More on Gene Editing

The recently-public discussion of gene editing has been going on for over a month now.  I have been meaning to try to catch up with some of it.  Tuesday’s post by Courtney Thiele got there first.  This post will attempt to amplify a bit on what Courtney wrote.

As Courtney pointed out, the technology involves making selective genetic changes of interest, including, but clearly not limited to, replacing or “repairing” disease-causing mutations such as those that cause sickle-cell anemia, Huntington’s disease, or thalassemia (a set of diseases in which hemoglobin is abnormal and its oxygen-carrying capacity impaired).  These are but examples.  There is more than one editing tool: so-called zinc-finger nucleases, or, in the more recent reports, “clustered regularly interspaced short palindromic repeats” (CRISPR)-Cas9. 

The approach is powerful for studying genes in cell-based systems or animals, and could also be useful for designing cellular therapies using adult stem cells or induced pleuripotent stem cells, which do not involve the destruction of embryos and so avoid some of the ethical concerns with embryonic stem cell research and development.  Again as Courtney pointed out, the situation gets much more troublesome if editing of human embryos or human germline changes, inheritable essentially permanently down generations, are pursued.  Moral status of human embryos and the concerns related to human enhancement, and then some, come into play.

Recent rumor had it that a scientific paper was about to be published in which genes were edited in human embryos.  The New York Times article Courney linked to reported that the work had indeed appeared in print.  The paper was in the Chinese journal Protein & Cell, from a group of Chinese scientists, after reportedly having been rejected on ethical grounds by Science and Nature.  A Nature news article addresses whether it is ethical even to publish such work; another Nature news article describes the results, and the surrounding debate, further.  (Both Nature news articles are accessible without subscription.)

The scientists doing the work believed it was ethical (although apparently the editors of Protein & Cell do not necessarily agree) because the “defect” in the 86 embryos they injected with CRISPR-Cas9 was that they were from eggs that had been fertilized by two sperm each, so they could not be brought to live birth.  Of those, only 71 survived 48 hours (to 8-cell stage), 54 were genetically tested, only 28 were successfully spliced, and only 4 had the desired genetic repair.  They also found a “surprising” number of “off-target” (read: unintended) genetic changes on other parts of the genome.

This result fits with concerns raised in the run-up to the publication (whose reflections, in turn, substantially agree with Courtney’s).  A March 27 commentary by Gregory Kaebnick, editor of the Hastings Center Report, is particularly helpful.  Focusing on the risks of the procedure, Kaebnick identified two problems—“making the genetic changes correctly (getting them into cells and then the genome in the right location) and making the correct genetic changes (actually achieving the results without accidentally creating new problems).”  The Chinese scientists ran into both problems.

Similar worries prompted two separate groups to call for a professional, self-imposed moratorium on any attempts at clinical use of these gene editing groups.  One group, led by Nobel laureates David Baltimore and Paul Berg (among other serious heavy-hitters), cited especially the risks of making “incorrect” genetic changes, the consequences of which might not become apparent for generations.  They also cited the “slippery slope” (their term, not mine) from therapeutic uses to “uses with less compelling or even troubling implications.”  This should sound familiar to anyone who has followed human enhancement discussions.  They recommended a process similar to the 1975 Asilomar conference addressing recombinant DNA technology, and said they had an initial meeting in Napa, California in January, but a much larger discussion involving society at large is needed before proceeding.  The second group argued that a moratorium should extend to ANY genetic modifications of human germline cells on the grounds that potential therapeutic applications do not warrant the risks to treated human embryos as well as future generations—and that the bar for approving such applications should be high indeed.

Kaebnick agreed with the calls for a moratorium.  So do I.  I note that the ethical conversation mirrors not only that around human enhancement, but also the historical discussion of IVF in the 1970’s.  And I (with Courtney) hear echoes of The Abolition of Man in the reflections of the scientists and ethicists here.  (Kaebnick invoked another application—being able to alter entire species such as mosquitos in ways thought desirable—but that is for another discussion.)  And I am inclined to agree with extending the moratorium to any work on the human germline.  But in so doing I note that one remedy proposed by the scientists; viz., use of PGD to select embryos in IVF, raises its own ethical concerns and is not a remedy I would endorse.

Fellow TIU bloggers:  this topic warrants extended engagement in a number of posts.  Would a therapeutically-limited germline alteration be acceptable if safety is assured and no embryo dies in the process?  And if so, how do we get there? Should we humans not touch the germline at all, and if not, does that unacceptably foreclose an avenue to a future option against certain genetic diseases?  Is it possible to set any reasonable limits not just on applications, but on basic research, in this case? I for one will attempt to follow-up in future posts.  And I hope we can sustain some reflection in advance of this June’s CBHD conference on “Science, Research, and the Limits of Bioethics.”

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Mark McQuain
Mark McQuain
6 years ago

Antonio Regalado wrote a very nice summary article for MIT Technology Review called “Engineering the Perfect Baby” (MIT Technology Review, Vol 118, no. 3, May/June 2015 p27-33) which was actually published online prior to the Science editorial. In it, he quotes George Church, speaking of his Harvard Medical School Lab as “…the center of a new technological genesis – one in which man rebuilds creation to suit himself.” Although Church did not attend the Napa meeting, he has signed on to Jennifer Duodna’s global moratorium banning the use of CRISPR to generate genetically edited children.

Regalado also quotes John Harris, a bioethicist at Manchester University in the UK: “The human genome is not perfect. It’s ethically imperative to positively support this [CRISPR] technology [to make improvements in our species]’. Harris expressed similar desires in his book “Enhancing Evolution” I have always found his confidence that a species that randomly evolved (man) could non-randomly (meaningfully) enhance itself.

In my past life, I was a systems programmer, often working on code written by others no longer part of the project. The code was simple compared with the human genome, perhaps only tens of thousands of lines of computer code. I knew the computer language and the machine hardware. Yet, more often than not, making some small change in one section of the code negatively affected another remote section of code initially thought unrelated. I worry that the analogy to the human genome is similar. Not only is the human genome code larger, and I would argue far less understood despite having what we believe is the correct sequence, but no human wrote the initial code.

No germline editing on humans. We are not as smart as we think we are.

Mark McQuain
Mark McQuain
6 years ago
Reply to  Mark McQuain

Clarification: Harris is the one who believes we randomly evolved. Random creation seems somehow oxymoronic