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I’ve just returned from participating in an engaging and highly interactive translational research innovation symposium at Duke University this past Thursday put together by Dr. David Epstein at the Duke Eye Center and Chancellor Victor Dzau, and featuring both University faculty and invited external speakers. Four key themes emerged:
Theme 1: Driving science into application remains difficult but desirable
I was struck by the range of participants eager to push science into the clinic, from PhD chemists and biologists to internists and surgeons (and, of course, ophthalmologists). A vigorous entrepreneurial spirit was apparent, a determination to do something outside the usual academic practice.
I was equally struck, however, by the challenge of giving form to this spirit, something I appreciate is a more general concern: how does a university (or any organization, although for now I’m thinking particularly about academic centers) capture and channel this visceral but relatively inchoate yearning?
From what I heard Thursday, it sounds like the three basics may be culture, coordination, and capital.
Culture: As sick as I am of hearing the phrase, “culture is everything,” I understand the point. Culture really matters – and academic leaders can play a vital role either passionately encouraging and supporting entrepreneurship (Susan Desmond-Hellmann and Tom Byers stand out in my mind here), or offering only tepid lip service. Arguably the most valuable aspect of culture are the presence of positive examples, faculty members and students who’ve actually done this – developed a product, started a company, pushed an innovation into the clinic and changed medical practice.
This also suggests an opportunity to initiate a virtuous cycle – once you have a nucleus of entrepreneurs, a critical mass, the excitement can spread virally (case in point: I suspect that almost every undergraduate at Stanford has considered forming a company at one time or another), and following the success of Mark Zuckerberg, the same may now be true at Harvard.
Coordination: While the idea of forming a company, or developing a technology for licensing, may sound sexy, the reality tends to be more complex, and (in the case of start-ups) typically involves far more work than the participants had originally anticipated. It’s also clear that while there may not be a formula for innovation, there are discrete structural activities that can be done in an environment to support, nurture, guide and sustain innovation, as several faculty members from Duke’s Fuqua School of Business emphasized. Some learning is inevitably didactic (learning the rules of road), but most is experiential, and a crucial element seems to involve learning how to work as team, to transform the germ of an idea into something concrete. The best learning, clearly, is real world experience; seeing and solving the real-world challenges experienced as you try to transform an idea into an actual (often commercial) product or service likely represents the most useful training of all.
Capital: This wasn’t discussed extensively at this week’s meeting, but was an important subtext. Capital plays a vitally important role in driving innovation, and the availability of capital can be transformative – just as the lack of same can be a problem. New York’s recent arrival on the national entrepreneurial scene is arguably a testament to the power of the capital, intelligently deployed, to ignite a primed innovation community.
Theme 2: Think differently
Exhorting people to “think differently” seems about as useful a hollering at your microwave to “cook faster.” Yet, several examples from this meeting suggested that are actually approaches to deliberately think about problems in slightly different ways.
Dean Nancy Andrews, for example, presented interesting social science data I hadn’t previously seen highlighting the value of diversity in innovation; it turns out that heterogeneous teams tend to solve difficult problems more effectively and apparently more creatively than teams with less diversity. This ties in nicely with the suggestion (that I’ve heard frequently, though I can’t speak to the evidence base) that breakthroughs tend to occur at the intersection of disciplines.
Keynote speaker and legendary MIT bioengineer Robert Langer emphasized the value of multi-discipline collaboration as well; such interactions have been a defining characteristic of his career, and also the foundation, beginning with his decision to pursue his post-doc not in a chemical engineering division, but rather in the lab of a pediatric surgeon, the late Judah Folkman.
The emphasis on unexpected ideas tied in very well with a second point Dean Andrews also made, about the unique value of students on entrepreneurial teams; not only do they tend to be energetic, of course, but they are also relatively naïve, and can ask the fundamental, vital questions overlooked by those with more experience.
The idea of thinking differently was a key message of my talk (which also highlighted the broad transformative potential of robust phenotypic measurement), and also a significant theme of the talk given by Geoff Duyk, a physician-scientist by training, and currently managing director of TPG’s in-house biotech VC fund; not surprisingly, Duyk is a big believer in the concept of intellectual “cross-training.”
Both Duyk and I highlighted the need to look beyond the traditional model of early stage innovation (pathway -> target -> drug), and consider other types of innovation that could improve health – including innovation in devices, services, processes, and care delivery (topics I’ve also discussed in previous commentaries — for example here, here, and here). Of particular interest, Duyk highlighted the unique healthcare needs and opportunities associated with countries in Central and South America, as well as Asia, providing an often underappreciated global perspective, and an important reminder of the value of thinking outside the border as well as the box.
Theme three: Pharmascolds still have academics running scared.
As impressed as I was by the interest of university researchers in moving their research out of the university and into practice, I was even more struck by their fear (articulated to some extent publically, and to a far greater extent privately) of the pharmascolds, an anxiety that took many forms. Junior faculty were concerned that working with industry in any way might jeopardize their relationship with the NIH, and introduce a prohibitive array of complications and requirements into their already busy lives.
To a person, everyone emphasized the need to be completely transparent and open; there was unanimous agreement here. The problem, rather, was the seemingly excessive and gratuitously onerous requirements associated with this transparency, a level of micromanagement (one might argue nanomanagement) that was perceived at times to be absurdly heavy-handed, and more likely to inhibit university/industry collaboration than enhance it.
There was also a strong sense that partnering with industry is still viewed in many academic circles as collaborating with the enemy, a relationship that threatens to stigmatize the researcher – a disgraceful phenomenon, in my view: we should be celebrating, not castigating, the researchers who seek to drive their science into practice, not just into papers and prestige.
The view from a subset of the many senior leaders with whom I spoke was, if anything, even more concerning – though hardly surprising. Several senior faculty members strongly believed that the media had their crosshairs fixed squarely on academics who work with industry, and any academic leader who tried forcefully to defend or support these relationships was likely to be taken down. Paranoid as it sounds, I’ve heard this from a number of academic leaders at a range of institutions, highlighting the perceived ferocity of the pharmascold attacks, as well as the courage of the rare academic leaders – such as Desmond-Hellmann – willing to stand up and forcefully make the case that driving science into application (a) is core to a research university’s public mission, and (b) can be powerfully facilitated through well-structured collaborations with industry. (See here as well.)
Theme four: Role of the champion and the opportunity to make a difference
The two highlights of the symposium were the first talk of the day by Langer, and the last talk of the day, by Y.T. Chen. Each seminar highlighted the tremendous impact of an impassioned innovator.
Langer’s talk discussed the arc of his career, including the initial challenges he faced as he struggled to get a new technology patented. It’s often said that the mark of a true scientific breakthrough is that it seems obvious – but only after someone suggests it. The trouble, of course, is that if you’re the one who suggests it, a patent reviewer can then decide it seems obvious, which was the trouble he initially encountered (he persevered and eventually received his patent).
He also highlighted the excitement and many challenges of developing new products and forming new companies, and you are reminded that just being brilliant and uncommonly creative – as Langer is (see this brief profile I wrote for Boston Magazine several years ago) – isn’t enough; success also requires exceptional persistence, and a lot of gritty work.
Chen’s talk, to close the symposium, offered a poignant and modestly-presented reminder of why translation is so essential; Chen is a physician-scientist (pediatric geneticist) who, motivated by the searing experience of a patient’s memorial service, ultimately developed the first treatment for Pompe Disease, a rare, devastating, historically fatal lysosomal storage condition that afflicts muscles leading to debilitating weakness and frequently death; following the development of a enzymatic replacement strategy by Chen – and its subsequent development and commercialization by industry (Synpac, later Genzyme, now Sanofi) – many children with this disease have a significantly improved chance of living a much better – in some cases, relatively normal – life, especially if treatment is initiated very early.
As I listened to Chen’s talk, I found myself wondering about this model of innovation, this narrative of the intrepid, determined physician-scientist successfully shepherding a discovery from the lab into the clinic. It’s a compelling vision – it’s what I had in mind when I decided to pursue an MD/PhD, and I know it’s what many of my colleagues were thinking as well.
But now, I’m torn: part of me worries that while this model has great narrative appeal, it may be more the exception than the rule; more often, progress may involve a number of discrete, and often disjointed advances, that over time are integrated into a more complete picture, and ultimately give rise to novel therapies. Moreover, by holding up these sorts of dramatic exemplars, we may not only be misleading future researchers but also encouraging the wrong behaviors – celebrating the iconic crusader, rather than the conscientious collaborator (although notably Chen was apparently both), the charismatic entrepreneur rather than the boring but relentlessly effective CEO (see here).
The thing is, I can’t escape my fundamental belief – and it really is just a belief — in the absolute primacy of the clinical champion, the inquisitive physician or scientist who is determined to drive science into application. I believe deeply in the unique ability of highly motivated champions to walk through walls, and accomplish what other, more grounded researchers might never attempt. I recognize the narrative of the intrepid entrepreneur, but I also believe in it.
I hope we continue to highlight the accomplishments of clinical champions like Y. T. Chen, like Judah Folkman, like Peter Pronovost (incidentally a nice example of a champion pursuing systems innovation). These exemplars may not be representative of everyone who has contributed impactfully to medical progress and scientific translation, but they offer an inspirational reminder of the power of what can be achieved with a focused mind, a committed heart, and little bit of luck.
David Shaywitz, M.D., is an adjunct scholar at AEI
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