Tag Archives: gene

Top 5 talks of the 3rd International Summit on Human Genome Editing

The final statement came by email this morning statement-from-the-organising-committee-of-the-third-international-summit-on-human-genome-editing

Remarkable progress has been made in somatic human genome editing, demonstrating it can cure once incurable diseases. To realise its full therapeutic potential, research is needed to expand the range of diseases it can treat, and to better understand risks and unintended effects. The extremely high costs of current somatic gene therapies are unsustainable. A global commitment to affordable, equitable access to these treatments is urgently needed. Heritable human genome editing remains unacceptable at this time.

And well, my subjective selection of  the best talks is also here (unfortunately the video quality is poor and there is no way to timestamp the URL, so you have to recall the time marks below).

As always masterful moderation by Robin Lovell-Badge including the fire alarm ;-) My top 5 talks are

  1. Chinese legislation whitewashed at 1:03:10
  2. David Liu excellent overview at 1:25:14
  3. Filippa Lentzos with a super nice talk on hopes and fears at 2:53:25
  4. Tue Kiran Musunuru with another excellent overview at  2:18:54
  5. Rising star Tina Rulli at 1:28:29

(Jennifer Doudna 4:25:17 was a bit disappointing when talking about my research field involving asthma and microbiome.
The two father mouse of Katsuhiko Hayashi that gained wider attention [Guardian, Nature, …] is found at  3:14:02.


The Lancet and scientific integrity

We have learned in the past that the Lancet published editorials that clearly separated the journal from the publisher Elsevier

Reed Elsevier’s response is that the sale of military equipment is legal, government supported, and tightly regulated. However, The Lancet‘s collaborations in child survival and health-systems strengthening, for example, risk being tainted by Reed Elsevier’s promotion of the “selling process” of arms.

Of course you can’t sell weapons and distance yourself from selling weapons at the same time…

Fundamental and non fundamental objections of genome editing in humans

Braun, Schickl and Dabrock try to “map the underlying ethical arguments” (p6ff in “Moral Hazard” 2018) against human genome editing.

The various objections against germline genome editing can basically be divided into (1) fundamental (i.e. against the context of research and application) and (2) non fundamental (i.e. only against the context of application) arguments. The most prevalent fundamental arguments are (a) arguments of human dignity (b) arguments of naturalness and (c) slippery slope… The most common argument within the ethical (as well legal) debate on the use of genome editing techniques, like CRISPR technologies, is the safety argument as a non fundamental objection.

While I think the differentiation of fundamental vs non-fundamental is important for discriminating relevant from irrelevant arguments, the definitions are not fully clear. What is “context of research” – subject, object or objective? And what is “context of application” – the procedural conditions?

“Fundamental” may not be the best label as “fundamental” in German usually claims to be the  only right doctrine. Anyway, a fundamental argument will be an argument that cannot be easily overcome by a counter-argument as it is it is deeply grounded, heavy-weighted and basis for other conclusions.  A non-fundamental is just a non fundamental argument that can be rebutted immediately or in the foreseeable future.

The classification of fundamental by Braun, Schickl and Dabrock is even problematic as well. “Naturalness” is not a fundamental argument as it is nearly impossible to define a “natural” human genome. IMHO “slippery slope” is also not a logical argument at all – having more fear mongering elements than a  strict consequentialist logic.

I would therefore like to split any fundamental objections by the disciplines where they originate: (a)  philosophical/theological anthropology (b) biology and (c) sociology.

-- anthropology
  .. human dignity
  .. missing embryonal consent
  .. genetic heteronomy
-- biology
  .. off target risks / safety
  .. unknown genetic background effects
  .. unknown next generation effects
  .. dissolution of species boundaries
-- sociology
  .. missing societal consensus
  .. new naturalism
  .. new eugenics
  .. new racism
  .. medical necessity
  .. ethics vote
  .. no pre-tests
  .. no trial exit strategy
  .. conflicts of interest
  .. consent without alternatives
  .. and all Krimsky rules

Safety could of course could be a fundamental argument as set out by Nüsslein Vollhard: we can not 100% predict from one cell the fate from another cell.

Maybe this very first classification of arguments could be a further step into a more rational ethical discussion.

Braun, Schickl and Dabrock write on the same page that “the potentiality argument … which is considered to be the strongest argument for absolute embryo protection, is increasingly criticized by ethicists” citing Schöne-Seifert et al 2013 and  themselves as Schickl et al 2014. Their argument: we can reprogram now adult cells, the potentiality is therefore not a unique property of the human embryo, the embryo therefore has not any unique value, the embryo does not need protection.
I ask – instead of REVOKING potentiality of the human embryo why not EXPANDING potentiality to reprogrammed stem cells?
I have also doubts that a “reprogrammed” stem cell will ever have the unique potentiality of an embryo in situ for 3 reasons:
1. a stem cell is not a de novo creation but just a replication.
2. a stem cell will never replicate the complicated epigenetic pattern of an embryonic cell (which is a unique part of the embryonic identity, putting the Schickl argument in a row of genetic exceptionalism arguments).
3. lastly there is never ever maternal support of a stem cell, ignoring the complex biological support chain of human embryos.

And of course potentiality cannot be denied from a biological standpoint. It can be even exactly quantified: One of three fertilized eggs will develop into a human.


Gene Doping using CRISPR/Cas

After some first  experiments in human embryos, there is a new Chinese paper in the Journal of Molecular Biology showing that also gene doping is possible in mammals.  Myostatin deficiency otherwise leads to some really impressive super strength children while it is now possible to knockout this gene artificially.  Hopefully the WADA will test for myostatin gene activity in Rio 2016!
Addendum 4 Dec15: An International Summit Statement On Human Gene Editing says

It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application.

Both conditions are unlikely to be ever met.

The asthma and glaucoma island

Dr. Zamel, one of the PIs of the Tristan da Cunha study pointed me today to the interesting 30 min BBC documentation online at Allergy Canada

Allergy Island is an exclusive documentary on the history of asthma in Tristan da Cunha and the discovery of the gene related to asthma in that highly inbred community by the expedition that I did in 1993. I went in May 2008 to Tristan da Cunha with the BBC crew to film both parts for the entire month.

Fat receptor leading to obesity?

I have recently argued that much of the”obesity epidemic (which even expands now due to the economic crisis) is being due to processed food that fools our sensory system. A new paper (doi:10.1089/omi.2008.0031) now gives me some more support

Taste perception plays a key role in determining individual food preferences and dietary habits. Individual differences in bitter, sweet, umami, sour, or salty taste perception may influence dietary habits, affecting nutritional status and nutrition-related chronic disease risk. In addition to these traditional taste modalities there is growing evidence that “fat taste” may represent a sixth modality. Continue reading Fat receptor leading to obesity?

Forget about genes IV

Here comes probably one of the first papers that say NO to a gene for depression. As expected it is a meta-analysis:

Contrary to a previous report, an analysis of 14 previous studies does not find an association between a serotonin transporter gene variation, stressful life events, and an increased risk of major depression … “A more serious concern … is that the findings of this [Caspi et al] and other nonreplicated genetic associations are now being translated to a range of clinical, legal, research, and social settings such as forensics, diagnostic testing, study participants, and the general public. It is critical that health practitioners and scientists in other disciplines recognize the importance of replication of such findings.”

no stool test;-) nothing!

ORMDL3 – more inconsistencies in the Nature paper

It seems that CEA just published my rather critical view of the recent ORMDL3 association paper. My letter had been first submitted to “Nature” but rejected after review.
A rebuttal seemed to be necessary as the authors repeatedly highlight ORMDL3 as a new asthma gene – in the printed Nature paper, in the Nature podcast and in the accompanying press releases. They even continue with reviews saying that

Completion of the human genome sequence and the advent of genome-wide association studies have resulted in the identification of two novel asthma susceptibility genes, ORMDL3 and CHI3L1, in the past year.

Continue reading ORMDL3 – more inconsistencies in the Nature paper