, which would take time.  Suppose we knew beyond a shadow of a doubt that, in this case, the sickle hemoglobin gene mutation, a single point mutation, were definitively and selectively repaired in a new unborn human being, and we could treat a small but sufficient number to know that, at least into their young adulthood, they had no other adverse health consequences whatsoever, and maybe even had begotten unaffected infant children.  Would we consider this an unambiguous good?  I’m not so sure.  For one, we would have formed, in the first instance, an absolute dependence on in vitro conception—not that such is not the state of affairs in many cases, anyway.  But a mindset that “procreation the old fashioned way” is too dangerous would be fostered.

 

For another, the past and ongoing basic research would have included creation and destruction of human embryos—nascent human beings—for research purposes.  Well, maybe the horse would have left the barn, as is argued for the development of certain vaccines now widely in use.

 

The National Academies’ report focuses on human uses of gene editing—“gene therapy,” enhancement, and heritable changes.  Meanwhile, on the European continent, apparently they are not so sure whether they want to permit gene editing in plants.

 

And, of course, where there’s cutting edge science, there are patent applications, with an uncertain outcome in part because the techniques are already moving beyond CRISPR/Cas9.

 

More to follow on this.  In the meantime, interested readers may also want to revisit this short treatment of the topic.

Fetal tissue research furor continues

At the end of 2016, the Select Investigative Panel of the House Energy and Commerce Committee published its report—all 485 pages—of its investigation into procurement of tissue from aborted fetuses for research.  The investigation had been prompted by the 2015 undercover videos from David Daleiden and his “Center for Medical Progress,” which was adduced to support charges that Planned Parenthood clinics, in particular, had violated existing federal law in the performance of abortions and transactions to provide tissue from aborted fetuses to firms supplying medical research.

The Committee’s majority, of course, was Republican.  The Democrat minority on the Committee published a rebuttal.  The Executive Summary of that can be found here, and one link to the full minority report is here.

The majority report, as publicized, takes Planned Parenthood and several entities to task, and the minority rebuttal not only defends those groups but decries the majority’s tactics in the hearings.  I don’t intend to comment on those here.

Rather, I want to make limited remarks about the scientific contentions between the majority and its critics.  The journals Nature and Science have pushed back on several fronts.  In particular, the editors of Nature called the report “fantasy politics” that revised “the long history of the role of fetal-tissue research in vaccine and therapy development.”  The editors, writing, I suppose, under space constraints and the assumption that their audience knew that history as they know it, did not recount details.  The majority report does go into considerable detail, on pages 376 and following.  As I read the report, the majority admitted that fetal cells have been used in vaccine research and production, but their argument was that such cells need not be.  (Another Nature writer helpfully points out that the cells in question are cell lines, particularly two called WI-38 and MRC-5, used most notably in the development of vaccines against Rubella.)  The majority claims that the science of vaccine research has moved beyond the need for new fetal tissues.

Science took this point on directly, listing several vaccines that are still produced in WI-38 or MRC-5, rebutting statements in the majority report that fetal cells had “never” been used to produce a polio vaccine, and that “none” of the currently-licensed vaccines in the US are produced using fetal cells.

On the face of it, Science appears correct, but here’s a more extended excerpt from the majority report (pages 379-380, references eliminated from post for brevity but present in the original):

“The fetal-derived cell lines WI-38 and MRC-5 were adopted by the pharmaceutical industry as tools for the production of vaccines shortly after they were developed in the 1960s.And for a small minority of vaccines, these tools are still used today. However, these historic fetal-derived cell lines are still in use today for primarily economic, not scientific reasons. Obtaining FDA approval for a new vaccine is very labor intensive and costly. Consequently, once FDA approval has been secured for a particular method of producing a vaccine, Pharmaceutical companies tend to rely on this method, to avoid incurring new costs associated with “validating” the safety and efficacy of new procedures. Three major Pharmaceutical players (Merck, GlaxoSmithKline and Sanofi) adopted the fetal cell lines MRC-5 and WI-38 in the 1970s, shortly after they were developed. These companies were successful in gaining FDA approval for vaccines produced in these cell lines, and have continued using them ever since. However, viable alternatives exist and are used by other pharmaceutical companies for production of very similar vaccines (see Exhibit 9.3). [Blogger note:  I have not reviewed  “Exhibit 9.3.”]…

“Of the nearly 75 vaccine formulations currently approved by the Food and Drug Administration for use in the United States, only 11 (directed against Zoster, Varicella, Rabies, Rubella, Hepatitis A, Polio and Adenovirus) are produced using historic, fetal-derived cell lines, and none are produced using freshly isolated fetal tissue. Importantly, alternative vaccine formulations that do not rely on fetal-derived cell lines are available or all but five of these diseases (Adenovirus, Hepatitis A, Rubella, Varicella and Zoster), and there is no scientific reason these vaccines could not be produced using animal cell lines. For example, although vaccines against Hepatitis A are produced using the historic fetal-derived cell line MRC-5, modern vaccines against the related Hepatitis B virus are produced using genetically engineered yeast cells. In fact, the vast majority of modern vaccines are manufactured using bacteria, yeast or animal cells—and all of them could be manufactured in this manner. Human fetal tissue is outdated technology that is not necessary for modern vaccine production or research. For example, current vaccine research for HIV/AIDS, Cancer, Malaria and Ebola does not rely on human fetal tissue (see Exhibit 9.3.).”

Now, I am not an expert in vaccine production.  I will say that the majority report did seem thoughtful on this point.  Review it and the rebuttals for yourself.

The scientists otherwise complain that the Committee majority—clearly and admittedly opponents of abortion—wrongly discount the scientific merit of fetal tissue research, and the need for fetal cells, not replacements or surrogates, in that research.  The majority, they say, was too breezy about the possibility of using alternate cells or laboratory models.  Fetal tissue is more useful in certain research into HIV/AIDS, other infectious diseases, and especially to try to understand fetal development.    And fetal cell transfer is being studied again as a potential treatment for Parkinson’s disease.

But, as I have argued in the past, the empiric arguments from potential utility miss the ethical point.  Maybe cells procured a certain way will “work better” than alternatives, but have they been ethically procured?  And if not, we should limit the kinds of experiments we’re doing to what can be done within ethical boundaries.  If you don’t think unborn children warrant projection of life, or as human research subjects, except on the variable decision of someone else, then the expediency needs of the researcher win out.  If you do, there are limits.

And you should.

“The [Customer] Patient is Always Right?”

I recently received email notification of the 2016 update of the “Medscape Ethics Report: Life, Death, and Pain.”  Follow the link to view a slide set summarizing the results from 7505 surveyed physicians, 63% of whom were female:

  • Physician-assisted suicide (PAS) for “terminally ill patients”: DOCTORS now favor it, 57%-29%, up from 46%-41% in 2010. The proportion saying “it depends” remains at 14%.  What’s driving this?  Regard for patient autonomy—something that, as I and others have argued, can be elusive, to say the least, when it comes to PAS.  Sample comments include this one (emphasis mine): “It is shocking that this is a controversial topic.  Medicine is a secular institution and we must honor the wishes of our patients.”  SHOCKING??  When the heart of medicine is a covenant between doctor and patient that should include a regard for life that does NOT rest on whether one accepts there is a God?
  • PAS for “non-terminally ill patients with irremediable suffering”: Yes 28%, No 46%, “it depends” 27%.  To all those who said yes to the first question but something else to the second—you don’t get to make that distinction, IF your concern is patient autonomy.  If you counter that the point is that death sometimes is a better course for the patient, you are substituting some level of professional judgment in place of patient autonomy.  I don’t think one can have it both ways.
  • “Would you treat a family that refuses vaccinations?” 23% say no, 19% say “it depends.”  So much for patient autonomy.  No details about what vaccinations (HPV?)  Oh, and reluctance is HIGHER among pediatricians than family docs or internists.
  • Only 50% would tell a patient he or she is inexperienced in doing a procedure before performing it. I lived through “see one/do one/teach one,” as I assume all physicians do in their training, but I’m tempted to say, so much for informed consent.  In this day of “consumer empowerment,” we should encourage patients to ASK the question, and have an idea what they will accept for an answer.  Or maybe we should make our procedure consent forms a bit more like human research consent forms, and require that a number be specified on the form placed before the patient.
  • Only 49% think a terminally ill patient should be permitted to try “any” experimental treatment. This is a harder one to word a question about. Perhaps more on a future post.
  • 12% say life support is being withdrawn too soon, 88% say it’s not.
  • 21% would treat a patient against his or his family’s wishes, 45% would consider it. Another crack in Fortress Autonomy.
  • An increasing number would perform an abortion in some cases even if personally opposed—45% overall, 55% of OB-GYNs.

There’s more—check it out.  But it looks like this is not my father’s—or my, or Hippocrates’s—profession.

The 14-day rule: Time to double down?

The “world’s leading scientists” gathered at University College London on 7 December 2016 to explore extending the 14-day limit on embryo experimentation from 14 days to 28 days. Presently the consensus of that meeting is not known. The Guardian has published a nice summary of the background and future implications of the issue (link HERE). Jon Holmlund offered his comments in this blog back in May when researchers artificially grew human embryos to 13 days gestation. Since this issue is back in the news, a few additional thoughts are offered below.

Space does not permit a detailed history of the details of the discussion behind the original 14-day rule endorsed by the Warnock Committee in the UK (see HERE for one such extended summary). The original limit was arbitrary but coincided with the development in the embryo of the primitive streak, a precursor to the nervous system, such that experimentation on an embryo before this stage was believed to eliminate the possibility of that embryo experiencing pain. The implementation of the 14-day rule essentially permitted experimentation to proceed resulting in the successful development of IVF.

Regardless of the ethics, the 14-day rule has been a hard barrier scientifically until just recently. Just because we can breach the 14-day barrier, why go beyond? Allowing experimentation on the embryo out to 28 days would allow scientists to learn about the process of gastrulation, the process that lays down the body plan and where the three tissue layers (ectoderm, mesoderm and endoderm) begin to subspecialize. If we have ethically permitted experimentation on embryos up to 14 days gestation, shouldn’t we just nudge it out a little further?

To quote Jon Holmlund: “In the name of God, forbear!” Interestingly, for different reasons, Mary Warnock agrees with him. Per the Guardian article, she worries:” If we raise the limit, objectors could argue that the 14-day rule has remained intact simply because no researcher had the technique to keep an embryo alive for so long, and that now one has been discovered the rush down the slippery slope will follow. They will say: ‘We always knew that the slippery slope would prove itself.’”

Experimentation on a human embryo at 14 days of gestation is still experimentation on a human being made in the image of God. Perhaps the upcoming debate on extending the 14-day rule will actually result in Warnock’s fear, that we agree that the original 14-day limit was indeed too long to be slipping and sliding?

Zika and Genetically Modified Mosquitoes

Just last week, I received a call from a pollster.  It’s election season and I live in a hotly contested ‘swing state,’ so I wasn’t surprised.   What surprised me were the questions I was asked, mostly about the Zika virus—its spread and possible prevention.  One question especially caught my attention:  Are you in favor of genetically modified (GM) mosquitos?   Bioethics in a poll question!  I could hardly contain my excitement.

Floridians have grown accustomed to mosquito treatments.  (See a recent report from the CDC, here.) The government begins by spraying pesticide and encourages residents to get rid of any standing water.  Screens and insect repellent also are part of the strategy.

There have been some accounts that the pesticide has had undesirable consequences, including the death of bees.  It also produces a concern that pesticide cannot possibly be beneficial to the environment.  If traditional methods used to control mosquito populations have not been successful, GM mosquitoes offer a measure of hope.  Neuhaus and Caplan note, “The mosquitoes are genetically engineered to express a ‘self-limiting’ gene that kills offspring before they reach adulthood.”

The possibility of GM mosquitoes is not new.  According to Ernst, et al., the “Florida Keys Mosquito Control District proposed the first release of a GM mosquito” to help combat an outbreak of dengue fever in Key West, Florida.   Now, with concern growing over the Zika virus, GM mosquitoes have become an issue once again. There will be a non-binding referendum in November for the Keys to express their view as to whether or not the GM mosquitoes should be released.

Neuhaus and Caplan speak out for implementation of this proposal.  They believe it to be in the best interest of the public and the environment.  They base their conclusion in part on the FDA’s conclusion that saw no long-term problems with the release of GM mosquitoes. Others, especially those who live in Key Haven (the site of the release) are voicing their concerns.

Public health officials must always consider the public good.  They wrestle with possible unintended consequences and must think beyond solving the problem of the moment, by consider the long-term effects of their decisions.  I agree with Ersnt, et al, who observe, “Novel public health strategies require community engagement.”  If the Mosquito Control Board finally decides to proceed with GM mosquitoes, many will be watching to see what, if any, long-term implications will follow.  Perhaps you might have a genetically modified species in your neighborhood in the not-too-distant future.

Public discussions on human gene editing

On August 3, the National Academies of Science, Engineering, and Medicine posted online the slides and talks from its July 12 meeting to discuss public implications of the Human Gene-Editing Initiative.  A total of four meetings plus a related workshop were held: an introductory discussion in December 2015, followed by three more substantial meetings plus the related workshop in February, April, and now July of 2016. 

I’m still working through the materials, notably Francis Collins’ slide set from the July 12, 2016 meeting, addressing regulatory processes, in utero gene editing, and other topics.  But what first caught my eye was a brief written statement from the same meeting, from Ron Cole-Turner of Pittsburgh Theological Seminary.  In it, he states that Christian opinions on human gene editing are not monolithic; that, far from being reflexively in opposition, those opinions are quite open to editing even of the human germline as long as safety concerns are addressed, embryos are not sacrificed in the process of research, and therapy rather than enhancement are in view.

I must say the statement disappointed me.  The “safety argument” is the most prominent ethical concern raised in discussions of whether editing human genes in heritable ways is ethically permissible.  We certainly want assurances that we would not put the “edited” individuals at risk, and we really would want some level of certainty that the downstream effects would not be disastrous.  But of course, the latter may be impossible to assess, since adverse consequences could be subtle and might become apparent over many generations.

Beyond that, I thought Cole-Turner’s statement was too limited, with no mention of questions of informed consent, and with no deeper reflection on how human germline editing might (I would say, would) alter the way we look at ourselves, each other, our children, and the human race in general.  The push would be further toward seeing humans as plastic, alterable entities without limit, and, beyond questions of “simple” justice (how would we keep from making benefits available only to the rich?), would create a class of, as C.S. Lewis suggested, “conditioners,” or as contemporary European thinkers have put it, a class of engineering humans who work on other, engineered humans.  Finally, Cole-Turner did not really engage the concern that there is a constant eugenic temptation in humanity that would likely re-assert itself with force.

Cole-Turner’s statement was not proud; he opened by admitting that no one person could speak for all Christians.  And maybe brevity was necessary on the occasion of the committee meeting.  But I still would hope for more robust “religious” inputs at sessions like this.  Otherwise, one gets the feeling that all that is sought is a token religious imprimatur on the most cutting-edge biotechnologies of the “brave new world.”

Follow the link in the first sentence of this post, and the statement by Cole-Turner, as well as other materials from all the meetings, may be reviewed in detail.  It is good that these are posted, because, although it’s easy to say that a thorough public discussion of transformative biotechnology should be held with all stakeholder groups, only so much is generally done to achieve that.  Even interested parties, like your humble correspondent, have limited time to devote to the details.  But more of us in the general public should labor to make time to dig in deeper.

ADDENDUM: After posting the above I went back to the link (top of this post) and read through the slides from Dr. Collins.  Readers of this blog should by all means do so as well.  At the end, he muses about the level of acceptability of 28 current or possibly future interventions, placing them on a grid of when they will be in practice vs. level of ethical concern they prompt.  The slides are self explanatory and worth musing over.–JTH

The surprisingly small benefit of some very (expensive) Big Ideas

Last week, JAMA published online a Viewpoint provocatively titled, “What Happens When Underperforming Big Ideas in Research Become Entrenched?” The overarching Big Idea to which the article refers is the “narrative positing that a combination of ever-deeper knowledge of subcellular biology, especially genetics, coupled with information technology will lead to transformative improvements in health care and human health.”

The article highlights three technologies that are integral to the Big Idea but that have not lived up to their promise. The first is genetics/genomics; as an example of unfulfilled promise, the authors trenchantly observe, “Sixty years after the discovery of the genetic defect, no targeted therapy has emerged for sickle cell anemia” — one of the simplest genetic diseases, caused by a single gene. The second is stem-cell therapies; the authors point out one analysis of studies of stem cell therapies, in which the supposed effectiveness of the therapy was directly proportional to the number of factual discrepancies in the published study. The third is electronic health records (EHRs), which have cost billions, but have not realized either the improved care and cost savings that were their major selling point.

Despite the lack of evidence of real benefit, these three technologies have received vast amounts of NIH and government monies. The article recommends changes such as the “NIH should fund many more high-risk, unconventional ideas instead of supporting the same familiar highly funded research fronts.” It also calls for accountability for funded studies to show real benefit.

The article’s title asks what happens when underperforming big ideas become entrenched — vast amounts of money and energy are wasted — and suggests solutions. But the article does not address why those Big Ideas have become entrenched in the face of all evidence, and this must be addressed before solutions can work. I do not pretend to have a definitive answer. But I think there is an even Bigger Idea that overlies all of these lesser ideas: the idea that more technology is inherently good, and in higher-tech medicine will be our salvation.

For example, look at those things that have been shown to make “transformative improvements” in mortality, morbidity, and life expectancy: Quitting smoking. Getting off the couch and doing a bit of exercise. Eating your fruits and veggies. Getting immunized.

Now, which sounds more exciting for research funding: stem cells that we confidently assert can cure Parkinson’s even though we can’t quite prove but it’s pretty obvious that they should, or finding ways to get more grocery stores into poor neighborhoods whose most affordable food source has golden arches in front of it?

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.

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.

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.