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 splice the two ends back together, or you can insert another sequence of frames.
Jennifer Doudna, biochemist, interview with CBS, 2015
Now imagine that you can do the same thing in the genetic code, the code of life.
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 stitching of DNA sequences (any DNA) at will. Geneticists rejoice. And they promise (again) the treatment of everything. Companies are rubbing their hands. Should we have stopped them earlier?
…
If the above reminds you of something, you are right. This is how it started, under the title genetic tailoring: the great bluff, the reference of cyborg 8 (Flevares 2017) to the “holy grail” of biotechnologists and geneticists. To the technique called crispr/cas9, which promised maximum ease and accuracy (at the lowest possible cost…) in the modification of dna at will. Human and not only. For therapeutic reasons (and whatever else might arise).
For those who have no idea whatsoever about what this is about, a brief description. By copying the natural defensive action of a bacterium (with the not-so-pleasant name streptococcus pyogenes – pyogenic streptococcus) against viruses that attack it, two geneticists (Jennifer Doudna and Emmanuellle Charpentier) managed to copy the mechanism and design its programmed application. The bacterium, in order to disable the viruses, “cuts” their DNA and replaces it with another, of its own production – changing the genetic code and consequently disabling the virus. The techno-scientific appropriation of this process involves on one hand the design of a small sequence/substitution and on the other hand the construction of a “genetic scissors” that will cut at specific points, and only as much as needed, to change the “bad piece” with the new, “correct” one.
The technique created by the two geneticists was something like a “godsend” for genetic engineers, who were already experimenting with other methods – with pathetic failures. Crispr/cas 9 promised something that until then was a dream: cutting with high precision at selected points of the DNA to be corrected, and replacing it (again with precision) with an artificial sequence, constructed as RNA. The failures of previous methods were due to the fact that the DNA was not “cut” only where the target was but also randomly (or so biotechnologists understood it) and at other, unintended, points of the sequence. Crispr/cas 9 promised this too: intervention, correction just in place.
Despite the techno-scientific enthusiasm from the beginning (2012), there were some reservations about the possibility that CRISPR/Cas9 might not be so accurate. The first related studies had mixed results. Some researchers did not find “interventions” of the process at other points in the DNA sequence; others claimed they did. This uncertainty did not prevent the initiation of the method’s application; initially not in humans, but in animals.
About a decade ago, for example, English veterinarians discovered that a “line” of King Charles Spaniel dogs produced a percentage of male offspring who exhibited severe muscular dystrophy before closing their first year of life. A gene was identified as responsible which, according to biotechnologists, is responsible for the production of a muscle protein called dystrophin – a diagnosis that had already been made in children with a similar problem. As the only treatment, veterinarians had hormone therapy.
Until the invention of crispr/cas9, various geneticists fell face-first in trying to find a solution to the issue. The dystrophin gene is large, and there are many different sequences that could be responsible for muscular dystrophy. A research team from the medical center of the University of Texas claimed to have found some of these sequences responsible for 15% of normal dystrophin flow; if these could be replaced via crispr/cas9, poorly developed spaniels could be treated. Indeed, last summer, the team published their successful results from live trials in Science. The certainty of this particular team was such that they even created a startup, named Exonics, aiming for what is called “high-risk philanthropy” (following the model of “venture philanthropy”). That is, inviting volunteers with muscular dystrophy and limited response to other therapies to become experimental subjects in the uncertain quest for genetic therapy… Naturally, with the goal that, if the method proves successful in humans, they will secure its commercial patent…
Someone might be skeptical, but this is how biotechnology progresses. The Texas team did nothing illegal, since crispr/cas9 promises so much (and initially risk-free) that internationally 17 permits have been granted for clinical trials of the method on humans, for leukemia, brain cancer and a form of anemia. Just in early last September, Chinese biotechnologists from Shanghai Polytechnic University and the Third Medical University of Guangzhou announced the successful (?) application of crispr/cas9 in repairing in human embryos (always in the laboratory) a genetic abnormality responsible for Marfan syndrome. 1 According to their announcement in Molecular Therapy, the Chinese geneticists had success in 16 out of 18 experimental embryos, “without adverse side effects.” Really?
However, a month and a half earlier, in mid-July, another group of researchers from the Sanger Institute in Cambridge published in Nature Biotechnology the results of the most extensive research so far on whether there are “off-target effects” in the application of CRISPR/Cas9. Their findings were far from celebratory: the “genetic scissors” continue to “cut” pieces of DNA even after completing their mission. Moreover, it makes cuts not only near the “target” but also farther away, in locations that might go unnoticed by a hasty (and positively predisposed) researcher. In fact, the study showed that the action of the CRISPR/Cas9 “genetic scissors” is unpredictable, either because it cuts uncontrollably, or because the cutting and stitching itself causes unknown “reactions” (and changes) throughout the entire length of the DNA.
So, is this scientific fraud? Is the treatment of muscular dystrophy in spaniels or the treatment of Marfan syndrome in human experimental embryos (consciously) a joke? Not exactly. It all comes down to the deep ideological certainties of scientists; in this case, biotechnologists and geneticists. While there is strong evidence from research within their own techno-scientific circles that the deterministic “reading” of DNA (gene A is responsible for A, gene B for B, etc.) does not actually hold true, and that it is unknown how DNA “works” (and not only human DNA), the ideological mainstream of genetics continues to insist that
a) it knows how DNA works;
b) it knows which “distinct gene” is responsible for what;
c) it can replace any “problematic gene” in the same way that someone can change a “worn-out” bolt in a metal structure without dealing with the rest.
Because, precisely, these are interventions in living organisms that unfold their characteristics (their phenotype) over time for a long or even very long period. Even if someone is momentarily certain they have corrected the gene (a) (as if to say: that they tightened the screw), they do not know, nor can they know, what consequences the repair method has caused at other points in the genetic code—consequences that may manifest after some time, even after years. The exact same applies to the chemical pharmaceutical industry. Theoretically, clinical trials for new drugs should last for years in order to detect adverse effects that might appear later. However, pharmaceutical companies have no reason to wait. They have therefore ensured, through state laws, to reduce the waiting/search period for side effects to a minimum, so they can launch their new drugs onto the market as quickly as possible. And if side effects appear? It is the doctors’ job NOT to attribute them to the pharmaceutical companies, but to anywhere else…
Thus, it is not specific “deceptions” in genetic accomplishments; the entire basis of mainstream genetic theorems is arbitrary!!! Depending on the time frame over which one observes the consequences of a particular genetic engineering intervention, a sense of certainty regarding the “therapy’s” effectiveness may indeed be created. Does it truly hold? No one can know.
Nevertheless, the deterministic one-way path of genetic engineering has a strategic advantage: it convinces societies (which perceive the body as a set of components; so why not also the “genetic code”?) and thus, it sells! It is commercially exploitable.
“Truth,” “effectiveness” are relative concepts for technoscientists, even if they swear otherwise… After the rather successful handling of the unprecedented (given the scientific data) crime of thalidomide, technoscientists and companies commercially exploiting one or another therapeutic patent have learned how to cover their formerly dirty tracks: by shifting the blame to the “unknown”… 2
Ziggy Stardust
cyborg #13 – 10/2018
- The “Marfan syndrome”, which according to statistics affects 1 in approximately 1500 people, concerns the insufficient production of the protein called “fibrillin” which is related (the protein) to the development of various tissues, from bones and muscles, to joint ligaments and connective tissues. Patients have “long bones” (and height) but often deformed and not resistant – etc. ↩︎
- Thalidomide, in the 1950s until the early 1960s, was a widely used “mild sedative” that was broadly prescribed to pregnant women to address various emotional disturbances during pregnancy. After years of animal testing, it had been certified as an “ideally safe” drug. It wasn’t. It resulted in the birth of over 10,000 severely deformed babies worldwide, who went down in history as “thalidomide babies.”
For many years, the manufacturing company (Grunenthal) denied that there was any connection between thalidomide and the deformities. In the lawsuits filed against it starting in the 1970s, they presented dozens of witnesses, “experts,” who claimed that animal testing had indeed never revealed anything alarming about the drug’s use in humans.
One of them, however, Ernst Boris Chain, a German-British biochemist and Nobel laureate from 1945 for his research on penicillin, had a different opinion in court: No pharmaceutical compound tested on animals, even if tested on several animal species, even primates, and under all conditions, offers any guarantee that the drug will have the same effect in humans…
This may be absolutely or partially true—we don’t know. What seems logical, however, is that if the consequences in experimental animals are long-term, the experimenters won’t see them. Either because they don’t want to, or because they didn’t deal with it, or because they didn’t have the time. If, for example, the experiments with thalidomide (before it entered commercial circulation) had been conducted on higher mammals, does anyone believe that the experimenters gave the drug to pregnant animals and studied the rates of malformations and deformities in the offspring of these mammals? Unlikely…
The side effect appeared (in a particularly high, albeit not absolutely universal, percentage) not in the mothers but in the next generation. And we are talking (regarding thalidomide) only about a “chemical.” Could a genetic modification display its adverse effects after one, two, or three generations? Why not? Who determines the “scientifically valid” timeframe within which the side effects of genetic engineering will or won’t appear? What does “safe” mean for genetic scissors?
(For the record: Grunenthal was ultimately acquitted…) ↩︎