Communications of the ACM

Technology strategy and management

CRISPR: An Emerging Platform for Gene Editing

By Michael A. Cusumano
Communications of the ACM, January 2019, Vol. 62 No. 1, Pages 21-23
10.1145/3292517
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When thinking about which areas of research might form the basis for new industry platforms, in the past we have focused on information technologies such as computers, Internet software, smartphones, cloud services, artificial intelligence and machine learning, and even quantum computing (see "The Business of Quantum Computing," Communications, Oct. 2018). These technologies early on had the potential to generate what we call "multi-sided markets" with powerful "network effects." Network effects are self-reinforcing feedback loops where, as the number of users or complementary innovations increase, the more widely used and valuable the platform becomes (see "The Evolution of Platform Thinking," Communications, Jan. 2010).

Another early-stage technology suited to platform dynamics is gene editing. Research began several decades ago, leading to various tools and techniques. It is still uncertain which approach will become the dominant foundation for further research and applications development, but there are some platform candidates.

One particularly promising technology is CRISPR, or "Clustered Regularly Interspaced Short Palindromic Repeats."¹² CRISPR refers to small pieces of DNA that bacteria use to recognize viruses. What scientists observed years ago is that specialized segments of RNA and associated enzymes in one organism can modify genes (DNA sequences) in another organism. For example, this happens naturally when the immune system in bacteria fight against an invading virus. In 2012, several scientists discovered they could use CRISPR sequences of DNA as well as "guide RNA" to locate target DNA and then deploy CRISPR-associated enzymes as "molecular scissors" to cut, modify, or replace genetic material. The potential applications include diagnostic tools and treatments for genetic diseases as well as genetic reengineering more broadly.⁸ An August 2016 article in National Geographic magazine described CRISPR's potential: "CRISPR places an entirely new kind of power into human hands. For the first time, scientists can quickly and precisely alter, delete, and rearrange the DNA of nearly any living organism, including us. In the past three years, the technology has transformed biology ... No scientific discovery of the past century holds more promise—or raises more troubling ethical questions. Most provocatively, if CRISPR were used to edit a human embryo's germ line—cells that contain genetic material that can be inherited by the next generation—either to correct a genetic flaw or to enhance a desired trait, the change would then pass to that person's children, and their children, in perpetuity. The full implications of changes that profound are difficult, if not impossible, to foresee."¹⁰

DNA resembles a programming language and data-storage technology, useful in different applications. Gene editing provides opportunities for companies to pursue product solutions, such as to build standalone diagnostic tools or gene therapies. It also enables some institutions and companies to create products, tools, or components that other firms can build upon. Like today's quantum computers, each use of CRISPR seemed to require specialized domain knowledge (that is, the genome of a particular organism and disease) and then tailoring to the application, such as to use CRISPR to design a diagnostic test or therapeutic product for a specific disease, or to reengineer a plant to fight off insects. But, along with rising numbers of CRISPR researchers, platform-like network effects and multisided market dynamics were also appearing and helping the industry evolve. In particular, more research publications have led to improvements in tools and reusable component libraries, which have attracted more researchers and applications, which in turn have inspired more research, tool development, applications, venture capital investments, and so on.

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DNA resembles a programming language and datastorage technology, useful in different applications.

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At the center of an emerging CRISPR ecosystem is a non-profit foundation called Addgene, founded in 2004 by MIT students. It funds itself by selling plasmids, small strands of DNA used in laboratories to manipulate genes. Since 2013, it has been collecting and distributing CRISPR technologies to help researchers get started on their experiments.¹⁴ The Addgene tools library consisted of different enzymes and DNA or RNA sequences useful to identify, cut, edit, tag, and visualize particular genes.^a There were also numerous startups, some of which have already gone public. CRISPR Therapeutics (founded in 2013) was trying to develop gene-based medicines to treat cancer and blood-related diseases, and collaborating closely with Vertex and Bayer. Editas Medicine (2013) and Exonic Therapeutics (2017) were tackling diseases such as cancer, sickle cell anemia, muscular dystrophy, and cystic fibrosis.^b Beam Therapeutics (2018) planned to use CRISPR to edit genes and correct mutations.¹ Mammoth Biosciences (2018) was following more of a platform strategy and developing diagnostic tests that could be the basis for new therapies. It was broadly licensing its technology and encouraging other firms to explore therapies based on its testing technology.¹¹ In fact, Mammoth's goal was to create "a CRISPR-enabled platform [italics added] capable of detecting any biomarker or disease containing DNA or RNA." In a recent public statement, the company summarized its strategy to cultivate an applications ecosystem: "Imagine a world where you could test for the flu right from your living room and determine the exact strain you've been infected with, or rapidly screen for the early warning signs of cancer. That's what we're aiming to do at Mammoth—bring affordable testing to everyone. But even beyond healthcare, we're aiming to build the platform for CRISPR apps [italics added] and offer the technology across many industries."³

Commercialization of CRISPR systems was still years away, and the technology had limitations. It was better at screening, cutting, and rewriting rather than inserting DNA.⁴ And only recently have medical centers and companies applied to start CRISPR-related clinical trials. There were also alternative technologies with different strengths and weaknesses. In particular, TALEN (Transcription Activator-Like Effector Nucleases), another gene-cutting enzyme tool, was more precise than CRISPR and more scalable for some non-laboratory applications, though it was more difficult to use.⁶ In general, CRISPR was in the lead, with several universities and research centers, startup companies, and established firms actively publishing papers, applying for patents, and sharing their tools and depositories of genetic components. Most researchers were also focusing on CRISPR-Cas9, a specific protein that used RNA to edit DNA sequences.

One concern is that the business models of biotech startups and pharmaceutical companies depended on patent monopolies, making the industry ultra-competitive and locking applied research into protected silos. The result was potentially a "zero-sum game" mentality. This contrasted to the more cooperative (but still highly competitive) spirit of "growing the pie" together that we generally see with basic science and which we saw in the early days of the personal computer, Internet applications, and even smartphone platforms such as Google's Android. Of course, CRISPR scientists openly shared and published their basic research.⁷ And though the U.S. Patent Office already has granted hundreds of patents related to CRISPR, patent holders usually offered free licenses to academic researchers, even those still under litigation.

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Ethics and social issues might hinder widespread use of gene editing.

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Ethical and social issues might hinder widespread use of gene editing. The controversies centered on how much genetic engineering should we, as a society, allow? Experts already disagreed about the safety of genetically altered plants and animals that contributed to the human food supply.¹³ Scientists can deploy similar technology to change human embryos and cells, such as to treat genetic diseases or potential disabilities. But should we allow parents to edit their children's genes, such as to select for blue versus brown eyes, or a higher IQ?⁵

In sum, platform dynamics were influencing areas outside of information technology. It was not so clear, though, how to use the power of the platform wisely and safely, and what types of government monitoring and self-regulation were most appropriate. These issues were likely to become fierce topics of debate as CRISPR and other gene-editing technologies evolved into widely used platforms for medical, food, and other applications.

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