CRISPR-Cas is a suiteof genetic engineering tools with wide-ranging technical applications and worrisomeethical implications, the latter of which I’ve provided Journal covers on thecover page to posit. This suite of toolsutilizes a nucleic acid-based targeting molecule and a single enzyme, Cas,which can itself be modified and engineered – albeit, not as readily – to affectvarious outcomes. While less efficientin DNA editing than previous state of the art methods such as TAL-Endonucleases(TALENs) and Zinc Finger Nucleases (ZFNs), CRISPR-Cas is cheap, pliable, andaccessible to moderately skilled molecular engineers lending credence to thephrase bandied about that it is democratizing biomolecular engineering. The promise of such a tool is vast, yet twoscientific figures, and their representative institutions, went head-to-headover the exclusive rights to utilize CRISPR-Cas technology in humantherapeutics and other biotechnology related applications. This battle spurs or renews many interestingquestions surrounding life sciences patent law, specifically, how the societal benefitsand personal disadvantages of collaborating versus siloing in the sciences andtech development arena should be treated as a nuanced balancing act or whether,which is currently the case, exclusive rights ought to be granted on the binarybasis of first-to-file over first-to-invent. To set the scene, in 2012, Jennifer Doudna,Professor at UC Berkeley together with Emmanuelle Charpentier, Martin Jinek,Krzysztof Chylinki, Ines Fonfara, and Michael Hauer published in the journalScience their discovery of the mechanism behind an ancient form of adaptiveimmunity discovered in E. coli publishedas “A programmable dual-RNA-guided DNAendonuclease in adaptive bacterial immunity.
” In 2011, prior to the seminal publication Doudnafounded Caribou Biosciences, Inc., whose sweeping “singular focus is – the advancementof new applications for CRISPR-Cas gene editing that will help bring thetremendous promise this technology holds for patients and consumers to reality.” (Caribou Biosciences Inc., 2018) Feng Zhang, one of now twelve core faculty membersat The Broad Institute, a joint MIT-Harvard multidisciplinary biomedical researchinstitute in Cambridge, MA, had simultaneously switched from TAL- and light-basedgenome engineering to CRISPR-Cas systems, publishing 58 papers since 2013directly related to CRISPR-Cas biology and applications as counted under the ‘publications’link on his laboratory’s website (The Zhang Lab, 2015).
Briefly, this covers basic molecularstructure elucidation, the discovery and engineering of variant Cas and Cpfenzymes, viral delivery of the genetic components to specific tissues – importantlyincluding human cells – as well as exploring various screening and therapeuticapplications. In 2013, Editas Medicine wasfounded and both Doudna and Zhang sat on the Board of Directors. Despite the fact that Doudna applied for theCRISPR patent first, Zhang/MIT-Harvard was awarded the patent (No. 8,697,359)in 2014 as a result of applying for an expedited review process which cost $70,following up on a 299-page provisional filed in 2012. Doudna left Editas soon thereafter and foundedIntellia Therapeutics Inc. In 2015,Berkeley filed a claim on behalf of Doudna, entering into litigation with Zhangand the Broad. As Robert Kolker statedwith all the grandiosity he could muster, “Doudna and Zhang may haveto take the stand, each asserting under oath that she or he deserves the patentfor what may well be the biological advancement of our age.
The stakes aresky-high. Billions of dollars in revenue. Control over entire industries yet tobe born. And, perhaps, the future of human evolution.” In 2016,Editas raised $120M in Series B funding and went public with an IPO valued at$94.
5M. Intellia goes public the same year, netting $108M. Charpentier, coauthorto Doudna’s seminal paper founded Crispr Therapeutics, which raised $198M inventure capital, and an additional $440M in contracts with industry partners.