“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.”

Gene editing for genetic enhancement

By Steve Phillips

I appreciate the prior posts by Jon Holmlund and Mark McQuain regarding the recent announcement of the birth of genetically modified twins in China. Much has been written about why this should not have been done, but something very significant has been left out of most of those responses. They have failed to mention that the scientist who created the genetically altered twins was doing a form of genetic enhancement. As I have noted before, the only real reason for anyone to do research on the genetic modification of human embryos is to enable the possibility of human genetic enhancement. The scientist involved in this situation has recognized that and directly pursued it. I suspect that his open pursuit of enhancement is one of the reasons why he has received such a negative response from those who otherwise support the permissibility of using human embryos for experimentation on germline genetic modification.

The primary argument presented for why this was wrong is that he has subjected two healthy human infants to the unknown risks of genetic modification without any corresponding medical benefit to the infants. The modification was disabling the gene that codes for a cell membrane receptor that the HIV virus commonly uses to gain entry into cells it infects. The hope was that these infants would have enhanced resistance to HIV infection, although not complete immunity to such infection. The infants themselves would not have been at increased risk for HIV without the modification, but the parents had a desire to have children with increased resistance because their father has HIV and is aware of the difficulty of living with the disease. Thus, the modification was being done to provide an enhancement desired by the parents and was not being done to infants would have otherwise suffered from a genetic disorder.

Most who support current research to develop effective techniques for human germline genetic modification take the position that the safety of doing this has not been established well enough to use the technique to create infants and that when the research does reach the point that genetically modified human infants are created it should only be in situations in which those infants would otherwise have had serious genetic disorders. They are correct that this technique is currently unsafe but fail to realize that we will probably never be able to establish the safety of this type of genetic modification, because that would require safety data from multiple generations of these infants’ offspring. The idea of restricting this technique to infants who would have been born with serious genetic disorders and the idea that this technique could be used to rid the world of these genetic disorders does not make sense. If a couple desires to have children and know that they are at risk to have a child with a serious genetic disorder and have no moral concerns about the destruction of human embryos involved in such things as genetic modification, they can pursue selection of an unaffected embryo using PGD and have no need to take on the additional risks of genetic modification. Using genetic modification to eliminate genetic diseases would require a Brave New World scenario in which all human beings are artificially conceived and natural conception is prohibited. Therefore, the only reason to pursue the genetic modification of human embryos is for the purpose of human enhancement.

Let me be clear that I agree that what the scientist has done is wrong because he has subjected these two infants to significant risk without any significant medical benefit. That is always wrong. However, the strength of the negative response from those who generally support research to develop human germline genetic modification is likely due to the fact that he has opened up to public scrutiny the real purpose of such research. He has also shown that it is not true that we can ignore ethical concerns about enhancement because we could regulate the use of genetic modification so that would not occur. Enhancement was the goal of the very first use of this technique to produce human infants.

The Genetic Singularity Point has Arrived

By Mark McQuain

November 2018 will go down as one of the most pivotal points in human history. Jon Holmlund covered the facts in his last blog entry. Regardless of what you think about the ethics of He Jiankui’s recent use of CRISPR to alter the human genomes of IVF embryos and his decision to intentionally bring those genetically altered twin girls to full term, one thing is perfectly clear – we humans are in charge now. Whether you believe in God or Nature as the Entity or Force that previously determined the arrangement of our genes, humans now sit at the adult table and will be gradually (rapidly?) making more of those genetic decisions. Like Kurzweil’s upcoming Singularity Point when computers develop sufficient artificial intelligence to design the next computer, humans have now reached the point where we can and are willing to design the next human.

The Genetic Singularity point has arrived.

While there are some scientists who are frustrated that our Institutional Review Boards and ethics committees have held us back this long, most of the rest of us are frankly stunned and uneasy that we have reached this point. But anyone who thinks our stunned uneasiness will prevent a repeat of this experiment or prevent a push to alter increasing portions of our human genome to change other genetic sequences will simply remain more frequently stunned and persistently uneasy, ethical arguments notwithstanding.

My reason for expecting this to be the case is I believe we will hear increasing demands of the form that now that we have the ability to change our genome, we have the responsibility to change our genome. In fact, it would not surprise me to see, in the not-to-distant future, insurance companies paying for the cost of IVF/CRISPR to modify your child’s genome to prevent disease/condition X to avoid paying for the later treatment of disease/condition X. Oh, you won’t be forced to do this. But, if you choose to rely on God or Nature for your baby’s genetic pattern, “we” won’t be responsible for his or her care. And, if big data can eventually be married to IVF/CRISPR to statistically improve one’s chances of having a smart/beautiful/athletic/successful baby, wouldn’t you want the same for your child? Since it will be our responsibility, how could a parent not choose to make their child the best that they could be?

This will be Gattaca writ large.

Being at the Genetic Singularity point, by definition, means we humans choose our next step. We have reached the point where we believe we are ready to select our future direction. It is up to us now to chart our own course. Our genetic trajectory is our responsibility. Our success or failure, or more broadly, our future good or bad, is finally ours to determine – really ours to assign.

So Man created mankind in his own image, in the image of Man he created them…And Man saw everything he had made, and behold, it was very good…

Sprinting Down the Road on “The Children We Want”

By Mark McQuain

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

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

Genomic Prediction is sprinting down that road.

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

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

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

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

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

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

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.

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.

Labs are growing human embryos for longer than ever before

BY JON HOLMLUND

That’s only a slight paraphrase of a news feature article this week in Nature.  The clearly-written article is devoid of scientific jargon, with helpful illustrations, open-access online, and readily accessible to the non-specialist.  Check it out.

Key points include:

  • Scientists who do not find it ethically unacceptable to create and destroy human embryos solely for research purposes continue to follow the so-called “14-day rule,” by which such experimentation is limited to the first 14 days after fertilization. At that point, the human nervous system starts to form and the time for twinning is past.
  • The 14-day rule is law in some nations, but until now has not been a practical issue because scientists have been unable to grow human embryos that long in the laboratory.
  • That technical limit has been sufficiently overcome that embryos are now surviving for almost 14 days. Scientists have not directly challenged the 14-day rule yet, but might, and would like to revisit it.
  • Experiments on human embryos in that time have included editing of critical genes to see what happens (sometimes they stop growing), and making hybrids of animal embryos with human cells whose purpose is to “organize” embryonic development rather than remain part of the developing individual.
  • Embryo-like structures, referred to as “embryoids” in the article, and sounding similar to “SHEEFs” (“synthetic human entities with embryo-like features”) are also being created. These entities don’t necessarily develop nervous systems in the same way as a natural embryo, prompting questions of just how much they are like natural embryos, whether the 14-day rule applies, and whether they raise other ethical concerns.

The last paragraph of the article, reproduced here with emphases added, is striking and more than a little ironic in light of arguments that embryos are “just a clump of cells”:

As the results of this research accumulate, the technical advances are inspiring a mixture of fascination and unease among scientists. Both are valuable reactions, says [Josephine] Johnston [bioethicist from the Hastings Center]. “That feeling of wonder and awe reminds us that this is the earliest version of human beings and that’s why so many people have moral misgivings,” she says. “It reminds us that this is not just a couple of cells in a dish.”

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.