Scientific Validity vs. Bioethical Violation?

In a previous blog entry, Dr. Riley covered the 30 December 2019 conviction of He Jiankui, the Chinese scientist who allegedly created the first genetically altered human babies born in November 2018, to three years in prison for “illegal medical practices”. His criminal conviction is somewhat surprising to me because I believe Dr. He must have received at least initial support from the Chinese government for his human genetic experimentation, particularly since he was allowed to travel to Hong Kong in late 2018 and make public a portion of his research. My surprise is that the almost universal uproar about the bioethical violations in this case can (at least presently) make even the Chinese government admit that a line has been crossed that warrants public condemnation and punishment of those involved. Though the crime cited was crossing a thinner bioethical line (lying on the informed consent about the risks of genetic engineering to the babies) rather than the fuller bioethical line (the actual risks of genetic engineering to the babies and humanity in general), a bioethical crime was committed.

There are other aspects of this story that need our bioethical consideration. Antonio Regalado in a recent Technology Review, describes the still circuitous path Dr. He’s research has taken en route to ANY publication. In fact, it appears that Technology Review is the first publication to make any portion of the original manuscript public (there is a link within the link provided above of excerpts of Dr. He’s manuscript). I cannot do justice to Mr Regalado’s sleuthful efforts at piecing together this story (it defies a simple summary) and encourage those interested to read his account in the link above.

Regalado reports that Dr. Howard Bauchner, editor-in-chief at JAMA, was given access to the original manuscript just days after the 2018 Hong Kong conference. Regalado found Dr. Bauchner to be generally supportive of genetic editing of embryos:

“I think it’s inevitable that it will move ahead, and I think it should move ahead… Oftentimes early scientific breakthroughs [such as organ transplantation and IVF] are seen as unethical, and then over time that changes, [as the technologies prove successful].”

In fact, a main dilemma for Bauchner remains the following: “If someone thinks it’s scientifically valid but not ethical, does that mean the study will stay in the shadows?…It’s such an interesting question.”

An interesting question indeed. One online repository of pre-published scientific papers called bioRxiv rejected the manuscript, likening the manuscript to a paper it might have received from Dr. Josef Mengele, the infamous Nazi death camp doctor. One might therefore wonder why Technology Review has published any portion of the manuscript. They are not a scientific journal per se, with strict peer review to validate the scientific method and results. They are a publisher of scientific news, and Dr. He’s experiment, regardless of it’s many bioethical failures, is certainly scientific news. Technology Review offers a more in-depth opinion as to why they believe it is appropriate to make the manuscript public.

Back to Dr. Bauchner’s interesting question. Does he mean by scientific validity that Dr. He’s experiment (may have) accurately edited the section of human genome that Dr. He claimed and therefore the scientific community should be able to learn from that? Even so, it still seems to me that that Dr. Bauchner is putting the scientific cart before the bioethical horse. Shouldn’t we decide whether it is right to edit the human genome in the first place before worrying about the validity of the technique to edit that genome?

TADA & Tinslee Lewis

In recent days, the Texas Advance Directive Act (TADA), signed into law in 1999 by then-Governor George W. Bush, has come under scrutiny because of the tragic case of Tinslee Lewis.

From press accounts  we learn that Tinslee is now 11 months old and suffers from several conditions which have led doctors at Cook Children’s Medical Center to conclude that any further treatment would only be harmful to her, adding to her already painful existence.   One of her doctors has said, “She is in pain. Changing a diaper causes pain. Suctioning her breathing tube causes pain. Being on the ventilator causes pain.”  TADA allows the hospital to stop such treatment after ten days if the patient’s doctors and the hospital’s ethics committee conclude there is nothing more that can be done and no other facility is able to take the patient.

Because Tinslee’s mother objects to the hospital’s conclusion, the case is now working its way through the court system. Last week a District Judge decided in favor of the hospital, but the next day the Second Court of Appeals in Fort Worth ordered a stay.

Observing the legal back and forth, the Washington Post points out, “In Tinslee’s case, however, anti-abortion groups are divided.  While Texas Right to Life took Lewis’s side, the Texas Alliance for Life and the Texans for Life Coalition have said they agree with the doctors.”  In a statement issued last week on the judge’s ruling supporting the use of TADA, the Texas Alliance for Life commented: “We don’t see how she could have ruled any other way.  As we have stated previously, Texas Alliance for Life supports TADA.  It is good public policy, it is constitutional, and it provides a balance between the patient’s autonomy and the physicians conscience protection rights to do no harm.”  

At the time of writing this post, there doesn’t seem to be a solution that will please all involved. Thus, we don’t hastily run to judgment here.  We acknowledge the hospital’s consideration of the futility issue (especially as it seeks to ‘do no harm’) as well as the pain of a family that wants to extend the life of their beloved child.  I would simply add that in all such cases, the human side of the equation needs to be considered.

2020, or 20/20?

Near the end of 2018, He Jiankui was on the world’s stage announcing that he had edited the genome of twin girls, in the hope of making them resistant to HIV. On Tuesday, December 31, 2019, the Wall Street Journal (WSJ) printed a report that Dr. He and two others have been convicted of “illegally practicing medicine related to carrying out human-embryo gene-editing intended for reproduction.” (online version here).

A court in Shenzhen concluded that the defendants had acted for “fame and profit,” when they “deliberately violated the relevant national regulations, and crossed the bottom lines of scientific and medical ethics.” For the crime committed, He received the most severe sentence. In addition to the three-year prison sentence, He is banned for life from “working in the field of reproductive life sciences and from applying for related research grants, “ according to the WSJ.

The Xinhua News Agency also noted that a third genome-edited baby had been born, and that this child, along with the previously born twins, “would be monitored by government health departments.” The WSJ did not state for how long the monitoring would continue. Not only were the children experimental subjects as embryos, but they continue to be subjects as well. Further, these genome effects will affect their progeny, potentially into perpetuity. Additionally, the Smithsonian Magazine reports that in the summer of 2019, He met with “investors to discuss a potential commercial genetic modification clinic in Hainan, which aims to become a ‘world-class medical tourism hub’.”  One might reasonably call this “a crime against humanity,” even if it does not include genocide of humans already born. (For further reading, see David Luban, “A Theory of Crimes Against Humanity”)

In the print edition of the WSJ, alongside the article on He is an article about Pastor Wang Yi of the Early Rain Covenant Church. Pastor Wang was sentenced on 30 December to nine years in prison. His crime was “incitement of subversion of state power and illegal business operations” (online article here).

Consider that a pastor receives a nine-year sentence for an offense against the State; and a scientist, a sentence of three years for a crime against multiple generations, and indeed, humanity. In the year 2020, we could use a check of our understanding of what is important in the life of the world. Would that our vision were 20/20 also.

Good news

The angel who surprised some shepherds outside of Bethlehem brought them good news. They were told that a baby had been born who would be a savior and that they were being invited to go and see him. I suspect the shepherds thought they deserved some good news. Things were not going very well. They were living in a nation that had been conquered by Rome and the recent requirement that everyone be registered in their hometown was for the good of Rome, not for them. It is likely that the kind of savior they were looking for was one who would save them from their Roman oppressors.

The shepherds answered the invitation and went to see this baby who was going to be a savior and told Mary what the angel had told them. Mary pondered this in her heart. She knew something the shepherds did not. She knew that this baby, who the angel said would be the Messiah and Savior, was not an ordinary child. He had been conceived miraculously by the Holy Spirit. She also knew that an angel had told Joseph that they should name the baby Jesus because he would save his people from their sins. That was a deeper good news than the shepherds probably understood.

When we think of good news in medicine it commonly means that a new more effective treatment has been developed or possibly that a disease that previously had no effective treatment can now be cured. Those things are good news, but however many new treatments are developed, we still all die.

The good news of Christmas gets at something deeper. The Bible helps us understand that the reason that the diseases and death that medicine battles exist in this world is because we and the world we live in are broken by sin. No matter how many new treatments we develop, medicine cannot address the underlying problem. The angel told the shepherds about the ultimate cure. A savior had been born who could reverse the effects of sin and death and save us from our sin. He could bring us eternal life. He did that by going to the cross and showed his victory over sin and death by his resurrection. That is good news.

Merry Christmas!

Can we hop the gene-editing train?

As Joy Riley pointed out on this blog on December 7, the world and the scientific community recently marked, with almost no fanfare, the one-year birthday of “Lulu” and “Nana,” the first (we think) and still only (we think) humans to have had their genes edited heritably—in a way that will be passed on to future generations.  Joy commented these children are “experimental subjects for life,” or, to use the phrase I found and discussed some time ago on this blog, “the babies are the experiment.”  To wit: it is not possible fully to assess and limit the risks of heritable genome editing before actually editing humans.  One must forge ahead.  Even if one were to edit a series of embryos, and abort them at different times during gestation to get a full assessment of their prenatal development, the questions about lifelong effects and effects on future generations would persist. 

And, as mentioned in other posts on this blog earlier this year, there is the issue of “nonphysical” harms to how we understand ourselves and our human existence.

A number of world scientific bodies are assessing, independently of each other, what regulatory safeguards should be instituted, on the assumption that heritable genome editing is something that should be pursued.  Last month, the journal Nature editorialized that efforts by the World Health Organization, US and UK scientific bodies, and a third international commission should not proceed separately (they are all due to report their findings in 2020), but should work together.  The editors apparently think that it would be straightforward, obvious, and right to adopt a moratorium on clinical applications of heritable genome editing, establish an enforced registry for all experimentation in this area, and expand the conversations to include representatives of people with disabilities.  If I read that correctly, it’s hard to disagree.

In the laboratory, things are moving fast and it is well-nigh impossible to keep up with the science or the conversations about it without that work being one’s main occupation.  A recent contribution linked by the Nature editors is called “prime editing” that appears to increase substantially the efficiency of gene editing, raising the prospect of correcting abnormalities associated with the vast majority of genetic diseases.  The relatively naïve, like your present correspondent, might wonder whether this approach could be limited to already-born people with genetic diseases, as treatment, rather than engineer the genomes of the unborn in an apparent attempt to eliminate these abnormalities from the human prospect.

Even thinking about the general public trying to influence where this work leads feels like assuming the role of an old-style hobo, trying to hitch a free ride by jumping onto a moving freight train.  One is liable to fall under the wheels.  But in the case of heritable genome editing, you’re likely to get run over anyway.

Dementia and the value of human life

Recent public reporting of some cases in Canada of people with dementia whose lives have been ended by euthanasia have caused me to think about the value of human life in those who have dementia. Canadian law requires the person whose life is ended by euthanasia to have mental capacity for informed consent, intolerable suffering, and a foreseeable death. It was initially thought that patients with dementia would not be candidates for euthanasia under the Canadian law because of the requirement for mental capacity, but now there euthanasia providers who have concluded that there are some patients with dementia who have sufficient symptoms from their dementia to qualify as having intolerable suffering but still have adequate decision-making capacity. The discussion there has focused on whether person who is at the stage of dementia that causes intolerable suffering can still have adequate mental capacity. I have a different concern.

When we try to define intolerable suffering in the context of euthanasia it appears to mean that the person who is requesting euthanasia has decided that the effects of an illness have reached the point that the illness has made his or her life not worth living. When we talk about intolerable suffering and euthanasia the first image that comes to mind is a person with excruciating and untreatable pain, but it turns out that pain is not the most common reason for people to request euthanasia. It is more commonly requested due to a loss of control and increased dependency. This is not surprising since we live in a society that places high value on independence and autonomy. However, is independence really what makes human life worth living or is that a widely believed but untrue fiction in our society? Aren’t we all dependent? As children we are dependent upon our parents. As we go through adulthood, we are dependent on spouses and friends. As we age, we become dependent on our children and neighbors. Loss of independence makes us more clearly human, not less human. The impairments of old age, whether they be physical or mental, make it harder for us to deny our dependency, but loss of control (which is what loss of independence is) and increased dependency should not be seen as something that makes life not worth living. It draws us deeper into the relationships that are an essential part of being human.

Living with dementia is difficult for the person with dementia and for those who love and care for persons with dementia, but it does not make the life of a person who has dementia not worth living. The person with dementia is still a person who has relationships that are important, even when the one with dementia can no longer remember who those people are, because the person with this dementia is still the same person. He or she is still the mother or father, sister or brother, or friend. He or she is still a uniquely created child of God. Our response to those who feel that life is no longer worth living because of the loss of cognitive abilities and independence should be to help them understand that their lives are worth living because they are valuable to us.

Sociopaths in Medical School

The NEJM recently had an interesting article calling on medical schools to do a better job identifying students who exhibit “unprofessional behavior” before allowing them to graduate. The link for that article is HERE (subscription required). While admitting that it was difficult to consistently and reliably identify such students, the authors claimed that every medical school staff annually could likely identify one or two students “whom they would not allow to care for their family.” The article goes on to describe the barriers that prevent medical schools from accurately identifying unethical behavior in their students and some of the problems associated with trying to use the limited data that is available to delay or even prevent such a student from graduating medical school.

Going so far as to label students with unethical behavior as sociopaths is admittedly hyperbole on my part for the sake of rhetoric. In my defense, the article does touch upon the fact that there are a few physicians, presumably in every class, who commit “criminal or malicious acts”. The authors then go on to ask how we might identify these individuals before they behave “unprofessionally”, ideally before they graduate medical school. I presently have no doubt that anyone who has ever attended medical school can think of at least one person in their graduating class whom they would prevent from treating their immediate family.

I heard an excellent lecture on this issue more than 15 years ago by Dr. John Patrick, former Associate Professor of Clinical Nutrition at the University of Ottawa, who now speaks worldwide on issues of medical ethics, culture, public policy and the integration of faith and science. In speaking to a group of medical students about the need for transcendence in Hippocratic Medicine in a lecture entitled “Meaning and Purpose in Medicine”, he says about the sociopaths in their midst (beginning at 38:25 in the audio):

“…you can name them in your class already, you know who they are. You could tell me in your class the two or three people who are likely to lose their licenses for immoral or bad behavior in the future. The faculty never have a clue. You know. But you have already left Christian ethics, and loyalty dominates your class, so you don’t tell us. We find out 5 or 6 years later when they lose their license. And nothing on their university transcripts but all the students are not surprised.”

I originally wondered about the veracity of this claim so, for several years, I conducted a simple survey of the first year medical students in our local medical school. For a period of time, I was the very first clinical lecturer the students heard as they prepared for their first exam on the anatomy of the spine, just 10 days after beginning medical school. At the beginning of the lecture, I asked the students to look at me directly and, without speaking or glancing at their fellow classmates, answer the following question in their head: “After being together for the past 10 days, have any of you met at least one person in your first year class to whom you would not trust to care for someone you loved?” Invariably, over half of the class smiled, many while quickly glancing in the direction of the same one or two potential sociopaths in their class.

Why is this bioethically important? Dr. Patrick contends, and I suspect many of the readers of this blog agree, while the study of medicine is a scientific endeavor, focused on the accumulation of scientific knowledge, the practice of medicine is mainly a moral endeavor. Physicians are trying to work with their patients to help them do what they “ought” to do, as agreed upon by both the physician and patient. Such an endeavor demands mutual respect and trust so there is no place for unethical behavior on the part of the physician caring for a vulnerable patient.

Sadly, as both Dr. Patrick and the authors of the recent NEJM point out, while we are fairly adept at selecting medical students who can handle the academic rigor and have sufficient self-discipline to succeed in medical school from a knowledge standpoint, we remain woefully inadequate at assessing the ethical character of those same students to make sure they have the necessary moral integrity to actually practice medicine.

Unless that can be remedied, we should expect the continued gradual replacement of rich, lifelong, covenantal doctor-patient relationships with sterile, limited, contractural provider-client partnerships.

[I encourage readers to follow the link to Dr. Patrick’s website for a wealth of audio lectures on bioethics, culture and the integration of faith and science. Begin with the above link for “Meaning and Purpose in Medicine”]

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.

Project Nightingale

Technology always seems to outrun ethics.  But just because something can be done does not mean that it should be done.  Usually this discussion is focused on the latest life-sustaining medical device, but with emergence of electronic medical records, a whole new set of problems have appeared

Last month, Rob Copeland of The Wall Street Journal (behind pay wall) published a report focusing on the partnership between Google and Ascension health subtitled:  “Search giant is amassing health records from Ascension facilities in 21 states; patients not yet informed.”  Google has named their efforts “Project Nightingale.”

The idea behind medical records being available on the cloud (or somewhere electronically) sounds very appealing at first.  However, it is not difficult to imagine “Project Nightingale” turning into “Project Nightmare” when it comes to patient’s privacy.  This was what drove a Google whistleblower to come forward: “why was the information being handed over in a form that had not been ‘de-identified’ – the term the industry uses for removing all personal details so that a patient’s medical record could not be directly linked back to them?  And why had no patients and doctors been told what was happening?”

Dr. David Feinberg, the head of Google Health, addresses the concerns that have been raised: “Google has spent two decades on similar problems for consumers, building products such as Search, Translate and Gmail, and we believe we can adapt our technology to help. That’s why we’re building an intelligent suite of tools to help doctors, nurses, and other providers take better care of patients, leveraging our expertise in organizing information.”  (I’m not sure using Google Translate as a positive example will bring comfort to many readers.) Feinberg also discusses the precautions that Google has put into place.

Since the original WSJ broke last month, Congress has gotten involved.  Consumer Affairs reports “that the U.S. Department of Health and Human Services has opened an inquiry into the project to determine whether it violates the Health Insurance Portability and Accountability Act of 1996 (known as HIPAA).”

Maintaining patients’ privacy is an important issue and must not be glibly overlooked.  It will no longer suffice simply to say that we trust Google (or Facebook, etc.) to do the right thing.