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CRISPR-Cas9: the keys to understanding a scientific breakthrough marked by bioethical controversy

Never had a yoghurt generated so much expectation. Nor so much controversy. The CRISPR-Cas9 system was discovered for the first time back in 2000, when Philippe Horvath and Rodolphe Barrangou were studying why certain bacteria suffered viral infections which reduced the productivity and yield in cultures.

Scientists at Danisco, later acquired by DuPont, had devoted themselves to sequencing the genome of Streptococcus thermophilus, a well-known bacterium in industrial cheese and yoghurt production. When studying this micro-organism, they realised that it contained repeated genetic sequences, which they called CRISPR.

Despite their unpronounceable name, the sequences served the microbes as virus recognition systems, fending off viruses with interfering RNA molecules. What they were faced with then was not merely a quirk of these lactic bacteria, but a key mechanism in adaptive microbial immunity. In 2012, the teams led by Jennifer Doudna and Emmanuelle Charpentier presented the CRISPR-Cas9 system in the journal Science as a key tool for editing the genome. Thus was born a new revolution in the history of genetic engineering.

 

                       Image: The Doudna research group

 

Indeed, CRISPR-Cas9 is reminiscent of the recombinant DNA technology developed in the seventies. Not only owing to its countless applications in fields such as medicine (with the development of modified macaques to better study disease or to precisely cure different pathologies), agriculture and the environment, but also due to its similarity with the "molecular scissors" which has enabled the spectacular development of biotechnology that we have witnessed in recent decades.

Undoubtedly, genetic modification has been instrumental in achieving, among other breakthroughs, recombinant insulin, crops resistant to drought or saline conditions, new vaccines and micro-organisms that clean up contaminated areas. Nonetheless, this scientific progress has been marked by extensive bioethical controversy. The birth of recombinant DNA technology was received positively, although it also gave rise to misgivings and fears owing to its implications. The same is now occurring with CRISPR-Cas9, a system which is characterised not only by editing the genome, but particularly by doing so in a swift, precise and effective manner.

The similarities between the birth of genetic engineering and Doudna and Charpentier's genomic editing have led a number of researchers to express the need to promote another Asilomar 2.0 Conference. That encounter, organised back in 1975 by Paul Berg, served to establish a moratorium on the application of genetic engineering, to discuss the possible benefits and dangers, and to debate on the importance of the principle of precaution: These three topics are once again on the table with the arrival of CRISPR-Cas9, particularly following the announcement made by Chinese researches in Protein & Cell, in which they disseminated the genetic modification of human embryos.

As Richard J. Roberts explained during the Lindau Nobel Laureate Meeting, “the Asilomar conference was promoted by young scientists of the period, with the aim of opening a bioethical debate”. The researcher, recipient of the 1993 Nobel Prize in Physiology or Medicine, believes that “there is no justification to prevent us from progressing in a responsible manner”. This opinion is shared by Elizabeth Blackburn, the discoverer of telomeres and telomerase, who maintains that “technology will always have potential benefits and possible drawbacks, when talking about either autonomous vehicles or genomic editing”.

 

                       Image: MIT Institute Archives

 

Just like what occurred with recombinant DNA technology, the creators of CRISPR-Cas9 systems are fully aware of the important bioethical implications entailed with this scientific breakthrough. In an article published in Science in March of this year, Doudna, along with other researchers, asked for a “prudent path forward” to be taken in the application of genomic editing. The document suggested the need to discuss the social, environmental and ethical implications of this technology, also urging the scientific community to refrain from using CRISPR-Cas9 to genetically modify the germ-line for possible clinical applications in humans.

Was science more rapid than bioethical reflection? According to Roberts, “research progresses quickly, much more so than national science academies”. For this reason, the meeting held in Lindau, with the attendance of young researchers and Nobel Prize winners, drew attention to the need to encourage a rational debate, in which the importance of communicating scientific results to the community is also highlighted. But as Hank Greely, a specialist in bioethics and law at Stanford University argues, “the possible implications of CRISPR-Cas9 go beyond the human species”. The expert agrees with the need to organise a conference similar to Asilomar, although he points out that the debate should also address all possible genetic engineering tools, not only that created by Doudna and Charpentier.

Greely also affirms that, as occurred with recombinant DNA, this technology may have an impact on the planet's biodiversity, in addition to being the focus of debate in other matters related with industrial property and patents. So what will happen from this point on? As all the specialists consulted explain, we stand on the threshold of organising a second Asilomar in the middle of the 21st century. And what will the outcome be? Although it is difficult to predict the outcome of bioethical debate, researchers such as J. Michael Bishop, also present in Lindau, point out that “the international scientific community will once again reach an agreement, as occurred in 1975, or more recently with research into stem cells”.