Baseball Statistics, Racism and 23andMe

I enjoy watching baseball on TV or even listening to a game on the radio. I am amused by the discussions of the announcers, usually around the 8th or 9th inning, particularly when the result of the game is already decided due to a lopsided score. The announcers begin doling out complex baseball statistics. As a former math and engineering student in college, I find this part of the game fascinating.

“Well John, I think this may be the first time Cincinnati Reds player Yasiel Puig has ever been involved in a late-game brawl with the entire Pittsburgh Pirates bench so soon after being traded to the Cleveland Indians earlier during tonight’s game and just 14 days after a Full Moon to boot.”

In baseball, as in life, if you specify an event in sufficient detail with enough variables, you are accurately characterizing that unique event. Some diehard baseball fans argue that with enough baseball statistics, the predictability of the outcome of any future game will become trivial.

In blog-related news, the New England Journal of Medicine recently had two thought-provoking “Perspective” opinion pieces dealing with racism in medicine. The first by medical student D.W. Paul, Jr. is entitled Ghosts of Our Collective Subconscious – What Blackface in a Yearbook Photo Means for Medical Education and the second by Dr. Tara Vijayan entitled ”Browner” – Creating Narratives of Race. Both are unfortunately available by subscription only. Among other things, both articles point out the obvious problems that occur when we reflexively categorize individuals by a single variable – such as one’s skin color – and attempt to predict current or future reality by that single variable. Habitually trivializing people in this manner results in prejudice, bias and bigotry.

This would never happen in baseball. For instance, I have yet to hear the following from an announcer:

“Well John, looking at the stat sheet on this next relief pitcher for the Pirates, it just says he’s white. For our radio listeners, from where I’m sitting, I must say our statisticians have nailed it as he is one of the whitest relief pitchers I’ve ever seen”.

I can promise you that when Yasiel Puig steps up to the plate, he doesn’t care about that relief pitcher’s skin color. He is far more concerned about the speed of his fast ball or the spin rate of his curve ball.

Enter 23andMe (or similar service). For the first time, the average person can send in a sample of saliva and get back a detailed DNA graph and report revealing the multiple countries of origin of their great grandparents and beyond. Having readily available DNA information may not be completely without its problems, and this blog has touched on some of these in past postings. However, one benefit of this technology may well be to convince people that we are a kaleidoscope of genetic material, much more complex, and far more interrelated, than our skin color alone would suggest.

If we are not going to treat our neighbors with the respect and dignity due unique image bearers of God, let us at least stop treating them as if they have only one variable worth considering – the color of their skin – and begin treating them like they have complex baseball statistics. Maybe then we will more accurately describe them, and, in doing so, perhaps better understand and appreciate them.

We should start now and not wait until the 9th inning.

Jeffrey Epstein & Transhumanism

In November 2018, journalist Julie Brown of the Miami Herald published an important three-part report called “Perversion of Justice,” describing the case of billionaire Jeffrey Epstein.  Brown’s reporting strongly indicates that Epstein’s punishment appeared relatively small when compared to the crimes that were actually committed.  The report, in part, led to further examination of the case and a recent indictment by the Southern District of New York.  Eventually the Secretary of Labor, Alex Acosta, resigned his cabinet position over questions about his role as a prosecutor in the case a decade earlier.

If the account of the crimes isn’t horrific enough, the New York Times reported last week that Epstein used his wealth to speak to prominent scientists about his goal to spread his DNA world-wide through impregnating groups of women at his New Mexico ranch.  In what reads like a creepy sci-fi novel, the articlereports: “Mr. Epstein’s vision reflected his longstanding fascination with what has become known as transhumanism: the science of improving the human population through technologies like genetic engineering and artificial intelligence.  Critics have likened transhumanism to a modern-day version of eugenics, the discredited field of improving the human race through controlled breeding.”

Epstein used his wealth and influence to ingratiate himself to the scientific community, according to the Times.  Prominent attorney Alan Dershowitz is quoted in the article: “Everyone speculated about whether these scientists were more interested in his views or more interested in his money.” Not surprisingly, several of the scientists contacted by the Times had a less than positive view of Epstein’s scientific musings.

One of the appeals of transhumanism is its goal to make humanity better through technology.  Living easily past 100 without all of the ailments of old age seems like a worthy goal. However, as is often the case, technology runs ahead of morality.  In Jeffrey Epstein’s case, it contradicts our understanding of basic human rights to think that the future belongs solely to amoral billionaires and the scientists they enlist in their causes.

Decrying Human Fetal Tissue Research Justification

The National Institutes of Health (NIH) released on 26 July “Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research.”  A new bullet point is required for “Human Fetal Tissue Research Approach.”   The applicant for funds is obliged to justify the use of human fetal tissue (HFT) in proposed research:

  • Why the research goals cannot be accomplished using an alternative to HFT?

  • What methods were used (e.g. literature review, preliminary data) to determine that alternatives could not be used?

  • Results from a literature review used to provide justifications

  • Plans for the treatment of HFT and the disposal of HFT when research is complete

  • Description of planned written, voluntary, informed consent process for cell/tissue donation, or description and documentation of process if cells/tissue were already obtained. Include a sample of the IRB approved consent form with the application or during the JIT process. The informed consent for use of HFT from elective abortion requires language that acknowledges informed consent for donation of HFT was obtained by someone other than the person who obtained the informed consent for abortion, occurred after the informed consent for abortion, and will not affect the method of abortion; no enticements, benefits, or financial incentives were used at any level of the process to incentivize abortion or the donation of HFT; and to be signed by both the woman and the person who obtains the informed consent. Include an assurance letter

  • Information must be submitted by the applicant Institution in a letter assuring the HFT donating organization or clinic adheres to the requirements of the informed consent process and documentation that HFT was not obtained or acquired for valuable consideration. . . . Applications proposing HFT research that do not include this assurance will be administratively withdrawn and not reviewed.

Journalist Nick Hazelrigg decried this as “Another Setback to Fetal Tissue Research Under Trump.”  Hazelrigg called the recently announced requirements for grant applications “the newest in a number of barriers . . . for fetal tissue researchers.” His first stated concern is that the applicant would have to “in a detailed manner, explain why no alternative methods could be used to accomplish the research.”  Secondly, Hazelrigg complains that both graduate and postdoctoral students who are supported by NIH training funds will be banned from using HFT in research.

Interestingly, on the same day the NIH released the new requirements regarding HFT research, the NIH Office of Laboratory Animal Welfare updated the “Vertebrate Animals Section” portion of their website.  Not only do grant applicants have to tell what kinds of procedures they plan for animals –inter alia, behavioral tests, blood draws, surgeries, and substance administration— but also justification for the use of animals is required.  Specifically:

Investigators must justify the use of animals in the proposed research. U.S. Government Principles require grantees to consider mathematical models, computer simulation, and in vitro biological systems. The justification should:

  • Indicate why the research goals cannot be accomplished using an alternative model (e.g., computational, human, invertebrate, in vitro).
  • Provide rationale for the choice of species (e.g., advantages of the species chosen and why alternative species are not appropriate).
  • Discuss why less highly evolved or simpler animal models are not appropriate. For example, the use of non-human primates, dogs, or cats should be thoroughly justified.

The justification for the number of animals, sex, ages, and other biological variables should be described in the Research Strategy.

We need to consider that the justification of use of resources is a common theme in human existence. Family members are accountable to one another for resources held in common. Business partners are also. When seeking a loan at a bank, the applicant has to justify the amount requested. These are true when only money is involved. When animal life is affected, the higher level of justification is rightly required. And when human life is involved, the highest level of justification should be demanded.

Restricting the use of human fetal tissue in research furnishes us all with the opportunity to consider our ways. In the words of Paul Ramsey, it gives us, the people,

final authority within constitutional limits in determining how in future we mean to be healed—when the means is human experimentation. The technical expertise of the medical research community cannot be the sole or chief arbiter in this matter, which is a question of morality and public policy.

(Ramsey, Paul. ”Introduction.” In The Ethics of Fetal Research, xxi. New Haven: Yale University Press, 1975.)

Contraception, Climate, and Population Control

This week’s New England Journal of Medicine (NEJM) carries an opinion piece (subscription required) pressing the concern that human-caused climate change should prompt a concerted effort to develop new methods of contraception and increase the ready availability of all forms of contraception worldwide.  About 222 million women in the lowest-income countries need family planning services, the author says.  About 40% of pregnancies (80 million out of a worldwide annual total of 210 million) are unintended, with similar rates in higher- and lower-income nations, it is said.  Past Malthusian fears about overpopulation had subsided with improved agriculture and a leveling, or even declining, fertility rate in many countries, but that appears now to have created a false sense of security, because the world’s population continues to grow, global warming and resource depletion are threatening sustainability of the ecosystem, and “naturalists” warn that half of all species living today may be extinct by 2100 because of human activity.  While the number of people the earth can support has been estimated at between 2 and 100 billion, the author prefers a more conservative “modern estimate” of 1.5 to 5 billion, as opposed to the current 7.7 billion.

Leaving aside the question of why the earth’s carrying capacity is a proper topic within the purview of the NEJM, the author says that currently available contraception is inadequate.  Sterilization “is not suitable” for people who want to have children, hormonal methods have side effects, and barrier methods are not reliably used.  (In case the reader wonders, abortion is not listed.)  Moreover, side effects notwithstanding, needing a prescription for much contraception limits availability and increases costs.  Development of newer methods, including some that would also protect against sexually transmitted diseases, could meet a large need, limit population “growth,” and have the further advantage of giving people more choices.

Unless one is fundamentally opposed to contraception on moral grounds, these suggestions may seem attractive on the surface.  Better, effective, preferably reversible, affordable, widely available, low-risk contraception would be welcomed by most people.  But the primary aim of this particular piece does not seem to be the well-being of individuals, but limiting the number of them overall.  One might object that pursuing limits on population is an invitation to tyranny, just in more sophisticated forms than one-child policies or forced sterilization.  One could not trust full reproductive freedom to “limit the excess population,” as Ebenezer Scrooge famously advocated.  Rather, controls would have to be instituted on who could have children, how many, and under what circumstances, not to mention trying to control what sort of people are brought into the world.  I do not think this is a farfetched concern.  After all, the NEJM writer thinks there are too many people already.  Might not someone (someone else, not the writer of the piece in question) think that some culling would be for the good of the ecosphere overall?  Getting back down to 5 billion from 7.7 billion would be a reduction of about 35%–an apocalyptic figure, to be sure.  I must confess that it would not entirely surprise me to see a future NEJM piece addressing population reduction.

Suicide in older adults

There is much discussion and debate within bioethics about the permissibility of physician-assisted suicide, but less discussion about suicide in general. We also spent a lot of time talking about end-of-life care and end-of-life decision-making. However, we tend to focus less on suicide in general and very little on suicide among older adults who are approaching the end of life but have no terminal disease. A recent program on NPR titled “Isolated and Struggling, Many Seniors Are Turning to Suicide” caused me to think about this.

Suicide rates in the US are generally increasing. When we think about suicide, many times we think about increases in teenage suicide rates but forget that middle-aged and older adults have higher rates of suicide than teens. Part of the reason for the higher rate of suicide in older adults is that their suicide attempts have a higher rate of resulting in death, but there are other things that put them at risk. Older adults suffer from isolation, loneliness, grief, and depression. The older we get, the more likely it is that we have lost family and friends close to us to death. That leads to the isolation, loneliness, and depression that can lead to suicide. Many older adults also live with chronic diseases which can lead to loss of ability to perform routine daily functions and cause a loss of independence. These things may also lead to isolation, loneliness, and depression. They can also result in feelings of being a burden to family members. The isolation experienced by the elderly not only leads to depression, but also makes it less likely that someone will recognize the risk of suicide and intervene.

Do our moral obligations to provide care for those at the end of life include dealing with the risk of suicide among older adults? I think they do. As physicians and other medical caregivers, it is important to recognize that suicide among older adults is a real concern and be alert to signs that a person may be at increased risk. Intervention can be lifesaving. We also have obligations as family members, neighbors, and fellow church members with those who may be at risk. Decreasing isolation can make a significant impact on the risk of suicide and all of us complaint role in that. Suicide in older adults is a real concern, and it is something we can impact.

“Safe” gene editing

The New England Journal of Medicine carries a brief article about “Controlling CRISPR-Cas9 Gene Editing” (subscription required).  The upshot: RNA used as a medicine, as in the case of “CRISPR” to edit genes, can hang around well after administration, and alter genes other than the ones intended to be altered.  These “off-target” effects could lead to unwanted clinical side effects.  You’d like to be able to shut the RNA medicine off.  Pharmaceutical companies that make and develop medicines from short RNA sequences have been doing just that—creating “antidotes,” if you’ll pardon the expression (bad use of the word, really—an antidote is to a poison, and the medicines are not poisons)—to reverse unwanted off-target effects of their medicines, should such effects occur.

Using CRISPR for gene editing to treat known genetic disease raises a similar concern, and the NEJM article cites a recent experiment indicating that such a “reversing agent” for CRISPR, if needed, might indeed be feasible.  So, suppose you are trying to treat someone with genetically-caused blindness, and there’s a risk that other genes might be affected.  You could give the “reversing agent” to block that.  Cool.  You’d want to get it into the right tissues—the right parts of the body—but the work described in NEJM suggests that might all be reality eventually. 

One challenge is: these RNA-based agents don’t always get into the parts of the body, or into cells, all that well.  The NEJM writer says that this new work into “controlling” CRISPR-based gene editing “of course, depends on the [reversing agent] delivery problem being solved, but that is a topic for another day.”

It’s been some time since your correspondent worked for a drug company making RNA-based drugs, and I’m not close to the work these days, but I would say that is most definitely a topic for another day.

So, why bring this up in a bioethics forum?  Because it’s one more matter that would need to be considered and addressed before charging into gene editing that can be inherited from generation to generation.  This, as the present writer has repeatedly held, is something that that the human race should never do.

But it’s bowling along.  The latest reports are that attempts to edit genes babies of deaf couples to prevent them from being born with genetic deafness are nigh in Russia.  Understandable, laudable goal, but we should not think that control of the process is nigh.   edium

Should Abortion be a Trivial Event?

A recent NEJM Perspective by Drs. Jane Henney and Helene Gayle is calling for reduction in the current restrictions on Mifepristone, previously better known as RU-486. Mifepristone, a progesterone blocker, which effectively opens the cervix of the uterus, when combined with misoprostol, which promotes contractions of the uterus, forms the two-pill combination marketed as Plan C – an effective, safe, self-administered home medical abortion. Arguing that the drug has been shown to be far safer than originally thought, and because many US women are accessing foreign internet sources of potentially suspect quality Mifepristone, Drs. Henney and Gayle are encouraging the FDA to make the drug available from regular US pharmacies rather than at special medical/surgical clinics from a restricted set of doctors as it is presently distributed.

At the time of its initial FDA approval in 2000, it was unknown whether mifepristone would have a high risk of excessive bleeding or incomplete abortions so it was approved under FDA Subsection H, which required that the drug be dispensed directly from a physician (rather than a pharmacy) who can provide blood transfusion or surgical abortion. Drs. Henney and Gayle argue that numerous studies since 2000 support that this level of restriction is unnecessary. This is not to say that the risks of Mifepristone are zero but rather, as one of their arguments goes, there are many other medications available from a pharmacy via prescription that have higher risks so why single out Mifepristone? They are not specifically calling for the medication to become “over-the-counter” (meaning available without prescription) but they list other countries where this is the case.

Their concern about the ease of obtaining Mifepristone (or Plan C) over the Internet is not exaggerated. A quick search of the Internet shows one advocate website called plancpills.org providing a report card where their own secret shoppers grade various Internet sites offering Mifepristone for sale. Another popular site called AidAccess.org offers an informative video, telemedicine consultation as well as foreign sourced Mifepristone and this site is presently one of the least expensive sources of the drug.

One of the statistics offered in support of abortion, especially medication-based abortion such as Plan C, is that these processes are safer for women from a morbidity and mortality standpoint than actually being pregnant, particularly the labor and delivery of birthing a baby. Of course, it (always) goes without saying that the same processes are nearly universally fatal for the baby. But, for arguments where the morbidity and mortality of the child are excluded, abortion, particularly medication-based abortion, has become a relatively safe process.

I have no doubt that the present restrictions by the FDA on access to Mifepristone will be reduced for the reasons Drs. Henney and Gayle have provided, perhaps eventually to point of making Plan C available over the counter.

Abortion is becoming a trivial event.

Abortion kills a human being.

Killing a human being should not become a trivial event.

Embryonic Legerdemain?

Developmental biologist Lewis Wolpert is credited with saying, “It is not birth, marriage, or death, but gastrulation which is truly the most important time in your life.” Gastrulation, simply put, means the embryo develops an axis and distinctly different cell layers. In the human embryo, gastrulation takes place during the third week post-fertilization. Formation of endoderm occurs over days 14-15, and the mesoderm begins to appear on day 16 (see Figure 1-11 here).  Ali Brivanlou, of New York’s Rockefeller University, identifies gastrulation, or the breaking of symmetry in the embryo, as the “major Holy Grail of developmental biology.”

Why is this so? During the third week after conception, the embryo has burrowed into the mother’s womb, and the peering eyes of scientists cannot visualize the events there. With the 14-day rule in place regarding embryo research, laws or guidelines in various locales outlaw or discourage (as in, do not fund) laboratory culturing of embryos beyond that point. So, Brivanlou’s lab “came up with a model of human embryos that is developed outside of the womb and is not the product of sperm and eggs, but the product of human embryonic stem cells that self-organize into complicated structures.”  These embryonic stem cells have formed what appears to be an embryo, but in Brivanlou’s terms, “could never become a baby.”

Dehumanizing the embryo is one of the essential components of making research on embryonic humans more palatable to the public. It will also be en essential step in a workaround of the 14-day rule. It appears that “model embryo” will join other terms such as “embryoids,” “gastruloids,” and “SHEEFs” as some element of humanity that scientists do not recognize as humans worthy of legal protection. Regarding Brivanlou’s “model embryo,” Harvard Medical School’s Dean George Daley calls it a “remarkable tool in a petri dish.” The “tool” with which Brivanlou and others concern themselves is both human and alive; otherwise, would they be interested?

Let’s think about this, using an analogue. If well-trained scientists could produce men and women without chests, what would be allowed? Would they have to call such men and women without chests “human”? Could they use men and women without chests for experiments?  Would the experiments have to be approved by institutional review boards?  Would the rest of us pay the scientists – handsomely – to do this? Could they win prizes?

Reclaiming the Lost Art of Dying

As I continue to reflect on the recent CBHD bioethics conference, there are several of the sessions that stand out to me. One was the presentation by John Kilner at the conclusion of the conference that I wrote about last week. Another was the very first presentation as the conference began. Lydia Dugdale spoke on the topic of “Reclaiming the Lost Art of Dying.” Many of us have recognized that there is a tendency for people in our current culture to die poorly. Dr. Dugdale suggested that our difficulty in dying well is related to our level of medical technology. Because modern medicine is able to do so much in treating and curing diseases, the allure of a cure can keep people from accepting the reality of death. She gave as an example a case of a woman with incurable cancer who never addressed the reality that she was dying because every time one treatment failed another was recommended.

She reminded us that there was a time in the middle ages when people were taught the art of dying well through a text titled “Ars Moriendi.” This booklet was published in the 1400s following the ravages of the bubonic plague in both literate and illiterate versions to help people prepare for death. It included instructions on preparing willfully for death and accepting it gladly when the time came. It spoke of avoiding temptations such as impatience, despair, pride, and doubt. It included a catechism pointing to the truths of the Christian faith and prayers for those who were dying.

She asked if something like this were possible for us today and suggested that bioethics could be a framework for learning how to die well. It can help us recognize our finitude and the limits of medicine. It can also point us toward community which can provide the support needed for those who are dying to die well. This may be as far as those in a secular setting, like the one in which Dr. Dugdale works, can go. However, those of us who share Christian faith should be able to take this farther. She challenged us with a quote from Jean-Claude Larchet’s book The Theology of Illness in which he says, “Ask God not in the first place for the return of health, but for what is spiritually most useful.” That points us back to what was understood in the days that the Ars Moriendi was written. Dying is an important part of our spiritual life, and we can grow spiritually through the experience of our own death as well as how we care for others as they die.

Good from Evil

I was given an article by a student of mine following his one month elective rotation with me in which we spent some clinical time discussing bioethical issues. The May 2019 web article by Sharon Begley from Statnews.com had to do with an interesting medical dilemma first presented in 2016 by Dr. Susan Mackinnon from Washington University in St. Louis. I have briefly summarized Begley’s article in the first part of today’s blog and extended her point at the end.

Dr. Mackinnon had a patient who was having severe leg pain following multiple knee surgeries. Dr Mackinnon was providing the final surgical attempt to isolate the nerve presumably being compressed by scar tissue in hopes of surgically decompressing that nerve to permanently relieve the patient’s severe pain. If the surgery was not successful, the only other option at that point was to amputate the leg. During the surgery, she used an old anatomy book called The Pernkopf Topographic Anatomy of Man, which unambiguously has the best illustrations of nerves around the knee, and successfully located and decompressed the nerve in question and successfully avoided an amputation.

So, what was the dilemma?

As Begley points out in her article, it came to light in the mid-1980s that the illustrations used in the Pernkopf atlas were based in part on the bodies of people executed by the Nazis in the late 1930s. The moral dilemma for Dr. Mackinnon was therefore:

“…even now, the Pernkopf illustrations are unsurpassed in their accuracy and detail, especially their depiction of peripheral nerves…and although a few journal papers may have an equally good, single illustrations, finding the right paper takes time that Mackinnon did not have as she stood over her patient.”

Dr. Mackinnon had been given the Pernkopf atlas as a graduation gift in 1982 but the Nazi history behind the atlas was not known until the mid-to-late 1980s, the full history of which only became known to her after the surgery. Should she continue to use an atlas that contains illustrations of the bodies of people executed by the Nazis? If used, is there a duty to inform a current patient about the nature of the atlas? Can sufficient good be derived from the atlas given the unspeakable evil required to create it to permit its ongoing use?

She posed her dilemma to Rabbi Joseph Polak, the Chief Justice of the Rabbinical Court of Massachusetts, who consulted Prof. Michael Grodin of the Elie Wiesel Center for Jewish Studies at Boston University. Their opinion became known as the Vienna Protocol, due to the origins of the Pernkopf atlas. Their response may be found in this link, which I believe is better read in the full context of the Vienna Protocol than summarized by your humble blogger. For those of you who must read the opinion before reading the entire protocol, please follow the link and scroll to the 4th to last page at number 12 in section C entitled “The Protocol and Recommendations”.

The evil that created the Pernkopf atlas was the Nazi occupation of and executions that occurred in Austria during World War II. It is no longer occurring. No one in the present is suggesting that we resume executing people to gain more anatomic drawings to complete additional volumes of the atlas. Any good resulting from the current use of the atlas isn’t being offset by any ongoing evil of creating more atlas. The evil of the Pernkopf atlas is contained in the past and, in that sense, finite. Containing the evil seems to be a necessary step in obtaining good from that evil.

I mention this in closing as I believe there are current analogies of activities performed in the name of scientific good where we condone ongoing evil. Studying fertilized ova until sacrificing them on Day 14 (an evil) in the name of learning about human reproduction (a good) is one modern day example. In Vitro Fertilization done to obtain a healthy baby with genetic traits we want (a good) that results in the death(s) of other fertilized eggs we don’t want (an evil) is another. There are other examples we have discussed within this blog. I believe we need to contain and hopefully discontinue these and other practices if we want to claim the information we gain can honestly be called good.