Gene-Edited Animals as Trailblazers

By Jon Holmlund


The Chinese researcher who says he edited the genes of two recently-born twin girls is named He.  He’s not a deity, that’s just his name.  (I don’t think it’s pronounced with a long “e,” by the way.)  His motivation appears to have been to be the first, to show that He could really do it. 

While scorn is mostly being heaped on He, this work has been going on in livestock for a long time, in attempts to make animals with leaner meat, or more meat, or ones that are disease-resistant, or more tolerant to hot or cold weather, or ones that have softer or more durable fur for shearing and making into cloth.  Or, cattle could be altered so they don’t have horns, and don’t have to be dehorned after birth.

Proponents consider this work to be just like crossbreeding, only a lot faster.  That’s an oversimplification, of course, since cross-breeding follows naturally occurring processes of genetic modification, not the synthetic editing of specific genes, but for the moment that’s beside the point.  The agriculture industry is keenly interested in it—the potential could be large.  Some governments want to push it.  Which ones?  You guessed it—China—but also the US, as part of the current administration’s efforts to reduce regulation and foster innovation.

Reportedly, some of these animals’ meat has been tested, and found safe.  (No claim, yet, that it’s delicious.)  But nothing commercial, at least not yet in the U.S.

One problem, though:  the animals have unpredicted other abnormalities.  Some pigs edited to be meatier also had an extra vertebra in their spines.  Some rabbits similarly edited had unusually large tongues.  And the edited animals often don’t make it to live birth, or even implant into adult females to cause pregnancy.  The process sometimes uses cloning to create the animal embryos in the first place, and it’s speculated that the cloning process, not the specific gene editing, is causing the problems with pregnancy.  But that’s not for certain.

In recent decades there has been a hue and cry over the safety of genetically modified plant foods, but they appear to be safe for human consumption, and they don’t fundamentally alter the biosphere.  The meat or milk or fur of genetically engineered animals would seem likely to be safe for human use, also, and if the animals really are created just for human use, some bizarre deformities may not be so objectionable.

Of course, that prompts questions of animal use and welfare that require more than a short blog post.  But in the case of humans, we would anticipate living with and caring for gene-edited offspring.  We would not be producing them solely for use or consumption.  Or would we—for example, for organs to transplant?  Probably not.

Proponents of limiting the use of artificial human reproductive techniques sometimes argue that it is good for children to be received as gifts, and that, rather than being “ordered to specification,” their specific characteristics be welcomed as something of a surprise.  I suppose that off-target effects of heritable human gene editing could prove to be surprises, indeed.

One scientist quoted in the general press says that, regarding editing animals, ‘if we don’t try, we will never learn.” Another, an animal advocate, says, again about the animal work, “I think it would be an understatement to say we should be more cautious…I think we’ve already gone over the line with animals, and now humans.”

For sure, and now, with humans, a major question will be, how will we regard and handle the mistakes?

“The Babies are the Experiment”

By Jon Holmlund


The Thursday, Dec 13 edition of the Wall Street Journal carries this headline:  “Doubts Arise Over Gene-Editing Claim.”  The work behind the recent report that the world’s first two gene-edited babies had been born has been publicly discussed, but the details have not yet been published for full scientific review.  Apparently scientists in the gene-editing field are reviewing the public presentation and finding it lacking:

  • Some, but not all, of the cells in the children may have been edited. One would expect changes in all of the cells, and this should be necessary for the overall stated medical goal (protection from HIV infection) to have a chance of having been met.

The edited babies may have variants of the edited gene that have not been fully studied and could have unforeseen health consequences.

The technique used to confirm the gene changes may not be sensitive enough to detect whether other, unintended and potentially undesirable gene changes had been made.

And perhaps most notably, the studies done in mice to demonstrate the feasibility of the technique, before editing the embryos that grew into the full-term babies, involve a different change in the target gene in mice than the change sought in the children. In other words, the animal studies appear not to be representative of the human situation.

This is a common problem for development of new treatments for cancer and other diseases.  Tests are initially done in animals—usually mice—to determine whether the putative new treatment appears to be working.  The animal models used never entirely reflect the human disease.  Some come closer than others.  But the way of handling that uncertainty is to define and limit the risks to people who subsequently have the new treatment tested on them in clinical trials.

In the case of the gene-edited babies, there’s really no way to limit the potential risks, at least not yet, if ever.  Ultimately, one has to strike out and make changes that could backfire for the recipient humans, or be propagated into their descendants with unpredictable effects. 

Accordingly, without good animal models, and appropriately extensive testing in them, then, as professor Sean Ryder of the University of Massachusetts Medical School is quoted as saying, “the babies are the experiment.”  Ultimately, heritable gene editing may just require a leap of biomedical faith.

We should just say, “no, we shall not.”

Human Embryos as Raw Materials

By Jon Holmlund


This past Tuesday, the Presidential Symposium at the 2018 Annual Meeting of the American Society of Hematology (ASH) addressed human gene editing.  The speakers included NIH Director Dr. Francis Collins, who spoke about somatic gene editing.  That’s the attempt to edit disease-causing genes in existing, fully formed individuals who have the disease in question, as treatment.  It’s generally well-addressed by our current ethical principles for human subject research, and it’s easy to agree that it is an appropriate use of gene editing technology, which has become so widespread—and, indeed, largely uncontrollable—because of the recently-discovered, highly efficient, easy-for-scientists-to-use CRISPR-Cas9 system.  The NIH has a specific Somatic Cell Gene Editing program.

Dr. Collins was followed by Dr. George Daley of Harvard, who presented a thoughtful case for proceeding with heritable gene editing—i.e., of germ cells (eggs and sperm) or, more likely, embryos, specifically during in vitro fertilization.  The recent editing of twin babies, announced in Hong Kong, was highly irresponsible, he said—in agreement with the vast majority of expert and general public commentators.  Fundamental principles of human subject research had been disregarded.  We must do what we can to guard against “hubris.”  Nonetheless, he agreed with the U.K.’s Nuffield Council opinion of earlier this year that ethical uses of human gene editing can be imagined.  Specifically, rare, serious genetic diseases untreatable by other means would qualify.  But rarity should not be a rigid requirement; there might be other genetic diseases for which future research would identify heritable gene editing as a viable if not preferred approach.  A “stop sign” or “red light” should be erected at enhancement—e.g., trying to edit genes to get more muscular or smarter people.  But this seems like a distant prospect.  Dr. Daley ended by endorsing a statement of the recently-concluded international symposium on gene editing in Hong Kong:  a “rigorous translational path” should be defined for human gene editing.  In everyday English:  steps to refine the technique in the laboratory should be taken, and steps needed to bring that work to the editing of people should be identified, in much the way that current regulated new drug development follows a series of well-defined steps.

But the actual translation should not go forward until there has been serious consideration of the societal and ethical concerns.  Some such efforts are happening now, he said.  I’ve blogged over the last few years about some of these, but you may not have heard of many, much less had a chance to contribute or had any way of thinking that concerns you might have would be properly represented.  Indeed, as I have said on this blog earlier this year (see my March 29 post, for example), it’s hard to imagine how to conduct social deliberation of the scale required by the utterly revolutionary prospect of human gene editing.  In a Q+A panel session, Dr. Collins asked Dr. Daley whether the answer to such deliberations might be “no”—might there be a decision not to proceed at all with editing human embryos?  Dr. Daley said, “yes, of course,” but I wonder.  For his part, Dr. Collins had sounded a highly cautionary note:  Embryo editing raises serious safety concerns, issues of informed consent, and questions about what it is to be human, he had said.  Perhaps its proper use would be so narrowly circumscribed that it really is not worth the trouble.  “Bad cases make bad law,” as it were, he had said.

After my post of last week, an inquirer had wondered aloud whether someone contributing to this blog might be able to figure out how many embryos had been destroyed in the run-up to the Chinese twins’ birth, or, for that matter, for the other laboratory experiments done so far in human gene editing.  Skeptical that such data exist anywhere, your correspondent nonetheless asked Dr. Daley in the Q+A whether there was any way reliably to estimate the “supply need” (I used that phrase) for human gametes or embryos in the course of the “rigid translational path.”  Dr. Daley of course could not make any more precise estimate than “very many embryos” would have to be destroyed in the process.  I must concur; I cannot see how a quantitative estimate could be made.  He allowed that moral objection to this would be one of the issues with this work, and commented that in the U.K., plans are to issue licenses for the necessary embryo experiments as part of an attempt to regulate them.

But the emerging picture is that human embryos are “raw materials” supporting the “translational” development of heritable gene editing, much as starting chemicals are raw materials for the production of a new drug.  That production process is governed by a panoply of regulations collectively referred to as “Good Manufacturing Practice,” a term that was applied to human gene editing more than once in the aforementioned ASH symposium.

I also asked whether the so-called “14-day rule” that scientists voluntarily follow as a time limit on human embryo research—i.e., don’t let them get more than 14 days old before killing them—would have to be relaxed.  Dr. Daley thought not.  I must say I wonder.  If embryos could be maintained in the lab for more than 14 days—something that still is not technically feasible, but is being actively contemplated by scientists in the field—might someone not insist that their development be followed as long as possible before taking the step of trying to bring them to term—that is, to full pregnancy and birth?

Perhaps not.  Unless more sophisticated “hatcheries” are developed, edited embryos would have to be implanted in a woman’s womb, after which there would be a progressively stronger presumption against aborting them, the older their gestational age.  But such a presumption would not be absolute under current American law and jurisprudence.  To be sure, the later a research abortion—currently prohibited in the U.S.—the greater a risk to a pregnant woman, not just the fetus being aborted.

And other intrepid actors, somewhere in the world, might well try to proceed outside a fully-regulated framework, purposefully setting up assessments at various gestational ages.

I must add that one liability of the line of thinking I have been taking here is that it might promote the misconception that the principal or even only reason to object to heritable human gene editing is a “pro-life, anti-abortion, religious” concern about the moral status of human embryos.  Not so, although the status of the embryo is a critical consideration.  There are lots of other reasons to object to this revolutionary development, and to say, as Dr. Collins suggested that “the answer should be ‘no.'”

About which more, much more, in the coming weeks.


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?

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.

Mumbling orphans—a bit more

Mark McQuain has raised the persistent, vexing issue of the pricing of drugs for rare diseases—in the case at hand, Sarepta’s eteplirsen (Exondys 51) for Duchenne Muscular Dystrophy, the disease over which the late comedian Jerry Lewis lost sleep every Labor Day weekend for years.

Mark provided an excellent summary (he calls it “crude,” but it’s anything but that).  In this case, the concern is not just price for a truly rare disease, but whether the drug showed sufficient evidence that it worked for FDA to approve it.  In the absence of alternative treatments, that was the truly tempestuous issue for Sarepta.  (Recall that under the 1962 Kefauver-Harris amendments to the Federal Food, Drug, and Cosmetic act, drug manufacturers in the U.S. may not sell a drug unless the FDA finds it not only safe, but effective—a standard that generally applies worldwide.)  It’s one thing for a drug to have a high price, but rather another if it doesn’t work, or doesn’t work very well.  (I decline to comment publicly about the Sarepta data; outside my expertise.  Those seeking a case in point may wish to consider Avastin for breast cancer.)

And to be sure the high price concern dogs other treatments that appear to work quite well—such as high-profile ones for cystic fibrosis or for cancer.  A case can be made that such drugs are worth the price, that too much government heavy-handedness risks stifling innovation, and that a search for the “just price” is misguided, but also, for sure, that society should share the costs of some of these drugs, that measures should be taken to limit out-of-pocket costs to disease sufferers, and that reimbursement approaches are ripe for overhaul.  In that last bucket: if drugs work only some of the time, only pay for the cases in which they do work; foster true competition (rather than having the costs of all drugs in a class go up when a new one is introduced, as if drugs were houses); eliminate the middle man (i.e., pharmacy-benefit managers that take a cut—that appears on the horizon); and the “biggie,” having government payers push back harder on prices.  At least some of these measures seem likely, and at least some seem warranted.

But overall, high costs for truly innovative treatments are justifiable, where no alternatives existed previously and especially when other, more expensive and quite possibly less effective medical treatments may be obviated (see: drug treatment for hepatitis C vs liver transplantation).  This is not to endorse price gouging for existent, cheap drugs that fall into an incidental monopoly (in which case, BTW, elimination of said monopoly, through regulatory facilitation of alternative sources, is warranted).

Public input into gene-editing decisions

Lyme disease is caused by a type of bacteria that lives in mice, which are considered a “reservoir” for the disease-causing agent.  Ticks bite the mice, pick up the bacteria, and then infect people when they bite them.  (Ticks are called the “vector” for the disease.)

If mice were immune to the bacteria, their immune systems would destroy them, and there’s be no reservoir, and no Lyme disease.  If scientists genetically engineered mice to make them immune—for example, by editing their genes—they could make progress toward that goal.  But to work, the mouse population would have to be predominantly made of bacteria-immune mice.  That could be accomplished by using “gene drive,” an approach that would make the altered gene spread preferentially and rapidly in the population.  However, doing that could alter the environment in unpredictable ways.

Because of the risks, scientists on the “Mice Against Ticks” project are determined that even if they succeed in genetically altering mice as suggested, they will not release those mice into the wild without full public awareness and approval.  They are holding public meetings—specifically, in Martha’s Vineyard and Nantucket—well in advance of the project coming to full fruition.  And they are trying to figure out, with the public, what level of communication and acceptance constitutes public approval.

Similarly, scientists in New Zealand would like to use a form of gene drive to greatly reduce the population of rats, possums, and other destructive predators that are decimating the environment.  And their public deliberations include seeking advice and, before taking action, buy-in from a network of Maori leaders.  Those conversations are so sensitive that the Maori objected when the scientists published a “what-if” type of article discussing the issues raised by the technology.  Among the concerns: some readers got the impression that gene editing of the animals was imminent, not hypothetical, as it still is.  Some of the news coverage of the Nuffield Council’s recent deliberations about the potential acceptability of heritable human gene editing seemed, likewise, to create the impression that the birth of the first gene-edited human is upon us—which it is not, not quite yet.

The public discussions above are two commendable moves toward true public involvement in decision-making about gene editing.  They were described in a recent Wall Street Journal article.  If you have subscription access, by all means read it.

PAS and “plain old” suicide

Last week, the folks from the Manhattan Declaration (whose key concern is freedom of religion) sent an email with a series of links—perhaps expanding their remit a smidge—one of which dealt with doctor-assisted suicide.  “Doctor-assisted suicide is contagious,” it said, along with this: “Doctor-assisted suicide increases overall suicide rates among the non-terminally ill everywhere it’s made legal.” And it also linked to a 2015 article on the subject from the Southern Medical Journal.

The SMJ authors were looking at whether overall and non-assisted suicide rates were different in states with legalized assisted death than in other U.S. states.  By their own admission, they did not have as much information as they would have liked.  They reviewed available information between 1990 and 2013. Two of the states were Vermont, which legalized assisted suicide in 2013 and had no cases that year, and Montana, which was not keeping count of assisted suicides.  That left them with assisted suicide data from Oregon (since 1998) and Washington state (since 2008).  (Since then, assisted suicide has also been made legal in Colorado, D.C., Hawaii, and California.)

In those two states, the total number of suicides and the number of non-assisted suicides had increased after the respective dates of legalization of assisted suicide.  However, the number of non-assisted suicides had also increased in the other states combined.  When I looked at their graph of the data, going back to 1990, there had been a decline in non-assisted suicide in Oregon, Washington, and other states between 1990 and 2000, with increases after that.  The number of these deaths per 100,000 population were higher in Oregon and Washington (and, indeed, much higher in Montana) than in the other states, but the slopes of the curves—the rates of increase—in Oregon and Washington looked similar to the other states.  Montana’s increase appeared sharply higher, but it’s hard to conclude anything about assisted suicide in that case because there were no data (nor for Vermont).

The authors commented that there had been estimates of how many surreptitious assisted suicides may have occurred outside of legalization, but admitted that firm conclusions were not possible.  They attempted to establish a statistical association between assisted suicide and nonassisted suicide, but the argument seemed inconclusive.  Follow the above link, read the article, and judge for yourself.

The core conclusion was that assisted suicide in its early years had not decreased overall suicide rates, as some of its advocates had argued it would.  Any relationship may become clearer as more information is available, assuming that numbers of assisted and non-assisted suicides are consistently and completely counted and recorded.  But that assumption is questionable at best.

In the meantime, it is important not to overinterpret limited data sets.  It’s also important to remember there are at least 5 reasons why assisted suicide is a bad idea:  it fundamentally alters the nature of medicine as a healing, life-preserving art and profession; its application cannot be reliably limited to those who freely request death or who are terminally ill (the slippery slope); it risks diverting energy and priority from true palliative care; if understood as a “right to die,” or a “right to be made dead,” it creates a duty for someone else to kill; and the notion of a “right to die” is self-contradictory if rights rest on preservation of life and well-being, as is the classical (i.e., pre-20th century) understanding.

In 2012, in his essay “Four Myths about Doctor-Assisted Suicide,” Ezekiel Emanuel wrote: “Patients themselves say that the primary motive [for assisted suicide] is not to escape physical pain but psychological distress; the main drivers are depression, hopelessness and fear of loss of autonomy and control. Dutch researchers, for a report published in 2005, followed 138 terminally ill cancer patients and found that depressed patients were four times more likely to request euthanasia or physician-assisted suicide. Nearly half of those who requested euthanasia were depressed.

“In this light, physician-assisted suicide looks less like a good death in the face of unremitting pain and more like plain old suicide. Typically, our response to suicidal feelings associated with depression and hopelessness is not to give people the means to end their lives but to offer them counseling and caring.”

And “plain old suicide” is, as we know, a problem that is getting worse all over the country.

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…”

Raiding the CRISPR


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.