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.

Labs are growing human embryos for longer than ever before

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

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 physician-assisted suicide

Recently, Dr. Arthur Caplan of NYU, on the Medscape service (subscription required), took on the question of whether physician-assisted suicide (PAS) should be allowed for old folks just because they are old, or because they want to die together.  There have been reports of just that.  While he supports PAS for terminal illness but objects that PAS for “suffering” in general is just too fuzzy, and therefore rejects broadening it.  An accompanying poll of doctors reported:  64-36% against PAS for old age, but 69-31% in favor of PAS for terminal illness.  As some advocates of PAS, like the editors of The Economist, have pointed out in the past, however, this distinction is highly difficult to sustain:  if someone is suffering “intolerably,” who are we to overrule that person’s wishes based on a diagnosis of the cause of said suffering?

Better is to recognize, as Neil Skojdlal noted this week, that real palliative care is not PAS, but is the ethical alternative.  And as Mark McQuain noted this week, changing the terminology confuses, rather than clarifies, the issues.  At least Dr. Lo, whose New England Journal of Medicine editorial Mark reviewed, accepted that not all physicians will accept PAS or be willing to offer it or refer for it.  He seemed to make room for that—unlike some advocates.

In a related item, Hastings center president Mildred Solomon “Calls for ‘Moral Leadership’ to Improve End-of-Life Care.”  In essence, she argues that over-emphasis on “autonomy” can be a way for doctors to abdicate their responsibility, and leave patients out to dry without guidance in end of life decision making.  She argues for a more relational approach, rethinking social supports to provide people with broader help in late life.  Makes sense.  She doesn’t address PAS in the brief piece I’m citing here, but I would certainly leave that out of the list of recommendations.

Coming home to roost

Hoo boy.

Scientists who want to study human embryonic development have heretofore been self-limited by a 14-day rule:  embryos can only be experimented on up to 14 days of age, when they start to develop a nervous system.  This is an attempt to avoid censure for unethical experimentation on human subjects, and is seen as something of a concession, since it does not accept that human life begins at conception.

And, inevitably, they seek work-arounds.  One reported this week by Nature is the creation of human chicken hybrid embryos.  Why would someone want to do this?  (Jokes about the San Diego Chicken are NOT called for here.)

Well, apparently 14 days of embryo age is when critical organization takes place, directed by “organizer cells” that don’t appear before then.  So a group of researches did this:  they took embryonic stem cells (which itself might well require creating and destroying an embryo), and made “embryo-like structures” that had cells that either were, or were just like, these “organizer” cells.  (Apparently these structures were not capable of growing into babies, but even if not, ethical issues remain.)  Then they transplanted these cells into chicken embryos, and watched the resulting hybrid grow, and learned something about how human embryos develop.  They figure this is less of an ethical problem than trying to experiment on a fully human embryo older than 14 days, and that hybrids like this might be able to take the place of experimenting on human embryos to answer many of their questions.

Other scientists disagree with this last statement, and still think they must experiment on fully human embryos to get their answers.

Either way, at a minimum it seems that this work will require creating embryos solely for research, and there is in principle no limit on manipulating the human organism in the name of knowledge.  Work is common on some kinds of “hybrid” animals with human cells, such as immune-deficient mice who have human cells transplanted to reconstitute their immune systems.  But that work usually is done with human cells transplanted into fully-formed mice, which appears different from early, hybrid embryos.

The article describing this work says that the hybrid embryos “didn’t live long enough to hatch.”  Wonder what they would have been like if they had.

A pause for doctor-assisted suicide in California

Readers of this blog probably saw this week’s news that a California judge blocked the state’s End of Life Options Act, the one that legalized doctor-assisted suicide in California.  The law passed after apparent failure in a regular California Legislature session, when its sponsors brought it up again in a special session that was supposed to be about Medicaid funding.  The judge said that inserting the assisted suicide law into that session violated the California state constitution.  So doctor-aided suicide is on hold in the state, for the moment.

Sort of a technicality, and celebration of the decision by folks (like me) who are staunch opponents of assisted suicide is likely to be short-lived.  Supporters will certainly challenge the ruling on appeal, perhaps win, perhaps also bring up the law anew in the Legislature, with (re)passage all but certain.

Legal assisted suicide is still bad policy, and assisting another’s suicide is still unethical.  But efforts against it have to address the attitudes and perspectives of our fellow citizens.  Allowing doctors and others to aid suicide poisons the central calling of medicine to protect life and to address human suffering accordingly.  It risks undermining proper palliative care.  It creates a “duty to kill” that someone has to step up to fill—or to be conscripted to fill, against moral objections that will be rejected as “inconsistent with standards of medical practice.”  It cannot logically be limited to the terminally ill (see Steve Phillips’s May 9 post on this blog) and cannot be reliably limited to those who freely and willingly choose death.  And it opens the idea of “rights” to misuse by those who desire death and to misappropriation by those who have reason to think that someone else should desire death.

Opposing assisted suicide is a longer undertaking, more than one vote or even series of votes, more than a court case with appeals.  It requires the cultivation of moral virtue by ourselves and our posterity.  It requires humble compassion subject to valuing the sanctity of human life.  It requires changed hearts.

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.

Raiding the CRISPR

The second installment from The Code, a series of 3 short documentaries on the internet about the origins of genetic medicine, addresses gene editing.  The current approach to this exploits “CRISPR,” or “Clustered Regularly Interspersed Short Palindromic Repeats,” DNA sequences initially discovered as a sort of bacterial immune system but very efficient at editing out undesirable genetic features, such as disease susceptibility mutations in plants or, for that matter, people.

For medicine, the CRISPR approach is one of the latest ways of approaching gene therapy.  For example, sickle cell anemia is caused by a single misplaced “letter” in the 3-billion-letter human genetic code.  (It’s actually 6 billion because there are two copies of each gene, only one of which is “read” to produce what the gene codes for.)  It’s a blood disease, one in which the red blood cells are defective, and to treat it definitively requires replacing an affected person’s blood cells with good, normal ones.  Sickle cell is inherited, and it shows up in kids, and, trust me, if you’ve ever taken care of someone with it, as I did 30-some-odd years ago in my medical training, you’d welcome a world in which people didn’t have to suffer from this.

The problem: where to get the good cells.  Answer: from a suitable donor, or perhaps by taking out some of the sick person’s bone marrow cells, editing the abnormal hemoglobin gene with genetic “scissors,” and infusing them back into the person’s vein, to take up residence in the bone marrow and flourish, normally, replacing the sick cells.  CRISPR is the genetic “scissors.”  The approach is still experimental, but promising.

Technical and safety concern: how can we be sure the scissors don’t go “snicker-snak,” as my old genetics professor used to say, in the wrong places, and change other genes?  They appear to be pretty accurate so far, but just how sure are we?

Bigger ethical concern: might we—should we—edit a human embryo—say, one diagnosed after IVF but before implantation—to nip the genetic disease in the bud, with the prospect of preventing future generations from getting the abnormal gene, and hence the disease, at all?

Hmmm…to cure—perchance to control?—that’s the rub.  Where would be draw the line?  Could we?  Why would we?  Why not try to edit as many diseases out of existence—and as many desirable traits into existence or predominance—as we could, technically?  Well, apart from the small problem that the genetic bases of most diseases are more complex than we yet understand (see last week’s video release from The Code), or the other small problem that editing multiple genes at once is, as of now, still a future prospect for genetic engineering and the field known as “synthetic biology,” is the concern that people making the decisions about what to edit become, as it were, the “actors,” or “conditioners,” to borrow C.S. Lewis’ term from The Abolition of Man, while those acted upon, and their progeny, are subjects—perhaps (unavoidably) unknowingly.  If this is in the context of doctor/patient relationships and specific diseases and informed consent (to the degree that is possible), and the like, that may be fine, but broader use raises concerns that should be obvious.

CRISPR-based gene editing is the most recent approach to gene therapy.  The bulk of the video is about other approaches.  It reviews past history, including efforts not to edit genes, but add good genes to replace missing or bad function of bad genes.  It also reviews the history of people dying from gene therapy research that was, in retrospect, charging ahead perhaps faster than it should have been.  And it mentions recent successes.  Still relatively scattered, but promising, and, if pursued under proper human subject research ethics, generally ethical.  It’s the prospect of heritable editing that gets worrisome.  And we should remember that, even for the ethical stuff, we humans can envision medical advances faster than we can make them reality.

These videos are good viewing for the general public.  Check them out.

New short videos on genetic topics

This week, an email from the Hastings Center promoted The Code, a series of 3 short documentaries on the internet about the origins of genetic medicine.  The three are being released one week at a time.  The first, released this week, briefly (12 minutes) reviews the determination, or sequencing, of the entire human genome, a project conducted in the 1990’s, and completed in 2000, by two labs—one in the government, one private—that initially worked in competition but ended working in collaboration.

It’s a nice review of the key points:

  • A person’s entire genome can be read fast—in a few hours—by an automatic process, at an ever-decreasing cost that now is on the order of $1000.
  • We still are FAR from understanding what the genetic code means for human disease. The number of cases in which there is a reasonably direct link between a single, or a small number, of genetic abnormalities and a gene, in a way that allows us to predict risk of disease or be able to make an enlightened selection of treatment, is still small.
  • With more reading of peoples’ genomes, and more computing power, what amounts to a massive pattern-recognition problem will likely yield more solutions that can be practically exploited to the benefit of human health. Some entities are collecting more peoples’ genomes in a database, for ongoing analysis and, at first, hypothesis generation—that is, “maybe this is a lead that could be acted on for benefit, after the proper follow-on research.”
  • But for now, we should not get carried away—”personalized medicine” is not generally “ready for prime time,” but useful only in a few specific situations, and often most appropriately the subject of new medical research. And one should be careful to get well-informed advice from a medical professional who is expert in genetic medicine, and not over-interpret what a commercial entity might be advising.  (But that, about which this blog has commented in the past, is for another time and another posting.)

This first video does not get into ethical issues—e.g., of justice, privacy, and the like.  But it is a good, quick, engaging overview suitable for the general public.  (BTW, I hate calling non-scientists and non-physicians “lay people,” a term I think best reserved to distinguish most of us from the clergy, and the abuse of which just reinforces the notion of medical scientists as a sort of “priesthood.”)

The second video in the series, due out next week, is on gene editing, and the third, the week after, will address companies that are willing to sequence your genes and tell you, for a price, what they think it might all mean.

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.