CRISPR babies

In November 2018, the world learned that a Chinese scientist, He Jiankui, had conducted an experiment that resulted in the birth of two gene-edited human babies.   Antonio Regalado broke the news on Nov. 25 in an article in MIT Technology Review.   Two days later, He gave a talk about this experiment at the Second International Summit on Human Genome Editing in Hong Kong.   His study was immediately, widely, and strongly criticized by the scientific community.    

There has been so much media reporting on this story that I have little to add, except a few links and personal comments.

STAT news has just published a great piece on He Jiankui's research timeline leading up to the story, mainly from the perspective of a few other researchers who had interactions with He during the period when he was planning, and carrying out, his human embryo work.   

At this time I remain opposed to gene-editing of human embryos with the intention of implanting the embryos to result in pregnancy.   This keeps in agreement with the ASHG statement on Human Germline Genome Editing.

He Jiankui's experiment was reckless for several reasons.  Here are three.

First, there has absolutely not yet been enough research to prove that gene-editing methods can be safely and effectively used in human embryos without unwanted side effects that could cause harm to the baby.    

Second, the particular gene (CCR5) and disease (HIV/AIDS) that were the targets of these experiments are very problematic.  Inactivating CCR5 may not always prevent HIV infection.  On the other hand, people who lack CCR5 have more severe symptoms if they are infected by West Nile Virus.   The embryos themselves were not infected with HIV, so the editing was intended to prevent a disease that the embryos did not carry, and is preventable in other, established ways.  This does not mean that HIV is not a serious problem, or that AIDS is not devastating.    It just means that the approach used here is very open to criticism from a scientific standpoint.

Third, it looks like the babies' parents did not have an ethically sound informed consent process.  The informed consent forms that the parents signed seem more designed to protect the legal exposure of the researchers than to inform the parents of the real risks and benefits of the experiment.

ASHG Position Statement on Human Germline Gene Editing.

An ASHG workgroup, of which I am privileged to be a part, has published a position statement in the American Journal of Human Genetics regarding our society's current views on human germline genome editing.   Here's a link to the ASHG press release.

Oregon researchers publish results on editing human embryos in Nature. Reduced mosaicism and insights into HDR in human zygotes.

Ma et al (PI: Shoukhrat Mitalipov) have published a highly anticipated paper in the Aug. 3 2017 issue of Nature:      Correction of a pathogenic gene mutation in human embryos.  

Release of the National Academies' Consensus Study on Human Genome Editing

The National Academies of Science, Medicine, and Engineering have jointly released their consensus study on Human Genome Editing: Science, Ethics and Governance.  The report was produced by a committee specifically created to consider this topic.   Here are links to either:

1. The report highlights, summarized in about 4 pages.  I recommend this!

2. The full report - it's over 200 pages.  You can download the full study from their website (you need to register to get the free PDF, but it's pretty painless) 

3. A one-page summary of the report.    

I can see that a "narrative" in the media coverage revolves around the report's cautious statement that human germline gene editing may be ethically OK, but: only in very specific disease-addressing situations; with appropriate oversight;  and some sort of public consensus/input.   In fact, this is probably the most contentious question the committee faced.   The committee clearly states that editing to produce enhancements, rather than to treat disease, is not recommended at this time.   On the other hand, somatic gene editing applications for treating diseases can be viewed essentially as technical improvements of "conventional" somatic gene therapies, for which the ethics and oversight issues have been dealt with for some years now.

There is abundant material in the full report and its summaries that calls for public input into the process of determining exactly what types of germline gene editing should be permitted.   For example, from the one-page report summary:  "Ongoing reassessment and public participation should precede any clinical trials of heritable germline editing".   This is a very clear call for public feedback. Nevertheless, at least some responses seem to argue that this sentiment was left out of the report.  I believe this to be purposefully misleading.  The report committee was co-chaired by a noted biomedical ethicist and regulatory expert.  Moreover, the committee has several additional bioethicists in its roster, who all are well acquainted with the need for communication between the public, scientists and policymakers in order for sensible policies to be created.    Furthermore - the report contains an entire chapter entitled "Public engagement".  !    

It is clear that the committee, and most scientists I know, feel strongly that any process of establishing policies, regulations or laws governing germline genome editing will absolutely require public engagement and feedback.

from Nature: CRISPR gene-editing tested in a person for the first time.

http://www.nature.com/news/crispr-gene-editing-tested-in-a-person-for-the-first-time-1.20988

Policy forum paper in Science on germline gene editing: "Editing policy to fit the genome?"

Back in late January, Rosari Isasi et al. published a policy forum paper in Science that discussed the issues surrounding genome editing policies around the world.  Key points discussed include the differences between "permissive" and "restrictive" viewpoints, whether restrictions on clinical applications also apply to research - and how vague legislative language sometimes makes this distinction unclear - and, how thresholds for acceptability have been applied in related contexts.

Nice maps are given that indicate the general level of regulation around the world for this issue and for related topics such as preimplantation diagnosis.    

Science. 2016 Jan 22;351(6271):337-9.  Isasi et al. GENETIC TECHNOLOGY REGULATION. Editing policy to fit the genome?

UK approves gene editing of human embryos for in vitro research purposes. (NOT for implantation/procreation).

The HFEA has approved an application from UK reserachers to perform specific gene editing experiments in human embryos for research purposes.  The embryos will not be cultured beyond the blastocyst stage (a small ball of ~250 cells).  The purpose of this research is to examine the development of cells that form the placenta and other tissues that support embryo growth.  This sort of research may lead to better understanding of why some miscarriages occur.

Reports from various news outlets:

BBC News

The Guardian

Washington Post