Britain’s experts on gene-edited babies

by Jon Holmlund

Some of the cable news shows ran segments on the report released this week by Britain’s Nuffield Council on Bioethics, “Genome editing and human reproduction: social and ethical issues.”  Full disclosure: I have not yet read the full report, only the short summaries (all of which are available for free download at the link here).

The TV teasers—”U.K. bioethics council says that gene-editing children may be morally acceptable” were accurate.  The key conclusion is that “the use of heritable genome editing interventions to influence the characteristics of future generations could be ethically acceptable in some circumstances” (emphasis theirs).  But the news folks made it sound like an attempt to birth an edited baby is around the corner, or at least fully green-lighted by Nuffield.

The summary of the report reads more modestly, acknowledging that such attempts are currently banned by law most places, and that making them legal could require “a long and complex legislative pathway.”  But the Council does take the view that at least some attempts, such as those to try to repair a lethal disease gene such as the dominant gene for Huntington’s disease, might be justifiable.  This blog has considered such an argument in the case of sickle cell anemia—single gene defect, well understood, circumscribed attempt to repair only that gene.  An argument can be made.

The Nuffield Council’s summary really is a list of general statements that, taken individually, are hard to take issue with, and are in some cases almost platitudinous.  The overall impression is, “yes, heritable human gene editing could be ethical, and probably should be considered, but only after a long public deliberative process, appropriate regulation, etc., etc.”  Nuffield offers two stipulations for ethically acceptable heritable human gene editing:

  • “Intended to secure, and is consistent with, the welfare of a person who may be born as a consequence” of the effort, and
  • Social justice and solidarity are upheld; that is, discrimination or social division should not be a consequence.

These statements are both too broad to be helpful.  In the first case, the Council acknowledges that some efforts could be attempts to enhance a person’s natural characteristics, not just treat a recognized disease, and that, except for the most genetically straightforward cases, the scientific and technical challenges are substantial.  In the second case, it would seem that pressures for discrimination based on social attitudes or economics (ability to pay for the procedure, medical insurance reimbursement issues) will be unavoidable.

Scientifically and socially, there will be unintended—or at least undesirable—consequences.  These may be known but considered acceptable.  For example, how many human embryos will need to be created and destroyed to perfect the procedure?  How many generations will need to be followed to rule out some late complication?  Can we really guarantee that “having babies the old-fashioned way” won’t become a thing of the past?  And, in spite of the laudable desire to bring healthy children into the world, wouldn’t this be a wholesale acceptance of the basic assumption that only the people we want to be born, should be born?

For these reasons and others previously articulated on this blog, heritable human gene editing falls into a small but critical group of biomedical undertakings that should not be pursued.

And, BTW, the remaining bugs in the system include, as reported this week, that gene-editing techniques appear to introduce errors more frequently than previously appreciated.  Given that heritable human editing involves more than just a few cells in a dish, a “presumption to forebear” should apply.

The TV news gave this about 5 minutes this week.  That’s the breadth and depth of our “public deliberation” beyond a few experts.  At the end of one segment, the host looked into the camera and said, “next up: are liberals or conservatives happier?”

As Neil Postman said:  “now this…”

Forcing RNA to, at least, Mumble…

BY MARK MCQUAIN

We are at a turning point in medicine where instead of supplementing patients with proteins or enzymes that their bodies fail to manufacture due to genetic abnormalities, we soon may be able to re-engineer the abnormal DNA, restoring the DNA’s ability to instruct the body to make those same proteins or enzymes. On our way to full-fledged genetic engineering, we have learned that DNA makes something called RNA, which can be thought of as specific instructions for assembling these vital proteins, telling cells exactly how to assemble protein building blocks, called amino acids, in their proper sequence. Even a very minor disorder in a very long amino acid sequence of a protein can cause that protein to function poorly or not at all. When bad DNA makes bad RNA, or when good RNA gets subsequently damaged or misread, the protein either gets assembled in a garbled fashion, or not at all. Think of RNA as the boss of protein production who can speak clearly, mumble or say nothing at all. Recently, there is one well-known disease where it looks like it is possible to force bad RNA that presently says nothing at all to, at least, mumble.

The disease is Muscular Dystophy (MD) and the missing necessary protein is called dystrophin. Dystrophin is responsible for the structural integrity of muscle. Poorly formed or garbled dystrophin results in a mild form of MD, such as one called Becker Muscular Dystrophy (BMD) where patients can live well into their 40s or 50s. If no dystrophin is produced at all, a severe form of the disease called Duchenne MD (DMD) results, in which muscles simply fall apart over a shorter period of time, causing patients to stop walking in their teens, usually dying in their twenties from cardiac or respiratory muscle failure. While it would be great to restore normal production of dystrophin in patients with DMD, one company called Sarepta, appears to be able to cause patients with DMD, who normally do not make any dystrophin, to produce a garbled dystrophin, giving them a milder BMD-like disease.

Consider the following sentence: “The big red fat cat bit the sly fox and ate the shy jay”. The individual letters represent the RNA sequence and the three letter words represent unique amino acid protein building blocks, resulting in a meaningful protein sentence – think of this as the normal dystrophin protein in a healthy person. If the RNA was missing the 22nd through 24th letters (the 8th word “sly”), the sentence becomes: “The big red fat cat bit the fox and ate the shy jay”. It is a minimally garbled version of the first sentence but still meaningful – think of this as the dysfunctional dystrophin in milder BMD. If the original RNA sequence was missing only the 7th and 8th letters, the sentence becomes: “The big dfa tca tbi tth esl yfo xan dat eth esh yja y”. This sentence has no meaning beyond “The big” – think of this as no dystrophin in severe DMD. If we could get the RNA reader to ignore the first letter “d” in the last RNA sequence, the sentence becomes: “The big fat cat bit the sly fox and ate the shy jay”. We are back to a minimally garbled version of the first sentence but still meaningful – think of this as another dysfunctional protein in a milder “Becker-like” MD. This is how scientists at Sarepta appear to have taken an RNA sequence that originally said nothing and forced it to mumble, producing a new garbled form of dystrophin, which works better than no dystrophin at all.

I realize this has been a long walk in the weeds for some of our regular readers but hopefully it has provided some helpful background into the current treatment of MD and a sense of how much further we have yet to go. I will use this blog entry as background for my next blog entry to discuss some of the bioethics around the cost of getting RNA to mumble.

For now and for me, advancing medical knowledge like this convinces me of how fearfully and wonderfully we are made. (Psalm 139:14)

Raiding the CRISPR

BY JON HOLMLUND

A couple of gene-editing news items from this week’s science literature:

First, Nature reports that a group in my “back yard,” at the University of California San Diego, has tested gene editing using the CRISPR approach in mice.  Recall that CRISPR is an acronym for a particular molecular mechanism, first discovered in bacteria, that is particularly efficient—though not perfectly so!—at editing genes.  The idea is to find a “bad” gene that you’d like to replace, for example to prevent or treat a disease, and edit it to be the normal version of that gene.

The kicker in this particular case in mice is that it tested something called “gene drive.”  In classical genetics, humans (and other higher organisms) have two copies of each gene.  In sexual reproduction each parent passes one copy of the gene to offspring, so the chance of a particular gene being handed down is 50%.

“Gene drive” is a technique designed to change those odds, and make a particular gene “selfish,” and much more likely to be passed on.  In fact, the idea is that transmission would be 100%, or nearly so.  If that worked, then a new gene would soon take over a population of organisms, and every member would, in a few generations, have that gene.

Why might that be a good thing?  Suppose you are interested in pest control, and you could use the technique to make, say, mosquitoes infertile.  Then they would soon all die off.  Or if you had some other “desirable” characteristic, you could make it so all members of a species (rodents?  Cattle?  People?) have that characteristic.  Assuming it’s determined by one gene, that is.

And assuming that the technique works.  In the mouse experiment, efficiency was only 73%.

That’s probably good news.   This is one of those techniques that could have serious unintended consequences if tried in the field.  Scientists have been warning about that.  It looks like it’s a way off, but something else to fret about.

The second item involves a clinical trial to treat sickle cell anemia.  In this one, blood stem cells from a person with the disease are removed from the bloodstream and gene-edited outside the body to make hemoglobin that is not as damaged as in the disease (SCA is an inherited disease in which the red blood cells have abnormal hemoglobin that doesn’t carry oxygen well).  Then the altered cells become the therapy, and are given back to the patient.

The FDA has put a “clinical hold” on this clinical trial.  Exactly why has not been publicly disclosed (it doesn’t have to be), and it sounds like the trial itself hadn’t started yet, but that the company developing it was getting ready to start.  This is, in my view, an approach to gene editing that does not pose special or particularly worrisome ethical issues, because the genetic changes are done on “adult” stem cells to treat an existing individual with a disease in a way that would not entail transmission of altered genes to future generations.

And, probably, it’s a case of “this too shall pass,” and the FDA’s concerns will be answered and the trial will proceed.

But check out the sidebar reporting this in Nature Biotechnology.  If you follow the link you will probably get a prompt asking for payment but I was able to sneak a free read on my screen.  If you go there, read below the separate quote (itself picked up from The New York Times) from Dr. George Church of Harvard:  “Anyone who does synthetic biology [engineering of biological organisms] should be under surveillance, and anyone who does it without a license should be suspect.”  Apparently he said that in response to “the publication of an experiment recreating a virus that has engendered fears that such information could be used to create a bioweapon. ”

The old “dual use problem,” eh?  We should really fret about that.

A safety concern with gene editing

BY JON HOLMLUND

Hat-tip to Dr. Joe Kelley for bring this to my attention…

As readers of this blog will recall, there is keen interest in exploiting recent discoveries in genetic engineering to “edit” disease-causing gene mutations and develop treatments for various diseases.  Initially, such treatments would likely use a patient’s own cells—removed from the body, edited to change the cells’ genes in a potentially therapeutic way, then return the altered cells to the patient’s bloodstream to find their way to the appropriate place and work to treat the disease.  How that would work could differ—make the cells do something they wouldn’t normally do, or make them do something better than they otherwise do (as in altering immune cells to treat cancer); or maybe make them work normally so that the normal function would replace the patient’s diseased function (as in altering blood cells for people with sickle cell anemia so that the altered cells make normal hemoglobin to replace the person’s diseased hemoglobin).

Or maybe we could even edit out a gene that causes disease (sickle cell anemia, Huntington’s disease) or increases the risk of disease (e.g., BRCA and cancer) so that future generations wouldn’t inherit it.  Or maybe we could edit genes to enhance certain health-promoting or other desirable qualities.

The recent scientific enthusiasm for gene editing is fueled by the discovery of the relatively slick and easy-to-use (if you’re a scientist, anyway) CRISPR-Cas9 system, which is a sort of immune system for bacteria but can be used to edit/alter genes in a lot of different kinds of cells.

It turns out that cells’ normal system to repair gene damage can and does thwart this, reducing the efficiency of the process.  The key component to this is something called p53, a critical protein that, if abnormal, may not do its repair job so well.  When that happens, the risk of cancer increases, often dramatically.  In cancer research, abnormal p53 is high on the list of culprits to look out for.

Two groups of scientists, one from the drug company Novartis and one from the Karolinska Institute in Sweden, have published on this.  P53’s thwarting of gene editing is particularly active in pluripotent stem cells, that are some, but not the only, candidate cells to be edited to create treatments.  These cells are also constituent cells of human embryos.  If the CRISPR-Cas9 process is used on these cells, p53 usually kills them off—unless it’s lacking or deficient, in which case it doesn’t, but also in which case it means that the altered cells could themselves become cancers, later on.

This is something that has to be monitored carefully in developing cells as medicines, so to speak, with genetic editing.  One does not want the patient to appear to be healed, only to develop a cancer, or a new cancer, later on.  One certainly would want to know the risk of that before editing an embryo—an unborn human, a future baby if placed in the right environment—to create a gene-edited human being.

Yet, as I’ve written here in the past, it appears that experimentation in heritable gene editing is pressing on.  I’ve argued, and continue to argue, that heritable human gene editing is a line that must not be crossed, that would place too much trust in the providence of the scientists/technologists who are the “actors” exerting power over fellow humans who become “subjects” in a deep sense of the term; that the risks to the subjects are undefinable; that it would enable perception of humans as “engineering projects”; that the gift of life would tend to be replaced by seeking to limit birth to “the people we want”; that the people acted upon are unable to provide consent or know what risks have been chosen for them by others, even before birth.  Rather than press ahead, we in the human race should exercise a “presumption to forbear.”

A counter argument is that, in limited cases where the genetic defect is limited and known, the disease is terrible, treatment alternatives are few or none, that the risks are worth it.  The recent papers seem to expose that line as a bit too facile.  How many embryos created (and destroyed) to develop the technique before “taking it live?”  Could we work things out in animals—monkeys, maybe?  How many generations to alter, create, and follow to be sure that a late risk—such as cancer—does not emerge?  Or maybe our animal rights sensibilities stop us from putting monkeys at such risk—maybe mice will do?

The new papers are dense science.  Frankly, I can grasp the topline story but have trouble digesting all the details.  More sophisticated readers will not be so impaired.  The news report, in the English of the general public, can be read here, the Novartis and Karolinska reports read (but not downloaded or printed) here and here, respectively.

More on genetic medicine

The third and final installment from The Code, a series of 3 short documentaries on the internet about the origins of genetic medicine, is entitled “Selling the Code.”  This is about genetic testing to try to predict risks of diseases, among other things.  Doctors use some of this testing in clinical care and a burgeoning amount of research.  A number of companies, such as 23andMe, will, for a (not-too-high) price, sequence your genes, or at least some of them, from a cheek swab sample you send, and then give you a report of what the results are and what they might mean.  In cases where there is a simple connection between a genetic abnormality and a disease—if you have the gene, you get the disease—the approach can be very helpful.  But it’s rarely simple.  Even for known cancer-propensity genes like BRCA1 and BRCA2, there are many variants, and what they mean clinically is far from fully known.  In fact, for most of the common disease we care about, like heart disease, diabetes, and most cancers, the story is complicated indeed.  So what to do with the information is often far from obvious, and careful genetic counseling by a physician who specializes in genetic medicine is a must.

23andMe ran afoul of FDA a couple of years ago, leading to a long process that resulted in FDA acceptance of a more limited menu of testing by the company.

And some companies will sell you “genetic information” for more trivial concerns—presuming to tell you something meaningful about what fitness regimen you should pursue, or what wine you’ll like.  Caveat emptor, I suppose, although the risks are low for some of this.

AND—companies like 23andMe keep anonymized data bases of the genetic information they get for and from their customers, and sell that information to drug companies to support the latters’ research.  An individual can’t be identified in the process (at least, not readily, see my January 2013 post about “DNA research and (non)anonymity”) but the data in the aggregate is valuable to the genetic sequencing company.

These kinds of concerns—particularly what to do with an individual’s information, but also the usefulness of having genetic data on a large group of people to understand disease and help discover new treatments—are germane to an ongoing project of the Hastings Center to assess the implications of genetic testing of the whole genomes of large numbers of babies, to screen for any of several dozen genetic diseases.   Again, most of the babies will be perfectly healthy, and the yield from screening for rare conditions is low.  But people arguably have a right to know about themselves, and parents to know about their newborns.  Yet still, to what end will we use information that we don’t fully understand?  Read a good Los Angeles Times article, that overlaps some of the points in The Code’s video, and provides other useful information in quick-and-easy form, here.

Finally, I was gratified to read that a project to synthesize an entire human genome in the laboratory is being scaled back, at least for now.  Apparently, they can’t raise enough money.  I bet would-be investors aren’t convinced they could own the results and guarantee a return on their money.  I fretted about this in May of 2016 and again in July of the same year.  I encourage readers to click through and read those, as well as the concerns raised by Drew Endy of Stanford and Laurie Zoloth of Northwestern, who criticized both the effort in concept and the closed-door, invitation-only meeting at Harvard to plan it.

That was two full years ago.  A lot is going on under our noses.

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 …