“Imago Dei” by any other name…

William Shakespeare reminded us that an object’s essence is not determined by the label we assign to it. No one has since proven Shakespeare wrong. Despite this fact, nowhere have labels been more strongly asserted than in the bioethical debate of abortion. Exactly what or who exists in the uterus of a pregnant human female? The list of labels is long and includes: “baby”, “the pregnancy”, “embryo”, “fetus”, “the products of conception”, “the unborn” and “potential future person”. These labels may honestly reflect an individual’s sincere belief or understanding of the essence of the object in question. But the labels can impede an honest discussion of and agreement upon the essence of that very object. Termination of a baby carries more moral alarm than termination of a pregnancy even though both refer to the same event. We even have different labels to identify the opposing groups on the abortion issue that avoid naming the procedure; Pro-Life and Pro-Choice.

With abortion being the third rail of social politics, it should surprise no one when we see our politicians on both sides of the aisle politically injured when mishandling the subject. When asked if a pregnant woman should be held liable for seeking an abortion in some hypothetical future where abortion is illegal, Mr. Trump eventually suggested she might be subject to “some form of punishment”(1), though later walked back the statement after realizing his assertion upset both Pro-Choice and Pro-Life groups. Since this was a legal rather than ethical question, a non-lawyer could similarly struggle to rationalize how one presently can be held criminally liable for the unintentional death of the fetus of a pregnant woman via a motor vehicle collision(2) but not held criminally liable for the intentional death of the same fetus under current (read: legal) abortion laws(3). No discussion was undertaken from an ethical standpoint to explain why punishment might be deserved in the first place.

Within a week of Mr. Trump, Ms. Clinton caused a different abortion controversy by “referring to the unborn as a person”, drawing the ire of her Pro-Choice supporters(4). The label “person” usually carries moral protection prohibiting, for instance, potentially fatal surgical procedures without informed consent, and abortion is certainly fatal, at least from the standpoint of the unborn, particularly when promoted to a person. Similar to a previous statement above, aborting a person carries more moral alarm than aborting the unborn.

For the Christian, the essence of the pregnancy, products of conception, embryo, fetus, unborn or potential future person must include the Image of God, the Imago Dei. It is this essence that provides moral boundary and ethical guidance regardless of other human attributes, whether potential or realized. See this recent blog entry for further detail.

As per Shakespeare, we cannot ignore the smell of the rose, regardless of how we choose to label it. Would that we could not ignore the essence of the Imago Dei, regardless of our ethical, social or political beliefs.

 

The pertinent portion of note 3: “If the mother can intentionally terminate the pregnancy at three months, without regard to the rights of the fetus, it becomes increasingly difficult to justify holding a third person liable to the fetus for unknowingly and unintentionally, but negligently, causing the pregnancy to end at that same stage. There would be an inherent conflict in giving the mother the right to terminate the pregnancy yet holding that an action may be brought on behalf of the same fetus under the wrongful death act.”

Translational Science as an Ethical Imperative

An acquaintance recently sent me a copy of an article from the December 7, 2015 edition of The New Yorker magazine, describing efforts of a neurosurgeon to use an unconventional approach to treating terminal brain cancer.  Follow the link and read the article for the whole story, but the physician in question was acting on anecdotes of people whose brain tumors had improved dramatically after serious post-operative wound infections. (Surgery is the front-line, but generally inadequate, treatment for these tumors.)  The physician purposely infected the wound of one of his patients with Enterobacter aeroenes, a bacterium normally found in the bowel and in human feces.

The first patient had a dramatic improvement and lived for a few years after—a highly unusual, positive result.  The second one did not do so well.  There was a small number of people treated in this way, and results were mixed at best.

From the article, it seems clear that this was a good doctor trying to help his patients—one who had done a practice-changing clinical trial and who understood that some treatments may “work”—that is, have a biologic effect as expected—but not help the patient—that is, the effect does not translate into any actual clinical benefit against the disease.  This is a common problem in the development of new treatments, especially for cancer, where clinical trials often do no better than showing “a correlation with a correlation with something you care about,” as a former senior official of the National Cancer Institute put it to me (not about this neurosurgeon’s approach, but about something else) some years ago.

“Innovative therapy” is not the same as “clinical research” or “human subjects research.”  The former is performed by a licensed physician using his clinical judgment to try to apply available means for the best care of his patient.  The latter tries to collect generalizable knowledge and, one hopes, help the study subjects in the process.  Often in clinical trials, especially the earliest trials of the newest approaches to therapy, the latter (“direct benefit” to subjects) is not attainable, but the former (the “indirect benefit” that may translate into future direct benefit for other people, or for society at large) is.  In early cancer trials, overoptimism, implicit or explicit, is often a concern, leading to something called a “therapeutic misconception.”

In this case, the doctor took pains NOT to create a therapeutic misconception.  He didn’t oversell the idea to his patients.  With the first case, the local IRB—the ethics board—did not think its oversight was needed, calling the approach “innovative therapy.”  As the number of patients receiving the attempted treatment increased, the IRB started to think it should get more involved.

To make the story short, enough was done without formal IRB review or FDA regulatory review that it was decided, in retrospect, that several people should be disciplined for, in essence, getting out over the end of their skis with the idea.  The author of the article contrasts this case with the Duke University studies into using a modified poliovirus to treat brain cancers, something that was the subject of a widely-noted report on 60 Minutes last spring (subscription required to view online).  That approach was studied in the laboratory for years before being tested in patients.

A big challenge with “alternative” or unorthodox treatment approaches for desperate diseases is that they are typically blind shots.  Now, if you know you don’t have long to live, you might be willing to let a blindfolded marksman shoot a wild animal off your head, knowing he might hit your head instead.  And, frankly, many new treatments are still “semi-blind” at least.  But (and leaving aside for now the whole question of how much of what kind of regulation is best) there is something of an ethical imperative for doctors exploring new treatments to perform the most disciplined scientific research they reasonably can to try to understand what is going on with their new idea, how to improve their chances of success, and how to limit undue risk to their patients.  It’s part of integrating medical research into good patient care, and it’s called “translational,” trying to translate a set of observations or laboratory results into a defined treatment with some reasonable estimates of the risks and benefits.

“Shrinking” IRBs and Cutting-Edge Bioethics

A recent conversation from my IRB work—for several reasons, I must limit the details of the case:

An IRB had received, for review and approval, a research protocol for gene editing of human embryos obtained from an IVF clinic.  The embryos would be at about the 150-cell stage—an early stage at which some (incorrectly, as I understand the science) believe a fertilized, dividing-and-differentiating zygote has not yet attained sufficient maturity to be called an embryo.  These embryos would have been “donated,” in compliance with current law and regulation, including informed consent from the relevant party or parties.  Further, the embryos would have been found to have a “life-threatening” mutation by preimplantation genetic diagnosis (PGD).

The first impression of the IRB’s primary reviewer (a scientific member for you readers familiar with regulations about the makeup of an IRB) was that the study was approvable on an expedited basis—that is, without a discussion at a full IRB meeting.  Current regulations identify nine categories of research eligible for expedited review.  The study in question arguably fits criterion #3:  “Prospective collection of biological specimens for research purposes by noninvasive means.”

Under current law and regulation, this is a reasonable view.  The Code of Federal Regulations (45 CFR 46.204) includes requirements for the protection of live human fetuses who are subjects of research.  The regulations define “fetus” as “the product of conception from implantation until delivery.”  Research involving dead fetuses, in whole or in part, including those obtained as a result of elective abortion, is to “be conducted only in accord with any applicable federal, state, or local laws and regulations regarding such activities.”  As the Congressional Research Service points out in a general reader-friendly FAQ document (go to https://www.fas.org/sgp/crs/misc/R44129.pdf), any research involving human subjects must be approved by an IRB in advance, but the dead fetus is not considered to be a human subject.

It’s logical to apply the same considerations to embryos used in research, and PGD, and, to be sure, IVF itself.  Of course, these embryos are usually destroyed in the process, and all the related issues of embryo or fetal tissue donation are raised in the process.  In the present case, were the research to be done on embryos intended for implantation and bearing in pregnancy, the embryos would be human subjects as well, and all the related issues—consent and others—that I and others have discussed on this blog in the past would apply as well.  It’s arguable that, to be sure all regulations are met, an IRB should send research like the proposal in this case to full review. (One question I would have is how strict is the definition of “life threatening” mutation.)

For those who, like me, argue that human life begins at conception and might like to see the current regulations changed, that probably would require a new statute—a law passed by Congress and signed by the president.

But none of those thoughts is my main concern here.  Rather, I think of the recent discussions of whether it is wise to edit the genes of human embryos or germline cells (eggs or sperm).  Scientists meeting in Washington DC recently issued a statement that it would be “irresponsible” to proceed with such editing in embryos intended for pregnancy.  There appeared to be at least a cautious embrace of basic research on editing genes in these cases, however, implying support for proposals like the one crudely outlined here.  But some leading scientists in the gene editing field disagree, arguing for a broader societal discussion first.

And, in that light, consider the shrinking role of the IRB.  I think the standard understanding of the IRB’s jurisdiction, in the early 21st century, is narrow—it is empowered only to address whether current regulations are being met.  Whatever the individual members of an IRB may think about the broader questions of the wisdom of forging ahead with human embryo or germline gene editing, I bet most IRBs would not think that it is not their business to weigh in on whether studies like the one described here should be done at all.  In other words, whatever societal discussion of these ethical issues is needed, the IRB is walled off from it.  Am I the only one who finds it ironic that IRBs, which had their genesis in the effort to prevent mistreatment of human research subjects, and whose members are required to have varying backgrounds, are considered unqualified to weigh in on matters like this?

Undiscussed issues in the debate over human germline genetic modification

Jon Holmlund’s 12/10 post on the use of somatic cell gene modification to treat sickle cell disease and two recent articles in The Telegraph have me thinking about human germline genetic modification again. One of the points in Jon’s post was that somatic cell genetic modification does not have the ethical problems of germ line genetic modification. The Telegraph articles discuss a group that has proposed a global ban on the genetic modification of human embryos and the views of the British government’s Chief Scientific Adviser, Sir Mark Walport, who advocates for Britain being at the forefront of this research.

While there are safety concerns with somatic cell genetic modification as with all new medical technology most agree that there are unique concerns with germline genetic modification. The group supporting the “Open Letter on Reproductive Human Germline Modification” focuses on the concern that this technique “could irrevocably alter the nature of the human species and society” in addition to safety concerns. Much of their focus is on the likelihood that the use of germline genetic modification would lead to a biological divide between the rich who could afford genetic modification and the poor who could not.

Walport takes the view that decisions about whether it is right to use human germline genetic modification are risk/benefit decisions and downplays ethical concerns other than safety. He is quoted as saying it was important to think about genetic engineering in a “sensible way” which involved “careful discussion and debate”’ of both scientific and ethical issues. “We shouldn’t think about technologies in a generic way. Is it a good or a bad thing,” he said. “There are potentially good uses and there are potentially abuses.” His consequential thinking excludes the possibility that there is anything inherently wrong with human germline genetic modification or the experimentation on human embryos required to develop this technique that he is supporting. It also assumes that modifying embryos so that parents who carry a genetic disorder can have biologically related children who do not have the disease they carry outweighs the potential harms.

While concerns about safety and concerns about social impact and inequality are valid, there some things that are being missed in the public debate. One is the issue of experimentation on human embryos. The request for permission by the Francis Crick Institute in London to do genetic modification experiments on human embryos in spite of the previous British ban on such research includes the stipulation that the embryos will be killed by 14 days after conception. These human embryos are being experimented on and destroyed with no benefit to themselves. This makes the research itself wrong no matter what benefit could possibly result from the research.

Another is the nature of the potential benefit of this technique. Sometimes it is expressed as having the potential to rid the human race of serious genetic diseases. That really is not true. Even if it would be amazingly successful it would only be able to allow parents who are carriers of a genetic disease and have the resources to know that they are carriers and the resources to undergo expensive reproductive technology to have a child who does not have that specific disease and who would not pass on that disease to his or her offspring. The disease would still be passed on by parents who did not know they were carriers or who did not have the resources to do this type of technology. That would not eliminate the disease from the human race. It is all about the reproductive “rights” of affluent parents and the profit that can be made by the reproductive technology industry in catering to their desires.

Babies and unnecessary pain in research

A Reuters news service article this week reported that many babies are subjected to excessive or unnecessary pain in the course of medical research.  The article provided a link to an online report from the journal Acta Paediatrica.

The authors of the article in question (freely available through the link above) summarized their review of 46 recent (previous 2 ½ years) clinical trials testing analgesic treatments for pain caused by medical procedures performed on neonates—babies in the first month of life.  As anyone who has visited the doctor knows, medical procedures can cause pain, sometimes more, sometimes less.

The article’s authors found that a majority of the studies used a concurrent control group that did not receive any analgesia, or placebo, to compare with an experimental analgesic drug or method.  The problem with that is that there are numerous standard pharmacologic and non-pharmacologic analgesic methods that may be used for neonates and older infants.  By denying those to some subjects, the investigators did a disservice to these neonates, the authors argue.  Their argument is entirely reasonable.  They further find fault with ethics committees that approve such research, journals that publish the results, and parents of the infants, who provided consent either out of ignorance or for some other unknown reason.  All of this should stop, they argue, in favor or research designs in which all subjects receive at least standard-of-care analgesia.

This looks like an easy one: a fundamental criterion for ethical research on human subjects is that risks be minimized to the extent possible and reasonable, and consistent with good scientific and medical practice.  Further, risks of research must be reasonable and proportionate to the likely benefits, direct (to the subjects) or indirect (to society at large, in the form of useful knowledge gained).  On one level, what we have here is unethical use of placebos.

As straightforward as this may be, I bet it is something that can easily get by IRBs/ethics committees.  I don’t follow pediatric research, for example, and had not known about some of the standard analgesic methods.  Several are quite simple—swaddling or stroking the baby, warming a heel before a pinprick, or giving the baby some sugar solution, for example.  I had no idea these had analgesic effect.  (I’m a father of two, but my sons are grown, and it’s been a while…)

To dig this information out may take rather more scholarship than most IRB members—scientific or non-scientific—are inclined or able to do.  But it’s essential.  Even more essential is proper scholarship by the researchers, who should know better, to design studies that are as ethical as possible.

A further point:  procedures that adults may not think so bad, like a vein stick or heel stick to draw blood, may hurt a baby like the devil.  The Reuters article cited separate research showing that needle pricks cause babies severe pain, and an expert in the study of pain was quoted as saying that a heel prick could hurt a baby all the way up to the knee.

Again, I had no idea.  Certainly medical practice should take this into account, and I imagine it does or it will.  But a simple blood draw on an adult is typically considered “minimal risk,” which is defined as causing no more pain or discomfort than is ordinarily encountered in normal daily activities of life or routine medical examinations or tests.  The implication is that even routine blood testing in infants should be considered more than minimal risk.  And ethical guidelines for research on children demand that more-than-minimal-risk studies in children clear a higher benefits hurdle than similar research in adults.

So, something else to watch out for.

Restoring Study 309: Figures don’t lie, but . . .

This week the BMJ published an article written under the “Restoring invisible and abandoned trials initiative.” This 2013 initiative was undertaken to bring unpublished trials to light and to correct misreported trials, “. . .to see whether access to and reanalysis of a full dataset from a randomized controlled trial would have clinically relevant implications for evidence based medicine.”  The BMJ article details the reanalysis of  Study 329, a 2001 study funded by GlaxoSmithKline (GSK) (then SmithKline Beecham), published in The Journal of the Academy of Child and Adolescent Psychiatry (no hack journal), and written, not by any of the 22 named authors, but by a GSK-hired ghostwriter. Study 309 purported to show that GSK’s antidepressant drug paroxetine was both effective and safe for the treatment of adolescents with depression. GSK’s marketing campaign based on the study touted its “REMARKABLE Efficacy and Safety,” and in the next year alone over two million prescriptions were written for children and adolescents in the United States.

The researchers for the BMJ article went back and laboriously dredged up original, previously-unavailable patient-level data from the trial and re-analyzed it using the original study protocol; essentially, they re-performed the original study, with two crucial differences: they weren’t being paid by the drug’s manufacturer, and they did not repeat the subterfuge employed in reporting the original study to mask the outcomes. Based on their independent analysis of the more-complete data set, their conclusions are that paroxetine is no more effective than placebo, and that it results in significant harms, including suicidal ideation. Along the way, they uncover the sleight-of-hand the original study used to come up with its conclusion, including practices like describing suicidal ideation as “emotional lability” (thus making it look like the drug in question didn’t cause suicidal ideation, just the far more benign-sounding emotional lability).

An accompanying article in BMJ details Study 309’s checkered history: it has come under repeated fire since 2002, and its falsehoods were a factor in the Department of Justice’s criminal charges against GSK. Amazingly (or not?), “None of the paper’s 22 mostly academic university authors, nor the journal’s editors, nor the academic and professional institutions they belong to, have intervened to correct the record. The paper remains without so much as an erratum. . .”

Meanwhile, many people, medical and non-medical alike, still believe, based on this study, that antidepressants like paroxetine are safe and effective for adolescents.  How many people have been harmed by these massive lies, perpetrated in the interest of making an illegitimate profit off of other people’s afflictions? This one seems to qualify for all three categories of deceitfulness: Lies, d__ned lies, and statistics.

The Personhood Problem

This week, a New York judge dismissed a case seeking to free and grant personhood to two chimpanzees being used in studies by Stoney Brook University. Manhattan Supreme Court Justice Barbara Jaffe issued a thirty-three page document outlining the reasoning behind her decision. A higher court had ruled on a similar case last year, so she was bound to follow suite.

The Nonhuman Rights Project, who sought to free these chimps, made arguments for personhood based on their powers of cognition and “their similarity to humans in DNA composition, communication, and self-awareness.”

There is more at stake with these kinds of decision than the rights of nonhuman animals, however. The kinds of arguments used to grant personhood to nonhuman animals also run the risk of questioning and potentially even removing the status of personhood from some humans. If we are to follow these kinds of criterion for personhood, we risk alienating young children, the elderly, and the disabled from having personhood.

Animal rights and pro-choice activists often have a similar list of qualifications for personhood that, either intentionally or unintentionally, exclude some people from personhood. In her famous argument against granting personhood to fetuses, Marry Anne Warren cites five necessary conditions for personhood:

1. Consciousness

2. Reasoning

3. Self-Motivated Activity

4. The Capacity to Communicate

5. Self-Awareness

If a being fails to meet any of one these criteria, Warren argues, that being is not a person. While her argument was designed to prove that a fetus is not a person, it is also strikingly similar to the arguments used by the Nonhuman Rights Project. Additionally, if this logic is followed, not only are some animals persons, but some humans are not persons, and these groups are already the most vulnerable in our society, especially the elderly and the disabled.

As much as I sympathize for animals used in research and kept in poor conditions, I have a responsibility as a Christian to “Learn to do right; seek justice. Defend the oppressed. Take up the cause of the fatherless; plead the case of the widow,” (Isaiah 1:17 ESV).

How can I address injustices toward animals without promoting logic that excludes some people from personhood? Is it possible to balance these two causes, or must one fall in favour of the other?

Opting out of informed consent?

In the process of conducting research for a project, I have recently encountered “opt-out” provisions in two separate contexts: medical research and organ donation. An opt-out provision presents a situation where consent is assumed, and in order to not participate in the research/procedure/donation an individual must take active steps to refuse consent. This stands in stark contrast with informed consent where before any type of procedure is done, the patient (or donor/donor’s next of kin) must affirmatively agree to any type of procedure being done to him/her. The National Institutes of Heath defines informed consent to mean “You are informed: you have received information about your health condition and treatment options. You understand your health condition and treatment options.You are able to decide what health care treatment you want to receive and give your consent to receive it.”(see here). Informed consent is the standard in the United States for both research and treatment. Beyond being just an example of the value placed on autonomy in the United States, it is our response to past harms and proactive approach to prevent exploitations of people in the future (think of the Tuskegee experience, for example).

So why are opt-out provisions even being considered? In both of the spaces where I have seen opt-out provisions being implemented (see this article) or proposed (see this article regarding a bill in Vermont), the commonality seems to be an extreme need and not enough resources to meet it. However, despite the extreme need, I believe we can come up with solutions that are not at the expense of informed consent.

I believe we need to be very cautious about adopting opt-out provisions. While I understand the need to find a creative approach to meet a need where there is a major lack of resources, I think that opt-out provisions present many other, and potentially more serious, concerns. What are your thoughts on opt-out provisions? Can you think of situation where they have been used in an ethical manner? Can you think of other creative approaches to dealing with meeting a lack of resources that maintains the standard of informed consent? I’m interested to learn more about your interactions with consent in an opt-out format.

Gene Editing—Trying to Get Specific

In a comment last week, Mark McQuain pointed out the article “Engineering the Perfect Baby” in the MIT Technology Review.  Freely accessible online, it describes, in non-technical terms, several of the routes that genetic editing may follow.  Perhaps the most explosive:  adult skin cell transformed into an induced pleuripotent stem cell that then is used to give rise to germ cells that are then genetically edited.  (Note that a treatment for infertility can be envisioned by this route, possibly not requiring any gene editing.)  Nearly everyone speaking publicly is calling for a moratorium on attempts to bring a genetically-edited human to birth.  Some expand that to call for a moratorium on the basic research into altering germline cells.  Reasons for their positions vary, but there are enough committed enthusiasts that basic research is likely to go forward.  Read the article.

Courtney Thiele and Steve Phillips commented insightfully on Lewis’s The Abolition of Man.  Steve’s 2012 article in Ethics and Medicine is a reminder of how much has already been written about the ethics of germline modification.  Read it if you can get it.  (Steve sent me a copy directly.) 

But there is a risk in focusing too much on “enhancement,” rather than on germline modifications to prevent/treat/eliminate certain genetic diseases.   And that risk is this: the technology can no longer be easily dismissed by virtue of its being far off in the future.  It is pretty much here.  So the question is:  is it everywhere and in all cases morally impermissible, in principle, to alter the human germline, or would a general moral prohibition admit of exceptions?  Were it possible to safely and truly selectively edit out the Huntington’s disease mutation, for example, in sperm, eggs, or intact human embryos, and make the process available to all who need it without regard to ability to pay, would we not embrace that?

I readily admit the counterfactual here.  From the standpoint of human subject research alone, any attempt to do what I just suggested would make for a lively IRB discussion for the foreseeable future.  But such objections were the most prominent ones posed against human IVF in the 1970’s.  Then Louise Brown was born.  Were the safety issues ironed out, would we fundamentally object to any inheritable alteration of the human genome (as one might hold that IVF is, by its nature, morally suspect)?  Or, does it depend?  And if it depends, how many “indications,” to use the pharmaceutical term, make the list?

Some proposing caution about human gene editing make this argument:  There is another, safer way—preimplantation genetic diagnosis, or prenatal diagnosis, with non-implantation or abortion of affected individuals, bringing only the healthy to birth.  Many conservative ethicists object to this alternative on the grounds of sanctity of human life.  I suppose one might ask whether gamete selection with regard to the gene in question might become possible.  I don’t know if that could ever be feasible.  It is tempting to think so, if it is possible to identify and correct a genetic defect with CRISPR, and verify that the repair had succeeded.  But again, I don’t know.

I think the “unknown unknowns” objection is a powerful argument.  (See Mark McQuain’s comment to my April 30 post.)  But what data would be needed to lay it sufficiently to rest to support some limited clinical applications?  In principle, could those data be obtained? 

Is there some short list of modifications that, if adhered to, would absolve the biotechnologist from the charge that she is one of Lewis’s “conditioners?”  Do any and all germline modifications in principle constitute “Nature’s conquest of Man?” I could imagine a “no” answer to that question being affirmed at some point in the future by many if not most “social conservatives.”

If some germline modifications could be embraced on moral grounds, then there would be no reason to presume to try to put a full-on moratorium on the basic research.  Regulation would be called for, after appropriate “public discussion.”  The editors of Nature called for such discussion this week.  They said last year’s WHO discussion about Ebola clinical research was a good example.  I’m not so sure; the report took a while to become public, was not all that detailed, and the detailed discussion was not all that well-covered by media.  The PCSBI’s process is admirably public, but how many people pay attention?

If, however, no heritable germline modification is acceptable in principle, then we could argue that even the basic research should not be permitted (assuming it could be stopped in practice).  Or, if no ethical experiment can be designed, the research should not go forward.  (Consider human neural stem cells in mice, or Hubertus Strughold, for example.)

I realize I am rambling here.  But I worry that fear of a dystopian future with engineered superintelligent kids of rich people, based either on Lewis or on what I understand to be the Continental concern about destroying human equality by subjecting human biology to engineering, is insufficient to address the renewed task that the current developments pose.

More on Gene Editing

The recently-public discussion of gene editing has been going on for over a month now.  I have been meaning to try to catch up with some of it.  Tuesday’s post by Courtney Thiele got there first.  This post will attempt to amplify a bit on what Courtney wrote.

As Courtney pointed out, the technology involves making selective genetic changes of interest, including, but clearly not limited to, replacing or “repairing” disease-causing mutations such as those that cause sickle-cell anemia, Huntington’s disease, or thalassemia (a set of diseases in which hemoglobin is abnormal and its oxygen-carrying capacity impaired).  These are but examples.  There is more than one editing tool: so-called zinc-finger nucleases, or, in the more recent reports, “clustered regularly interspaced short palindromic repeats” (CRISPR)-Cas9. 

The approach is powerful for studying genes in cell-based systems or animals, and could also be useful for designing cellular therapies using adult stem cells or induced pleuripotent stem cells, which do not involve the destruction of embryos and so avoid some of the ethical concerns with embryonic stem cell research and development.  Again as Courtney pointed out, the situation gets much more troublesome if editing of human embryos or human germline changes, inheritable essentially permanently down generations, are pursued.  Moral status of human embryos and the concerns related to human enhancement, and then some, come into play.

Recent rumor had it that a scientific paper was about to be published in which genes were edited in human embryos.  The New York Times article Courney linked to reported that the work had indeed appeared in print.  The paper was in the Chinese journal Protein & Cell, from a group of Chinese scientists, after reportedly having been rejected on ethical grounds by Science and Nature.  A Nature news article addresses whether it is ethical even to publish such work; another Nature news article describes the results, and the surrounding debate, further.  (Both Nature news articles are accessible without subscription.)

The scientists doing the work believed it was ethical (although apparently the editors of Protein & Cell do not necessarily agree) because the “defect” in the 86 embryos they injected with CRISPR-Cas9 was that they were from eggs that had been fertilized by two sperm each, so they could not be brought to live birth.  Of those, only 71 survived 48 hours (to 8-cell stage), 54 were genetically tested, only 28 were successfully spliced, and only 4 had the desired genetic repair.  They also found a “surprising” number of “off-target” (read: unintended) genetic changes on other parts of the genome.

This result fits with concerns raised in the run-up to the publication (whose reflections, in turn, substantially agree with Courtney’s).  A March 27 commentary by Gregory Kaebnick, editor of the Hastings Center Report, is particularly helpful.  Focusing on the risks of the procedure, Kaebnick identified two problems—“making the genetic changes correctly (getting them into cells and then the genome in the right location) and making the correct genetic changes (actually achieving the results without accidentally creating new problems).”  The Chinese scientists ran into both problems.

Similar worries prompted two separate groups to call for a professional, self-imposed moratorium on any attempts at clinical use of these gene editing groups.  One group, led by Nobel laureates David Baltimore and Paul Berg (among other serious heavy-hitters), cited especially the risks of making “incorrect” genetic changes, the consequences of which might not become apparent for generations.  They also cited the “slippery slope” (their term, not mine) from therapeutic uses to “uses with less compelling or even troubling implications.”  This should sound familiar to anyone who has followed human enhancement discussions.  They recommended a process similar to the 1975 Asilomar conference addressing recombinant DNA technology, and said they had an initial meeting in Napa, California in January, but a much larger discussion involving society at large is needed before proceeding.  The second group argued that a moratorium should extend to ANY genetic modifications of human germline cells on the grounds that potential therapeutic applications do not warrant the risks to treated human embryos as well as future generations—and that the bar for approving such applications should be high indeed.

Kaebnick agreed with the calls for a moratorium.  So do I.  I note that the ethical conversation mirrors not only that around human enhancement, but also the historical discussion of IVF in the 1970’s.  And I (with Courtney) hear echoes of The Abolition of Man in the reflections of the scientists and ethicists here.  (Kaebnick invoked another application—being able to alter entire species such as mosquitos in ways thought desirable—but that is for another discussion.)  And I am inclined to agree with extending the moratorium to any work on the human germline.  But in so doing I note that one remedy proposed by the scientists; viz., use of PGD to select embryos in IVF, raises its own ethical concerns and is not a remedy I would endorse.

Fellow TIU bloggers:  this topic warrants extended engagement in a number of posts.  Would a therapeutically-limited germline alteration be acceptable if safety is assured and no embryo dies in the process?  And if so, how do we get there? Should we humans not touch the germline at all, and if not, does that unacceptably foreclose an avenue to a future option against certain genetic diseases?  Is it possible to set any reasonable limits not just on applications, but on basic research, in this case? I for one will attempt to follow-up in future posts.  And I hope we can sustain some reflection in advance of this June’s CBHD conference on “Science, Research, and the Limits of Bioethics.”