National Academies panel leaves door a crack open to future human genetic modification

Early human embryosA National Academies panel on human genome editing chaired by Alta Charo and Richard Hynes released its report today. While it covered both somatic and germline (heritable) human genetic modification, the latter topic is far more contentious. You can see the National Academies summary of their report here. You can read the full report here.

On germline genetic modification using technologies such as CRISPR, the authors of the report carefully discussed potential benefits and risks to the use of this technology. On my first brief reading of it, the report is mostly appropriately cautious in terms of outlining the potential risks as well as societal and bioethical issues in addition to potential benefits.

As to the more controversial area of potential human germline genetic modification, I appreciate the fact that the report unambiguously says that human germline editing is not ready to be tried and lists numerous hurdles to address first. However, although the report tackles most of the key considerations and risks (and for that the authors should be commended), there is still an interesting undertone to the report’s discussion that seems to strive to justify leaving the door open to potential future use of human germline editing.

For instance, the report makes a point of noting mostly hypothetical instances where existing technologies such as PGD that are far less controversial may hypothetically fall down and so possibly might need to be supplanted by germline editing using techniques like CRISPR, but such instances are now and in the future would continue to be exceedingly rare. Too much weight are placed on these.

The other point that needs to be made is that hypothetical future germline editing in human embryos (or even done earlier developmentally in, for example, germ cells) with reproductive intent would have to be preceded by a great deal of research that involves PGD-like testing of human embryos to monitor efficiency and specificity of editing, chimerism, and other issues so it is not as though germline editing could avoid PGD-related issues or destruction of embryos.

I’m also not convinced that the personal need by some individuals to have a genetically-related offspring should be a major consideration in decisions related to the permissibility of human germline gene editing. The related concept of parental autonomy is given too much weight by the report. While this argument has both aspects that intuitively make good sense, it also has some that could lead to promotion of germline modification.

For instance, what if parents want their kids to have certain traits that become potentially available via germline modification? In this regard, the ability of researchers and policy-makers both in the US and more globally to prevent parents and practitioners from going down the path to use germline human modification for traits rather than strictly health conditions may prove to be quite limited and it’s not clear had to address that risk. The report in some places does not use strong enough language to counter the idea of human germline modification.

On the whole, I have favored a moratorium on germline modification, a step that this report does not take. Of course there are possible problems with a moratorium too including enforceability (lack thereof) and that once you have a moratorium it might be hard to escape it (e.g. if the government follows suit with legal steps) even if down the road the science were to back up getting rid of it. Note that as the report mentions, for at least some months longer, in the US the FDA cannot consider applications for any human embryo genetic modification and then there’s the Dickey-Wicker Amendment that disallows federal funding of anything that involves ‘destruction’ of human embryos and such things as using CRISPR modified embryos to do PCR for research would qualify as destruction. But then there’s loads of private money out there for research as well.

What are your impressions of the report?

For more of my thoughts and concerns on human genetic modification you can read my book GMO Sapiens and watch my TED talk (below).

Where are all the new CRISPR human embryo papers?

Last year I heard from several sources that there somewhere between 3-5 unpublished manuscripts reporting the use of CRISPR gene targeting in human embryos being shopped around at various journals in addition to the one that had been published. Since that time we’ve seen a grand total of one additional paper reporting on CRISPR of human embryos.

So what gives?

Were the sources wrong?

I don’t think so and I believe there are additional labs pursuing research on the use of CRISPR in human embryos.

Depending on the context, the oversight, and the training of those involved, there may be nothing wrong with these studies at all. In fact, they could be positive and teach us a lot if the teams are careful. However, CRISPR’ing human embryos without a good rationale and appropriate oversight is unwise. I also cannot imagine supporting use of CRISPR with the intent to make a modified new human being for many years to come if ever. You can learn more about the history of genetic modification and my views as well as those of CRISPR leaders in my new book, GMO Sapiens.

So where are all the CRISPR human embryo papers? I can think of a few main reasons why we haven’t seen more so far.

embryo human

Wikimedia Photo

Editors as gatekeepers? One possible reason we haven’t seen more CRISPR’d human embryo papers is that journal editors are reluctant to publish them and are acting as essentially gatekeepers for this kind of work. If true, what are the potential risks or benefits of such a de facto filtering system and what is the basis by which the editors are making such decisions?

Outcomes of first 2 pubs discouraged more? Another possibility is that other research teams have been discouraged by the first two papers reporting CRISPR use in human embryos. I can see at least two levels at which those considering working and publishing in this area might be reluctant to proceed because of the first two papers. On the one hand, both papers reported technical challenges with this research, which was discouraging. On the other hand, both papers were heavily criticized by some.

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Hateful politics infiltrate human genome editing debate in France

By Elliot Hosman

Summary.  A campaign calling for a moratorium on using CRISPR in human embryos was launched by a prominent French organization fighting for narrow understandings of life and family.

A recent campaign calling for a ban on “transgenic” human embryos was launched by one of France’s most prominent organizations fighting for “science”-backed “one-man-one-woman” families, and the exclusion of all other forms.

Stop Baby GMO Campaign

“Stop GMO Baby: Yes to therapeutic progress, no to transgenic embryos” (image via Alliance VITA).

Since March 24, more than 15,500 people in France have signed a Change.org petition started by Alliance VITA declaring (translated from French*):

“I ask my country to engage with all urgency to obtain an international moratorium – that is to say an immediate stop – on the genetic modification of human embryos, especially via the technique CRISPR-cas9.”

*all French materials and quotations presented in English in this post have been translated using Google and my college-level French. Suggested revisions to translations are welcome and will be noted. Alliance VITA offers some materials on its website in English.

In that time, volunteers have canvassed cities around France, handing out brochures explaining the breakthrough CRISPR genome editing technology, and tweeting pictures of their advocacy using Flickr and the hashtags: #StopBébéOGM, #ProtectHumanity, and #CRISPR-Cas9.

Alliance VITA’s opposition to using human gene editing for reproduction is widely shared, including by my organization, the Center for Genetics and Society. But a closer look at the Stop GMO Baby campaign in France reveals a troubling and at times explicitly hateful politics infiltrating the human genome editing debate. A polarization of the conversation about heritable human genetic modification along “right to life” and “natural family” fault lines threatens to derail public conversations about responsible regulation of science and medicine that serves the public interest.

Paul also recently flagged Alliance VITA’s Stop GMO Baby campaign, cautioning:

“I’m concerned that these campaigns that specifically target CRISPR could have negative effects on the freedom of us scientists to do responsible CRISPR research in the lab. … at least some of the motivation seems to be related to a “right-to-life” perspective. “

I share this concern, and we’re not alone. In a February article titled Gene editing: The next frontier in America’s abortion wars, the “last scientist in Congress” U.S. Representative Bill Foster (D-IL) told Politico’s Sarah Karlin that he’d been warned by scientists that “‘this issue will get all tied up over the abortion debate,’ interfering with the creation of ‘good policy decisions.’”

The Stop GMO Baby Campaign

Alliance VITA’s campaign materials on CRISPR take as their central point that CRISPR-Cas9 is an ethically neutral and promising technology that could help gene therapy, but that any use in human embryos or gametes is a red line no researcher in the world should cross. In their other words: “GM babies? No!” Here are some examples of their slogans and statements:

  • Campaign slogan: “CRISPR-Cas9: Yes to Therapeutic Progress, No to Transgenic Embryo!” (March 24, 2016) [Brochure PDF]
  • On February 16, 2016, Alliance VITA Research Director Blanche Streb stated on Catholic television: “The technique poses no ethical problems on its own, it’s the application that does.” (YouTube)
  • Alliance VITA General Delegate-CEO Tugdual Derville commenting on Kathy Niakan’s application to the HFEA in January 2016:

“Although this technique might be promising for genetic therapy, Tugdual Derville reminds us that when applied to the human embryo: “the danger is to cause the emergence of custom-made babies, with pre-selected genetic criteria, heritable modifications, with unknown consequences for future generations. The human genome is part of our most precious “heritage of humanity.” Its integrity must absolutely be preserved for future generations.”

In March, Alliance VITA released a study they conducted finding that 76% of French people support gene therapy, but oppose using CRISPR to genetically modify embryos in vitro. Some of their data conform to a number of other recent studies. But the slipperiness of public opinion polls that Pete Shanks describes in a recent survey of public opinion of human heritable genetic modification is on point here, as the framing of questions may lead to an overstatement of the sanctity of the embryo for the people who polled their opposition.

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NgAgo a-go-go: top 5 bullet points on upstart CRISPR challenger

NgAgoThe gene editing technology CRISPR has been arguably the top story in the biomedical world in the last two years, but going forward there is a CRISPR challenger in upstart gene editing technology NgAgo.

For more background on NgAgo and the key first published paper on its genetic modification characteristics see my post here. 

In the comments on that post and in discussions I’ve had with other researchers, some key points have crystalized on NgAgo versus CRISPR at this time. As a possible CRISPR challenger, how does NgAgo fare?

Broader possible applicability. The lack of a PAM site requirement for NgAgo means it is almost certain that for some specific gene editing applications, NgAgo will work and CRISPR won’t. Design of NgAgo guides seems to be a simpler matter too because no PAM is needed (more on guides below). In that first NgAgo paper they reported effective editing of 8 different genes with good efficiency so it’s unlikely there is a strongly required DNA sequence context needed for NgAgo. However, it is still formally possible that NgAgo in some contexts will have some kind of preference for certain DNA sequences.  Further study will help resolve this more concretely, but so far this is looking like a major plus for NgAgo.

DNA guides should be a lot easier. The use of DNA-based guides will make gene editing easier as opposed to RNA-based guides. At the very least you eliminate a cloning step and you can just order oligos, which you can phosphorylate in your lab to use as guides by transfection.

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In Depth Report from April 29th Paris Human Gene Edit Meeting

Editor’s note. Caroline Simons attended both the April 28th (see her report on that here) and 29th Paris meetings on human gene editing/genetic modification. Today, we have her in depth report on the April 29th meeting. I have posted her piece in full with only minor edits. If you are in a rush you can skip to the last page for Caroline’s top 10 takeaways from the meeting.

By Caroline Simons

The meeting of NAS and NAM which took place in Paris on 29 April was webcast live. A recording of the presentations will be posted in the coming weeks. This blog post is my record of the presentations and an attempt to give an overall impression of the discussions.

Paris Gene Editing Meeting

Credit, Caroline Simons

This meeting is one of a series which has been organized by the Committee to assist in its examination of the ‘scientific underpinnings as well as the clinical, ethical, legal and social implications of the use of human genome editing technologies in biomedical research and medicine.’ The Committee is examining both somatic and germline genome editing. It focuses on 7 areas in particular. These relate to the current state of the science, future directions and challenges, potential clinical applications, alternative approaches, and the efficacy and risks of gene editing in humans. The Committee asks if explicit scientific standards should be established to quantify off-target genome alterations, if current ethical and legal standards for human subjects research adequately address human gene editing technologies and what are the ethical, legal and social implications of the use of these technologies in humans. The Committee seeks to identify what principles or frameworks might provide appropriate oversight for these technologies and to assess the prospect of international harmonization of policies.

The Committee will prepare a report and make recommendations later this year. This report will ‘include a focus on advice for the United States’, and will ‘provide a framework based on fundamental, underlying principles that may be adapted and adopted by any nation’.

This 3rd Consensus Study Meeting was a larger gathering than the meeting of FEAM, the UK Academy of Medical Sciences and the Académie Nationale de Médecine France which was held the previous day. Attendees included European Commission representation, prominent scientists, philosophers, ethicists and lawyers from Europe, the US, Canada, China, Singapore and Malaysia. Three panels of speakers addressed the principles underlying governance, international governance perspectives and potential applications for germline editing. The meeting wrapped up with a moderated discussion among all of the attendees.

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