Forget the "Editing" Hype: Human Genome Action Painting Attempted in China

Recently, there's been a lot of hype around what's been referred to as genome editing. What it's all about is that there's a new bioetechnological strategy for effecting genetic modification in organisms, called CRISPR/Cas9, that has shown promise in facilitating more precise and specific changes of a genome more effectively than before. This is an important advance for laboratory biology research, as the effecting of specific genetic changes in the genome of organisms and study of how these "behave" in response to various stimuli, in different environments, and reproductively over generations is a basic way of advancing knowledge of basic biological mechanisms. However, as usual, there has also been some lack of temperance among those who immediately want to move the new promising lab-tool into practical "in vivo" applications, sparking calls for a global moratorium on practical application, akin to that famously adopted in 1974 at the Asilomar Conference to apply to the then novel recombinant DNA technology. In addition, there has been especially forceful calls to abstain from "editing" a human genetic germ line. The reasoning is an apparently sound precautionary argument to the effect that before practical applications are attempted, sufficient understanding of the technology, its potentials and limits, possible consequences and suitable security protocols, need to be attained and put into place.

At the same time, when new technologies are hyped like this, my bioethics alarm bells start ringing loudly for a number of reasons. We know from a long series of hyped new technologies that, while they may indeed over time prove to be advances compared to what has been previously available (though by far not always), the promises of new "clean", "precise" tool that will effect all that we aim for without any side-effects or mistakes is usually as credible as the promises of precision warfare foreboding the 2003 Iraq invasion – or worse. What one mustn't forget is that there are almost always substantial vested interests around, that have high stakes in having the tech they personally hold patents for, or stock in start-up companies that do, or have stakes in institutes or universities that do, and so on, appear in much better light that there is actual evidence to support. And, in this respect, CRISPR-Cas9 is no different. This is a basic reason to primarily interpret any positive claim about the technology outside of the bona fide peer reviewed scientific literature as part of a marketing campaign aimed at upping the the price of licensing fees, credit rating of the patent holder, attraction for external financial investors, and (if it is a start-up company) stock price pending a coming introduction into a stock exchange or a emission of new shares. Other agents with similar vested interests include those who have already invested in the product somehow, or those who want to peddle quack junk to people under the guise of novel science, much in the spirit the infamous stem cell clinics that continue to jack money out of the hands of conned, often desperate, people.

So, for me, it was no surprise when the reality of the "editing" showed its true face when a group of Chinese researcher recently applied it to human in vitro embryos (modified, so that they could never have resulted in a living human baby, but also never implanted to effect a pregnancy). What we learn from this study is that if there's any honesty among gene modification scientists, the "editing" misnomer should be dropped immediately:

The team injected 86 embryos and then waited 48 hours, enough time for the CRISPR/Cas9 system and the molecules that replace the missing DNA to act — and for the embryos to grow to about eight cells each. Of the 71 embryos that survived, 54 were genetically tested. This revealed that just 28 were successfully spliced, and that only a fraction of those contained the replacement genetic material. “If you want to do it in normal embryos, you need to be close to 100%,” Huang says. “That’s why we stopped. We still think it’s too immature.”
His team also found a surprising number of ‘off-target’ mutations assumed to be introduced by the CRISPR/Cas9 complex acting on other parts of the genome.

What we seem to be looking at in the reality outside of the hype is some sort of human genome action painting, where now and then a drop of the right colour lands in the right place, several other drops land where we absolutely do not want them to, but most of the result is just general heap of pint randomly applied by these the Jackson Pollocks of human genetics.

Moratorium? No shit?!!

US Approval of the GMO Salmon "Frankenfish" - Reasons for Continuous Caution Remain in the Absence of Added Value

Today, New Scientist reports about what looks like a landmark event in the USA and (due to the role of the US for the world economy, trade and global regulation affecting trade) global handling of the possibility of using genetically modified animals for food production. Other reports can be found here, here, here, here. The FDA, in a statement released on December 27, has cleared a particular brand of GM Salmon – dubbed the "Frankenfish" by my US bioethics colleague Art Caplan in a comment that is nevertheless cautiously positive of the development, at least from a food safety point of view – modified to internally produce more growth hormone and thus grow to full size faster on less feeding or larger size with maintained feeding levels. To forestall possible negative environmental impact, it has also been engineered to carry a sex-chromosome abnormality, rendering it sterile, and the production will take place in closed off settings, especially in its initial phases, where it will take place in tanks isolated from the natural environment. All of these things are expanded on in the NS piece and the links it provides. The proposal by the FDA will be open for public comment for 60 days.

Concerning the use of genetically modified organisms for food production, there are basically four issues to address: Is it good for anything, what is its benefits? How safe is it to eat and produce (in the same way as we would ask of any other crops or cattle)? How environmentally safe is it? Are the two safety levels mentioned sufficient to warrant production in light of the benefits? Art Caplan comments on the food safety side of the issue, something that has traditionally attracted lots of attention in the media. It is also angle often played by opponents of GMO for food, since immediate safety to consumers (and sometimes workers) is something that appeals very directly to people's sentiments and may thereby affect their moral and political views. However, the GMO industry likes the food safety side of the discussion very much as well, since – as a matter of fact – when assessed on the basis of actual evidence, GM food stands up pretty well compared to many more "traditionally" produced food. This is the point that Art is making and precisely for this reasons, I agree that food safety is not what the discussion should focus on with regard to GM food. However, this is far, far from deciding the issue, since there remains the environmental risk aspects of not the eating, but the actual production of the food. This has always and continue to be the overwhelming reason for a high degree of caution, skepticism and restraint in the GM food area.

In a very recent (and, I would say, seminal) book by David B. Resnik, Environmental Health Ethics, that I just finished reading and am about to review for the journal Public Health Ethics, this is the main conclusion to embrace, although it is held out that GM food may bring some rather particular food safety issues when the genetic modification concerns the production or resistance to toxic agents. Nevertheless, Resnik ends up supporting the notion of a regulated and supervised introduction of GM food, where a number of factors must be considered to decide an issue like that of the "Frankenfish" Salmon production. In my own thinking around the GM food issue – foremost in my book The Price of Precaution and the Ethics of Risk (in particular in chapter 6) – I reached a similar, yet slightly more specific, conclusion. One thing that Resnik lists among the factors to ponder is that of the value of the final product, however, there is not much of specific discussion of what the actual value of actual GM foods is (rather than what it may be). My own analysis, in contrast, takes this into account and ends up, because of this, in the position that, in fact, most actual GM food prospects are very difficult to justify in view of the environmental risks. This since most GM food provides no benefit whatsoever that cannot be had in other ways, besides a better profit margin for the producer.

So where do we end up regarding the GM salmon in light of this. Well, first of all, it should be underscored that the project has indeed put some impressive environmental safeguards in place. The environmental concerns with regard to GM food production are basically two, genetic leakage over species borders and (because of genetic leakage or other reason) ecological hazard, and these are indeed addressed by the sterility of the "Frankenfish" as well as the external measures, such as initial growth in isolated tanks. However, as we know, nature is a very complex system that we still understand only partially (to put is mildly), and there will of course be risks, uncertainties and things we currently don't know about remaining. The crucial question, therefore, is the last one formulated above, whether or not the added value of this particular product makes it worth allowing the introduction in view of the risks and uncertainties, given the safeguards described. It is here, that I become less optimistic than the FDA, Caplan and (possibly) Resnik. While there may certainly be envisioned a use of GMO technology to provide humanity with significant benefits to justify large scale introduction (under oversight) of GM food with safeguards of the sort described, the "Frankenfish" salmon, just as the "roundup ready" crops, does seem to provide benefit, first, merely of a monetary kind and, secondly, only to the producer. This is, in the GM salmon case, no different than the use of growth hormone or antibiotic feeding supplement in industrial farming. Therefore, I can see no added value of this product and thus it cannot justify its environmental risks, however small.