Human organ harvest

By Jon Holmlund

The ethical practice of human organ transplantation entails consent from a donor to donate an organ while still living (e.g., one of the donor’s two kidneys), or after dying (e.g., the heart).  In the latter case, it is still generally accepted that the donor must be dead first, and that the harvesting of the vital organ to be transplanted not be the cause of the donor’s death.  This is referred to as the “dead donor rule,” the interpretation of which is open to some controversy (about which more in a future post).  But it is still generally followed.

Periodically, one reads of suggestions or practice that violates this.  In 2006, the bioethics observer Wesley Smith posted comments about proposals in the medical ethics literature to the effect that some had said that patients permanently comatose but not dead, in what is known as a “permanent vegetative state” (PVS), could ethically not only have their organs harvested for transplant, but be human subjects for experimentation involving the transplant of animal organs into them, to try to learn how to improve that practice, called “xenotransplantation.”  Presumably, these “donors” would have previously “consented” to have their organs harvested—essentially, to be killed—if they became persistently comatose.  The validity of such “consent” is of course questionable, and the prospect of the practice should be seen as abominable.  An argument in favor seems to rely on the notion that it’s too risky to transplant animal organs into humans who have full brain function and seem to be more clearly alive than PVS patients (suggesting they be seen as dead), or that there is some envisioned state where a PVS patient could potentially benefit from the animal organ and give consent in advance.  The former is disturbing, and the latter implausible.  A link to one proposal that appears to be in favor is here, and to arguments raising concerns, here and here.

(More to follow in a future post on comments about xenotransplantation from the recent Hastings Center conference on the 50th anniversary of the development of brain death criteria.)

More recently (again with the blogger’s “HT” to Smith), not only is organ harvesting after euthanasia apparently performed, on occasion, in countries that permit euthanasia, but a transplantation medical journal has carried an article arguing for “organ donation euthanasia,” wherein someone who had previously requested euthanasia could also “request” organ donation while still alive—essentially, authorizing the removal of the heart as the means of active euthanasia.  Now, what is first in view is harvesting a kidney, which would not cause death, but if someone is in a state where euthanasia is perceived as a preferred option, why would someone want to undergo invasive surgery first? 

If euthanasia is accepted, then this troubling stance on organ donation will be difficult to resist.

At least the above pay lip service to “advance, informed consent.”  This week, an article in the Wall Street Journal calls attention to the covert but well-attested practice in China to accommodate demand for organ transplantation without the encumbrance of a waiting list, by harvesting organs from prisoners of conscience, such as political dissidents, who are given a mortal but not immediately fatal wound, then have their organs removed before they are dead—satisfying the “need” for a donated organ while finishing the prisoner off.  Because of this practice, several countries have prohibited their citizens to travel to China for “transplant tourism,” just going there to get their transplant.  What the Chinese seem clearly to be doing should not be supported, by anyone.

Gene-editing public discussions: looking ahead

By Jon Holmlund

Passing along word that the National Academies of Medicine and Science are planning an international commission on human gene editing, the editorial board of the New York Times has issued a welcome call to make the public discussion of the issues as broad as possible.  Read the whole thing, but this key graph is particularly important (emphases mine):

“As gene-editing technology advances toward the clinic, scientists will need to do more than listen to the concerns of bioethicists, legal scholars and social scientists. They will have to let these other voices help set priorities — decide what questions and issues need to be resolved — before theory becomes practice. That may mean allowing questions over societal risks and benefits to trump ones about scientific feasibility.”

See the 29 March 2018 post on this blog regarding two calls—the Times linked to one, and quoted from the author of the other—for broader discourse.  This discourse is urgently needed, but must go beyond risk-benefit discussions to the broader meaning of, and issues raised by, heritable human gene editing in particular.  (Somatic human gene editing, to treat a known disease in an existing individual in a way that cannot be passed on to the next generation, is less troublesome ethically, except insofar as it enables the heritable version of gene editing.)

The challenges to effective public deliberation of heritable human gene editing are formidable: getting truly wide participation; getting the scientists to inform and educate non-scientists without trying to lead them to a set of preferred conclusions; engaging the developing, as well as the developed, world; obtaining “religious input” that is more than token; and sustaining the conversation as long as necessary to hold attention in our short-attention world.

It seems that to execute on that will take a pretty large group of dedicated people engaged in a focused, full-time effort to make it happen.  Existing science and ethics groups, like the National Academies, may be the default nominees, but it also seems like a broader group of facilitating entities is needed.  The “global observatory” mentioned by the Times editorial would, as proposed, be established by an “international network of scholars and organizations…dedicated to gathering information from dispersed sources, bringing to the fore perspectives that are often overlooked, and promoting exchange across disciplinary and cultural divides.”

Hear, hear.  One hopes that this happens—and that individuals can find a way to help make it happen.  Spread the word—people should be encouraged to set aside time, energy, and mental space to consider this revolution for the human race.

Revisiting the definition of death

By Jon Holmlund

The Hastings Center shows Christmas Day 2018 as the date of publication of its report, “Defining Death: Organ Transplantation and the Fifty-Year Legacy of the Harvard Report on Brain Death,” arising from a 2018 conference of the same title at Harvard Medical School.  The full contents are freely available at the link above.  The occasion for the conference was the 50th anniversary of the 1968 report that defined brain death as one way to determine, alongside the more traditional use of cessation of the heartbeat and breathing, whether a person had died.  Report contributor Robert Truog puts it this way: brain death can be thought of as “permanent apneic [absence of breathing] unconsciousness.”

Subsequent to the 1968 report, the Uniform Determination of Death Act, formulated in 1981, stated that a human has died if there is either irreversible cessation of circulatory and respiratory functions, or irreversible cessation of all functions of the entire brain, including the brain stem.

Initially, according to one retrospective, the 1968 report was motivated mostly by a desire to determine when intensive medical care of a comatose person could be stopped and still be consistent with the aims of medicine, and, indeed, avoid a murder charge.  Nowadays, we often associate the use of the brain death criteria with the decision to harvest the decedent’s organs for transplantation, but that is said to have been a secondary concern in 1968, probably reflecting the state of organ transplantation at the time, as opposed to after the ensuing 50 years of development.

One reviewer in the report worries that concern about the use of brain death criteria has become “too philosophical,” as it were; the 1968 conferees were not trying to define death analytically, but prudentially, to guide the practice of medicine.  So contemporary critics shouldn’t be too harsh in their hindsight.  However, Robert Veatch counters that to ask whether the brain has irreversibly stopped functioning is not the same as to ask whether we should treat individuals with dead brains and beating hearts as dead humans.  He further comments that, since the brain also acts in some sense as a gland, secreting hormones, the current ways of determining brain death may not take that into account.  He identifies three broad approaches to defining death:  circulatory/somatic, whole-brain, and higher brain.  He lists at least six current significant disputes about brain death: whether patients and families should have the right to refuse treatment; which criteria to use to determine brain death; whether those criteria actually assess all the functions of the brain; whether doctors apply the criteria accurately and consistently, without excessive error; whether brain death as currently determined is truly irreversible; and whether whole-brain criteria should be favored over criteria around blood circulation or criteria that focus, more narrowly than whole-brain death, on higher-brain functions including loss of consciousness and associated loss of integrated function of body and mind.

Sections of the new report include essays reviewing and offering a contemporary critique of the concept of brain death, a discussion of whether “donation after [brief] circulatory determination of death” (DCDD) is an acceptable approach to obtaining vital organs for transplantation, whether the “dead donor rule”—briefly, the idea that one’s organs should not be removed from one’s body for transplantation into another person until that one (the proposed donor) has died—should be followed, using brain death to inform law and public policy, the future of xenotransplantation (specifically, transplanting animal organs into humans, known as xenotransplantation), and reflections on the case of Jahi McMath, the girl who was declared brain dead in 2013 after complications of a tonsillectomy, but whose body was subsequently kept alive at her parent’s behest until bodily functions finally failed to the point where she was declared dead to the agreement of all concerned in mid-2018.

There is much to consider here—particularly alongside the 2008 report, “Controversies in the Determination of Death” by the then-President’s Council on Bioethics.  Candor requires that your correspondent has in the past argued on this blog for the dead donor rule and has expressed concern about potential overzealous use of the “DCDD” approach by transplant surgeons in a hurry to procure organs for transplant to a needy, waiting recipient.  But a revisiting of the matter is in order, and a matter for future posts.  In the meantime, the cited reports are readily available on the internet for review by all interested parties.

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.

A Huge Step Closer to Fully-Artificial Human Reproduction

by Jon Holmlund

Last week, the Washington Post reported that scientists in Japan have created human egg cells—oocytes—in the laboratory from reprogrammed blood “adult” stem cells. This work has been published in the journal Science (open access to the abstract only; subscription or purchase required for the full scientific article; WaPo has a limit on free articles before subscribing).

This is large. And, I think, troubling.

The skinny: research on human embryonic stem cells is, in my view and many others, ethically unacceptable because human embryos have to be destroyed to obtain them, and because the earliest cells are capable of maturing into full human beings (babies) under the right circumstances, meaning that said earliest cells are tiny human beings. But about 10 years ago, “reprogrammed” stem cells were produced in the laboratory by taking adult cells and treating them so that they take on a primitive state. In that state, they aren’t capable of forming an entire human but they can be induced to become almost any cell in the body. This gives them tremendous potential for research and possibly treating human disease—much of that potential essentially ethical if proper research ethics are observed.

However, commentators wiser and more knowledgeable than I have said in the past that, in principle, these “reprogrammed” cells, also called induced pluripotent stem cells, could be made into human germ cells—sperm or eggs. To my knowledge, that had not been done before now. Now it’s closer to being reality. The Japanese scientists created early egg cells, too immature to be fertilized, but that is the next project. Add to that the possibility of “reprogrammed” sperm.

This raises the possibility of in vitro fertilization of one of these “reprogrammed” eggs to create a full embryo which, as in current IVF, could be implanted into a woman to impregnate her and, ultimately, bring a baby to birth. Treatment for infertility? Sure. Need to harvest eggs from a would-be mother or an egg donor? Not necessary, in principle. Would the baby turn out OK? Not known—after all, these are not “natural” egg cells we’re talking about.

The development raises at least the issues previously raised by human cloning. Heretofore, cloning would proceed usually by taking an adult cell’s nucleus, inserting it into an egg cell that had its nucleus removed, and treating the resulting new “egg” to develop, not an easy task and one on which progress has been limited. Now, the “artificial egg” would be fertilized to create a new human—at least one step less removed from natural reproduction, on its face anyway.

If fully implemented, it would complete the move to babies-without-sex. Wesley Smith sees “mass human cloning.” That’s only the half of it. The WaPo article also pointed out these possibilities: babies from cheek smears; babies created from a person’s cells without that person’s awareness or consent; more routine screening for genetic disease; IVF becoming the norm. Add to that the notion that full-on IVF could some day be possible, with cells maintained in the lab as raw materials to be “reprogrammed” to sperm and eggs, eliminating the need for identified moms and dads.

This is all a ways off yet, but that’s how all these humanity-altering changes start. Smith is right, that for this and other technologies (heritable human gene editing, animal-human hybrids, totally artificial life forms like “SHEEFs”), a massive public discussion is needed. Where I think he errs is in looking to government to do it. This will have to be grass roots. And making that happen will be a new career for somebody, and a tough way to make a living. But the train has left the station and is gaining momentum.

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).