Experimental Subjects for Life?

More than a year after the birth announcement of genome-edited babies in China, we are only slightly more informed of He Jiankui’s experimentation, the results of which are named “Lulu” and “Nana.” Although apparently approached, neither Nature nor the Journal of the American Medical Association (JAMA) chose to publish He’s work. Antonio Regalado reported on an unpublished manuscript in “China’s CRISPR babies: Read exclusive excerpts from the unseen original research” in Technology Review on 3 December 2019. The Technology Review article includes not only excerpts of the manuscript from He, but also reactions from Stanford law professor Hank Greely; University of California—Berkeley’s gene-editing scientist Fyodor Urnov; the scientific director of Eugin assisted reproduction clinics, Rita Vassena; and reproductive endocrinologist Jeanne O’Brien, from Shady Grove Fertility.

Regalado summarizes some of the problems with Chinese experiment as follows:

 . . . key claims that He and his team made are not supported by the data; the      babies’ parents may have been under pressure to agree to join the experiment; the supposed medical benefits are dubious at best; and the researchers moved forward with creating living human beings before they fully understood the effects of the edits they had made.

Greely points out the lack of “independent evidence” of the claims made in the paper. Urnov labels the paper’s claim of reproducing the usual CCR5 variant “a deliberate falsehood,” and calls the statement about the possibility of millions being helped through embryo editing “equal parts delusional and outrageous.” O’Brien’s concerns include the possibility of coercion of the couples involved, and, noting the social stigma of HIV-positivity in China, she poses the question of whether this was a genetic fix for a social problem. Certainly, the Chinese experiment raises many questions, including how a culture views children. Are children gifts to be received or projects to be completed? Is it appropriate to subject children to experimental research because we can? One of the quotes from the paper reads, “we have made a follow-on plan to monitor the health of the twins for 18 years and hope to then reconsent for continued monitoring through adulthood.”

We would be remiss if we thought that China alone plans to remake humanity. Vassena is quoted regarding He’s study:

Unfortunately, it reads more like an experiment in search of a purpose, an    attempt to find a defensible reason to use CRISPR/Cas9 technology in human embryos at all costs, rather than a conscientious, carefully thought through, stepwise approach to editing the human genome for generations to come.  As the current scientific consensus indicates, the use of CRISPR/Cas9 in human embryos destined to give rise to a pregnancy is, at this stage, unjustified and unnecessary, and should not be pursued.

Vassena, who directs a fertility enterprise, it should be noted, appears comfortable with impacting the human genome for generations to come:  It just needs to be a “reflective” and “mindful” approach. That is chilling. Would she, or the study’s authors, or Greely, or Urnov, or O’Brien sign up to be a science experiment for the rest of their lives? I would not consent—not for myself nor for my children—no matter how “reflective” or “mindful” the researcher happened to be.

Finally, “Lulu” and “Nana” should be known as more than the results of someone’s laboratory experiment. They are human beings, not laboratory rats or cells under a microscope to be studied at the will and convenience of the experimenters.

Determining Fairness in Healthcare

The New England Journal of Medicine (NEJM) had a recent Perspective on proposed bill H.R. 3 aimed at reducing federal spending on prescription drugs. A main component in the bill authorizes the Secretary of Health and Human Services to establish a “Fair Price Negotiation Program” that, beginning in 2023, would permit the secretary to negotiate with pharmaceutical companies the price paid by the federal government on 25 drugs each year. The article provides a broad overview of the bill as it discusses some of the economic pros and cons as well as the political back and forth that would be required to allow this bill to become law. The link is behind a subscription firewall but provides an option for free access to a limited number of articles with registration.

Call me cynical but anytime I see the word “fair” associated with a bill in Congress, I immediately wonder “for whom?” The article is quick to point out that the “negotiation” effectively means “price regulation and severe penalty for noncompliance” by the drug manufacturers. The article describes in general the method that will be used to set the maximum price of a given drug. How or why did Congress determine that method as the best for determining the Fair Price? Also, not all drugs will be included in the group subjected to negotiation. If it is good or fair (as determined by Congress) for drug prices to be determined/set/negotiated by our government, should not all drugs be negotiated similarly so they are fairly priced?

Bills like H.R. 3 are part of the larger discussion of what I call the ultimate “Rights vs. Obligations” in the delivery of healthcare. If healthcare is a human right, who is obliged to provide that right? In the present case of medication pricing, if the present cost of a drug is too high, who is obliged to offset that cost (read – pay the difference between “too high” and “fair”)? The provision of healthcare, generally, and the creation, testing and production of medications, specifically, have real costs. Are these costs fair? Who will pay these costs? The patient? The doctor? The hospital? The pharmaceutical industry? Should healthcare be for-profit? If so, how much profit? Should healthcare become a utility with strict(er) oversight? Can the market decide a fair cost or price? Can a utility board? Can our elected representatives? How about a group of really (and I mean really) smart, unelected bureaucrats?

Thoughtful answers to any one of these questions should be submitted immediately to your local congressperson. Collectively, they are presently the ones determining fairness (in a real bioethical sense) in healthcare.

Giving thanks for life

The “bio” in bioethics means life. Although it includes other types of life the focus of bioethics is on human life. The announcement a year ago of human infants born in China after their genes had been edited has caused us to think this year about how human life should come into being.

The story in Genesis of the creation of humans tells us some things about who we are. We learn that we are created beings made from the material substance of creation with the breath of life breathed into us by God. We are made to be male and female and complement each other. When we come together in marriage, we have been given the ability to bring new human beings into the world as a result of our union as one flesh. Each new child is given to us as a gift from God. We also learn that God made us in his image so that we are intended to reflect his glory in the world we have been given to steward. That sets us apart from other created life and puts great value on every human being.

How does all this impact how we think about how we bring new human lives into the world? It means we should remember that each new child is a gift from God who should be accepted unconditionally. Children are not intended to be something we make to fulfill our own desires. Each new human being from the very beginning of his or her life has great value. It means we should hesitate to modify the genetics of a new human being to give that child the genes that we think are best. It also means that we should show great respect to any human being who is a subject of research. Human subject research can be very important, but the subjects should enter in voluntarily giving of themselves as a gift to others. When we do research on human beings who are not able to volunteer, the research should cause no more than minimal harm. We should not see human embryos as a disposable resource for research.

As our family travels to our home to celebrate Thanksgiving together this year, I am thankful for each of their lives. I am thankful for my parents who brought me into this world and nurtured me both physically and spiritually. I am thankful for my wife whom God has given to me as a faithful partner and the children God gave to us. I am thankful for the spouses God gave to them and the children they have been given. Above all I am thankful to the God who gives us life.

Assisted Suicide and Disability

On October 9th, the National Council on Disability (NCD) released a report on the dangers of assisted suicide laws as they relate to persons with disabilities. The report provides a nice background on the history and justification of the Council’s position against assisted suicide as far back as 1997. The present report, available here, provides an update on its rationale for its continued opposition to assisted suicide laws. The report, and its references, provide an excellent resource for those of us who argue against assisted suicide regardless of the presence or absence of a disability.

Eight states and the District of Columbia have legalized assisted suicide in some form since Oregon led the way in 1994. Additionally, while lacking a specific assisted suicide statute, a state supreme court decision in Montana in 2009 is believed to provide a defense for physicians who practice assisted suicide. Oregon has provided the statutory framework for existing assisted suicide laws as well as proposed or pending legislation in states moving in this direction. As a result, every state where assisted suicide is legal claims that a primary need for the law is to preserve a person’s dignity, a claim that NCD finds particularly troublesome for people with disability:

The idea that hastened death is a pathway to dignity for people facing physical decline reveals the public’s extreme disparagement of functional limitations and a perception that “dignity” is not possible for people who rely on supports, technology, or caregivers to be independent or alive. Many hold the attitude that a person with a disability may be better off dead than alive.

Assisted suicide is often the cheapest “treatment” for many chronic medical problems affecting those with disability, a fact not lost on those responsible for state Medicaid budgets. NCD provided example after example of patients in Oregon who were denied treatment for their chronic or terminal medical care only to be offered coverage for assisted suicide within the same denial letter. Such crass efficiency was too much even for California, who in 2015, passed a law correcting this behavior: “[a]ny [insurance carrier] communication shall not include both the denial of treatment and information as to the availability of aid-in-dying drug coverage.” Many patients or their physicians eventually were provided the information on assisted suicide by the very same insurance carrier in a follow-up phone call.

Another major issue discussed within the NCD report was the relationship of depression and suicidal ideation in patients with a new disability:

Research overwhelmingly shows that people with new disabilities frequently go through initial despondency and suicidal feelings, but later adapt well and find great satisfaction in their lives. However, adaptation takes considerably longer than the mere 15-day waiting period required by Oregon-model assisted suicide laws.

Perhaps the most persistent concern by NCD since 1997 continues to be “the major gap between informing the patient of alternative options [such as palliative care programs and long term-term services/supports] and those alternatives actually being available and provided.” All statutes legalizing assisted suicide include provisions that require a full explanation of all of the programs, resources, and options available to assist the patient if he or she does not decide to pursue suicide. However:

Many people with disabilities find this to be a very shallow promise when they know that all too often the programs are too few, the resources are too limited, and the options . . . often nonexistent.

The concerns articulated in the NCD report warning of the dangers of assisted suicide apply just as forcefully for those without disability. We should join their efforts to educate law makers on a better way forward without assisted suicide.

“Why did you make me this way?!”

Recently, Jon Holmlund brought us up to date on an effort in Russia to proceed with CRISPR gene editing aimed at eliminating deafness. Coincidently, a recent MedPage article was posted regarding the ethics of using pre-implantation genetic diagnosis and IVF to purposefully select FOR an embryo with genetic deafness for a couple, both of whom were deaf. Both links discuss some of the ethical problems with using medical reproductive and genetic technology for these purposes. While we presently lack the ability to use polygene scoring to accurately “produce” the babies we want, I want to use the remainder of today’s blog to consider what obligations, if any, a genetic engineer (or parents that use their skills) may have toward future children designed using these growing array of genetic technologies.

Deafness seems to me to be rather curious in that it is considered either a serious disability or a desirable trait, depending upon your cultural worldview. No one in any culture would purposefully select for cystic fibrosis or Tay-Sachs diseases for their child. In fact, most want to use medical reproductive and genetic technologies to eliminate these diseases. On the other end of the genetic trait spectrum, some parents want to use these same technologies to purposefully select for more trivial traits for their children – hair and eye color, for instance. Given the triviality of these traits, I hear no one mounting an effort to genetically eliminate any particular hair and eye color. Perhaps I am living a sheltered life?

Nonetheless, with regard to deafness, prior to the promises of our new reproductive technologies, if you were born deaf and did not like it, you could only shake your fist at God or Nature. Now (or very soon), you can shake your fist directly at another human, such as your regional genetic engineer (or your parents who purposefully used her technological skills) and demand a direct answer as to why they purposefully made (or did not make) you deaf. Maybe this angst will be more widespread for the many more trivial traits such as eye or hair color rather than something more significant like deafness?

Building a child is about to become much harder for parents as they become directly responsible for both interior (genetic illnesses) and exterior (hair and eye color) design issues.

“Why DID you make me this way?!”

“Why did YOU make me this way?!”

I wonder how many genetic designers (or the parents that will ultimately bear the direct responsibility for having used the technology) really want that type of responsibility?

Is there already fine print in PGD-IVF contracts holding the doctors/scientists/geneticists harmless for the choices the parents make?

I can’t wait for the late night TV commercials: “Were you born with brown eyes and feel emotionally scarred because you have always wanted blue? Call our law offices as you may be entitled to financial compensation …”

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?

“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.

Stem Cell Rx No Longer For Sale on Google

Perhaps once a week, I will be asked by a patient about the potential benefits of stem cells for reversing the normal affects of age, particularly with respect to arthritis of the knee joints, hip joints or the degenerative discs in the lumbar spine. I believe one of the reasons for this interest has come from increasing advertisements by various clinics in my region of East Tennessee claiming stem cells are the answer for these problems. My region is not unique. A simple Google search on “stem cells for knee pain” yields ads for clinics offering such treatment.

Stem cells are cells that have potential to become any type of cell in the human body such as a new blood cell, nerve cell or bone/cartilage cell. Scientists are rapidly learning how to find or create stem cells, as well as how to safely use them to replace old or missing cells, thus restoring function in worn out, damaged or diseased areas of the body. In fact, stem cells are presently used to replace the bone marrow for some individuals with certain cancers and disorders of the blood and immune system, and in many of these cases, the results are lifesaving.

The problem is that stem cell treatment remains yet unproven in all other medical conditions, including the age-related arthritis conditions which I treat. This lack of efficacy has not stopped clinics from offering and patients from receiving stem cell injections with the hope of achieving improved function or cure. I am willing to grant that many offer these treatments with the sincere hope and belief that they are acting in their patient’s best interest, though I suspect not all have the patient’s best interest in mind. Unfortunately, there have been severe adverse events. Examples include blindness following an injection of stem cells into the eye, and loss of function with development of a spinal cord tumor following stem cell injection into the spine.

The FDA is trying to educate the public and prevent stem cells from being offered for unproven treatments. The FDA has the authority in the US to stop these unproven treatments and take punitive action if needed. This is not to suggest that the FDA is in the business of preventing legitimate investigation into the potential benefits of stem cells, such as this Mayo Clinic Phase 1 study looking at the risks of injecting stem cells in to the cerebrospinal fluid of patients following a spinal cord injury to see if this particular stem cell technique causes harm (with future studies needed to determine benefit).

The FDA is recently getting some help from Google. On September 6th, Google announced it would stop accepting ads for unproven medical treatments, including stem cell therapies. It is early in the effort and the initial link above still has four ads for non-bone marrow stem cell treatments returned with the Google search. Maybe by the time you read this blog entry, the stem cell ads for unproven treatments will be gone.

I am hopeful that stem cells will eventually provide patients with safe therapies that repair injury and return patients to normal health. Offering that promise without the studies that prove such benefit is unethical and potentially harmful. It is good to see Google favoring human welfare over financial profit.

Bioethics as Comedy

Sometimes comedy takes a cultural activity to its logical conclusion to reveal an absurdity that is so humorous everyone will talk about it. Sometimes a bioethical argument takes a cultural activity to its logical conclusion to reveal an absurdity that is ethically so troublesome hopefully everyone will talk about it. Recently, popular comedian Dave Chappelle combined the two.

Sponsored by Netflix and speaking at The Tabernacle in downtown Atlanta, Mr. Chappelle offered the following bioethical observation during his comedy monologue. I have removed all descriptive adjectives non-essential to his main argument. Speaking about abortion as a woman’s right to choose, he observed:

“I don’t care what your religious beliefs are or anything. If you …[are a man,]…you need to…[keep quiet]…on this one, seriously. This is theirs, the right to choose is their unequivocal right. Not only do I believe they have the right to choose, I believe that they shouldn’t have to consult anybody, except for a physician, about how they exercise that right.

Gentlemen, that is fair. And ladies, to be fair to us, I also believe that if you decide to have the baby, a man should not have to pay. That’s fair. If you can kill this…[baby,]… I can at least abandon them. It’s my money, my choice. And if I’m wrong, then perhaps we’re wrong.”

Mr. Chappelle comedically paired “My body, my choice” with “My money, my choice” and something well short of bioethical hilarity ensued. Regardless of what you think about his proposed moral equivalency, a simple Google search on the above quoted portion of his comedy monologue suggests this particular “bioethics as comedy” approach certainly has everyone talking.

For the record, I agree that he is right that both are wrong.

A meaningful life

The MIT Technology Review recently published an interview with Ezekiel Emanuel, chair of the University of Pennsylvania’s department of medical ethics and health policy, entitled “A doctor and medical ethicist argues life after 75 is not worth living.”  It appears to be a follow-up to a provocative article that Emanuel wrote in The Atlantic five years ago, “Why I Hope to Die at 75” (Emanuel makes clear in the interview that he did not choose that title.)

After stating that he is not advocating euthanasia, Emanuel makes some thought-provoking points in the interview.  For example, he observes that we don’t spend enough money on children: “one of the statistics I like to point out is if you look at the federal budget, $7 goes to people over 65 for every dollar for people under 18.”  To truly affect impactful change, it seems wise to focus on the health of children.

Emanuel also challenges the idea that a longer life span means a healthier life: “We’re having more disabilities.  We have people with more problems.  And even more important, for most people, is the biological decline in cognitive function.” For Emanuel, cognitive decline calls into question any advances made in average life span.  Apparently, 70 is not the new 50.

When asked about the ‘iconic innovators in Silicon Valley—people like Peter Thiel and Larry Ellison,’ Emanuel does not pull his punches: “. . . [T]hey’re fascinated with life extension [in general]? Naw, they’re fascinated by their life extension. They find it hard to even contemplate the idea that they are going to die and the world is going to be fine without them.”  Though somewhat pointed, Emanuel’s comments underscore some of the issues with individuals pursuing ‘immortality.’  Is it really for the betterment of society or an unhealthy preoccupation with self? 

To me, Emanuel’s most troubling remarks come when he addresses the issue of people who are active well into their 80s: “…when I look at what those people ‘do’, almost all of it is what I classify as play.  It’s not meaningful work.  They’re riding motorcycles; they’re hiking.  Which can all have value—don’t get me wrong.  But if it’s the main thing in your life?  Ummm, that’s probably not a meaningful life.”

Emanuel’s wish to die in his mid-70s reflects his interpretation of what a meaningful life is.  For him, meaning consists in doing research, publishing findings, and contributing to the academic community and by extension, the public life.  Even the thought of mentoring young people, though important, doesn’t appear to hold Emanuel’s interest for long.  

What constitutes a meaningful life?  While meaning is a very personal question, I would like to affirm the important role that the elderly play in our community.  Perhaps their ‘productivity’ is not the same as it used to be, and their health is in decline, but those are not adequate measures of meaning.  It seems to me that those who are well along life’s journey have much to share with their children and friends about living. There is meaning beyond this, of course, but at the very least it is a move away from the “be productive or die” perspective.

My hope is that society’s definition of meaning will eventually expand and more fully include people of all ages.