Resources regarding ethics of gene editing

Recently, two resources have become available regarding gene editing and the issues raised by it.

First, the National Academies of Science, Engineering, and Medicine have made available an archive of its February 22 webinar about human gene editing.  The home page for the Academies’ human gene-editing initiative is here.  A link to the archived webinar is here.  The slides can also just be viewed here.

Second, Issue 1 of Volume 24 of the journal The New Bioethics is dedicated to human gene editing.  The entire issue, or individual articles from it, are available online for purchase, or for viewing if you have access through an academic institution.  Article titles deal with, for example, differentiating gene editing from mitochondrial transfer, comparing ethical issues with gene editing vs embryo selection, and “selecting versus modifying” to deal with disabilities.

I have not been through these materials in any detail, yet.  The webinar looks a smidge promotional, co-sponsored as it was by the Biotechnology Industry Organization (BIO).  But it also recommends the Academies’ report on the status of human gene editing, and summarizes key recommendations, which include limiting efforts (at least for the present!) to editing “somatic,” or, if you will, “adult” cells to make them into cellular therapies for recognized diseases.  This is well within the existing ethical and regulatory regime governing clinical research and treatment development, as opposed to the deeply problematic prospect of heritable gene editing, or attempts to edit genes for human enhancement, both of which the report and the webinar (at least the slides) counsel that we NOT rush into.  The New Bioethics articles look thoughtful and worth reviewing, which I hope to do (and comment on) in the near future.

DIY CRISPR Kits – Gene Editing for the Rest of Us

One might think with the amazing advance of technology and easy access to nearly infinite data via the Internet that we, as a society, would see a reduction in false claims of benefit for novel medical procedures and untested medications. Sadly, it seems to be just the opposite. I seem to be spending gradually more time with my patients reviewing the results of their internet research for new solutions for their chronic back pain. Their efforts are laudable even though the “hoped for” benefits claimed in their researched solutions are woefully lacking. Unfortunately, often this exercise in reviewing the outside data takes valuable time away from the remainder of the office visit.

Reviewing false or confusing information is one thing but preventing patients from self-experimentation with untested medications or unproven treatments is another. Enter the biohacker and companies offering do-it-yourself (DIY) kits claiming to allow anyone to experiment with CRISPR (a method of genetic editing) for self-administration. Emily Mullin covers biohacking and DIY CRISPR very nicely in her recent article in the December Technology Review. To me, this has the feel of the 1980s when a curious kid with some basic programming knowledge, an inexpensive computer and a modem can access previously forbidden government systems, potentially unleashing havoc on the rest of us (WarGames, anyone?) After all, now that we know the human genetic code, all we need is for someone to just provide the instructions and tools for editing that code, then anyone could tweak their own DNA. Easy peasy lemon squeezy, right?

Recently, the FDA has been busy trying to prevent medical clinics from administering untested stem cell treatments (see Neil Skjoldal’s recent November blog entry on (Stem Cell Clinics & the FDA). Imagine the significant increase in the scope of the regulatory problem if individuals can order a DIY CRISPR kit off the Internet!

While we might chagrin at the naiveté required to believe the street-side pitch of the Old West Carter’s Little Liver Pill salesman, that same pitch via a modern tech savvy YouTube video (complete with separate internet links) somehow offers a new level of legitimacy. The Technology Review article speculated that one of the featured companies was preparing not a vaccine but a treatment for herpes. In less than 8 weeks from the article’s publication, Aaron Traywick, CEO of Ascendance Biomedical, publically self-injected himself with his firm’s untested and non-FDA approved “treatment” for herpes. The linked article by Reegan Von Wildenradt in the popular magazine Men’sHealth offered an excellent counter as to why this type of “science” might be suspect, including quotes from ethicist Arthur L. Caplan at NYU in support of the standard FDA process for screening medical treatments.

We often lament in this blog that technology is advancing so rapidly that we fail to have a fair public hearing and discussion of the ethics involved in a particular biomedical advance. Now it seems our time may be better spent speaking out first about the basic risks of the new technology and doing our best to support the FDA in their massive task of policing the Internet to prevent a DIY CRISPR kit from falling into the wrong hands – ours.

P.S. – I’m accepting names for the title of the future Hollywood blockbuster where the son of Matthew Broderick and Ally Sheedy injects himself with his own DIY CRISPR-modified DNA and …

Citizenship, Surrogacy and the Power of ART

A recent LA Times article by Alene Tchekmedyian explores a complicated case involving birthright citizenship, surrogacy and same-sex marriage. Briefly, a California man, Andrew Banks, married an Israeli man, Elad Dvash, in 2010. At the time, same-sex marriage was not legal in the US leaving Elad unable to acquire a green card for residency (via the marriage) so the couple moved to Canada where Andrew has dual citizenship. While in Canada, the couple conceived twin boys, Aiden and Ethan, using assisted reproduction technology (ART) whereby eggs from an anonymous donor were fertilized by sperm from Elad and Andrew and then implanted within the womb of a female surrogate and carried to term. When the US Supreme Court struck down the federal law that denied benefits to legally married gay couples in 2013, Elad applied for and was granted his greed card. The present controversy occurred when Andrew and Elad applied for US passports for the twins. US State Department officials required detailed explanation of the boys’ conception, eventually requiring DNA tests which confirmed Aiden to be the biological son of Andrew and Ethan to be the biological son of Elad. Aiden was granted a US passport while Ethan was denied. The family has since traveled to the US (Elad with his green card and Ethan with his Canadian passport and temporary 6 month visa) where they are now suing the State Department for Ethan’s US birthright citizenship. They are arguing that the current applicable statute places them wrongly in the category of children born out of wedlock rather than recognizing their marriage, thus discriminating against them as a binational LGBTQ couple.

Birthright citizenship is a complicated legal arena and I am no lawyer. The US is even more complicated because we allow birthright citizenship to be conferred jus soli (right of the soil) in addition to jus sanguinis (right of blood). The twins were not born in the US so establishing “bloodline” is needed. The law specifies conditions where one parent is a US citizen and one is not a US citizen, and there is further differentiation depending on whether the children of the US citizen were born in or out of wedlock. They also vary depending on whether the US citizen is male or female, with the law more lenient (easier to acquire citizenship) for the child of a woman than of a man.

While the legal challenge here will almost certainly involve potential issues of discrimination of LGBTQ binational couples, the problem is really with the current legal definitions of parent as it relates to surrogacy in general. The State Department actually has a website dedicated answering questions related to foreign surrogacy and citizenship. The real issue is that the State Department relies upon genetic proof of parentage for foreign surrogacy births. In the present case, the surrogacy occurred outside the US, Elad is the genetic father of Ethan and Elad is not a US citizen; therefore Ethan is not a US citizen. While I’m deep in the weeds here, technically, Aiden and Ethan are not fraternal twins in the usual sense but rather half siblings (and this assumes that the donor eggs are from the same woman; otherwise the boys would be unrelated despite sharing the same pregnant womb through the magic of ART). Had Ethan been physically born via surrogacy in the US, he would have acquired his citizenship via jus soli (see US map for surrogacy friendly states near you).

This problem is just as confounding for heterosexual couples using foreign surrogates, and the problem is global. A more detailed technical legal discussion may be found here. A heterosexual couple using donor eggs and donor sperm and using a foreign third party surrogate would have exactly the same problem establishing US citizenship for “their” child. A similar problem would exist for an adopted embryo gestated in a foreign country by a foreign surrogate. If either the egg or the sperm of the US citizen is used for the surrogate birth, the child would be granted birthright citizenship.

The main difference for homosexual couples is that only one spouse can presently be the biological parent. I say “presently” because with ART it is theoretically possible (and may become actually possible in the future) to convert a human somatic cell into either a male sperm or a female egg. At that point, both spouses within a same-sex marriage could be the biological parents of their child. The present legal issue is not the result of a cultural prejudice against anyone’s sexuality but with the biological prejudice of sex itself. ART has the potential ability to blur the categories of sex as culture is now blurring the categories of gender. Should we consider this a good thing?

Given the present technological limits of ART, the simple issue of US citizenship could be resolved in all these cases if the US citizen parent simply adopted the child. Elad correctly points out that while adoption of Ethan by Andrew would grant Ethan US citizenship, it would not grant Ethan birthright citizenship, a necessary requirement for Ethan to someday run for US president. ART may be forcing us to look at changing our definition of parent but should it change our definition of biology? Ethan is the biological son of Elad. He is able to be the legally adopted son of Andrew and enjoy the benefits of US citizenship as currently does his half brother Aiden. He is not able to become the biological son of Andrew and enjoy the additional benefit of birthright citizenship via jus sanguinis.

Should we change the definition of birthright citizenship because ART is changing our definition of parent?

Update on clinical studies of human gene editing

The January 22 edition of The Wall Street Journal carried an article the essential message of which was, “the Chinese are ahead of us in gene editing.”  Specifically, more human clinical trials are active in China than in the US using gene editing in some form to treat people with specific diseases.  Some of these trials use the “hot, new” CRISPR-Cas9 approach to gene editing.  Almost all of the active ones are in China, although one has recently been approved by regulators to begin in the U.S., at the University of Pennsylvania.  That one appears not yet to be recruiting patients.  In most of these “CRISPR” trials, cells are removed from a patient’s body, altered in the laboratory to make them more likely to treat the disease in question (in this case read: attack a cancer), and injected back into the patient.  They are thus variations on a 30-or-so-year-old approach of using cells that have been modified in some way to treat cancer.

The difference here is that the cells have their genes edited, and that raises potential safety risks, such as, what happens if the wrong genes are “edited,” and the altered cells go nuts and do something undesirable?  Because of this, human trials of gene editing in the U.S. are closely regulated, including having to pass scientific and safety review by the “RAC” (that’s for “Recombinant DNA Advisory Committee,” in case the acronym made any of you think of the Spanish Inquisition…then again, I have had researchers who have had to go through it suggest that the analogy is apt…).

The RAC was established back in the late 1970’s when drugs started being made with recombinant DNA, and trials of gene therapy using genes inserted into viruses were conducted.  A famous case of that work going awry raised concerns about oversight, and slowed things down substantially.  And as it stands now, the U.S. regulatory process for this work is cumbersome.  In China, not so much—a local ethics review board looks at a proposal, and off they go.  The WSJ makes it sound like informed consent for the Chinese studies may be a bit thin, too.  U.S. experts are quoted as saying not that we need less regulation, but that they (the Chinese) need more, to bring them back to our speed.

Perhaps so.  My point here is that this work is going on.  Examples like those cited here seem to me to fall under the existing regulatory regime for human trials, and don’t pose the same sort of ethical issues as the potential for inherited gene edits—that is, editing embryos and babies.  That’s a different kettle of fish.

One Chinese CRISPR trial appears not to alter cells outside the body, but actually try to administer the genetic material to make an edit to a cervical cancer-causing gene.  That poses similar safety concerns to other gene therapy approaches, including some with “zinc finger” editing technology, like a currently-active U.S. study to treat hemophilia, a disorder in which someone has a genetic flaw that makes them susceptible to excessive bleeding and the goal is to repair the offending gene.

In considering this work, I think it’s important to distinguish use of the gene-editing approach for incremental steps to treat human disease, like the cell therapy approaches, or true “gene therapy” approaches in which a “corrected” gene is administered to a patient, from the more problematic possibility of editing individuals in ways that can be inherited.  The latter is what worries me.  I wrote about this last November 9 and November 16.   And yes, the current Chinese work should be more closely regulated.  Doubt we have any control over that.

An FDA blog post from a year ago (by the former FDA Commissioner) provides a useful, brief discussion of the FDA’s approach to regulating various applications of genetic editing.  Worth reading.

Is Your Polygenic Risk Score a Good Thing?

Back in October, Jon Holmlund wrote a blog entry regarding the popular company 23andMe and their collection of your health-related information along with your genetic material. I missed the significance of that relationship at the time. It took a recent article in Technology Review by my favorite technology writer Antonio Regalado to raise my ethical antennae. In his article, he explains the nexus of big data mining of genetic data and health information (such as is collected by 23andMe) and its future potential use to select embryos for IVF, selecting not only against polygenic diseases such as type 1 diabetes but potentially for non-diseases such as height, weight or even IQ.

Yikes.

Pre-implantation genetic diagnosis (PGD) already is used to select for particular embryos for IVF implantation that do not have genetic patterns such as cystic fibrosis or Down syndrome. Diseases that result from multiple genes (polygenic disorders) presently defy current PGD methods used to detect future diseases. Using Big Data analysis of health information compared against linked genetic data, scientists are getting better at accurate polygenic risk scores, statistical models which may more accurately ‘guess’ at an embryo’s future risk for not only juvenile diabetes but also later-in-life diseases (such as heart disease, ALS or glaucoma) or other less threatening inheritable traits (such as eye color, height or IQ) that result from multiple genes (and perhaps even environmental factors). There is confidence (hubris?) that with enough data and enough computing power, we can indeed accurately predict an embryo’s future health status and all of his or her inheritable traits. Combine that further with all of the marketing data available from Madison Avenue, and we can predict what type and color of car that embryo will buy when he or she is 35.

Ok, maybe not the color…

Seriously, companies such as Genomic Prediction would like to see IVF clinics eventually use their expanded statistical models to assist in PGD, using a proprietary technique they are calling Expanded Pre-implantation Genomic Testing (EPGT). Consider the following two quotes from Regalado’s article:

I remind my partners, “You know, if my parents had this test, I wouldn’t be here,” says [founding Genomic Prediction partner and type 1 diabetic Nathan] Treff, a prize-winning expert on diagnostic technology who is the author of more than 90 scientific papers.

For adults, risk scores [such as calculated by 23andMe] are little more than a novelty or a source of health advice they can ignore. But if the same information is generated about an embryo, it could lead to existential consequences: who will be born, and who stays in a laboratory freezer.

Regalado’s last comment is dead-on – literally. Who will be born and who stays in the freezer is another way of saying “who lives and who dies”.

Technologies such as EPGT are poised to take us further down the bioethical slope of choosing which of our children we want to live and which we choose to die. For the sake of driving this point home, let’s assume that the technology becomes essentially 100% accurate with regard to polygenic risk scoring and we can indeed determine which embryo will have any disease or trait. Since we already permit the use of single gene PGD to prevent certain genetic outcomes, should there be any limit to polygenic PGD? For instance:

(A) Should this technology be used to select against immediate life threatening illnesses only or also against immediate mentally or physically permanently crippling diseases that don’t cause death directly?

(B) Should this technology be used to select against later-in-life diseases that are life threatening at the time or also against mentally or physically crippling diseases that don’t cause death directly? (Would it make a difference if the disease occurred as a child, teenager or adult?)

(C) Should this technology be used to select against non-disease inheritable traits that society finds disadvantageous (use your imagination here)?

(D) Should this technology be used to select for inheritable traits that society finds advantageous (a slightly different question)?

Depending upon your worldview, until recently, answering Questions A through D used to be the purview of God or the random result of chance. Are we ready (and capable) to assume that responsibility? Make your decision as to where you would draw the line then review this short list of famous scientists and see how many on that short list your criteria would permit to be born.

Are you happy with that result? Would you call it good?

It would be nice to get this right since it now appears to be our call to make…

More about gene therapy and human gene editing

To my post of last week, add the case of a 44 year-old man who has received gene therapy for an inherited metabolic disease called Hunter’s syndrome. This is another example of a form of gene editing as true therapy.  That is, an existing individual is given a construct intended to edit his genes to introduce a gene that makes an enzyme that is lacking in the disease, and that causes terrible problems.  In this case, as part of a clinical trial, the construct, using a so-called “zinc finger” technique, is intended to introduce the gene into only about 1% of the patient’s liver cells.   If successful, the damage already done by the disease won’t be affected, but it’s progress may be arrested, with the potential to avoid having to have repeated, costly treatment with the missing enzyme protein itself.

Cool idea–and well within the current regulatory ethical regime.  The edit would not be inherited, and unborn humans don’t have to be sacrificed to develop the technique.  The adult patients are capable of giving informed consent.  Trials in children would come later, controlled by accepted ethical experimentation on children in clinical trials.

In a separate note, on a separate topic, Nature Biotechnology is editorializing that inherited gene editing is way behind mitochondrial replacement therapy (MRT), the “3-parent baby” approach to treating genetic problems, and will likely have limited use in the future.  Why?  Because it is likely that preimplantation genetic diagnosis (PGD) after in vitro fertilization (IVF) will be preferred to identify and give birth to babies unaffected by serious genetic disorders.  The journal editors argue that gene editing would be preferred only in those few cases where PGD cannot avoid passing on a disease–for example, in cases where it is known that all embryos from a fertilizing couple would be affected. Otherwise, the gene editing would not be worth the trouble.

MRT, on the other hand, has been studied more and is closer to being used to treat unborn humans who have diseases that MRT could treat.  Thing is, those diseases are also rare, on the order of 1000 cases per year in the US, and technically, gene editing would probably not be too useful for those.

There is a lot of talk about using a mix of gene editing and PGD to eliminate certain genetic disease from the human prospect.  I recently wrote about the Chinese government working on this.  To achieve the goal absolutely, every born human would have to be a product of IVF.

And the risk of some of the disorders is low enough that the absolute risk in any one “natural” pregnancy would be low.  So why go to the trouble of trying to eliminate the risks utterly?  (I think that’s a rhetorical question.)

The title of the editorial in question is “Humans 2.0.”  Indeed.

There’s gene therapy and there’s gene therapy

I’ve seen a number of different things described in the general press as “gene therapy.” But they are indeed different.  It’s important to be specific.

For one, there’s the situation where a set of mature human cells are obtained from the person to be treated and genetically altered outside the body to make them into a potentially useful treatment, then re-administered (by vein) to the patient.  Such is the case with so-called “CAR-T” therapy, which is well handled by current regulatory structures.  Main ethical issues: common human subject research concerns, regulation of the quality of the cells, and whether the treatment, which can be dramatically effective, is worth the high price.

Then there are situations where a diseased tissue is altered to make it normal, like the recent report of how a mutation in the skin of a boy was altered, and the repaired skin grafted back on, to spread over most of his body and replace the defective skin.  Again, way cool, well dealt with by current ethical and regulatory structures.

Or, similarly, Spark Therapeutics’ LUXTERNA, which is a gene injected into the eye to repair a defective gene causing blindness, literally restoring some sight, recently recommended for approval by an advisory committee to FDA.   Truly a gene made into a therapy.

Where the ethical issues get thorny is when one speaks of possibly editing a gene in a person–likely an unborn person very early in development; i.e., and embryo–in a way that can be inherited over generations.  I and others have discussed this recently on this blog.  See for example my post of last month (October 5).  Adherents say that there are serious diseases demanding cures, and that those who would counsel caution are obstructionists who fret too much about enhanced Olympic athletes.  (Example here, but subscription required.)  But the ethical issues are several: How safe and reliable will the technique be, and how much testing should be required before trying to birth “edited” babies?  How many embryos will have to be destroyed to perfect the approach?  How can we know whether there will be unforeseen long-term effects, after several generations?  How much should we care about that?  How will discrimination be avoided?  What are the implications for control of human reproduction–no more babies from sex? And who will decide and control that?

And–where, short of the Olympics, will it all end?  Should we try to edit genes that are known to increase cancer risk, to eliminate them from the human race?

The Hastings Center recently convened journalists to discuss some of the ethical issues with gene editing.  But even then, they are more concerned about whether there is a parental duty to “edit” the next generation.  Precautionary deliberations appeared to be limited to environmental concerns from the use of “gene drive” to spread genetic modifications rapidly through entire plant or animal species.  (Fair enough, but I’d extend the precautions to humans, where “gene drive” is not an issue.)  And, helpfully, the Hastings symposium did ask, will general press coverage necessarily be biased because reporters’ sources are the very scientists who tend to be enthusiasts?  In any event, the Center should not only do more public education events, but should make much more of the detailed content from such symposia available to the public for free, online, much as the Presidential bioethics commissions do.  As it is, we are left with their brief press releases, usually.  Thin gruel, IMHO.

Two cases of genetics ethics issues

There is an ongoing NIH-sponsored database effort called the Genotype-Tissue Expression (GTEx) project the goal of which is to collect data on genetics–not just DNA gene sequences, but also gene activity, looking at “expression,” which is reflected in the RNA that is transcribed from genes–in a wide range of human tissues.  The tissues are obtained from deceased voluntary organ donors.  The ethical issues are not unique, but representative of the challenges that our bioinformatics age present.  Organ donors’ consent to donate a broader range of tissues is not documented in advance, nor is it assumed, but, like organs, the tissue specimens must be collected soon after death to prevent decay from compromising their usefulness.  That means that consent for the tissue donation has to be obtained from grieving survivors, immediately after a loved one’s death that is often unexpected and shocking, and duress is unavoidable.  The donation request comes out of the blue and donors’ survivors often don’t recall what they agreed to.  The genetic expression information is usually not provided to the donors’ families, a situation that seems to be less tenable with the passage of time and the increase in genetic research.  And there is the persistent issue of minority representation (the information could be valuable to help improve the health of minorities on a population basis), and the resurgent issue of whether the donors’ survivors ought to benefit from any financial gains that might come from the research.

Read a brief story about it here.

A story about the company 23andme includes an observation that its 2 million customers constitutes “the largest genetic study the world has ever known.”  You can get a kit in the mail, send some saliva, and get back information about genes that might be associated with a number of traits, many trivial, like earwax consistency.  With only limited FDA-approved exceptions for rare, clearly understood genetic diseases, you can’t get much health-related information from the company.  FDA’s concern about such information being misleading, with potentially harmful consequences, almost sunk the company in 2013.  But the data is still valuable to researchers, and to drug companies trying to use it to discover new drugs.  So 23andme asks its customers for health information online, and drug companies can pay them, not for the actual data, which 23andme keeps to itself, but for results of analyses 23andme does on the data. I don’t know what sort of consent process is applied, but I’m guessing that an IRB was not involved.  By the way, 23andme’s is now adding its own attempts to become a drug company in its own right, using drug development ideas that might spring from the genetic information it has for its customers.

Human gene editing marches on

Nature has recently carried two new reports of human gene editing.  In one, embryos donated from an IVF clinic had a gene critical to very early development altered, to study what happens when you do that, and try to understand early human development more than we now do.  In the other, scientists studied editing of an abnormal recessive gene, specifically the one causing a type of blood disorder called thalassemia, by using cloning to create a new embryonic version of an adult with the disease.  (This made it technically easier to start in the laboratory with an embryo that has the disease, because it is genetically recessive, meaning that both copies of the gene are abnormal.)  This follows earlier publication of similar work to edit dominant mutation-causing genes, in which the embryos arose because of new IVF, done in the lab, by the scientists, using donated eggs fertilized with sperm from a male donor who carried the abnormal gene.

In all three cases, the main biologic approach, and the main ethical issues, are the same.  The main differences were which genes were being edited, and how the embryos were obtained.

This prompted Nature to run an editorial to say that it is “time to take stock” of the ethics of this research.  Read the editorial here.  The key points:  This is important work that should be undertaken thoughtfully.  Accordingly, donors of any embryos or cells should be fully informed of the planned research.  Only as many embryos should be created as are necessary to do the research.  Work on embryos should be preceded by work on pluripotent, or “reprogrammed,” stem cells, and if questions can be fully answered by work with those cells, then it may not be necessary to repeat the studies on whole, intact human embryos, and if that is not necessary, perhaps it should not be done.  Finally, everything should be peer reviewed.

I agree that editing work in non-totipotent cells should be at all times favored over work on intact embryos, but if one holds that an embryo is a human being that should have the benefits of protections afforded human research subjects, then Nature’s ethical principles are rather thin, little more than an extension of animal use provisions for studies in which early humans are the raw materials for the development of new medical treatments.

Included was a link to the journal’s policies for considering for publication any reports of experimentation on living organisms.  Those policies include this paragraph regarding modification of the human germline:

“In deciding whether to publish papers describing modifications of the human germline, we will be guided by safety considerations, compliance with applicable regulations, as well as the status of the societal debate on the implications of such modifications for future generations. We have established an editorial monitoring group to oversee the consideration of these concerns. (The monitoring group includes the Editor-in-Chief of Nature publications, the Nature Editorial Director, the Head of Editorial Policy, Nature Journals and the Executive Editor, Life Sciences.) This group will also seek advice from regulatory experts to ensure that the study was conducted according to the relevant local and national regulations. In this evaluation, we will be strongly guided by the guidance issued by the International Society for Stem Cell Research: Guidelines for the Conduct of Human Embryonic Stem Cell Research (http://www.isscr.org/home/publications/guide-clintrans ).”

I want to be reassured by their invoking “the status of the societal debate on the implications of such modifications for future generations,” but the weaknesses are first, that debate is just not very robust, and “society” is generally in a position of accepting, more or less uncritically, the ongoing technical push; and second, that the ones considering the status of the issues will more or less naturally view them through the relatively narrow researchers’ scope I describe above.  To be sure, the goals at a minimum appear to be to ensure that the research is not reckless, that it meets technical standards, that obtaining and creation of embryos is relatively limited in scope, and that nobody, for now, is trying to bring gene-edited embryos to human pregnancy, much less birth.  At least, not until the scientists and regulators tell us they think it’s time to try that.

Is Obfuscation Ever Helpful in Science or Ethics?

Obfuscation and science would seem to be polar opposites. The scientific method hinges upon correctly identifying what one starts with, making a single known alteration in that starting point, and then accurately determining what one ends up with. Scientific knowledge results from this process. Accidental obfuscation in that three-step process necessarily limits the knowledge that could potentially be gleaned from the method. Peer review normally identifies and corrects any obfuscation. That is its job. Such peer review can be ruthless in the case of intentional obfuscation. It should be. There is never any place for intentionally misrepresenting the starting point, the methods or the results.

Until now?

In an excellent article in Technology Review, Antonio Regalado describes the current status of research where human embryonic stem cells “can be coaxed to self-assemble into structures resembling human embryos.” The gist of the article is that the scientists involved are excited and amazed by the stem cells’ ability to self-organize into structures that closely resemble many features of the human embryo. Perhaps more importantly, per Regalado:

“…research on real human embryos is dogged by abortion politics, restricted by funding laws, and limited to supplies from IVF clinics. Now, by growing embryoids instead, scientists see a way around such limits. They are already unleashing the full suite of modern laboratory tools—gene editing, optogenetics, high-speed microscopes—in ways that let them repeat an experiment hundreds of times or, with genetic wizardry, ask a thousand questions at once.”

This blog has reported on Synthetic Human Entities with Embryo-like Features (SHEEFs) before (see HERE and HERE for starters). The problem from a bioethical standpoint is this: is what we are experimenting upon human, and thus deserving protections as to the type of research permitted that we presently give to other human embryos? Answering that ethical question honestly and openly seems to be a necessary starting point.

Enter the obfuscation. Consider just the following three comments from some of the researchers in the article:

When the team published its findings in early August, they went mostly unnoticed. That is perhaps because the scientists carefully picked their words, straining to avoid comparisons to embryos. [One researcher] even took to using the term ‘asymmetric cyst’ to describe the [amniotic cavity-like structure] that had so surprised the team. “We have to be careful using the term synthetic human embryo, because some people are not happy about it,” says [University of Michigan professor and lab director Jianping] Fu.

“I think that they should design experiments to focus on specific questions, and not model everything,” says Insoo Hyun, professor and ethicist at Case Western University. “My proposal is, just don’t make the whole thing. One team can make the engine, another the wheels. The less ambiguous morally the thing is that you are making, the more likely you can do your research unimpeded.”

“When Shao presented the group’s work this year, he added to his slides an ethics statement outlined in a bright yellow box, saying the embryoids ‘do not have human organismal form or potential.’”

This last comment seems to contradict the very emphasis of the linked article. As Regalado nicely points out: “The whole point of the structures is the surprising, self-directed, even organismal way they develop.”

Honestly, at this point, most are struggling to understand whether or not the altered stem cells have human organismal form or potential. I suspect everyone thinks they must or else researchers would not be so excited to continue this research. The value of the research increases the closer a SHEEF gets to being human. If our techniques improve, at what point does a SHEEF have the right to develop as any other normal embryo? Said differently, given their potential, and particularly as our techniques improve, is it right to create a SHEEF to be just the engine or the wheel?

Having scientists carefully picking their words and straining to avoid comparisons is not what scientists should ever be doing. Doing so obfuscates both science and ethics. Does anyone really think that is a good thing?