Since its inception four decades ago, genetic engineering has become a source of great hope in healthcare, agriculture and industry. But it also caused deep concern, not least because of the laboriousness of the genome editing process. Now a new technique, CRISPR-Cas, offers both precision and the ability to alter genome text at multiple locations simultaneously. But this did not remove the cause for concern.
The genome can be seen as a kind of musical score. In the same way that notes tell musicians in an orchestra when and how to play, the genome tells the constituent parts of the cell (usually proteins) what they should do. The score may also include the composer's notes that indicate possible changes, excesses, which may be added or excluded, as the case may be. For the genome, such "notes" arise from the life of cells over many generations in a constantly changing environment.
The genetic program of DNA is akin to a fragile book: the order of its pages can change, and some even move into the program of other cells. If a page is, say, laminated, it is less prone to damage as it flips. Likewise, elements of the genetic program, protected by a strong coating, are better able to penetrate into various cells and then reproduce as the cell divides.
Subsequently, this element becomes a rapidly spreading virus. The next step is a cell that reproduces the virus - useless or harmful - to develop a way to counter it. And in fact, this is how the CRISPR-Cas process first emerged to protect bacteria from invading viruses.
This process allows acquired properties to become inheritable. During the first infection, a small fragment of the viral genome - a kind of signature - is copied into the CRISPR genomic island (an additional fragment of the genome, outside the text of the parental genome). As a result, the memory of the infection persists for generations. When a descendant of a cell is infected with a virus, the sequence will be compared to the viral genome. If a similar virus infected the parent of the cell, the descendant will recognize it, and special mechanisms will destroy it.
For scientists, this complex deciphering process took many decades, not least because it contradicted standard theories of evolution. But to date, scientists have figured out how to replicate the process, allowing humans to edit specific genomes with utmost precision - practically the holy grail of genetic engineering in nearly 50 years.
This means scientists can use the CRISPR-Cas mechanism to fix problems in the genome - the equivalent of typing errors in written text. For example, in the case of cancer, we would like to destroy those genes that allow tumor cells to multiply. We are also interested in introducing genes into cells that have never received them by natural genetic transmission.
There is nothing new for these purposes. But with CRISPR-Cas, we are much better equipped to achieve them. Previous methods have left traces in modified genomes, contributing, for example, to antibiotic resistance. In contrast, a mutation produced by CRISPR-Cas is no different from a mutation that arose spontaneously. That is why, the US Food and Drug Administration has ruled that such ingredients should not be labeled as genetically modified organisms.
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If several genes had to be modified, the previous methods were especially difficult because the process had to be done sequentially. Thanks to CRISPR-Cas, the ability to perform genome modifications at the same time has allowed the creation of mushrooms and apples that do not oxidize or turn brown when in contact with air - a result that requires the simultaneous deactivation of several genes. These apples are already on the market and are not considered genetically modified organisms.
Other applications are in development. The so-called gene generation procedure to manipulate the genome can reduce the harm caused by disease-carrying insects. The targeted modification of gametes in mosquitoes - the world's most deadly to humans - would render them incapable of transmitting a virus or parasite.
But the use of CRISPR-Cas must be approached with caution. While this technology can prove to be a boon in the fight against many deadly diseases, it also carries serious and potentially completely unpredictable risks. First, because genomes reproduce and spread by reproduction, modifying an entire population will only require modifying a limited number of individuals, especially if the organism's life cycle is short.
Moreover, given the ubiquity of hybridization among neighboring species, it is possible that modification of one mosquito species will also gradually and uncontrollably spread to other species. Analysis of animal genomes shows that such events have occurred in the past, with species being captured by genetic elements that could affect ecosystem balances and species evolution (although it is impossible to say how). And if changing the mosquito population is dangerous, it is not known what could happen if we modify human cells - in particular, germ cells - without careful analysis.
CRISPR-Cas technology is ready to change the world. The main challenge today is to ensure that these changes work.
Antoine Danchin