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Bw the Gene Hackers

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Bw the Gene Hackers ANNALS OF SCIENCE THE GENE HACKERS A powerful new technology enables us to manipulate our DNA more easily than ever before. BY MICHAEL SPECTER t thirty-four, Feng Zhang is the leagues mentioned that he had encoun- could defend themselves in the same youngest member of the core tered a curious region of DNA in some way. The day after Zhang heard about facultyA at the Broad Institute of Har- bacteria he had been studying. He re- CRISPR, he flew to Florida for a ge- vard and M.I.T. He is also among the ferred to it as a CRISPR sequence. netics conference. Rather than attend most accomplished. In 1999, while still “I had never heard that word,” Zhang the meetings, however, he stayed in a high- school student, in Des Moines, told me recently as we sat in his office, his hotel room and kept Googling. “I Zhang found a structural protein capa- which looks out across the Charles River just sat there reading every paper on ble of preventing retroviruses like H.I.V. and Beacon Hill. Zhang has a perfectly CRISPR I could find,” he said. “The from infecting human cells. The project round face, its shape accentuated by more I read, the harder it was to con- earned him third place in the Intel Sci- rectangular wire-rimmed glasses and a tain my excitement.” ence Talent Search, and he applied the bowl cut. “So I went to Google just to It didn’t take Zhang or other scien- fifty thousand dollars in prize money see what was there,” he said. Zhang tists long to realize that, if nature could toward tuition at Harvard, where he read every paper he could; five years turn these molecules into the genetic studied chemistry and physics. By the later, he still seemed surprised by what equivalent of a global positioning sys- time he received his doctorate, from he found. CRISPR, he learned, was a tem, so could we. Researchers soon Stanford, in 2009, he had shifted gears, strange cluster of DNA sequences that learned how to create synthetic ver- helping to create optogenetics, a pow- could recognize invading viruses, de- sions of the RNA guides and program erful new discipline that enables sci- ploy a special enzyme to chop them them to deliver their cargo to virtually entists to use light to study the behav- into pieces, and use the viral shards that any cell. Once the enzyme locks onto ior of individual neurons. remained to form a rudimentary im- the matching DNA sequence, it can Zhang decided to become a bio- mune system. The sequences, identi- cut and paste nucleotides with the pre- logical engineer, forging tools to re- cal strings of nucleotides that could cision we have come to expect from pair the broken genes that are respon- be read the same way backward and the search-and-replace function of a sible for many of humanity’s most forward, looked like Morse code, a se- word processor. “This was a finding intractable afflictions. The following ries of dashes punctuated by an occa- of mind-boggling importance,” Zhang year, he returned to Harvard, as a mem- sional dot. The system had an awkward told me. “And it set off a cascade of ex- ber of the Society of Fellows, and be- name—clustered regularly interspaced periments that have transformed ge- came the first scientist to use a mod- short palindromic repeats—but a mem- netic research.” ular set of proteins, called TALEs, to orable acronym. With CRISPR, scientists can change, control the genes of a mammal. “Imag- CRISPR has two components. The delete, and replace genes in any ani- ine being able to manipulate a specific first is essentially a cellular scalpel that mal, including us. Working mostly with region of DNA . almost as easily as cuts DNA. The other consists of RNA, mice, researchers have already deployed correcting a typo,” one molecular bi- the molecule most often used to trans- the tool to correct the genetic errors re- ologist wrote, referring to TALEs, which mit biological information throughout sponsible for sickle-cell anemia, mus- stands for transcription activator-like the genome. It serves as a guide, lead- cular dystrophy, and the fundamental effectors. He concluded that although ing the scalpel on a search past thou- defect associated with cystic fibrosis. such an advance “will probably never sands of genes until it finds and fixes One group has replaced a mutation happen,” the new technology was as itself to the precise string of nucleo- that causes cataracts; another has de- close as scientists might get. tides it needs to cut. It has been clear stroyed receptors that H.I.V. uses to in- Having already helped assemble two at least since Louis Pasteur did some filtrate our immune system. critical constituents of the genetic tool- of his earliest experiments into the The potential impact of CRISPR on box used in thousands of labs through- germ theory of disease, in the nine- the biosphere is equally profound. Last out the world, Zhang was invited, at teenth century, that the immune sys- year, by deleting all three copies of a the age of twenty-nine, to create his tems of humans and other vertebrates single wheat gene, a team led by the own research team at the Broad. One are capable of adapting to new threats. Chinese geneticist Gao Caixia cre- day soon after his arrival, he attended But few scientists had considered the ated a strain that is fully resistant to a meeting during which one of his col- possibility that single bacterial cells powdery mildew, one of the world’s 52 THE NEW YORKER, NOVEMBER 16, 2015 TNY—2015_11_16—PAGE 52—133SC. BW CRISPR’s unprecedented ability to edit genetic code will make possible a new generation of medical treatments. ILLUSTRATION BY TODD ST. JOHN THE NEW YORKER, NOVEMBER 16, 2015 53 TNY—2015_11_16—PAGE 53—133SC.—LIVE ART—R27279—PLEASE USE VIRTUAL PROOF 4C most pervasive blights. In September, Inevitably, the technology will also the answers have become attainable, Japanese scientists used the technique permit scientists to correct genetic and we are closing in on a sort of grand to prolong the life of tomatoes by turn- flaws in human embryos. Any such unified theory of genetics. “I am not ing off genes that control how quickly change, though, would infiltrate the sure what a Golden Age looks like,” they ripen. Agricultural researchers entire genome and eventually be passed Winston Yan, a member of Zhang’s hope that such an approach to en- down to children, grandchildren, great- research team, told me one day when hancing crops will prove far less con- grandchildren, and every subsequent I was with him in the lab, “but I think troversial than using genetically modi- generation. That raises the possibility, we are in one.” fied organisms, a process that requires more realistically than ever before, that technicians to introduce foreign DNA scientists will be able to rewrite the t least since 1953, when James Wat- into the genes of many of the foods fundamental code of life, with conse- son and Francis Crick character- we eat. quences for future generations that we izedA the helical structure of DNA, The technology has also made it pos- may never be able to anticipate. Vague the central project of biology has been sible to study complicated illnesses in fears of a dystopian world, full of man- the effort to understand how the shift- an entirely new way. A few well-known ufactured humans, long ago became a ing arrangement of four compounds— disorders, such as Huntington’s disease standard part of any debate about sci- adenine, guanine, cytosine, and thy- and sickle-cell anemia, are caused by entific progress. Yet not since J. Rob- mine—determines the ways in which defects in a single gene. But most dev- ert Oppenheimer realized that the humans differ from each other and astating illnesses, among them diabe- atomic bomb he built to protect the from everything else alive. CRISPR is tes, autism, Alzheimer’s, and cancer, are world might actually destroy it have not the first system to help scientists almost always the result of a constantly the scientists responsible for a discov- pursue that goal, but it is the first that shifting dynamic that can include hun- ery been so leery of using it. anyone with basic skills and a few dreds of genes. The best way to under- For much of the past century, biol- hundred dollars’ worth of equipment stand those connections has been to test ogy has been consumed with three es- can use. them in animal models, a process of trial sential questions: What does each gene “CRISPR is the Model T of genet- and error that can take years. CRISPR do? How do we find the genetic mu- ics,” Hank Greely told me when I promises to make that process easier, tations that make us sick? And how visited him recently, at Stanford Law more accurate, and exponentially faster. can we overcome them? With CRISPR, School, where he is a professor and the director of the Center for Law and the Biosciences. “The Model T wasn’t the first car, but it changed the way we drive, work, and live. CRISPR has made a difficult process cheap and re- liable. It’s incredibly precise. But an important part of the history of mo- lecular biology is the history of edit- ing genes.” Scientists took the first serious step toward controlling our genes in the early nineteen-seventies, when they learned to cut chains of DNA by using proteins called restriction enzymes.
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