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).

First 3-person IVF baby born via “rogue” experiment at Mexico clinic?

Today we got the first report of a baby being born via so-called “3-person IVF”, sometimes called 3-parent IVF, in which the DNA of three people contribute to an offspring.

Before discussing this further I have to emphasize that we need proof that this is indeed really a 3-person IVF baby via genetic testing. Until that data is released publicly we should all be cautious on this news. Apparently the clinic plans to present such data later.

Assuming it is a 3-person IVF baby, which seems most likely, I discuss the key issues below.

For the 3-person IVF baby, it is hoped to be free of mitochondrial disease (the whole point of doing the procedure), but there are serious risks here. The doctor doing this experiment was John Zhang of New York University and New Hope Fertility Center, but he did it in Mexico.

john-zhang-with-3-person-ivf-baby

John Zhang holds the baby; New Scientist picture

I’m deeply concerned by this news.

The fact that Zhang went to a place where he reportedly himself said, “there are no rules”, to do this illustrates that this 3-person IVF procedure was not given proper regulatory and ethical oversight. It feels more like it was done in secret.

Marcy Darnovsky, Executive Director of The Center for Genetics and Society referred to this kind of thing as “rogue experimentation” in a press release. In a sense she’s right about this, in particular because the world’s experts are really still trying to sort out the core issues surrounding this kind of technology. It is an understatement to say this was jumping the gun. 3-person IVF is not permitted in the US due to safety concerns.

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New Herbert lab Nature paper reinforces mitochondrial replacement Achilles heel

Today a new Nature paper from Dr. Mary Herbert’s group in the UK has found a key problem with mitochondrial replacement therapy that fits with data from others.

The goal of preventing mitochondrial disease using various kinds of genome transfer technologies is a noble one, but mitochondrial replacement therapy has faced a number of technological challenges including perhaps most prominently the carryover and subsequent amplification of diseased mitochondria.

This mitochondrial replacement carryover issue was clearly defined in an excellent recent Cell Stem Cell paper from Dieter Egli’s lab, which demonstrated some cases of pronounced carryover and/or amplification of certain mitochondrial types following nuclear transfer. For more on my perspectives on the Egli paper see here.Herbert mitochondria Nature paper

In the data from the Herbert group paper, the same kind of problem is evident despite the use of a somewhat different adaptation of this technology in which pronuclei are transferred instead of nuclei or spindles from the mom-to-be. In the new paper, Hyslop, et al., the data point toward mitochondrial carryover as a significant problem still to overcome. Some scientists and politicians in the UK successfully pushed for governmental approval there to proceed with mitochondrial replacement therapy in humans last year, but I argued that this technology was not ready for prime time yet due to a number of gaps in our knowledge of both mitochondria themselves in germ cells and also what happens in actual human embryos post-genome transfer.

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First anti-CRISPR political campaign is born in Europe

Campaigns are underway in several European countries against the possible use of genetic modification in humans to make designer babies and one has a distinctly anti-CRISPR tone.

Stop Baby GMO

Stop Baby GMO Website images

For example, in France a group is pushing an anti-GM baby campaign and the same kind of thing is going on in Switzerland, which I blogged about recently. In Switzerland it appears the campaign is targeting legislation related to preimplantation genetic diagnosis (PGD) so it seems that campaign is using the possibility of designer babies (pretty much a non-issue for PGD) and the animosity toward GMO foods amongst some in Europe as a wedge to get votes against PGD.

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UK should freeze mitochondrial replacement as Egli paper ID’s serious problem

An important new Cell Stem Cell paper from Dieter Egli’s lab points to an inherent, serious problem with so-called 3-person IVF or mitochondrial replacement technology that warrants putting an immediate hold on all efforts to use it in humans. I have pasted the graphical abstract from the paper below.

Egli genetic drift paper

Graphical Abstract, Cell Stem Cell

For years a few of us scientists and policy groups have argued strongly that this experimental technology is far too risky to try in humans for reproductive efforts in the near future. There were simply not enough data to support the reasonable expectation that the technique would be safe and effective to use to create new children. I felt so strongly I wrote an open letter to the UK Parliament suggesting that they not proceed and this led to a bit of a kerfuffle.

The UK leadership approved the clinical use of 3-person IVF, which was a bold, but highly risky decision.  I believe the UK is now going to have to step back and authorities there should now freeze all clinical efforts at 3-person IVF/mitochondrial transfer for the time being because of seriousness of this new paper’s findings.

What concerns me specifically?

One of the big potential issues about 3-person IVF raised by those of us who earlier argued for more time and more data before pulling that regulatory approval trigger to proceed with use in humans is that the nuclear transfer from the mom-to-be’s egg into the donor’s enucleated egg would bring some diseased mitochondria with it and those faulty mitochondria could amplify. The new paper from Egli’s lab proves that this kind of thing can happen. It suggests that in some cases this troublesome phenomenon is likely to occur after 3-person IVF and in my view this is likely to lead to health consequences for the future offspring.

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