Monday, March 23, 2015

DNA surgery baby “custom” – The Times (subscription)


 A new method would rewrite the DNA of sexual cells in humans. Researchers are calling for caution

Rewrite embryo’s DNA to obtain a “perfect” baby. An idea that debate and who returns to the agenda when gene modification techniques have progressed dramatically. Originally the return of this emerging controversy of the information reported by journalists of the magazine of the Massachusetts Institute of Technology in Boston (MIT Technology Review) and The Independent in Britain: laboratory research led by the Leading geneticist George Church of Harvard University, would focus on the modification of DNA in human egg cells in culture.

Even if these unpublished works are not intended, according to George Church itself to produce an embryo, the feasibility of the technique raises concerns. Several warning texts have been published in parallel by researchers in recent days in the two most prestigious scientific journals, Nature and Science. Two voices: in Nature , we propose a moratorium, that is to say, the temporary suspension of research on rewriting the DNA of human germ cells (ova and sperm). The second current, less categorical, in which George Church belongs, wants to discourage this practice while continuing fundamental research to evaluate its usefulness for therapeutic purposes.

The legal context is very different from one country to another. A study published in 2014 by a Japanese bioethicist found that of 39 countries studied, 29 had laws or recommendations prohibiting the manipulation of DNA in germ cells for clinical purposes. This is the case of many European countries, including Switzerland. In the US, there is no law that prohibits a moratorium but under the vigilance of the drug regulatory authority (FDA) and National Institutes of Health (NIH). On basic research on germ cells and on surplus embryos, “the bioethics landscape is very heterogeneous even in Europe,” says Alexandre Mauron, director of the Institute for Ethics Humanities History from the University of Geneva.

Several methods make possible these rearrangements of the genome by targeted cuts DNA: the nucleases in “zinc finger” (zinc finger), said TALEN and especially the most promising technique, called CRISPR-case.9. The latter is actually the sum of several discoveries made since the 1980s; it has enjoyed tremendous growth since 2012.

CRISPR-case.9 is a mechanism derived from the cellular machinery of bacteria, in which he plays the role of the immune system. It can recognize and cut DNA viruses that infect the cell. This mechanism has been recovered and adapted by biologists to target specific DNA sequences and make a break in one or more sites with surgical precision. He can change a gene, to introduce a new or remove it.

“The CRISPR-case.9 technology bypasses the laborious processes previously used by biologists to modify the DNA, comments Jinek Martin, professor of biochemistry at the University of Zurich, expert CRISPR-case.9, and one of the authors of the article Science . It is more specific and effective. It is a tool that works in many model organisms, such as bacteria, yeasts, plants, insects, rodents, primates and human cells. “

In fact, several studies experiments have shown the effectiveness of this “DNA Surgery” in adult human cells, raising the hope of curing diseases by altering the genome of the cells. In March 2014, researchers at the University of Pennsylvania (USA) managed to rewrite the DNA of a type of white blood cells in 12 patients infected with HIV to prevent the virus from entering. The study confirmed the safety of the technique. However, the researchers used the “zinc finger” method and not CRISPR-case.9 to modify the DNA. “There is no published clinical study on a gene therapy using CRISPR-case.9″ says Martin Jinek. “The DNA of the surgical technique in itself is very promising; it has the potential to get out of purgatory gene therapy where it is a long time, says Alexandre Mauron. This is a reason to hope before that to be afraid. “

The authors of the text published in Nature , who led the work on HIV, emphasize the importance of distinguishing between DNA surgery applications in adult cells – for gene therapy – and germ cells. These are the origin of the embryo after fertilization; if their DNA is changed, this redesign will be shared by all cells of the body and thus transmitted to the offspring of the individual. It is this transmission to future generations that worries authors. Alexandre Mauron tempers “This prophetic tone is excessive. The sacredness of the genome for future generations is naïve. For everything we do, as the degradation of our environment, has an effect on the human species. Request a moratorium is absurd, it is necessary that research continues to bring more knowledge and enable proper consideration. “

The use of CRISPR-case.9 to modify an embryo already been performed in mice. And in 2014, a team of Chinese researchers announced have succeeded in genetically modifying a monkey with the CRISPR-case.9 technique applied on the embryo in a single cell. But “to date, we do not know the potential long-term effects of the CRISPR-case.9 mechanism. It is not 100% effective and does not always lead to expected changes according to Martin Jinek. And biochemist added: “We are not sure that targeting is done exactly in the space provided.” Mutations may occur elsewhere in the genome. But the researcher to ensure that in humans it has been done in monkeys, “the technology would not be very different and we are almost there.”

Beyond risks that are not yet assessed, is modifying genes of germ cells or embryo really relevant? “For now, this procedure is not tenable, says Alexandre Mauron. To prevent a mutation of a serious illness in the embryo of a couple of parents, preimplantation genetic diagnosis (PGD) is preferable. “This method consists in making a fertilization in vitro and select one or embryos that do not carry the mutation, without affecting their genome. PGD ​​is allowed in France, and a new law allowing the was passed by parliament in Switzerland in December 2014. It will be submitted to a popular vote on June 14.

The Geneva bioethicist concluded. ” People who want to make the change in the DNA of germ cells must convince first that it serves a purpose. “

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