Think of a cinematic film. You identify a specific sequence of frames that you want to replace. If you have a film reel, you go and cut the celluloid, and paste the two ends back together, or you can insert another sequence of frames. Now imagine that you can do the same thing in the genetic code, the code of life.
Jennifer Doudna, biochemist, interview with CBS, 2015
The unthinkable became possible.
David Baltimore, biologist, December 2015
It is called Clustered Regularly Interspaced Short Palindromic Repeat/Cas9. You can remember its acronym: CRISPR/Cas9. It is the latest so far invention – miracle of genetic engineering: it allows the cutting and sewing of DNA sequences (any DNA) at will. Geneticists rejoice. And they promise (again) the treatment of everything. Companies are rubbing their hands. Perhaps we should have stopped them earlier;
the bacteria of the oryx
Since the late 1990s and early 2000s, geneticists have discovered how to harness a natural defense mechanism of various bacteria. In order to protect themselves from viruses, they produce a type of enzyme that “cuts” viral DNA at various points, rendering them useless. For the first time in 2005, the use of such an enzyme was tested experimentally in the laboratory, which geneticists named “zinc finger” and is produced by the bacterium Flavobacterium okeanokoites. The method was a significant “step forward” in genetic engineering, but it had several disadvantages. It was expensive ($5,000 for each experiment), and furthermore, the specific enzyme was difficult to guide accurately to predetermined sites on the target DNA. Finally, it cut only one (of the two) sequences of the double helix each time, causing the target DNA to self-repair.
And then came, in 2012, Jennifer Doudna, a biochemist at the University of California, and Emmanuelle Charpentier, a microbiologist at the Max Plank Institute in Berlin, to announce a “leap.” They had studied the defensive action of another bacterium, Streptococcus pyogenes. In order to defend itself against viruses, this streptococcus develops a technique that consists of creating two small RNA sequences. One of these (which geneticists named “guide RNA”) copies a point in the DNA sequence of the hostile virus. These two “defensive” RNA sequences shape a “biological vehicle” by adding the protein/scissors, which geneticists named Cas9. Under the guidance of the guide RNA, Cas9 cuts the virus’s DNA at the points corresponding to the ends of this RNA/mimicry. Subsequently, the other RNA sequence (created by the bacterium), a sequence that is different from the one that was cut, is installed in its place. The virus “repairs” its cut DNA by filling in the donated-inserted RNA sequence. And so it forcibly changes its genetic code, and becomes harmless: an impressive (and “natural”…) genetic montage, to the detriment of the enemy…
This particular bacterium does something else as well. The pieces of enemy DNA that it cuts from attacking viruses, it incorporates into its own DNA in order to (scientists believe) use them as reference material to create “guide RNA” for future attacks (by similar) viruses. The name, therefore, “Clustered Regularly Interspaced Short Palindromic Repeat” refers to this “storage/integration” of enemy fragments… It does not appear in the name “crispr”, nor in the celebratory adoption of the method at the heart of genetic engineering… But it concerns the defensive behavior of the pyogenic streptococcus…
The advantages of the crispr/cas9 method were recognized with enthusiasm internationally, like fire spreading through dry grass. To begin with, this method cuts both strands of the double helix simultaneously. Doudna and Charpentier found a way to combine an artificial “guide rna” (cr/rna, mimicking the dna sequence/target that needs to be “cut”) and also an artificial “trans-activating crispr rna” (tracr/rna, replacement rna) into a synthetic “single guide rna” (sg/rna), which can direct cas9 anywhere it “needs” to go. After this, any geneticist who wants to “cut” any sequence in any dna of any species can quickly and easily design the sg/rna they want, and order it from a specialized laboratory for only 65 dollars.
Cheap, easy to use, and effective: crispr/cas9 is now the “multi-tool” of genetic engineering. Not the perfect tool – in fact “not the tool for which the most prominent geneticists would put their hand in the fire.” Not yet. It has been found, for example, that cas9 goes and “cuts” the dna at other sites, not only at the targets. There is also a structural problem: the nucleotide sequence that has been targeted may exist two or even more times, at different points in the dna strand (“homologous” sequences). The cas9-sg/rna complex can go astray, and strike elsewhere; or even elsewhere… However, these are problems that concern the specialists. Thus, for example, at the end of 2015 Feng Zhang, a synthetic biologist at MIT and Harvard, created with his team a synthetic version of the cas9 enzyme, by replacing some of its amino acids. In this way (he claims that) he “calmed down” its action, so that it does not act on other sites except the sequence(s) for which it is deployed each time.
do geneticists play dice?
It is now the most powerful tool we have in biology. For every biological process that concerns us today, we can identify the entire set of genes that cause it. Something like this was impossible before.
David Sabatini, biochemist
It is, indeed, the dream of every geneticist; the dream of all those professionally involved with genetic modification. And there is no animal species on the planet (perhaps, in the future, on others too) that is excluded from the research / professional (and, quickly, very quickly, commercial) “temptation” of genetic modification. For a good purpose – isn’t that always the motive?
For example, there is a problem that we ignore, perhaps you too: the tomato virus. It affects various tomato plant varieties (we assume: all of biotechnological origin; do “old” tomatoes exist anywhere in the world?) causing plant debilitation, abnormal leaf development and fruit destruction. Despite the efforts of various scientific fields to suppress it, no effective treatment had been found; until recently.
A group of biologists decided to test the crispr/cas9 method. They chose to experiment on a variety of tobacco (plant), which serves as a “model organism” for geneticists, and is also susceptible to the tomato virus… First, they designed sg/rna targeting both coding and non-coding nucleotide sequences of the virus, and introduced them into viruses that are harmless to this particular tobacco variety. Then they “infected” the tobacco plants with these harmless viruses. After a week, they infected the same plants with the tomato virus, and after another ten days they analyzed the plants to see if they had been infected by the tomato virus. Guess what: the experiment was almost completely successful. The experimental tobacco plants either had not been infected at all by the aggressive and destructive tomato virus, or had significantly reduced symptoms of infection.
Genetic modifications of various living species were known, until now, as designed mutations. The “war” regarding them continues to the extent that there is an extremely well-founded suspicion about the chain consequences that genetic modification of an organism has on the others with which it has any eco-physical relationship. However, the suspicion focuses mainly on food; not, for example, on insects. The genetically modified mosquitoes that would supposedly eliminate the Zika virus did not cause any repulsion or fuss.
The ease and low cost of crispr/cas9 (and its improvements) makes it ubiquitous for the genetic cut-and-paste of everything. In this sense, its scope goes far beyond the idea we have for food and their organized production in the 21st century: microorganisms that have been deployed via crispr/cas9 to “target” specific species (let’s say: edible ones) do not need the approval of any state authority in order to circulate; and to make a post variety of one or another edible species also “genetically improved” via crispr/cas9, urgently necessary. In other words: such a biological war will not be officially declared.
And it won’t even be easy to detect. Until before the invention and expansion of CRISPR/Cas9, designed mutations in plants and animals were implemented only after a period of experimentation, involving gene insertions into the DNA of one or another species in a somewhat random (and in any case not “safe”) manner. Patenting these applications made them accessible to specialists who oppose the release of genetically modified DNA into the environment; and this, in turn, fueled social rejection of genetically modified foods with solid arguments. With CRISPR/Cas9, it is almost impossible to subsequently determine whether a change in the genome is random or designed and laboratory-made. And if this change is malicious and has not been patented or published, then it is essentially “invisible.”
The ease and extremely low cost of crispr/cas9 has opened the research (initially) appetite for what geneticists call genetic drive (“gene drive”). In other words, it is about the genetic modification of ecosystems; not just “individuals” of a species. With the older techniques, the designed mutations were transferred very slowly to the next generations of the x or y mutated species. This was due to the fact that the mutation occurred in one of the pair of chromosomes, and consequently was transferred “by half” to the next generation. A mutation made with crispr/cas9 (or whatever similar more advanced method is invented in the future) is transferred entirely to the next generation; it becomes a standard genetic trait. A designed mutation in a mosquito species will be transferred to its eggs immediately: genetically modified (via crispr/cas9) insects and various microorganisms are already not just experimental fields but commercially exploitable species. However, the genetic modification of a species as a whole (even of an insect) cannot but have chain consequences throughout the entire ecosystem; consequences that can neither be predicted nor, of course, designed. The remedy against such eventualities is commonplace: states must legislate the specifications and limits of use of crispr/cas9…
All these developments are unfolding at a very rapid pace: biotechnology laboratories, geneticists, and companies interested in commercial exploitation are numerous across the planet. In many countries, with different legislations; or even with different “awareness” (or ignorance) of the issues. The trajectory of patents and funding for research and applications of CRISPR/Cas9 (see tables above) shows that any “legislative restrictions,” if they come at all, will come belatedly—that is, far too late. And they will be merely symbolic, intended to “reassure public opinion.” Because the low cost and technical simplicity of genetic engineering via CRISPR/Cas9 have already achieved what some call the democratization (!) of genetic engineering. Even “mid-level” laboratories can now engage in it, without being officially “registered” or “legal.” Could it be that the time is near when we will be told that certain “terrorists” possess the technology and the means, and are preparing for a biological “Revelation”? Not at all unlikely.
At the same time, however, all these things are happening while faithfully adhering to the line of genetic determinism. Four months ago (cyborg no 7, genetic predetermination; no thanks!) we described that “hard” genetic aristocracy is outdated; but only among “specialists.” As a social ideology it works just fine, because it appears to propose causes and offer solutions (at the micro-scale of genes) even though, in reality, it’s nothing more than another mass techno-scientific deception. The known (to specialists) regarding genome function is decreasing rather than increasing in relation to the unknown as related research progresses.
But trade is a different story. Obviously, sales of salvation of one kind or another are not achieved with “maybe” and “we don’t know.” Genetic engineering and its current diamond in the crown, crispr/cas9, is a kind of “technological/commercial answer” based on the one-dimensional deterministic pattern: we know (or are about to learn) everything about genes (yours). However, because this is simply an ideologically and commercially useful lie, the rapid spread of crispr/cas9 is doomed to spawn monsters.
ethics editing
Genetic modification in human embryos using current technologies may have unpredictable consequences for future generations. This makes it dangerous and unacceptable from an ethical standpoint.
Edward Lanphier, founder and (until last year) president of the biotechnology company Sangamo BioSciences
Deliberately staying away from research that could save lives means that we would be morally responsible for the predictable and preventable deaths of all those who could have benefited from this research.
Julian Savulescu, bioethicist
Many rest content with the hope of the much-talked-about “scientific ethics.” Indeed, geneticists (like many others), in order to soothe not only the often justified concerns about their work but also the questioning of their (social) role, have taken care to internalize “ethical questions.” Or more accurately, they have taken care to keep them for themselves, formulated in such a way that directly or indirectly, sooner or later, they lead to the question of scientific / research freedom.
The catalyst for such well-guarded “ethical deliberations” is (what else?) the use of genetic modification techniques on human cells. Regarding the use of CRISPR/Cas9, the trigger was provided in April 2015, when a group of Chinese researchers, led by Junjiu Huang, experimentally employed the method on human tripronuclear zygotes—early embryos that do not survive, as their cells contain the nuclei of one egg and two sperm cells, and are not suitable for other clinical uses. Their goal was to successfully “cut” the endogenous β-globin gene sequence, which, if mutated, causes a fatal blood disorder known as β-thalassemia. The experiment was not particularly successful for many reasons, including the fact that Cas9 “cut” DNA at off-target sites as well. Huang himself acknowledged that significant improvements must be made to the method in order to reduce its inaccuracies.
Regardless of the Chinese experiment’s announcement, beyond confirming that Chinese capitalism is not at all “behind” in cutting-edge technologies, it caused the expected “moral uproar” among geneticist circles worldwide. It is the same “moral uproar” that has erupted with every previous biotechnological application in humans: from DNA recombination to artificial insemination. As had happened in previous instances, so now, the “experts” and professional advocates of the “scientific ethics” of genetic engineering split into two camps. One trend called for a “voluntary moratorium” on CRISPR/Cas9 research in human cells until safe conclusions emerge from research and applications in other species. The other trend mocked these appeals, reminding that in the past, vaccines or transplants had initially been considered ethically problematic. If you ban something, the probability that humanity will benefit from it is zero. If you don’t ban it, the probability is greater than zero. This “wisely” stated, for example, Steven Pinker, a specialist in “consciousness sciences” at Harvard.
However, a technique that promises so much is “beyond morality”; certainly beyond the discussable techno-scientific kind. While geneticists were wondering (or pretending to wonder) “what is right,” the UK’s Human Fertilisation and Embryology Authority granted permission on February 1, 2016, for the first use of CRISPR/Cas9 on healthy human embryos. The relevant application had been made a few months earlier on behalf of a research program that has no direct therapeutic purpose, nor even as a pretext. It is a kind of genetic “basic research,” into the role various genes play in the development of the human embryo. But, of course, those who conduct such research first gain advantages over those who follow. And the techno-scientific world, with a more flexible or tighter (or no) “morality,” remains above all a capitalist world. That is: with the purpose of profit.
Here’s what happens. There are countries that prohibit the modification of the human genetic code, and there are others that do not prohibit it, to the extent that it appears as research (in the first case, 15 European countries belong). The only difference, which looks serious at first glance but is not in essence, lies in the funding of such research projects. In official funding, we must say; from public/state accounts.
But this problem is easily fixed. Research teams are often multinational; which means that geneticists from countries that do not fund their research can wonderfully collaborate with others who secure state funding. And, of course, there is always the large pool of private/corporate funding. No problem, then.1
fear and social relations
Such technoscientific moves, when they become widely known outside of “specialists” (rather rare), cause dread. Fear. Informatics / cybernetics produce various applications / gadgets that familiarize individuals and societies with an abstract (and fetishistic) idea of “new technologies” – and their supposedly good purposes. Genetics, neuroscience and biotechnology do not have the same public relations model. They remain largely separate, laboratory-based, “dark” for the future of our species. Due to their subject matter. Consequently, awareness that genetic engineers can assemble (and) the human genome at will would cause great concerns; even if such news were served with the familiar garnish of combating various incurable diseases. Which is roughly the same (as legitimization of technological leaps) for at least a century.
But where do these fears and anxieties come from? From at least two factors, which are the same across the entire spectrum of technologies within the new capitalist model. First, the “average citizen,” even if they have some specialized education outside of genetics, remains ignorant of exactly what (and why) is happening in biotechnology laboratories. They are easily subjected to any ideological processing, starting from myths about “technoscientific progress for the good of humanity” and extending all the way to the opposite extreme, to myths about a biological Armageddon. Second (and to some extent as a consequence of the first), there is no social oversight whatsoever over the “what” and “why” of technoscientific research—for example, genetic research. Those who should be subject to control, namely the technoscientists themselves, have monopolized for themselves the “responsibility” of being the overseers. This is done, supposedly, in the name of scientific freedom.
There are therefore two huge gaps between the technoscientists of the 21st century and the capitalist societies that fund their research, applications and trades. The first is epistemological. The second is political. And although we would risk being accused as autonomous workers for wishful thinking, we believe there are two critical questions:
A) Should we know without, at the same time, needing a hundred lives to reach the “specialized knowledge” of the technicians of one or another kind? And if the answer is “yes”, how can this be achieved?
B) Should research and applications deemed dangerous be able to be prevented, through social (and not state) choices and decisions? Would such a thing be a “restriction of scientific freedom”?
The second question, which seems “philosophical” (and anyway intriguing), is perhaps easier to answer. None of us is “free”! We are all historically determined, we live within intelligible or unintelligible social constraints; and anyway no one funds us to feel (or pretend to be) free! The exact same applies to technoscientists, especially when they are outside their sanctuaries/laboratories. Moreover, their specializations are not products of any “freedom of choice” on their part. They are products of statistical distributions; starting from educational systems and the general divisions of labor of each era. Finally, any research is necessarily subject to the rules of its funding; and/or to the constraints of academic prestige, research and university bureaucracy, etc. This means: no technoscientist is “free”, one way or another.
Consequently, to prevent any research and application of crispr/cas9 in any living species, if a broad “social body” (and not the circle of interests of geneticists, bioethicists, and genetic entrepreneurs) with good knowledge of the subject were to judge, by majority, that these researches and applications constitute a risk disproportionately large in relation to any potential benefits, this would not be merely and tyrannically “restricting scientific freedom.” It would be a reminder to specialists that they are not, after all, freer than any of us, and certainly not participants in some metaphysical, “divine freedom.” And, furthermore, it would be a practical exercise of the responsibilities, and especially the moral responsibilities, of each and every one of us, as social subjects.
The epistemological gap, however; this is harder to address. It is the result of a well-calculated (state and capitalist) distribution and hierarchy of knowledge (within or outside quotations) that has become even more pivotal in the phase of “cognitive capitalism.” Consequently, the epistemological gap, beyond its “technical” aspects, has a political origin and basis: the intellectual (and political) subjugation of the subordinates through the distribution not of “knowledge” but of ignorance.
However, even so, there are still possibilities for “non-conventional” learning; that is, outside the existing educational systems.2 Only that their utilization depends on disposition, orientation, and available time. If the first two are subjective, the third is not.3
What remains? To seriously address, individually and collectively, this epistemological gap (which is synonymous with the disappearance of criticism) before we are definitively “transformed.” Not only genetically, but also informationally / cybernetically…
Ziggy Stardust
cyborg #08 – 02/2016
- Indicatively: on December 1, 2016, a group of 36 scientists from around the world (more than 15 countries, including Saudi Arabia…), published in the journal Nature the results of a study on the use of crispr/cas9 on living somatic cells – that is, what is “forbidden” here and there. The underlying idea (?) is that if crispr/cas9 can be used to massively genetically modify a large number of cells in a (human) organ, then an effective therapeutic method for incurable diseases could emerge… (Of course, any talk about potential but not yet studied side effects can only be considered as anti-scientific prejudice… when you have such a significant technological step right in front of you…) ↩︎
- Z. S., who signs this report, has no education in biology, genetics, etc. He is “self-taught – in general / basic matters”, if such a characterization is allowed. ↩︎
- The orientation towards a substantial reduction of the basic working time, as has been indicated by the autonomists (30/900), has a direct relationship with this issue as well. ↩︎