Manipulating the genome could lead to very unexpected results this is what two FDA scientists US Food and Drug Administration, Alexis Norris and Heather Lombardi have discovered. The experts have signed an article still under review but already public to evidence an error that is easily detected and which is not sufficiently informed as Norris explained.
The mistake has to do with calves and their horns. For years, dairy cows, white with black spots, do not usually have horns. For farmers, this bone extension is a problem: cattle overcrowded in the stables can hurt each other, and the farmers themselves. The solution is quite painful for bovids, since it consists of dehorning, that is, burning the horns that begin to sprout with an incandescent iron.
A less bloody solution was provided three years ago by an American biotechnology company called Recombinetics and consists of genetic editing to replace a specific DNA sequence with another. The best known genetic editing technique is called CRISPR , but the researcher Daniel Carlson and his Recombinetics team used another similar technique in 2014 called TALEN.
Carlson replaced a sequence of 10 nucleotides in the Holstein horned dairy cow (the one with black spots) with 212 nucleotides from another type of cow, the Angus, which is usually black and without horns. Nine months later, in 2015, two calves were born, Buriand Spotigy , with its pretty spots, and no horn feature. The researchers published their finding in the journal Nature Biotechnology in 2016. It is a “natural” genetic variant obtained by saving generations of cows crossings.
Buri and Spotigy have served to illustrate in dozens of conferences how well genetic editing techniques work. In June of this year, the lobby of biotech agriculture companies (such as Recombinetics) got Donald Trump to sign an executive order to “speed up” the control processes for this type of genetic techniques in agrifood products, while in Europe hundreds of institutes of investigation asked the European Parliament steps in the same direction.
However, FDA scientists, analyzing Buri’s genome in a public database, have certified an awkward truth : DNA also contained spurious genes. More specifically, of some plasmids used during the process. In principle, they do not affect the phenotype, although they are genes that confer resistance to antibiotics (to plasmids).
Plasmids are small pieces of bacterial DNA used to introduce into the cell the instructions for cutting and modifying DNA. In principle, plasmids, after carrying out their task, should be left out of the DNA. However, Norris and Lombardi have shown that this is not the case: plasmid sequences became part of the Buri genome , making it technically a transgenic organism (that is, whose DNA contains genes from other species).
“Our analysis demonstrates why a regulatory look at intentional genetic alterations in animals is necessary, although these modifications attempt to replicate mutations that occur in nature,” Lombardi and Norris explain. Although they stress that “genomic editing is a promising technique,” they add that “things can go wrong and unintended alterations can occur. That does not mean that it happens, or that it is dangerous. However, being the science so new, we should at least ensure that the alterations do what is intended and that they are safe. ”
In a note sent to this newspaper, from Recombinetics admit that they should “have verified that there were no plasmid integrations”, although they remember that their objective was to ensure that the sequence was correctly inserted, that it produced the desired effect and that there had been no improper insertions In this sense, all were “positive results.” Daniel Carlson on the other hand defines what happened as a “carelessness.”
“I wish we would have caught it then,” he tells this newspaper, “but we have always made all the information of totally transparent way Fortunately, the animal was only for research and not for trade We have to take maximum care to detect spurious insertions, but I still think that genetic editing works very well,and that these animals can be a benefit to society. ”
“Our analysis demonstrates why a regulatory look at intentional genetic alterations in animals is necessary, although these modifications attempt to replicate mutations that occur in nature.”
“The technique used by Recombinetics was based on an outdated approach,” says Joanna Loizou, principal investigator at the Center for Research of Molecular Medicine of the Austrian Academy of Sciences (CeMM) in Vienna. “Genomic editing can now be done without plasmids. We are able to synthesize and purify the necessary enzymes and we can insert them into the cell thanks to small electrical discharges that make the cell membrane more porous ”. Loizou is optimistic.
“It is true that we have to implement the most efficient mechanisms to control that the modifications we make are inserted at the correct point and at no other point in the DNA, and that no other sequence has been suppressed. However, with these precautions I do believe that putting CRISPR modified plants at the same level as transgenic plants from the regulatory point of view is an exaggeration, ”he concludes in reference to the request to the European Parliament also supported by the CeMM.
“It would not be so quick to say that the absence of horns is positive for cows,” says the director of the science, technology and society program at Harvard Kennedy School, Sheila Jasanoff in an email to this newspaper. “It may be useful to farmers, but there are still philosophical problems about how we should face alterations in other species. And there is always the question of side effects that could arise in the long term. Mutations are only rarely innocent, ”he says.
“Often procedural shortcuts in science occur when people smell the sweet smell of commercial success. The protocols are set aside in the race to be the first. Then, they declare that the rules are too slow to keep up with science. But perhaps they are violating norms that do exist or entering an area where there are none, with the idea that, if the work is successful, that will already be a sufficient legitimation. As a jurist,