National Academies panel outlines ‘stringent’ criteria for human germline editing
Every year at this time, MedPage Today‘s writers select a few of the most important stories published earlier in the year and examine what happened afterward. One of those original stories, which first appeared Feb. 14, is republished below; click here to read the follow-up.
WASHINGTON — Clinical trials involving “heritable germline editing” are not yet ready for prime-time, according to a report from the National Academy of Sciencesand the National Academy of Medicine.
However, heritable germline editing — genetic manipulations that can be passed down to offspring — could potentially be allowed in the future for “serious disease or conditions” and with strict oversight, provided certain criteria are met, according to a committee of science, healthcare, and legal experts that made up the Committee on Human Gene Editing.
The report is the result of a year-long examination of the science and policy of human gene editing and its ethical ramifications.
In weighing the benefits and risks of these techniques, the committee decided that “caution is absolutely needed, but being cautious does not mean prohibition,” said R. Alta Charo, JD, committee co-chair and bioethics scholar at the University of Wisconsin Law School in Madison.
According to Charo, the committee agreed to six “strict” and “stringent” criteria under which germline editing could begin to be considered:
- Lack of reasonable alternatives
- Limiting to genes “convincingly demonstrated to cause or predispose” one to serious illness
- “Credible pre-clinical and/or clinical data” regarding the potential risks and benefits
- Strong and continuous oversight during clinical trials
- A broad plan for long-term, multi-generational follow-up
- Extensive and continued review of “health and societal benefits and risks” that involves public engagement
“If those conditions are met, it was the committee’s conclusion that germline heritable editing clinical trials would be permissible — not obligatory, but permissible,” she said, adding that “we are not even close to the amount of research we need before you could actually move forward at a technical level, in terms of the precision and safety, in this particular technique.”
The committee also weighed in on non-heritable clinical trials or the editing of somatic cells.
Basic scientific trials in this category of genome editing are underway, and are in the nascent stages of clinical trials and applications. Treatments that enable “corrected” genes to implant themselves in cells, often using a virus, have shown promise in research studies of cystic fibrosis, HIV, and Duchenne muscular dystrophy.
Since these changes cannot be inherited by future generations, they should be allowed to continue only when the research or therapy aims to treat or prevent disease or disability, and not for the purpose of genetic enhancement, according to the committee.
New technologies such as the CRISPR-Cas9 — an enzyme that can slice DNA at targeted points — offer the possibility of altering an individual’s genome, or even a generation’s genome. CRISP-CAS9 is easy, efficient, and relatively cheap, as committee members noted, and with its introduction, the risk of off-target events or “mistaken edits” is shrinking.
Instead of worrying “it’s too risky,” stakeholders are now beginning to shift their focus to the ethical ramifications of germline editing, said committee Jeffrey Kahn, PhD, MPH, director of the Johns Hopkins Berman Institute of Bioethics in Baltimore.
Rather than fully opening a door that was previously closed for germline editing, Kahn told MedPage Today that the report is more “like a knock on the door. The door’s not open yet.”
He pointed out that the committee’s criteria are “pretty rigid,” and not necessarily easy to meet. In addition, in the U.S., the NIH Recombinant DNA Advisory Committee and the FDA also have regulations regarding germline editing.
The NIH committee previously stated that it will “not entertain proposals for germline alterations,” so those restrictions still need to be relaxed, Kahn noted, describing the NIH stance as “more than a door — that’s a locked door.”
Rules about germline editing are not necessarily as strict in other countries. For instance, in 2015, scientists at Sun Yat-sen University in Guangzhou, China, were the first to use CRISPR-CAS9 on human embryos, according to Nature.
While the embryos were defective and could not have led to a live birth, the experiment was likely tied to a call for a moratorium by an international group of scientists on gene editing that could cause “inheritable changes to the genome,” according to The New York Times.
Former Director of National Intelligence James Clapper expressed concern that CRISPR could be used as a weapon of mass destruction, according toScience.
In the current report, the committee issued guiding principles “that should be used by any nation in governing human genome editing research or applications.” These are:
- Promote well-being
- Transparency
- Due care
- Responsible science
- Respect for persons
- Fairness
- Transnational cooperation
“These overarching principles, and the responsibilities that flow from them, should be reflected in each nation’s scientific community and regulatory processes,” said committee co-chair Richard Hynes, PhD, of Massachusetts Institute of Technology in Boston, in a press release.
Charo noted that the guidelines set forth in the report, including its criteria, might be weighted differently in different jurisdictions.
“In some countries, [germline editing] is entirely illegal,” she noted, adding that some states have made embryo research unlawful.
“The bottom line is that there is no planetary government with enforcement power, but the goal of the human genome initiative [and] the goal of this study committee is to help develop international norms that will be influential, with the policymakers, with physicians, with researchers, with patient groups … so that to the greatest extent possible, there is some global agreement” on a set of guiding principles that aim toward beneficial purposes, Charo stated.
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