December 9, 2016
By Mark Terry, BioSpace.com Breaking News Staff
There is a tendency, when discussing CRISPR/Cas9 technology, to focus on Emmanuelle Charpentier and Jennifer Doudna. In June 2012, when Charpentier was at Umea University in Sweden, and Doudna was at the University of California, Berkeley, they published a paper in Science that described using the technology to cut DNA sequences in test tubes. Charpentier and Doudna co-founded CRISPR Therapeutics with Rodger Novak. Doudna originally founded a company, Caribou Biosciences, then went on to co-found Editas with Feng Zhang and George Church.
Feng Zhang
Feng Zhang is sometimes added almost as an afterthought, but STAT recently profiled the 34-year-old scientist, suggesting he’s anything but an afterthought.
But before that, a few other facts. First, CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. It had been originally identified in bacteria, that used it to fight viruses. An enzyme, Cas9, can cut DNA. CRISPR identifies specific sections of DNA and Cas9 cuts it. So the system itself is being used to edit DNA and replace sections of it.
Second, there are contentious lawsuits pending on who discovered CRISPR/Cas9, Charpentier and Doudna, or Zhang. U.S. patent law has made some changes in the last decade or so. For the longest time, the discover was first-to-file. In recent years, the patent ownership has shifted to first-to-discover, which is also sometimes more difficult to prove.
Charpentier and Doudna published their paper in Science in June 2012. Zhang, who had been working on CRISPR/Cas9 for quite some time, was aware of their paper and sent his own paper to Science on October 5, 2012, which was published online in early January 2013, along with a similar paper published by George Church, where Zhang worked during a fellowship at Harvard.
Because of the first-to-invent changes, Zhang submitted laboratory notebooks that showed his laboratory was the first-to-invent, as opposed to Doudna and Charpentier’s first-to-file.
As a result of the first-to-invent system, MIT won the key patent, with Zhang listed as the inventor, in April 2014. Berkeley has appealed, arguing, according to STAT, “that Doudna and Charpentier achieved the key CRISPR breakthrough—in particular, identifying the three molecules that are crucial to making CRISPR work—and that Zhang’s success in animal cells was just an extension of their work.”
Zhang told STAT that, in his opinion, Doudna and Charpentier only “showed that you can cut DNA in test tubes.”
That will undoubtedly be determined eventually by the courts. Meanwhile, who is Zhang?
Born in China, he moved to Des Moines, Iowa when he was 11 years old. As a high school student, he worked as a volunteer in the gene therapy lab of John Levy at Methodist Hospital. There, he trained in using viruses to insert jellyfish genes for a bioluminescence molecule into human melanoma cells. This causes the cancer cells to glow. He went on to a full scholarship at Harvard, and worked in influenza-virus research in the lab of Xiaowei Zhuang, majoring in chemistry and physics. He graduated from Harvard in 2004 and went to Stanford, joining the neuroscience lab of Karl Deisseroth.
Deisseroth, another grad student, Ed Boyden, and Zhang, invented optogenetics, which STAT describes, “in which light-sensitive proteins are slipped into neurons so light can activate specific neural circuits.”
Zhang went on to a position at Harvard’s Society of Fellows. It didn’t come with a lab, so he “begged and borrowed space in labs of senior Harvard scientists.” It was there that he started working on other types of gene editing, primarily with “zinc fingers.” He also worked on another gene-editing technique, TALES. Both zing fingers and TALES are difficult to work with.
As the Fellows appointment ended, he joined MIT’s McGovern Institute for Brain Research and the Broad Institute. In 2011, he first heard about CRISPR and teamed up with graduate student Le Cong to shift from TALES and zinc fingers to CRISPR.
One thing Cong and Zhang did was bypass working with CRISPR in bacteria, and went directly to human and mouse cells. And the rest, at least when it’s sorted out by judges and lawyers, is history.
Zhang, 34, is married with a daughter, and is noted as being the youngest head of a laboratory at the Broad Institute in Cambridge, Massachusetts.
