Approaching Immortality?

By Neil Skjoldal

With the death of President George H. W. Bush this past weekend, the country seems united in eulogizing him for, among other things,  having lived “a well-lived life,” because amidst his accomplishments, he was able to reach 94 years of age.  This brought to mind a recent article published in The NY Times, “How Long Can People Live?”  In it, health writer Nicholas Bakalar observes, “There is considerable dispute, however, over how long humans might live under optimal circumstances.”

The brief article discusses the possibility of drug therapies designed to kill old cells, while leaving young cells in place.  Apparently many are working on research projects to see what may be possible.  Even the well-known drug metformin will be tested to see its effectiveness against age-related diseases.   Bakalar is not overly optimistic.  He clearly states, “No serious scientist believes in immortality.”   Rather the goal is to assure a “healthier old age than ever before.”

I find Bakalar to be reasonable in his assessment.  Of course, one can question whether trying to extend life past 100 years is the best use of limited resources when there are so many other health issues with which to contend.  However, perhaps a ‘healthier old age’ could reduce some of those very high medical costs at the end of life which seem to plague our health care system.

I do not anticipate that I will be jumping out of an airplane at an advanced age like President Bush, but I am interested to see if any of the health issues related to old age can be addressed in a meaningful way.

The Genie is Out of the Bottle

By Jon Holmlund

 

Much has already been written and said—mostly in condemnation–about this week’s announcement of the birth of the first gene-edited baby (or, better, babies—there are twins).  A gene was altered in embryos created through in vitro fertilization, and then the embryos were transferred to their mother, who carried them to term and, reportedly, normal delivery.  The babies are said to be in good health.

A couple of good summary articles, written for non-specialists, are online from Science News and the science journal Nature. Follow those links to read more than your correspondent can write here in a short blog post.

The scientist who did this used the CRISPR-Cas9 system to alter a gene called CCR5, which is a receptor, or docking post, for the HIV virus.  Presumably, altering CCR5 would reduce the risk of HIV infection if not prevent it altogether.  The twins’ mother is reportedly not infected with HIV, but the father is.  How much risk this placed the babies at is questionable—usually, babies infected with HIV become infected because of transmission from an infected mother.  HIV can cause infection through other receptors, and altered or disabled CCR5 can increase risk of other infections.  So, overall, the medical need was questionable, there were (actually, are, one needs to see how their health is in the future) potential correlative risks to the babies, and there were likely other means to avoid what appears to have been an unlikely prospect of these babies getting HIV from their father.  Because of concerns like this, ethicists have been arguing that the action violates human research ethics, in which risks to subjects must be minimized, and benefits must outweigh risk.  Any ethics board reviewing a proposal would assess this rigorously, and ask whether there are safer alternatives to the research.

The experiment is said to have worked in this sense—analysis of their DNA shows that the target gene, and no other genes, was altered as intended.  Clearly, the rationale for the editing was to show that it could be done.  George Church, ever the risktaker in the name of “advancing the field,” argued in an interview that because HIV is incurable and there is no vaccine for it, that constituted an unmet medical need in this case.  He also argued that the scientist in question only failed to complete the proper “paperwork,” and that there might be long-term safety issues with heritable gene editing but that would not be dispositive because he is quite confident that those risks will be small, like the risks of diagnostic medical imaging.  To all of which we must respond, “rubbish.”  We do not know what the long-term risks are, ethics boards are rigorous about risk assessment for any and all experimental procedures, and the medical need in this specific case was dubious.

Nature reports that this work “has prompted an outcry from scientists, who are concerned that [the scientist] leap-frogged international discussions on the ethics of such interventions and has put the children at risk of unknown long-term health effects. ‘This experiment exposes healthy normal children to risks of gene editing for no real necessary benefit,’ says bioethicist Julian Savulescu.”  For those who are not formal students of bioethics, Julian Savulescu is hardly a Luddite or a God-fearer who is nervous about new technologies.  He’s right, in this case.

Note the concern about “leapfogging” discussions of the ethics.  This point is also well-taken.  Scientists have been arguing that broad, public discussion of the ethics of human gene editing is urgently needed.  On March 29 of this year, your correspondent—who is scrambling to catch up even to this week’s commentary—posted about two such arguments.

But the genie is out of the bottle, and things are moving faster than most folks can keep up with.  The work reported this week was from China, but was not part of some Chinese government effort—it appears to have been entirely on private, intrepid initiative.  As a writer in the San Diego Union Tribune wrote this week, Pandora’s box has been opened and can’t be closed.

This week’s announcement came at the international conference on gene editing, in Hong Kong.  The two days’-plus of proceedings, including a session with the scientist who did the work discussed here, can be accessed online.  The conference main web page is here.  The proceedings archived on webcast appear to be accessible here.  A summary of the Q+A with the scientist is here.

Oh, BTW—at the end of the Nature summary linked at the top of this post was a chance to vote on whether this application of gene editing was justified.  I voted “no,” as did 82% of respondents at the time I voted.  That left “yes” at 18%.

18%?? For real?

Thanksgiving and ethics

By Steve Phillips

It is good at times for us to stop and think about why we do the things that we do and what they mean. Tomorrow is Thanksgiving Day, a holiday that our society enthusiastically celebrates with lots of food, the gathering of families, and sporting events, followed by intense shopping. Historically Thanksgiving in America began with a group of Christians expressing their gratitude to God for what he had done for them. Christians continue to see this holiday as one during which we pause to remember what God has done for us and take time to express our thanks to him.

However, many in our society no longer believe in a personal God to whom gratitude is due. What does it mean to celebrate Thanksgiving if a person believes that those things that they are pleased to have are theirs due to a combination of chance and their own effort? Or if in our entitlement culture they believe that all that they have are things that they deserve. If that is the case, there is no reason for giving thanks and no one to whom thanks can be given. Instead of being a time of actually giving thanks to the one who has graciously given good gifts to us, the holiday has become a celebration of affluence and good fortune. Sporting events and shopping fit that very well.

How does this relate to ethics? The two different meanings of Thanksgiving correspond with two different ways of thinking about how we ought to live. For those of us who see Thanksgiving as a time to remember that the good things that we have come from God, it also reminds us that we are created beings who are made by and dependent on the God who has given us the things that we are thankful for. Remembering this helps us realize that God is the source of all that is good and that our understanding of what is right and how we ought to live comes from him as well. The alternative meaning of the Thanksgiving celebration is self-focused. If there is no God to be thankful to, the celebration is about the fulfillment of personal desires. That correlates with the ethics of moral individualism in which moral values are based on how a person feels and focused on fulfillment of personal desires.

Whether we see Thanksgiving Day is a time to actually give thanks to the God who is the giver of all good things or not makes a big difference in how we think about ethics.

Sprinting Down the Road on “The Children We Want”

By Mark McQuain

Almost exactly one year ago, this blog asked rhetorically whether your polygenic risk score was a good thing. Jon Holmlund raised this issue again last week, mentioning a company called Genomic Prediction. This company’s claim about the merits of their technology deserves close ethical scrutiny and is my reason for mentioning them yet again.

Genomic Prediction is increasingly calling for IVF clinics to use their version of expanded pre-implantation genetic diagnosis (EPGD), that is using big data analysis to select which embryo to implant – literally choosing the embryo you want based not upon the presence of single point genetic mutations known to be harmful but polygenic sequences (multiple genes, and even multiple upon multiple genes) statistically related to increased risk for complex diseases like heart disease and diabetes. Jon discussed the ethics of selecting “the children we want”, hinting that selecting for eye color or sex was “a step” further down the road.

Genomic Prediction is sprinting down that road.

Just last month, Genomic Prediction entered into discussion with some IVF clinics in the U.S. to screen embryos for “mental disability”. Per the firm’s co-founder Stephen Hsu:

“[EPGD] isn’t accurate enough to predict IQ for each embryo, but it can indicate which ones are genetic outliers, giving prospective parents the option of avoiding embryos with a high chance of an IQ 25 points below average”

This claim is entirely different from a claim that this particular embryo has this particular single point mutation that will cause this particular disease. Rather, the present claim of EPGD is better stated like this: When we saw this same polygenic pattern in some large number of prior embryos, a majority of them had an IQ 25 points below normal. Some questions naturally follow: Did any have above average IQs (and how far above average)? How big is the majority (75%, 85% or 97%)? How many embryos were studied to come up with this statistic?

Gamblers like Las Vegas odds makers are beginning to use big data analysis to better predict the outcome of sports contests. The result is that the Las Vegas odds makers can tell us that when number one ranked University of Alabama plays unranked Citadel in 1000 football games, Alabama will win 999 times. That also means that Citadel will win one of those 1000 games, and, prior to the start of the game, you never know which of those 1000 games you are watching. Last weekend, at halftime, Alabama and Citadel were tied 10-10. At that point, it looked like Citadel was going to win that one game out of 1000 and defy the odds makers.

And that is the point. Many have already decided that it is good to terminate the life of an embryo if he or she has a point mutation for a serious disease. Is it just as good to terminate the life of an embryo if he or she has the mere risk of some non-disease trait we find undesirable like the wrong eye color, sex or intelligence? Do we really have sufficient data to make this decision? How much risk is too much or too little? How do we know if the decision is a good one? Will the decision get us the “Children We Want”? Is it really our decision to make?

It is necessary we answer questions like these if we wish to take on the responsibility to decide who lives and who dies, a decision that we previously relegated, depending on your worldview, to God or Nature.

A Bit More on “The Children We Want”

By Jon Holmlund

 

The Wall Street Journal recently asked “Is it ethical to choose your baby’s eye color?”  This can’t be predicted precisely, yet, because the inheritance involves several genes, but in principle it’s at least possible to play the odds by trying to predict the probability of eye color.  The article in question discusses how one clinic, Fertility Institutes in Encino, CA, is offering an “eye color probability” test (my term, not their) as part of embryo screening, for $370.  From the website, it looks like Fertility Institutes offers the whole 9 yards of reproductive technology—egg freezing, embryo sex selection, preimplantation genetic diagnosis (PGC), surrogacy, and so on.

Also mentioned is a New Jersey-based company, Genomic Prediction, that is offering “expanded” PGD to predict which embryos are at high risk for developing heart disease or diabetes.

I suppose by including the links to these entities I’m providing them free advertising, but I thought it important to document where information can be found.  I am NOT endorsing their services.

I take a conservative position on these technologies, and have been suspicious of IVF itself, since before its advent in 1978 (when I was in college), as fundamentally separating sex from procreation.  Here, however, the larger point is that, as we use PGD to predict an increasing range of traits, we adopt, little by little, an attitude of requiring that children entering the world are “the children we want.”  Even if one argues for PGD to screen for very severe genetic defects that would be incompatible with robust life—or maybe life at all beyond a few days or even hours—it is harder to argue for screening out people who may be at risk for diseases like diabetes but who otherwise could live very full lives.  Ditto for risk of heart disease, or breast or ovarian cancer, or the presence of Down Syndrome, or even Huntington’s disease.  And selecting for sex or eye color is a step further down the road as well.

Watch GATTACA if you’ve never seen it.  That’s the extreme, sci-fi scenario—but as with gift giving, it’s the thought, the motive, that counts.

Abortion by mail, part 2

By Steve Phillips

Last week I wrote about a European organization that has begun providing the medicines used for medical abortions by mail to women seeking abortions in the US following an online consultation. This violates the current restrictions that the FDA has on the prescribing of mifepristone, the primary medicine used for medical abortion. The restrictions exist due to safety concerns with the use of the drug. Those who think that those restrictions should be ended cite FDA statistics that show that serious harm to women who take the drug are quite rare. I concluded that the data indicate that it is hard to support the restrictions based on the risk of harm to a woman who chooses to use mifepristone.

I mentioned that there is another, somewhat perverse, risk that is usually not discussed which enters into the decision about whether the prescribing of should be limited to a certified prescriber dispensing the medicine in a clinical setting. That is the risk to the embryo/fetus. Those who support the use of mifepristone cite an effectiveness rate of 95-97%. That means that over 95% of the time the use of mifepristone in early pregnancy causes the death of the embryo/fetus and along with the use of misoprostol the pregnancy is ended with a medically induced abortion. In the 3 to 5% of cases in which this does not occur, some result in the death of the embryo/fetus, but the products of conception are retained within the uterus and may present some risk to the mother. As noted above, the observed risk to the mother turns out to be quite low. Sometimes when the process of medical abortion fails the embryo/fetus may survive. Mifepristone is an anti-progesterone. We know that medicines which alter the hormonal environment of an embryo can cause congenital anomalies. Therefore, there is a risk that if an embryo does not die and a subsequent surgical abortion is not done an infant may be born who suffers from congenital anomalies due to exposure to the medicines which were intended to cause a medical abortion. To prevent this, it is recommended that women who take the medicines for medical abortion who do not abort within the usual period of time have a surgical abortion. That would be the primary reason to support the FDA’s requirement that these medicines only be dispensed in a clinical setting by a certified prescriber. The role of the certified prescriber is to make sure that no embryo who is exposed to mifepristone survives to be born with the possible congenital anomalies.

Thus, we have a situation in which our society, as represented by the FDA, has decided that it is permissible to give a pregnant woman a medicine that will kill the embryo/fetus living inside her, but only if the medicine is dispensed in such a way that it can be assured that the embryo/fetus will be killed and not survive with an abnormality caused by the medicine. I said this was perverse. It is what we get when we have a society that puts a higher value on avoiding suffering than the value placed on human life.

Wir wussten nicht

By Mark McQuain

It has been said that “the only thing necessary for the triumph of evil is that good men do nothing.” Implied in this statement is that, first and foremost, the good men and women must be aware of the evil before they could be held morally obligated to act against that evil. There are subsequent issues associated with that obligation, such as does one even have the ability to act and, if so, how much personal harm or risk must one endure before being morally absolved of the responsibility to act. Regardless, knowledge of the evil is a requirement before moral culpability to act against that evil can be expected or assigned.

Therefore, a claim of “we did not know” would certainly absolve people of any moral responsibility from failing to act. But only if that denial is true. Challenging the validity of such a denial is reasonable because the denial is the easiest way to escape moral culpability. Consider the following two examples where claims of “not knowing” were possibly used to avoid moral responsibility.

When the Dachau concentration camp was liberated by the U.S. Seventh Army at the end of World War II, it was reported that the local German townspeople denied that they knew what was going on at the camp, claiming “Wir wussten nicht” – “We did not know”. General Walton Walker started the practice of bringing local townspeople to view such camps by ordering the Mayor of the town of Ohrdruf and his wife to visit the Ohrdruf labor camp. After the visit, it was reported the Mayor and his wife returned home and killed themselves.

Did they really not know?

Recently, the movie “Gosnell: The Trial of America’s Biggest Serial Killer” was released with minimal coverage by Hollywood or mass media. Reportedly, the producers had to resort to crowdfunding to initially get the project off the ground. Kermit Gosnell was a physician in Philadelphia who operated the Women’s Medical Society Clinic where he performed late term abortions. He and his clinic had multiple complaints and legal actions related to unsafe office practices as well as several procedure-related deaths prior to eventually being raided on unrelated drug dispensing charges. What the investigating officials found upon raiding the facility would fairly be described as a “House of Horror” for the unsanitary conditions, use of untrained staff, expired medications and multiple fetal remains randomly strewn around the clinic. Dr. Gosnell was convicted of first degree murder in the deaths of three infants, involuntary manslaughter on one female patient and 21 felony counts of performing illegal late-term abortions. During the trial, state and city regulators were repeatedly called out for their failure to act sooner, given the high volume of prior allegations and complaints.

Did they really not know?

Wir wissen nicht. (We do not know.) And, perhaps, we will never know.

Bioethics & “Three Identical Strangers”

By Neil Skjoldal

I recently had the opportunity to watch the 2018 documentary Three Identical Strangers, which tells the story of triplets Bobby Shafran, Eddy Galland, and David Kellman.  They were separated shortly after birth in the 1960s and adopted by three different families through the Louise Wise adoption agency in New York City.  The way they happen to find out about each other in 1980 is fascinating.  It created a media sensation at the time, including an appearance on The Phil Donahue Show.

The documentary starts by sharing their thrill of discovery, which included the many similarities that the brothers have, even though they spent the first 19 years of life apart.  However, it eventually moves to some of the larger and darker questions that lingered for each of the adoptive families—the biggest of which was, “Why weren’t we told that there were siblings?”  And as you might suspect, the agency representatives did not provide many helpful answers.  The parents’ feelings of anger and bewilderment resonated with me as an adoptive parent.

Eventually the brothers came to find out that they were part of a “twins study” conducted by noted psychologist, Peter Neubauer.   The study involved the brothers being interviewed and filmed individually every year through the first few years of their lives, with them not knowing that their brothers even existed.  Their parents were told it was a study of adopted children, not a study of twins.

The documentary leaves little doubt where it stands on the ethics of this matter.  From some of those interviewed, it appears that the purpose of the study was to address the classic “nature vs. nurture” question.  However, the harm done to these brothers (and the others who were unknowingly involved in the study), making them feel like ‘lab rats,’ undermines any positive value that the study may have had.  That Neubauer’s research remains sealed at Yale until 2066 adds fuel to the fire that something unethical was done.

In a blog post on www.psychologytoday.com, Dr. Leon Hoffmann asks whether it is reasonable to expect researchers of previous generations to follow our contemporary standards.  He asserts that both the original researchers and the producers of the documentary are guilty of self-deception.  This is a point worth considering as we look back; however, this case is from the 1960s and those impacted are still very much alive.

It is difficult for me to disagree with the assessment of reviewer Neta Alexander of www.haaretz.com:  “’Three Identical Strangers’ is thus a faithful representation of the spirit of the times. It’s about the way in which the authorities and those with power – headed by a charismatic and respected psychologist – abuse their powers in the name of science.”  Three Identical Strangers stands as a timely reminder that there should be safeguards and limits to research.

Abortion by mail

By Steve Phillips

A recent article on the CNN website reports on a European organization called Aid Access which has recently made the medicines used for medical abortion available to women in the US by mail. The organization utilizes telemedicine in the form of online consultations to prescribe the abortion drugs from a pharmacy in India to be mailed to the woman desiring an abortion in the US. It is clear that this violates FDA regulations. To ensure the safe use of mifepristone the FDA currently requires that the drug, which has no medical indication other than induction of abortion, is only available to be dispensed in clinics, medical offices and hospitals, by or under the supervision of a certified prescriber. At issue is whether those restrictions should be lifted to allow more open prescribing of mifepristone.

The appropriate reason for the FDA to have additional restrictions on certain drugs is safety. Those who advocate lifting the restrictions on mifepristone argue that the safety of this drug has been established and cite FDA statistics that the risk of death from using the drug to induce medical abortion is only one in 155,000. This makes its use much safer than either surgical abortion or continuing a pregnancy to term. Those who oppose lifting the restrictions counter with concerns that the unsupervised use of the drug may also lead to failure to diagnose ectopic pregnancy and can result in situations that require surgical intervention, which may have increased risk in an unsupervised patient.

While there are risks to the use of mifepristone, it is hard to make the case that the risk of harm to the mother is high enough to warrant the additional restrictions that currently are required for this drug. That makes it hard to justify limiting access due to true concern about the risk to the woman whom uses it. This is not the case for another regulation regarding abortion. Laws that require abortion clinics to meet the same standards as outpatient surgery centers have a clear justification. Surgical abortion has similar risks to other outpatient surgeries, so it is reasonable to require the same safety measures for an abortion clinic and an outpatient surgery center.

There is one risk related to the use of mifepristone, which is not usually discussed, which does support the additional restrictions on its distribution, but in a somewhat perverse way. That will be the focus of my next post.

Where do I Store the Name of your Dog?

Following a long office day of wrestling with my current nemesis, our office electronic medical record (EMR), I was pleased to read a lovely article by Dr. Taimur Safder in the current NEJM entitled “The Name of the Dog”. I’ll not summarize it as the link is free and the article is short and makes the point of today’s blog wonderfully.

I realize the EMR is not actually alive and, lacking agency, is unable to act as my archenemy and cause my downfall, or that of my patients. Further, I have a degree in electrical engineering so the technology of the EMR is not the issue either. I will grant that current and future data mining of the EMR may benefit untold numbers of patients. I will also concede that EMRs will (eventually) be bolstered with AI tools that will improve diagnostic accuracy and reduce or eliminate costly unnecessary testing.

My concern is that the EMR causes me to focus so much on the data collection that I spend less time getting to know my data source (my patient) as more than the sum total of discrete data points. There really isn’t any good place in the EMR to put the name of my patient’s dog. If I am going to treat my patient as more than a something, perhaps as a someone, then more than just reductionistic data acquisition and processing will have to take place.

With that in mind, please take a moment to view one of my favorite paintings by Sir Luke Fildes at the Tate Gallery called “The Doctor”. The painting depicts a country doctor sitting at the bedside of a young patient, with the child’s parents in the background. One can imagine the concern of the child’s father and almost feel the anguished prayers of the child’s mother, but both are interestingly relegated to background positions in the painting. The focus of the painting is the focus of the lamp in the painting – the country doctor and his patient.

Medicine in the 19th Century was limited in terms of meaningful data collection and limited further by actual effective treatments. In other words, the EMR of the 19th Century could have been completed in mere minutes and the diagnosis and treatment, such as it was, rendered in a few minutes more.

Given those limitations, perhaps not surprisingly, one gets the sense that the depicted outcome was far from certain and also that the country doctor had been in the home a while – there was at least time for tea at the table. What on earth was he still doing there? Maybe in absence of a definitive diagnosis and immediate cure, what the doctor could provide was his time, his empathy and his focused, loving concern. One gets the sense he would likely remain with his patient and the family as long as he was needed to offer what help and hope he could.

That seems like a reasonable example of how one imago Dei might care for another.

Would that I could consistently convey that level of steadfastness, that empathy and that loving concern to all of my patients without frantically looking for that special place in my EMR to store the name of your dog.