As the CRISPR approach to gene editing moves from the lab to the marketplace, it promises to become yet another example of a disruptive innovation. At first, such innovations take hold because they offer so much convenience that it hardly matters whether they lack all the advantages of more established (and highly developed) alternatives. Then, having democratized a pursuit once confined to a select few, a disruptive innovation gathers strength, simultaneously building and benefiting from a diverse constituency of users and developers. Ultimately, this constituency is what makes an innovation truly disruptive. Users and developers essentially take over, enhancing the original innovation, pushing it toward increasingly demanding applications.
In the case of CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, the initial appeal is that it makes gene editing fast, easy, and cheap. A CRISPR-based system, even in the hands of relative newcomers, may home in on nearly any gene of interest. It allows users to avoid resorting to alternative technologies such as TALENs (transcription activator-like effector nucleases) and ZFNs (zinc-finger nucleases).
Both of these alternatives rely on proteins to recognize particular DNA sequences, unlike CRISPR, which relies on RNA. While TALENs and ZFNs are well characterized and capable of great specificity, they oblige researchers and developers to engineer new proteins in order to target new DNA sequences. With CRISPR technology, one need only prepare a new scrap of RNA, called guide RNA. This, needless to say, is a relatively trivial task. It can be accomplished in days or weeks rather than months or years.
And so CRISPR has democratized gene editing. But fledgling democracies tend to have growing pains, and CRISPR is no exception. CRISPR, it is often noted, may give rise to a wide range of off-target effects. That is, the guide RNA used in CRISPR gene editing may lock onto a stretch of DNA that is only approximately (not perfectly) complimentary, and a CRISPR-associated protein (the Cas9 nuclease) may snip DNA in unfortunate places, silencing genes meant to be left alone, or even permitting unintended additions of genetic material.
Where CRISPR originated—as an adaptive immune system for bacteria—it may not matter terribly if CRISPR-Cas9 complexes are a bit overzealous in seizing and cutting apart DNA from infectious viruses. But where CRISPR is headed—the creation of model organisms and the development of therapeutics—an extremely high degree of specificity is mandatory.
At present, such specificity is available with TALENs and ZFNs, which have been refined for decades and are beginning to show promising clinical results. Good news, it would seem, for them. They may, however, find that they are becoming sustaining innovations.
Both sustaining innovation and disruptive innovation are terms of art coined by Clayton Christensen, a professor at Harvard Business School who is best known for writing The Innovator’s Dilemma. According to Christensen, sustaining innovations risk becoming isolated in their own value networks while disruptive innovations create new ones that ultimately prove larger and richer. Prominent examples of sustaining/disruptive pairs include telegraphy/telephony and mainframe computing/PC computing.
In either case, the “sustainer” and the upstart “disruptor” had their respective advantages. Yet the sustainer’s advantage was subject to erosion, while the disruptor’s advantage was difficult, if not impossible, for the sustainer to emulate. (For example, telegraphy had unequaled geographical reach, whereas telephony introduced voice communications.) In the case of CRISPR, a disruptive advantage (other than speed and ease of application) is the ability to simultaneously introduce mutations in multiple target genes. In general, this kind of efficiency eludes TALEN-based and ZFN-based platforms.