dextriminta 19 points 20 hours ago*
Thought I should list out some points for folks to consider/ponder upon before making any snap judgments if this study was appropriate/ethical or not. Thought that folks might need some background/framework to properly understand why this is seen as controversial and received such overwhelming criticism.
1) Is there proper scientific foundation behind CRISPR-cas9 technology?
While this confers the ability to disrupt select targeted genes, the reality is that this technology still needs some refining. Recent research (actual article here, and a news summary here for those who prefer an easier read) has found that this technique isn’t accurate, has significant off-target activity, and can potentially create large sequence deletions and complex rearrangements. Currently humanity does not have a sufficient understanding of the extent of damage that CRISPR-cas9 may cause, and neither do we fully understand the down-stream effects of eliminating select genes will have. Using such an inaccurate technique with a rather high risk of doing unintended harm is simply unacceptable.
Answer: The technology still needs refinement, and using any medical technology that has not been properly evaluated is simply unacceptable.
2) Is there any real clinical need?
AFAIK the couple in question belong to a HIV/AIDS volunteer group where only the gentleman has diagnosed HIV/AIDS. The lady does not carry HIV, I believe. In terms of wanting a HIV-free offspring, existing treatments (eg sperm washing, screening, in-vitro fertilisation, PrEP/PEP) can already to that. This study does not ‘treat’ this couple at all, and instead exposes the couple & and unborn baby to unnecessary harm from gene editing, making it unjustified from a treatment perspective.
Answer: There are other ways for the couple in question to ensure their offspring will not catch HIV from their father that confers less harm - making this an unnecessary ‘treatment’.
3) Wouldn’t HIV-immunity be beneficial to all humanity?
The catch is - we do not fully understand the effects of disrupting CCR5 (the receptor that was targeted). A small portion of northern Europeans carry a mutation in CCR5 that makes them ‘HIV immune’ (technically only immune to HIV-1 strains but other HIV strains still exists so…). However we also know that CCR5 has important roles in the activation and coordination of immune system. If we regard CCR5-disruption as acquiring true HIV immunity for arguments sake, such an individual would also have a less than optimal immune system as compared to the general public, and be more susceptible to other infections. For the pair of twins that were born, this would be an absolutely shitty trade-off to have considering their parents are well educated about HIV, and can potentially steer their kids away from future HIV infections.
Answer: We do not fully understand what happens when this receptor is disrupted. If the trade-off of being HIV immune is to have a shitty immune system, then that’s a pretty bad trade-off to have.
4) Has this study undergone appropriate ethical review by an independent ethical committee?
All trials/studies involving any human tissue has to undergo extensive ethics review and be approved by a panel that is independent and does not have any conflict of interest. Based on Chinese news outlets, the 7 individuals who signed the ethics approval previously have now denied their involvement and claim that this approval form was ‘forged’. It should also be noted that a couple of the panel members are not necessarily ‘independent’, and one member mentioned that ‘he does not remember any meeting about this’. This goes to show how poor the administrative/regulatory environment is, and raises the possibility that this study might not have been evaluated at all.
Answer: It is likely that an independent ethical review was not carried out properly.
- What is the difference between this study and all the other existing gene-editing trials on humans?
This study involves the alteration of germ cells (ie cells that have reproductive potential, such as sperm cells or egg cells). Existing clinical trials only involve somatic cells (ie cells in your body, except egg/sperm cells). Gene edits on somatic cells stay with that person and will never be passed (any edits made to say cells on your skin stay with you and will never be passed to your children or grandchildren). Gene edits on germ cells can be problematic as any intended and unintended consequences, be it benefit or harm, can be passed on. Hence strict regulation exists surrounding research involving human embryos where research can only be conducted on either non-viable embryos, or if researchers commit to destroying any embryos used by day 14. It is a bad idea to potentially introduce problematic or defective genes into the human gene pool, where these defective genes can be passed on to subsequent generations.
Answer: This study involves sperm/egg cells, and any intended or unintended consequences are here to stay in the human gene pool. Existing gene editing studies are done on somatic cells and cannot be passed on to future offsprings.
- What about the girls? What will happen to LuLu & Nana?
It is said that the parents received some compensation as part of participating in this study. He also revealed during the Hong Kong conference that LuLu & NaNa will be actively monitored for the next 18 years, at which further consent will be sought for subsequent long term monitoring. While I can draw some parallels from those long-term cohort studies (eg Framingham cohort, a long term study that allowed us to learn more about heart diseases), we really cannot say for sure how the girls will react to this considering they are the experimental subjects and this study can never be un-done in any way. Another parallel could be observed from long term studies of children born of IVF/ICSI. Simply put, we cannot assume how favourably or unfavourably LuLu & NaNa or the society will see this, and this uncertainty should not be one for LuLu & NaNa to bear. But I definitely hope that society will view them favourably and similar to those from IVF/ICSI studies - that they are worthy human beings living on this planet, nothing more, nothing less.
Answer: We aren’t sure how LuLu & NaNa or society at large will react to this in the future, but I’m personally hoping for the best.
7) Are we trying to play god by interfering with a natural process?
I think this is the million-dollar question that the bulk of online discussions/debates are about. There isn’t a clear answer to this to be honest. Personally I think this would be an interesting question knowing many used to consider babies born from in-vitro fertilisation (aka test-tube babies) and organ donation/transplant as ethically-questionable decisions, and many still consider them to be unethical at this point in time. This is a question for humanity to answer. Attempting to hack our biology is not necessarily a bad thing to do (making humans capable of photosynthesis will Really curb global warming), but it must be done in a safe manner that does not expose individuals to unnecessary harm/risks.
Answer: This is a question for all to answer. But the bottom line is that any interference, if any, must be done in a safe way and does not expose individuals to unnecessary harm/risks.
I hope this should ideally frame the discussion a bit, so that we don’t see all the hasty conclusions and toxicity that I am seeing now on Chinese social media. I’m also happy to for any questions/discussions about clinical trials or experiential ethics if anyone’s interested.
Side point: Personally I’m not a fan of how the fertility doctors decided to put 2 embryos back. For IVF, more embryos =/= greater chance of viable pregnancy or greater chance of take-home baby. Modern IVF clinics that are respectable and ethical adopt a ‘One at a time’ policy’. The only scenarios where multiple embryos are put back would be that the mum is on the older side (usually >40 years of age) and with embryos that don’t look super healthy. Twin pregnancies generally carry greater risks than singleton pregnancies, and to me this is just exposing mum and baby to unnecessary risks.