Deep Brain Stimulation: the New Mood Modifier?

A patient of mine recently had a deep brain stimulator (DBS) placed to reduce her severe tremors. The stimulator has worked very well to almost eliminate her tremor but has resulted in a side effect that causes her personality to be more impulsive. Her husband notices this more than the patient. Both agree that the reduction in the tremor outweigh the change in her personality though her husband has indicated that her personality change has been more than he imagined when they were initially considering the surgery. He has commented that if her new impulsivity were any stronger, he might be inclined to reverse the process. As one might imagine, the patient sees no problem with the impulsivity and remains extremely pleased with her newfound lack of tremor.

I share the preceding clinical vignette as backdrop to a recent article in Nature describing research funded by the US military’s research agency, The Defense Advance Research Projects Agency (DARPA – the same group that sponsored the early development of the Internet), where they are looking into modifying neural activity with the goal to alter mood, and eventually cure mental health disorders. Using patients that already have DBS stimulators in place for treatment of epilepsy or movement disorders such as Parkinson’s Disease, scientists are developing algorithms that “decode” a person’s changing mood. Edward Chang, a neuroscientist at the University of California, San Francisco (UCSF) believe they have a preliminary “mood map” and further believe that they can use the DBS stimulators to stimulate the brain and modify the local brain activity to alter the patient’s mood. The UCSF group describes this as a “closed-loop” (using the stimulator to both receive and then stimulate the brain). Chang further admits that they have already “tested some closed-loop stimulation in people, but declined to provide details because the work is preliminary.”

If scientists are on the verge of changing your mood, might they not also be on the verge of creating your urges? Professor Laura Cabrera, a neuroethicist, and Professor Jennifer Carter-Johnson, a lawyer, both at Michigan State University, argue we need to begin worrying about that possibility and further that we need to begin considering who is responsible for those new urges, particularly if those urges result in actions that cause harm against other people. The article does a masterful job of the ethical-legal ramifications of just what happens when your DBS causes you to swerve your car into a crowd of people – Is it your fault or did your DBS make you do it?

Returning to my patient, the alteration in her behavior is an unwanted but not a completely surprising result of her DBS to treat her movement disorder. Despite the informed consent, her husband was not prepared for the change in her personality. The treatment to correct my patient’s movement disorder (a good thing) has altered my patient’s personality (a not-so-good thing). My patient’s husband might even argue that his wife is almost a different person post DBS.

When we modify the brain in these experiments, we are intentionally modifying behavior but also risk modifying the person’s actual identity – the “who we are”. As the DARPA experiments proceed and cascade into spin-off research arms, we need to be very clear with patient-subjects in current and future informed consents that the patient who signs the consent may end up very different from the patient who completes the experiment. How much difference in behavior or urges should we tolerate? Could the changes be significant enough that they are considered a new person by their family and friends?

And if that is true, who should consent to the experiment?

Toward true public engagement about gene editing

The March 22, 2018 edition of Nature includes two thoughtful, helpful commentaries about improving the public dialogue around “bleeding edge” biotechnologies.  In this case, the example is gene editing, of which one commentator, Simon Burall from the U.K., says, “Like artificial intelligence, gene editing could radically alter almost every domain of life.”  Burall’s piece, “Don’t wait for an outcry about gene editing,” can be found here.  The other commentary, “A global observatory for gene editing,” by Harvard’s Sheila Jasanoff and J. Benjamin Hurlbut from Arizona State, can be found here, and an umbrella editorial from the editors of Nature is here.  All are open-access and all are worth reading by any citizen who would like to be informed at even a general level about the ethical discussions of biotechnology.

The three share this tone: more inclusiveness, more humility on the part of scientists, and willingness to have difficult conversations are called for—and have been generally lacking in past efforts to engage the public in discussion of the implications of new biotechnologies.  In the view of Jasanoff and Hurlbut, even the much-admired 1975 Asilomar conference that established boundaries on recombinant DNA research and its applications, was too narrow, focusing on technically-definable risks and benefits but not taking time to reflect more deeply on the ultimate ramifications of what the scientists were doing.  The experts dominate, and lecture—gently, but clearly—the “laity.”  This can create a sort of foregone-conclusion effect: getting people comfortable with the research agenda and the scientists’ and technologists’ (including industry players’) goals is the true point.  The possibility that some work simply should not be pursued for a while may scarcely be expressed, much less heeded.  As Hans Jonas said in a reflection about Asilomar, “Scientific inquiry demands untrammeled freedom for itself.”

Burall, Jasanoff, and Hurlbut seem to be saying, repent from that, as it were.  Don’t just have a panel of a dozen scientists or so meet for a single seminar or webinar with a dozen or so non-scientists (with, I might add, the token clergyperson).  Create a clearinghouse for a wide range of views on what gene editing really might mean, and how humans should respond.  Open the dialogue to a large number, not just a few, non-scientists from a wide range of perspectives.  Pay attention to cultures other than the developed West—especially the global South.  Perhaps start with seminars that are cooperatively organized by several groups representing different interests or stakeholders, but don’t stop there—create a platform for many, many people to weigh in.  And so on.

They don’t suggest it will be easy.  And we do have a sort of clearinghouse already—I call it the Internet.  And we’d want to be sure—contra John Rawls—that viewpoints (yes, I’m thinking of God-centered perspectives) are not disqualified from the outset as violating the terms of the discussion.  And, perhaps most importantly, what threshold of public awareness/understanding/agreement would be insisted upon to ground public policy?  Surely a simple popular majority would be suspect, but unanimity—achievable in smaller groups, with difficulty—would be impossible.  And concerns about “fake news” or populist tendencies run amok (the “angry villagers”) would be unavoidable.

But, as Jasanoff and Hurlbut say, “In current bioethical debates, there is a tendency to fall back on the framings that those at the frontiers of research find most straightforward and digestible…[debate must not be limited by] the premise that, until the technical capability does exist, it is not necessary to address difficult questions about whether [some] interventions are desirable…Profound and long-standing traditions of moral reflection risk being excluded when they do not conform to Western ideas of academic bioethics.”

Bingo and amen.  How to make it happen, I am not sure.  Jasanoff and Hurlbut say they are trying to get beyond binary arguments about the permissibility or impermissibility of germline genome editing, for example.  Still, I don’t see how the “cosmopolitan” public reflection they advocate can go on without agreeing on something like a fairly firm moratorium—a provisional “presumption to forebear,” as I like to put it—while the conversation proceeds.  And hey, we’re the Anglosphere.  We’re dynamic, innovative, progressive, pragmatic, visionary.  We don’t do moratoria.   Moratoria are for those Continental European fraidy-cats.  Then again, these writers are seeking a truly global discussion.  And past agreement by assembled nation-states appears to have at least slowed down things like chemical and biological munitions (recent events in Syria notwithstanding).

These authors are doing us a service with their reflections.  Read their articles, give them a careful hearing—and note that their email addresses are provided at the end.  Maybe I’ll write to them.

Resources regarding ethics of gene editing

Recently, two resources have become available regarding gene editing and the issues raised by it.

First, the National Academies of Science, Engineering, and Medicine have made available an archive of its February 22 webinar about human gene editing.  The home page for the Academies’ human gene-editing initiative is here.  A link to the archived webinar is here.  The slides can also just be viewed here.

Second, Issue 1 of Volume 24 of the journal The New Bioethics is dedicated to human gene editing.  The entire issue, or individual articles from it, are available online for purchase, or for viewing if you have access through an academic institution.  Article titles deal with, for example, differentiating gene editing from mitochondrial transfer, comparing ethical issues with gene editing vs embryo selection, and “selecting versus modifying” to deal with disabilities.

I have not been through these materials in any detail, yet.  The webinar looks a smidge promotional, co-sponsored as it was by the Biotechnology Industry Organization (BIO).  But it also recommends the Academies’ report on the status of human gene editing, and summarizes key recommendations, which include limiting efforts (at least for the present!) to editing “somatic,” or, if you will, “adult” cells to make them into cellular therapies for recognized diseases.  This is well within the existing ethical and regulatory regime governing clinical research and treatment development, as opposed to the deeply problematic prospect of heritable gene editing, or attempts to edit genes for human enhancement, both of which the report and the webinar (at least the slides) counsel that we NOT rush into.  The New Bioethics articles look thoughtful and worth reviewing, which I hope to do (and comment on) in the near future.

The Bioethics of a Modern Death Mask

By the time you read this, a company called Nectome will have pitched its business plan to investors at Y Combinator as a company who has designed a technology called Aldehyde-Stabilized Cryopreservation to preserve all of your connectome, which is all of your brain’s interconnected synapses. Doing this, they argue, can preserve your memories, allowing the company to effectively “upload your mind”. One problem with the technology is that the process is 100% fatal as you have to die during the cryopreservation process to make an accurate connectome.

Oddly, the fact that you have to die for the process to be successful is not considered a deal breaker. Twenty-five individuals have already plunked down the $10,000 deposit to be first on the list to eventually have their brains perfectly preserved in this manner. The process also depends upon future scientists being able to figure out a way to use these perfectly embalmed brains to “reboot” their consciousness. Never mind that no one presently knows how that rebooting process might work or whether the present process captures everything that will be necessary some 100 years in the future when the complete technology will hopefully actually exist. Presumably, smarter people will have all of that detail eventually worked out. What is important at present, particularly if you have a terminal disease, is to preserve your brain so you can be rebooted in the future. A new state law in California called the “End of Life Option Act” makes the application of this novel technology legal for terminal patients (at least as best as can be determined as the legal details have yet to be tested in court). A very nice overview of this new technology and the new company itself may be found in the latest Technology Review article by Antonio Regalado.

There are scientists, such as neuroscientist Ken Hayworth, president of the Brain Preservation Foundation, who believe that a connectome map could provide the basis for reconstituting a person’s consciousness. At its base, this theory assumes that the physical brain is not only the necessary but presumably the sufficient source of consciousness. Capturing the synapse pattern would certainly be essential for recreating the hardware (and perhaps the software) of the brain to restart one’s electrical pattern leading presumably to rebooting one’s consciousness.

I have a couple of ethical problems with this technology, though I am sure there are more. The most obvious is that the process hastens the death of the individual, regardless of their terminal illness. The person will not be dying from their illness but from the cryopreservation process. This technology would not be legally possible without the new California law that will ascribe the death to the terminal illness rather than Nectome’s cryopreservation process, presumably shielding Nectome from product liability suits. Only in California could a terminal patient’s family sue the manufacturer of their vehicle for a malfunction in the brakes that resulted in their loved one’s premature death as they were in the process of driving their loved one to a Nectome facility to die by brain cryopreservation with the hope that the loved one could live again.

Another ethical problem is the transhumanist lure of a brain being rebooted, effectively allowing immortality of one’s consciousness. Aside from the presently unproven science of the rebooting process, who would be the recipient of the successful rebooted consciousness? By that I mean “who” (or what) is regaining consciousness? If the physical brain is the basis for consciousness, and recreating a new but exactly reproduced connectome is the thing that becomes conscious, would it really be you becoming conscious, or someone or something else entirely? Who really enjoys the rebooted memories? What if it is not really you that is being rebooted but someone or something else with your life’s memories? This would be the worst “bait and switch” advertising scam ever devised! What till the FTC begins filling suit. But seriously, are we just our consciousness or a necessary combination of physical mind and body, or a necessary combination of spiritual soul and physical mind/body? What exactly are we? Why do we think we can achieve immortality in the first place? If we can, is the Nectome method the right way of going about this process?

The Christian faith argues for a different process, but uses language such as “dying to self” and being “born again”, which sound similar to Nectome but are indeed very different. Per Nectome, if you die, using our cryopreservation technology, you can live again by regaining your consciousness in the future. The biblical concepts of being born again and dying to self reflects a believer having faith in the salvation offered by Christ’s death on the cross and subsequently humbly subjecting oneself to God’s will rather than one’s own will for the future, both temporally on earth and eternally in heaven.

I recommend the Christian process of being born again rather than the modern death mask soon to be offered by Nectome.

DIY CRISPR Kits – Gene Editing for the Rest of Us

One might think with the amazing advance of technology and easy access to nearly infinite data via the Internet that we, as a society, would see a reduction in false claims of benefit for novel medical procedures and untested medications. Sadly, it seems to be just the opposite. I seem to be spending gradually more time with my patients reviewing the results of their internet research for new solutions for their chronic back pain. Their efforts are laudable even though the “hoped for” benefits claimed in their researched solutions are woefully lacking. Unfortunately, often this exercise in reviewing the outside data takes valuable time away from the remainder of the office visit.

Reviewing false or confusing information is one thing but preventing patients from self-experimentation with untested medications or unproven treatments is another. Enter the biohacker and companies offering do-it-yourself (DIY) kits claiming to allow anyone to experiment with CRISPR (a method of genetic editing) for self-administration. Emily Mullin covers biohacking and DIY CRISPR very nicely in her recent article in the December Technology Review. To me, this has the feel of the 1980s when a curious kid with some basic programming knowledge, an inexpensive computer and a modem can access previously forbidden government systems, potentially unleashing havoc on the rest of us (WarGames, anyone?) After all, now that we know the human genetic code, all we need is for someone to just provide the instructions and tools for editing that code, then anyone could tweak their own DNA. Easy peasy lemon squeezy, right?

Recently, the FDA has been busy trying to prevent medical clinics from administering untested stem cell treatments (see Neil Skjoldal’s recent November blog entry on (Stem Cell Clinics & the FDA). Imagine the significant increase in the scope of the regulatory problem if individuals can order a DIY CRISPR kit off the Internet!

While we might chagrin at the naiveté required to believe the street-side pitch of the Old West Carter’s Little Liver Pill salesman, that same pitch via a modern tech savvy YouTube video (complete with separate internet links) somehow offers a new level of legitimacy. The Technology Review article speculated that one of the featured companies was preparing not a vaccine but a treatment for herpes. In less than 8 weeks from the article’s publication, Aaron Traywick, CEO of Ascendance Biomedical, publically self-injected himself with his firm’s untested and non-FDA approved “treatment” for herpes. The linked article by Reegan Von Wildenradt in the popular magazine Men’sHealth offered an excellent counter as to why this type of “science” might be suspect, including quotes from ethicist Arthur L. Caplan at NYU in support of the standard FDA process for screening medical treatments.

We often lament in this blog that technology is advancing so rapidly that we fail to have a fair public hearing and discussion of the ethics involved in a particular biomedical advance. Now it seems our time may be better spent speaking out first about the basic risks of the new technology and doing our best to support the FDA in their massive task of policing the Internet to prevent a DIY CRISPR kit from falling into the wrong hands – ours.

P.S. – I’m accepting names for the title of the future Hollywood blockbuster where the son of Matthew Broderick and Ally Sheedy injects himself with his own DIY CRISPR-modified DNA and …

The Brain and The Internet

The current Technology Review contains an article by Adam Piore featuring Dr. Eric Leuthardt, who, as the title claims, is “The [Neuro]Surgeon Who Wants to Connect You to the Internet with a Brain Implant”. After spending Christmas with my married millennial children, I am convinced there are no further connections required. But Dr. Leuthardt isn’t satisfied with clumsy thumbs and smartphones – he wants a hard-wired, direct brain-to-Internet solution. The article nicely covers both the history and current “state-of-the-art” technology of brain-machine interfaces, as well as the barriers we have yet to solve before Dr. Leuthardt’s dream of a brain-internet connection is a reality. I encourage a full read of the entire article as backdrop to the questions I will focus upon for the remainder of this blog entry. Dr. Leuthardt’s research partner, Gerwin Schalk, a computer scientist focused on decrypting the vast volume of brain electrical signals from the current implants used, sets the stage with the following quote:

“What you really want is to be able to listen to the brain and talk to the brain in a way that the brain cannot distinguish from the way it communicates internally, and we can’t do that right now,” Schalk says. “We really don’t know how to do it at this point. But it’s also obvious to me that it is going to happen. And if and when that happens, our lives are going to change, and our lives are going to change in a way that is completely unprecedented.”

What would it mean for us to develop and implement a brain interface separate from our current physical senses of seeing, hearing, smelling, tasting and touching? What Schalk and Leuthardt want is to develop a brain interface that is as good at receiving sensory input as our current five senses and equally as good at affecting our physical environment as our current voice, arms and legs. But it doesn’t have to stop there (and in fact, I do not believe it would). If the brain cannot distinguish data input via these new artificial links from data input via “normal” physiology, why not insert novel visual, auditory, olfactory, tactile or motor information as well as linkages amongst these – the experiences of which become actual memories. How could one tell memories in which you had actually participated from ones that were virtual? Would it matter? Anyone had any trouble with unwanted Internet ads or computer viruses lately?

For the record, I am generally all-in for most replacement artificial body parts, such as heart, lung, skin, kidney, liver and limbs (allowing for the bioethical concerns generally voiced on this blog). I am admittedly concerned as we develop technologies that start accessing (and potentially augment or replace) portions of the human brain, as I think that this starts to tinker with an individual’s very sense of self – one’s identity. Does altering the brain’s manner of sensory processing potentially also alter the brain’s experience of sense of self? Until we answer that question, we should tinker extremely cautiously or perhaps not at all (I am presently favoring the latter).

Of course, all of this skirts around the larger issue of exactly where my sense of self lies. Does my brain completely contain and therefore solely determine my identity or is my identity part of a more complex interface between the physical brain and a non-physical soul? That is a big question for a six-paragraph blog to answer but one that deserves consideration as we seek to develop artificial interfaces within the brain that not only change the way I experience my environment but potentially how I experience my self.

With regard to hooking my brain directly to the Internet, given what I’ve seen of the Internet to date, I will leave my thumbs and smartphone as my interface of choice, at least for the near future.

The Hubris of Head Transplantation

As a rehabilitation physician with an interest in acute spinal cord injury, I try to keep abreast of neuroscience research both in animals and humans that might suggest a breakthrough in spinal cord injury recovery. Sadly, despite increased awareness by the general public from high-profile individuals who suffered this devastating injury (notably Christopher Reeve and his foundation), ongoing research in chemical, cellular transplant (including some stem-cell) and electrical stimulation, and advances in emergency medical and surgical management of the acute spinal injury, medical science has not seen dramatic improvement in spinal cord injury functional recovery since I began my practice almost 30 years ago. I spend some time reviewing the results of my patient’s Internet research into “claims of cures” as they desperately look for any solution to their disability. I thought I had seen everything until I was given a 2015 link to a TEDx talk by Italian neurosurgeon Dr. Sergio Canavero and saw a subsequent recent USA Today article regarding his plans for an imminent head transplant scheduled to occur in China sometime later this month or early next year. In fairness, 99.999% of the scientific news coverage condemns the planned surgery (including the TED community) and the popular news coverage consistently leads with a picture of Gene Wilder in his role in the Mel Brooks movie Young Frankenstein (as in this link)

In short, Dr. Canavero is planning to remove the head of a patient who has a severe progressive musculoskeletal disease and transplant it onto an otherwise healthy brain-dead individual who will act as the donor body. Canavero claims that unlike random high-energy trauma that destroys a significant section of the spinal cord as a result of an accident, his technique uses a precision cutting instrument that minimizes cord trauma, combines this with cryopreservation techniques that cool the head down to 12 degrees Celsius during the transplant, and uses a substance commonly used as a laxative called polyethylene glycol (PEG) to reconnect the spinal cord on the donor body followed by proprietary electrical stimulation of the donor body spinal cord to maximize recovery. Sounds pretty easy, right?

Ignoring the ethical issues for a moment, the main overarching technical problem is that the head transplant technique has yet to work when tried on any animals. Subsections of the technique have shown limited benefit such as using PEG to encourage spliced segments of spinal cord to heal. But a success (partial at best) in one small area never guarantees success on a broader application. Condemning this whole endeavor from an ethical standpoint is therefore a moot exercise. Recommending such a surgical procedure that has never been successful should be ethically abhorrent regardless of anyone’s worldview.

One final comment may be worth considering. If you watch the TEDx YouTube link of Dr. Canavero to the bitter end, he gives you a hint at what motivates his work. He makes the case for eventually perfecting his technique such that the human brain can become immortal. Transplanting a head onto a younger body (and repeating the process) effectively allows a head to live forever. He suggests connecting a head to a machine to achieve the same result. He is really talking about immortality of the human consciousness and actually refers to the brain as a filter for consciousness. It seems the pinnacle of human hubris to believe that we can achieve for ourselves immortality unless it were already available to us.

I suggest that John 6:47-51 offers a better way.

“Nervy” SHEEFs, pain, and moral status

In May of this year, my brief essays (literally, “attempts”) on synthetic human entities with embryo-like features, or SHEEFs for short, sought to ask what sort of human cellular constructs might or might not enjoy full human moral status; to wit, the right to life.  Some experimenters with SHEEFs have suggested that, since they may bypass the early (14 days of life) markers that normal, or (if you will) canonical, human embryos demonstrate, a different moral approach is needed to determine ethical boundaries for these experiments, and the suggestion was that the capacity to feel pain would be a good substitute.

In my May 11 post, I suggested that a SHEEF with even part of a human nervous system must be accorded the right to life.  I made what is, I confess, a breezy connection between said nervous system, however rudimentary, and the identification of a human soul, on the grounds that bodily expression of human capacities commonly is through the effects of the nervous system.  The capability of any such capacities, I wanted to hold, would mark a SHEEF as a “human being” deserving of moral status.  This would distinguish it from, for example, a tissue-engineered trachea, or a kidney, or maybe even a heart, although human heart have, in their automatic conduction systems, a sort of “nervous system” capacity, I suppose.  Still, it didn’t seem to me (Edgar Allan Poe notwithstanding?) that a tissue-engineered heart would be considered a “human being,” the sort of being with “the intrinsic capacity to develop sentience, to ponder the universe, to comprehend the inevitability of mortality, to seek purpose, to yearn for love, and to suffer?”

That last quoted phrase is from a welcome essay by Dr. William Cheshire in the Fall 2017 edition of the journal Ethics & Medicine.  In his essay, “The moral significance of pain for synthetic human entities derived from embryo-like cells,” he argues, to put it all too briefly, that the ability, the realized capacity, to feel pain is an inadequate marker of human moral status.  Why?  Because some humans are incapable of nociception—physical responses to noxious stimuli.  Indeed, local anesthetic makes an otherwise fully-thriving human numb, for a while.  To say that all SHEEF experiments are OK as long as the entity doesn’t feel pain is to reduce meaning to pain, pleasure, and happiness.  Dr. Cheshire muses about a hypothetical creature, designed and bred in the laboratory, that is “sentient…possessing a complete brain composed of human neurons, yet lacking critical genes necessary for the capacity to experience pain…Rather than ask, what does it mean for a human organism to experience pain, a better question is, what does it mean to be the kind of being that experiences pain?  What does it mean to be the kind of being who has “the intrinsic capacity to develop sentience,” etc?

I was surprised when I saw that Dr. Cheshire chose for an epigram to his essay this sentence from my May 11 post:  “A moral boundary is approached when a human nervous system is brought into the plan.”  I read his essay as a criticism of my approach, but I still think the latter has merit.  I still think that some human tissue engineering with some SHEEFs might be ethical.  At the same time, I think that attempts to make too complete, too complex a SHEEF—for example, one with a whole human body except the head—would be monstrous.  I suppose that such a being would have to have a fair amount of human autonomic nervous system to function at all, and so would fall under my criterion.  And I also think that a quest for a “minimal human genome” or a “minimal human” would be frankly unethical.  (I understand synthetic biologists to be interested in the former but nobody to be suggesting the latter.)  To be ethical, experiments would have to observe serious limits from the concept stage.  And a concept of “how far can we go before we truly have the kind of being with the intrinsic capacity…?” would be out of bounds.

Check out this June 15, 2017 cartoon from the New Yorker

Uterine Transplantation – for Men?

Susan Haack began exploring the topic of uterine transplantation in women on this blog back in February 2014. In just under 4 short years, the technology has not only successfully resulted in live births in several women who received the uterine transplants, but outgoing president of the American Society of Reproductive Medicine, Dr. Richard Paulson, is suggesting we consider exploring the technique in men. While there are certainly hurdles to overcome (need for cesarean section for the actual birth, hormone supplementation, complicated nature of the transplant even for cisgender women), Dr. Paulson does not consider these barriers insurmountable for transgender women.

Dr. Julian Savulescu, professor of practical ethics at Oxford, has cautioned that initiating a pregnancy in a transgender woman may be unethical if it poses significant risk to the fetus. The above-linked article misquotes his concern as a concern over “any psychological harm to the child born in this atypical way”. The following is his actual quote from his own blog:

Therefore, although technically possible to perform the procedure, you would need to be very confident the uterus would function normally during pregnancy. The first US transplant had to be removed because of infection. There are concerns about insufficient blood flow in pregnancy and pre-eclampsia. A lot of research would need to be done not just on the transplant procedure but on the effect in pregnancy in non-human animals before it was trialled in humans. Immunosuppressives would be necessary which are risky. A surrogate uterus would be preferable from the future child’s perspective to a transplanted uterus. Uterine transplantation represents a real risk to the fetus, and therefore the future child. We ought to (other things being equal) avoid exposing future children to unnecessary significant risks of harm.

One putative benefit might be the psychological benefit to the future mother of carrying her own pregnancy. This would have to be weighed against any harm to the child of being born in this atypical way.

His concerns are the baseline medical risks involved in using a transplanted uterus to conceive a child regardless of the sex of the recipient. None of his concerns relate to the psychological harm to the child potentially caused by a uterine transplantation in a transgender woman as opposed to a cisgender woman. Savulescu is explicit in the beginning of his blog that “[t]he ethical issues of performing a womb transplant for a [sic] transgender women are substantially the same as the issues facing ciswomen.” Is the only risk to the child “born this atypical way” just the additional need for hormone supplementation in the transgender woman compared to the cisgender woman? Can we really know, a priori, what all of the attendant risks to the child really are with uterine transplantation in a transgender woman?

Regardless, let’s assume Savulescu is correct, that there is indeed no ethical difference between carrying a child to term via uterine transplantation between a cisgender woman and a transgender woman. There certainly can be no ethical difference between carrying a child to term via uterine transplantation between a transgender woman and a cisgender man. If the foregoing is true, can there be any ethical barrier preventing a man via uterine transplantation to use his sperm to fertilize a donor egg and carry his baby to term? After all, per Savulescu, all we need be concerned about from a bioethical standpoint are the technical issues/risks of uterine transplantation regardless of the recipient’s biological sex or self-identified gender.

In Genesis, God created two complimentary sexes and stated this difference was good. We are moving toward eliminating differences between the sexes and arguing that this is good. Both of us cannot be correct.

I wonder if Dr Haack thought that we would get this far down this particular bioethical slippery slope in four short years?

Is Your Polygenic Risk Score a Good Thing?

Back in October, Jon Holmlund wrote a blog entry regarding the popular company 23andMe and their collection of your health-related information along with your genetic material. I missed the significance of that relationship at the time. It took a recent article in Technology Review by my favorite technology writer Antonio Regalado to raise my ethical antennae. In his article, he explains the nexus of big data mining of genetic data and health information (such as is collected by 23andMe) and its future potential use to select embryos for IVF, selecting not only against polygenic diseases such as type 1 diabetes but potentially for non-diseases such as height, weight or even IQ.

Yikes.

Pre-implantation genetic diagnosis (PGD) already is used to select for particular embryos for IVF implantation that do not have genetic patterns such as cystic fibrosis or Down syndrome. Diseases that result from multiple genes (polygenic disorders) presently defy current PGD methods used to detect future diseases. Using Big Data analysis of health information compared against linked genetic data, scientists are getting better at accurate polygenic risk scores, statistical models which may more accurately ‘guess’ at an embryo’s future risk for not only juvenile diabetes but also later-in-life diseases (such as heart disease, ALS or glaucoma) or other less threatening inheritable traits (such as eye color, height or IQ) that result from multiple genes (and perhaps even environmental factors). There is confidence (hubris?) that with enough data and enough computing power, we can indeed accurately predict an embryo’s future health status and all of his or her inheritable traits. Combine that further with all of the marketing data available from Madison Avenue, and we can predict what type and color of car that embryo will buy when he or she is 35.

Ok, maybe not the color…

Seriously, companies such as Genomic Prediction would like to see IVF clinics eventually use their expanded statistical models to assist in PGD, using a proprietary technique they are calling Expanded Pre-implantation Genomic Testing (EPGT). Consider the following two quotes from Regalado’s article:

I remind my partners, “You know, if my parents had this test, I wouldn’t be here,” says [founding Genomic Prediction partner and type 1 diabetic Nathan] Treff, a prize-winning expert on diagnostic technology who is the author of more than 90 scientific papers.

For adults, risk scores [such as calculated by 23andMe] are little more than a novelty or a source of health advice they can ignore. But if the same information is generated about an embryo, it could lead to existential consequences: who will be born, and who stays in a laboratory freezer.

Regalado’s last comment is dead-on – literally. Who will be born and who stays in the freezer is another way of saying “who lives and who dies”.

Technologies such as EPGT are poised to take us further down the bioethical slope of choosing which of our children we want to live and which we choose to die. For the sake of driving this point home, let’s assume that the technology becomes essentially 100% accurate with regard to polygenic risk scoring and we can indeed determine which embryo will have any disease or trait. Since we already permit the use of single gene PGD to prevent certain genetic outcomes, should there be any limit to polygenic PGD? For instance:

(A) Should this technology be used to select against immediate life threatening illnesses only or also against immediate mentally or physically permanently crippling diseases that don’t cause death directly?

(B) Should this technology be used to select against later-in-life diseases that are life threatening at the time or also against mentally or physically crippling diseases that don’t cause death directly? (Would it make a difference if the disease occurred as a child, teenager or adult?)

(C) Should this technology be used to select against non-disease inheritable traits that society finds disadvantageous (use your imagination here)?

(D) Should this technology be used to select for inheritable traits that society finds advantageous (a slightly different question)?

Depending upon your worldview, until recently, answering Questions A through D used to be the purview of God or the random result of chance. Are we ready (and capable) to assume that responsibility? Make your decision as to where you would draw the line then review this short list of famous scientists and see how many on that short list your criteria would permit to be born.

Are you happy with that result? Would you call it good?

It would be nice to get this right since it now appears to be our call to make…