Saturday, December 12, 2015

CRISPR in the New Yorker

Earlier CRISPR posts here.
New Yorker: At thirty-four, Feng Zhang is the youngest member of the core faculty at the Broad Institute of Harvard and M.I.T. He is also among the most accomplished. In 1999, while still a high-school student, in Des Moines, Zhang found a structural protein capable of preventing retroviruses like H.I.V. from infecting human cells. The project earned him third place in the Intel Science Talent Search, and he applied the fifty thousand dollars in prize money toward tuition at Harvard, where he studied chemistry and physics. By the time he received his doctorate, from Stanford, in 2009, he had shifted gears, helping to create optogenetics, a powerful new discipline that enables scientists to use light to study the behavior of individual neurons.

Zhang decided to become a biological engineer, forging tools to repair the broken genes that are responsible for many of humanity’s most intractable afflictions. The following year, he returned to Harvard, as a member of the Society of Fellows, and became the first scientist to use a modular set of proteins, called TALEs, to control the genes of a mammal. “Imagine being able to manipulate a specific region of DNA . . . almost as easily as correcting a typo,” one molecular biologist wrote, referring to TALEs, which stands for transcription activator-like effectors. He concluded that although such an advance “will probably never happen,” the new technology was as close as scientists might get.

Having already helped assemble two critical constituents of the genetic toolbox used in thousands of labs throughout the world, Zhang was invited, at the age of twenty-nine, to create his own research team at the Broad. One day soon after his arrival, he attended a meeting during which one of his colleagues mentioned that he had encountered a curious region of DNA in some bacteria he had been studying. He referred to it as a CRISPR sequence. ...

... CRISPR has two components. The first is essentially a cellular scalpel that cuts DNA. The other consists of RNA, the molecule most often used to transmit biological information throughout the genome. It serves as a guide, leading the scalpel on a search past thousands of genes until it finds and fixes itself to the precise string of nucleotides it needs to cut. It has been clear at least since Louis Pasteur did some of his earliest experiments into the germ theory of disease, in the nineteenth century, that the immune systems of humans and other vertebrates are capable of adapting to new threats. But few scientists had considered the possibility that single bacterial cells could defend themselves in the same way. The day after Zhang heard about CRISPR, he flew to Florida for a genetics conference. Rather than attend the meetings, however, he stayed in his hotel room and kept Googling. “I just sat there reading every paper on CRISPR I could find,” he said. “The more I read, the harder it was to contain my excitement.”

... Zhang was awarded the patent, but the University of California has requested an official reassessment, and a ruling has not yet been issued. Both he and Doudna described the suit to me as “a distraction” that they wished would go away. Both pledged to release all intellectual property to researchers without charge ...

... “No single person discovers things anymore,” George Church told me when we met in his office at Harvard Medical School. “The whole patent battle is silly. There has been much research. And if anybody should be making a fuss about this I should be making a fuss. But I am not doing that, because I don’t think it matters. They are all nice people. They are all doing important work. It’s a tempest in a teapot.”

... George Church disagrees. “It strikes me as a fake argument to say that something is irreversible,” he told me. “There are tons of technologies that are irreversible. But genetics is not one of them. In my lab, we make mutations all the time and then we change them back. Eleven generations from now, if we alter something and it doesn’t work properly we will simply fix it.”

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