Addressing gene editing with “thin” bioethics

Yesterday’s post on this blog, by Steve Phillips, warned that a narrow, “rules limited” approach to bioethics reduces ethics in science and medicine to matters of regulatory compliance and risks making thoroughly logical conclusions based on faulty premises that are adopted without regarding “deeper ethical thinking” for which scientists’ thinking must be brought under the discipline of broader humanitarian reflection if correct basic notions of what it is to be human, and what humans should be up to, are to be arrived at.

A different but closely related way to look at this was suggested by John Evans of the University of California, San Diego in his contribution to Human Flourishing in an Age of Gene Editing, a new collection of essays, edited by Erik Parens and Josephine Johnson.  In brief, Prof. Evans commented that too much of bioethics is “thin,” reduced to the Belmont principalism (respect for persons/autonomy; beneficence/nonmalificence; justice) governs human subject research.  This “thin” bioethics is convenient for regulators to use to derive a manageable set of rules, and for scientists to, if you will, hide behind (my expression, not Prof. Evans’s).  Rather, he writes, we must be willing to criticize the assumption that all we need to ask about technology is how to use it, and seek a deeper wisdom about what is a good or worthy human life, for individuals or communities.  In making this argument, he appeals to “critics of technology,” both politically conservative (Leon Kass) and politically liberal (Jacques Ellul).  Jacques Ellul!  How often does anyone hear him mentioned anymore?  How many of us have read him?  (I venture fewer than should!) 

This criticism of worshipping at the Belmont altar, if you will, is hardly new, but it’s critical, especially when something as profound as heritable human gene editing is being considered.  You see, Belmont principalism is quite robust when asking how to deal with clinical trials.  But it really most closely applies to things like regulated drug development, and germline gene editing goes far beyond drug development.  It isn’t drug development at all, and cramming it into the conceptual framework of drug development is fundamentally misguided.

Nonetheless, the International Commission on the Clinical Use of Human Germline Genome Editing appears to be proceeding merrily along the drug development path. The second meeting, in London, is next month; one can sign up for a webcast. Just check out the agenda, especially day 2’s planned sessions on risk-benefit analysis and defining “a translational pathway.”  That language applies to new therapy development, not fundamental alterations of human inheritance.

One should keep in mind also that the assumption one can assess risks and benefits is only as good as one’s data.  This week it is reported that scientists have retracted an analysis suggesting that babies edited for an HIV-susceptibility gene might be at risk of relatively short life spans, something this blog poster readily jumped on in his June 6, 2019 post.   But, then again, so did the prestigious journal Nature Medicine, so I guess I shouldn’t beat myself up too much.  Seems the researchers didn’t define matters carefully enough.  Even if this particular analysis, from a large database of human genetic data, was flawed, similar analyses in the future might be helpful, it is argued.  Until more is known, it is further argued, one should not seize on a retracted analysis to infer a full “green light” to edit unborn babies’ genes.  But that may take “thicker” bioethics than whatever risk-benefit analysis we think we can muster now.

The importance of premises

In an interesting article in the Hastings Center Bioethics Forum, titled “Hannah Arendt in St. Peter’s Square,” Joseph Fins and Jenny Reardon write about the importance of deep ethical reflection in dealing with the ethical challenges of biomedical research. They point out that when ethics becomes a matter of simply following a set of rules we can end up in the wrong place. Even such fundamentally good concepts as informed consent and the need to have research proposals reviewed to be sure that they are ethically sound can lead to a mindset of regulatory compliance, essentially following the letter of the law, while leading to poor conclusions about what we ought to do. In the end they suggest that in order to facilitate deeper ethical thinking regarding new areas of biomedical research we need more interdisciplinary conversation between the sciences and engineering on one hand and the humanities and social sciences on the other. I think this is quite true and is a strong argument for a liberal education in its classic sense.

However, I find it particularly interesting how the thinking of Hannah Arendt enters into their discussion. Arendt was a German Jew who fled from Europe to the US in the Nazi era. She wrote about the kind of thinking that allowed the totalitarian regimes of Hitler and Stalin to gain control. Fins and Reardon focus on her idea that logical thinking can lead from a seemingly self-evident statement to a replacement of common sense with thinking that leads in a direction that is very wrong. They see a culture in medicine and science that considers ethics as a matter of regulatory compliance rather than deep reflection an example of this.

What I find most interesting in Arendt’s thinking is the idea that logic will lead to faulty conclusions if the premise is not true. The problem that she saw in the thinking leading to totalitarian regimes was not that the thinking was illogical. The problem was that the seemingly self-evident statements which were used as the premises were false. When we apply that to ethics it means that we will only reach sound ethical conclusions when we begin with moral premises that are true. A liberal education with interplay between the humanities and the sciences is one way to seek true premises for our ethical thinking in the wisdom that can be found in the interplay of academic disciplines. Another is to recognize that the existence of common sense morality suggests a source of moral wisdom that is beyond human wisdom. Christian ethics finds its premises in that higher source of moral wisdom. A Christian liberal education integrates them both.

Humanoid Mass Production

Henry Ford would be proud.

We now have the ability to mass produce humanoids, embryonic cells derived from human embryonic stem cells or induced pluripotent stem cells (the latter can be made from adult cells). These cells are specifically designed by researchers to have some but not all of the necessary elements to be fully human. The goal is to grow these humanoids beyond the current 14-day limitation imposed on research studies on human embryos that ARE fully human.  In theory, these humanoids are physiologically similar enough to humans that by observing their growth and development, scientists hope to learn about human development. By design, the claim is that humanoids are different enough from humans that they would not/could not /should not live outside the Petri Dish. The original report in Nature may be found here.

I use the Henry Ford analogy on purpose. He revolutionized the automobile industry by standardizing the manufacturing process such that less skilled laborers could sequentially assemble an automobile. This allowed the cars to be built faster, at higher volume and far less expensively. Previously, higher skilled craftsmen machined each unique part for each unique car. Though the cars looked the same, their parts were not interchangeable. The process was painstakingly slow, resulting in a very low production volume at a very high price. With mass production, cars became far more common,  much less expensive and, to some extent, disposable.

Moving toward a standardized “mass production” process will have the same effects for humanoid production. Standardizing the manufacturing process will reduce the variance of a given humanoid, making the scientific study of its growth more reliable, reproducible and less expensive, all good things from a scientific standpoint. Will it also cause us to view the humanoids as more disposable?

I continue to want more discussion on the moral status of humanoids before more experimentation is permitted, particularly as we extend their lifespans. Whatever they are, at minimum, they are living entities.  Humanoids must be more than the sum total of their individual cells otherwise we humans would not have so much interest in their development. How human-like does a humanoid have to be before we should consider additional human-like moral/ethical protection in humanoid experimentation?

Or their mass production?

Medicare Fraud — Again

Today’s Miami Herald [limited access] is reporting that there are on-going scams targeting the elderly by doing unnecessary DNA tests on them, with the intent of committing Medicare fraud. The article states, “Genetic testing . . . has become so corrupted by racketeers that the Justice Department recently unveiled its first nationwide take-down of 35 suspects accused of fraudulently billing $2.1 billion to Medicare.”

The article outlines the case of Richard Garipoli, of Loxahatchee, Florida (located in Palm Beach County).  He is the owner of Lotus Health, a telemedicine company.  According to the report, he is “currently charged with defrauding Medicare and receiving kickbacks while collaborating with labs that billed more than $326 million for Cancer Genomic tests, known as CGx tests.  The Medicare program paid more than $84 million to the labs, located in Georgia and Pennsylvania, which in turn paid kickbacks to Garipoli and other unnamed co-conspirators between January 2017 and September 2019 . . .”

This report is another reminder that the seemingly endless attempts to bring down health care costs in this country (especially as we approach another election season) will not be successful unless such large-scale fraud is stopped.  Additionally, it continues to be troubling that these types of scams single out the elderly.  Targeting those among the most vulnerable, in an effort to defraud the government, is a violation of the most basic principles of bioethics.  It is now in the government’s interest not only to recoup these funds, but to take measures to reassure our elderly citizens that they can expect to be safe from scams in their twilight years.

Failing the Grade in Transplant Ethics

On 3 October, ProPublica published “‘It’s Very Unethical’: Audio Shows Hospital Kept Vegetative Patient on Life Support to Boost Survival Rates,” an article detailing aspects of the organ transplantation program at Newark Beth Israel Medical Center in New Jersey. Specifically, the article revealed portions of an April 2019 audio recording from a weekly meeting of transplant physicians, nurses, social workers, and transplant coordinators. One patient discussed was a 61-year-old man named Darryl Young, who had received a heart transplant on 21 September 2018. Mr. Young had never awakened after surgery, but the director of the heart and lung transplant program, Dr. Mark Zucker, expressed the “need to keep him alive until June 30 at a minimum.” Another transplant surgeon hoped that the transplant program would progress to the point of not having to “think about this ethical dilemma of keeping somebody alive for the sake of the program.”

At issue—at least in the transplant realm—is the “need” of hospitals to keep patients alive for at least one year after organ transplantation.   Why? The Center for Medicare & Medicaid Services (CMS) dictates the rules for transplant centers to exist and to receive funding. Two measures CMS uses for this are the 12-month survival of patients and the functioning of the transplanted organs at 12 months (see page 6/84 of linked article).  The penalty for not meeting the desired CMS algorithms is high. CMS can launch an audit of the transplant program and/or revoke Medicare funding, which pays for the transplants. When programs are not funded, they cease to exist.

There are other issues in this story as well: ethical issues that deserve our best thinking. One glaring problem is that of treating people as means to an end, cogs in a wheel.   The case of Mr. Young is sadly exemplary, but he surely is not the only one. Pressure to maintain the transplant program will be felt by all of the participants in one way or another. Everyone is responsible for his or her actions, certainly, but each person downstream of a decision may well be used as a cog in a wheel. The penalties for non-compliance at different levels may be varied, but are no less real. Additionally, can patients, or their family members/surrogate decision makers, refuse any procedures once they are in the transplant system?

The current CMS rules were instituted on 28 June 2007. This 2006 article from the Los Angeles Times presents some of the backdrop for such rules:

  • Medicare, which funds most of the nation’s transplant centers, requires programs to perform a minimum number of transplants and to achieve a specific survival rate to be certified for funding. The benchmarks vary by organ, and there are none for kidney transplants.
  • Three dozen heart transplant programs didn’t meet federal standards for survival or volume. They accounted for 43 more deaths than expected.
  • Altogether, the programs examined by The Times had 71 more patients die than expected within a year of transplant.

It appears the 2007 rules represent a pendulum swing from 2006. A golden mean is desired and preferable. It is time to look for one.

Fewer U.S. Twins and the Development of IVF

Readers of this blog may have seen the report in the general press that, after three decades of increases, the rate of twin births in the U.S. has declined by 4% from 2014 to 2018.

Those three decades correspond to the era of IVF, since the birth of Louise Brown in England in 1978.  It seems likely that changes in IVF practice contributes at least in part, if not substantially, to the trend in twin births.

Specifically, doctors at IVF clinics are more commonly implanting only one, rather than more than one, embryo back into a prospective mother’s womb with each attempt at a live birth.  Multiple pregnancies—even twins, not just “Octomom” scenarios—carry increased risk for mother and babies.  Previously, two or more embryos were implanted in an effort to increase the chance that at least one would make it to live birth.  Sometimes, “selective abortion” was practiced to reduce the number of initially multiple pregnancies to one.  Now, it appears that gradually increasing success rates of IVF are supporting single-embryo transfer as a standard practice.

The Centers for Disease Control and Prevention (CDC), which provides a substantial amount of information on the current status of IVF on its website, summarizes the changes in the percentage of single-embryo transfers in recent years—increasing from 11.6% of non-donor-egg transfers in 2007 to 39.9% in 2016.

To the extent that this reduces the practice of selective abortion and, one hopes, decreases the number of embryos created but kept frozen, never to be born, at IVF clinics, this is a welcome development.  The Christian Medical Dental Association takes the position that, in IVF, the number of embryos should be kept to a minimum, and all embryos created should be so created with the intent of having the genetic mother carry all of them in pregnancy, to live birth one hopes.

IVF remains a transformative enabling technology that facilitates contractual arrangements for reproduction, profound changes in the structure of families, and the use of pre-implantation genetic diagnosis to control what sort of people are allowed to be born.  One might view these developments as non-physical harms, that alter our overall experience of being human in ways that may properly be subject to question.

And: the rate of twin birth is still twice what it was in 1980.  If one sees a mom or dad pushing a stroller with fraternal twins, chances are they are IVF kids.

Screening that benefits the screener

I teach it course on human diseases for students in a public health program. One of the things that we talk about is asymptomatic disease. If a disease has no symptoms the only way that we can detect it is by screening. For screening to be beneficial it needs to be able to detect asymptomatic diseases accurately and there needs to be something which can be done that will help those in whom the asymptomatic disease is diagnosed. Many times, a screening test will only be accurate if the test is used to screen a selected population which is at risk. Sometimes there are asymptomatic diseases which we can detect accurately, but the people diagnosed do not benefit because there is not something we can do to make their life better than it would be if the asymptomatic disease had not been diagnosed. Since the purpose of screening is to help people, there is no reason to do it if the people being screened will not be helped. That idea is based on the principle of beneficence. Everything that we do in medicine should be done for the benefit of the person being treated.

Some people do not follow that moral principle. There have always been some who have used the practice of medicine to benefit themselves more than those they were treating. That is why the Hippocratic physicians had to put a statement about beneficence in their oath. One of the ways that the principle of beneficence can be violated is for some people to encourage other people to do screening that will not benefit those being screened but will benefit the one doing the screening. One of the examples I see most often is supposedly low cost ultrasound screening for such things as carotid stenosis. Those doing the screening can make a significant amount of money by screening everyone who will accept their pitch but the people being screened do not benefit. It is currently not recommended to screen for asymptomatic carotid stenosis because there is no evidence that intervention is beneficial for those who are diagnosed and some evidence that intervention may cause more harm than good.

As new technology is developed it is subject to being used in a way that violates the principle of beneficence. One of the new ways to do that is with genetic screening. A recent article in the health news section of Reuters.com describes the fraudulent promotion of genetic screening to older adults in the US. Again, this is screening being done to benefit screeners who have collected huge sums from Medicare while providing no benefit to those being screened.

These abuses do not mean that we should not do screening. It simply means that screening should be done the right way. We should choose which screening tests we use and which people we screen with those tests based on how the screening will benefit those who are being screened. We should not do it to benefit those who are doing the screening.

Different answers to “Why?”

Sometimes when we ask “Why” we are really asking the mechanical or causation question: “How did something come to be?” In a billiards game, one might ask: “Why did the 8 ball go into the side pocket?” A valid answer might be: “It was struck by the 3 ball.” A reasonable follow-up question might be: “Why did the 3 ball strike the 8 ball?” Answer: “It was struck by the cue ball after a billiards player struck the cue ball with her stick.” These are correct mechanical explanations as to how the 8 ball came to go into the side pocket.

Sometimes when we ask “Why?” we are really asking: “For what purpose did something come to be?” In the previous billiards game, the answer to the question: “Why did the 8 ball go into the side pocket?” might be: “The player struck the cue ball which struck 3 ball which struck the 8 ball which went into to the side pocket so she could win the billiards game.” There was a purpose behind or beyond the physical or mechanistic description of the 8 ball falling into the side pocket.

Two opinion pieces asking “Why?” from medical and bioethical aspects were published within a week of one another and provide similar examples. The first was a NEJM Perspective by Anthony Breu entitled “Why is a Cow? Curiosity, Tweetorials, and the Return to Why” (subscription required). The second was by Stephen Phillips in this blog entitled “Why do we do this?”

In the first article, Dr. Breu begins with the classic infinite regression example of his 4-year old daughter asking “Why” to every response he provides to her previous “Why” question.

Daughter: “Why was [so-and-so] sleeping?”
Dr. Breu: “Because it was nighttime.”
Daughter: Why was it nighttime?”
Dr. Breu: “Because the earth rotates.”
Daughter: “Why does the earth rotate?”

Dr. Breu paused at this point because he did not immediately know why the earth rotated. He jokingly recalled that his own father terminated these inquisitions with: “Why is a cow?”, which Dr. Breu quickly learned meant the “Why Game” was over. The rest (and real emphasis) of the article discussed the benefits of encouraging medical curiosity in his students and the particular benefits of “Tweetorials”, Twitter posts that answer in-depth medical explanations of pathology. “Why does an acute hemorrhage cause anemia?” His Tweetorial provided a mechanistic answer to the question of why (or how) does anemia result from an acute hemorrhage.

Dr. Breu closes his article with the following answer to his daughter’s last question:

…the Earth rotates because of the angular momentum that resulted from asymmetrical gravitational accretion after the Big Bang. And if my daughter asks me “Why was there a Big Bang?,” I’ll be forced to reply, “Why is a cow?”

In the second article, Dr. Phillips answers the question: “Why do we do this?” by succinctly describing the purpose for which we Trinity Bioethics bloggers write the bioethics articles that we write. We believe there is purpose behind or beyond the human biology that we study determined by a loving God in whose image we are made. As such, our bioethical inquiries seek to understand whether the human purpose of a particular medical technology or procedure is complementary or contrary to God’s purpose. Why? As Dr. Phillips explained, because God loves us and has asked us to love our neighbor.

Maybe that is an answer to “Why was there a Big Bang?” (and “Why is a cow?”)

Why do we do this?

Many of the posts on this blog involve cautions that there are things in medicine which we are capable of doing and which some want to do that we should not do. Much of the time those cautions go unheeded by our society. For fifty years we have been saying that we should not perform abortions, but many unborn human beings continue to lose their lives. We give reasons why we should not do euthanasia, but PAS becomes legal in state after state. We write about why we should not alter the genes of human embryos, but the research continues. Is it just that we are anti-medical science and like telling people what they should do?

No. We do it out of love. Sometimes it is love and concern for people who are powerless and cannot speak for themselves. It is because of our love for the person who is aborted as a fetus or comes into being as the result of a genetic manufacturing project rather than being accepted unconditionally as a gift. It is out of love for the Canadian man who chooses euthanasia because he cannot obtain the 24 hour a day care he needs to live life with ALS.

It is also out of love for those who do things that are wrong. Love for the physician who performs abortions or euthanasia. Love for the researcher who uses human embryos as research subjects destined to die. We do it for the sake of the gospel which tells us that we have all done wrong and are destined for judgment unless someone intervenes. The gospel that tells us Jesus did intervene by his death and resurrection and has made forgiveness and restoration available to all who confess their wrongdoing and put our trust in him. We do it for those who will miss out on the amazing grace of the God who died for us if they listen to a culture that says that anything you desire to do is right and there is no need to ask for forgiveness for anything.

“Velvet Eugenics”

Human Flourishing in an Age of Gene Editing is a new collection of essays, edited by Erik Parens and Josephine Johnson.  In the introduction, the editors explain they are concerned with “nonphysical harms” of human gene editing.  That is, these harms would not affect bodily systems, but harm “people’s psyches…[their] experiences of being persons,” and could impair human flourishing.  These harms could be incurred not only by gene editing but also by use of other “reprogenic” technologies such as preimplantation genetic diagnosis (PGD) and prenatal diagnosis.

Your correspondent has just begun to read this collection.  In the first entry, “Welcoming the Unexpected,” bioethicist Rosemarie Garland-Thomson of Emory University, takes the view that flourishing is not a matter of proximity to some ideal of health or human excellence, but is, for each person, a growing into expression of that person’s unique capabilities.  Accordingly, rather than embrace a project of eliminating disabilities, society should work to make the environment more welcoming to people with those conditions—many of which, after all, need not impair a person’s ability to live a life of happiness and contribution to others.  Communities have an obligation, she says, “to support the distinctiveness of its members according to the egalitarian principles of justice, liberty, and equality,” and “build environments that…support the widest spectrum of embodiments…in which human embodied existence can successfully thrive as it is.”  Put another way, we should not be building a regime in which we are deciding what sort of people we will allow to be born, but we should be ready to welcome and embrace the ones who are.  In this, Professor Garland-Thomson sounds a “caution against an aggressive normalization imperative…an outlook of humility about the human capacity to control future circumstances through present action…against the arrogance of [what one writer called] ‘the danger of a single story.'”

We should, she writes, adopt a stance of “growing” rather than “making” human beings, and “reconsider the logic of a velvet eugenics that would standardize human variation in the interest of individual, market-driven liberty and at the expense of social justice and the common good.”  In this, she embraces the argument of contemporary German philosopher Jurgen Habermas that rejects “a liberal eugenics regulated by supply and demand.”  One can be forgiven for hearing in this an echo of C.S. Lewis’s worries about “conditioners” in The Abolition of Man.

This is set in the author’s description of her ongoing friendship with three other women, all, like her, married PhD’s who like good wine, good food, and are amply supported by technology and community.  One of her friends is congenitally deaf, another has hereditary blindness, the third has a genetic muscular condition, and the author herself was born with what is now called “complicated ectodactyly,” with “asymmetric unusual hands and forearms.”  The sort of thing your correspondent understands the Chinese to be trying to eliminate through the use of PGD.

A remarkable essay to lead off a collection that appears worthy of careful consideration.