Prepare to release Crispr in an unprepared world


Back in the In the 1980s, researchers began to notice a strange pattern in the genes of many microbes. There would be some of the DNA that read the same back and forth, then some of what looked like junk food, then another palindrome, and so on. Nobody knew what the segments were for, but they were striking enough for two scientists in Europe to call them "short palindromic repetitions regularly interspersed," or Crispr for short.

It turned out that the mysterious sequences constituted an immune system. When a microbe was exposed to a new virus, it cut a sample of the invader's DNA (the junk) and stored it safely between two divisors (the palindromes). Thus, if the virus returned, the microbe could simply consult its archives and send the appropriate immune response.

The task of determining the details of this process has been entrusted to a subsequent generation of scientists. In 2011, a microbiologist, Emmanuelle Charpentier, determined that the Crispr regimen had three key ingredients: an enzyme that acts like a chisel, cutting the strands of the double helix of DNA; a guide RNA, which tells the scissors where to cut; and a component that locks the scissors in place. The following year, Charpentier joined biochemist Jennifer Doudna. The two men wonder what is the question of billions of dollars: could they exploit this system and use it to modify genes?

The tool that they eventually created – also known as Crispr, which is confusing – not only worked, but it also wiped out all the existing technologies of water . To edit a gene using Crispr, you only need to tell your ARN guide an address corresponding to a particular location in the genome. The scissors then cut the selected gene, or even a tiny fragment of the gene, and insert a substitute as needed. (A natural repair mechanism automatically assembles the whole thing.)

The result was transformative. On the one hand, Crispr works in almost every animal that scientists have tried, from silkworms to monkeys, and pretty much in all types of cells – kidney cells, cardiac cells, and so on. (The previous techniques of gene modification even had problems with ratsIn addition, Crispr is both fast and cheap. Before Doudna and Charpentier make their discovery, it may have taken more than a year to design a mouse with a single mutation. Now it can take as little as two days of work. And while the new editing technique sometimes produces typos, it is much more precise than its predecessors. A scientist told me that with Crispr, he only needs 10 cells to get at least one perfect mutation. In the past, he would have had to handle about a million cells to achieve the same result.


The WIRED guide of Crispr

Scientists around the world have spent the last seven years perfecting this new tool, using it to study the underlying genetics of diseases, accelerate the development of drugs and improve the performance of bacteria and industrial cells. Now they are ready to take it out of the lab and into the real world. Some of their first applications are already promising. Thus, two summers ago, ExxonMobil announced that it had used Crispr to double the amount of biofuel generated by marine algae. Nannochloropsis gaditana. German researchers have recently found a way to create Crispr'd pigs resistant to African swine fever, a disease that has ravaged farmers in sub-Saharan Africa.

But other uses of technology have been more disturbing. Last November, a Chinese researcher, He Jiankui, announced the birth of the first genetically modified babies in humanity, binoculars with a Creep version of the CCR5 gene, which he said immunized against certain strains of HIV. (The fact that it has changed to the embryo stage means that girls will transmit their modified DNA.) The experiment was largely condemned, deemed unethical, unnecessary and potentially dangerous. The Chinese authorities call it "abominable". But this also bodes well for the next phase of Crispr's development: from a universally adopted laboratory tool to a tool potentially capable of constantly modifying species, ecosystems and populations.

This phase will result in a series of new ethical and regulatory decisions. To get out of it, we need a good knowledge of the facts and a clear understanding of the many benefits and risks of Crispr. But we also have to face a difficult question: where do we want, as individuals and as a society, to go beyond this technology?

Jennifer Kahn (@JenniferMKahn) wrote about Ocean Cleanup in issue 26.10.

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