Engineering Breakthrough Research: High-Tech Has it Hardwired

Zusman, Edie E

doi: 10.1227/01.neu.0000398209.63950.c7
Science Times

It is not by accident or serendipity that Apple continues to produce brilliant products that clobber competitors and delight consumers who line up for the latest high-tech gadget. By design, Apple's management system is optimized to create distinctive products like the iPod and iPhone. With the right combination of strategic clarity, patience and strong leadership, this method of innovation can be duplicated, argues Chris Morrison, in How to Innovate Like Apple, published in Interactive Business Network in August, 2010.1

According to Morrison, Apple's motto: “Think different,” empowers employees and then challenges them to strive for excellence and never be satisfied with “good enough.” The company's infrastructure is designed for innovation; its unorthodox approaches include ignoring fads, taking tough stands on issues it can win, flattening hierarchies to hasten decision-making and paying little attention to market research and competition.

If the American medical research establishment hopes to break the stranglehold on innovation perpetuated by entrenched public and private research mechanisms—and yield more breakthroughs more often—it might look to Apple's management practices and organizational structures for inspiration and instruction.

Fortunately, there are strong signs in the United States that the infrastructure that enables research is becoming more effective and efficient and that the gap wedged between the worlds of pure science and the development of breakthrough treatments is narrowing.

Researchers have long explored the kinds of environments that either foster or stifle innovation.

In his 1962 book The Structure of Scientific Revolution, Thomas S. Kuhn cites age and inexperience as key factors: “Almost always the men who achieve these fundamental inventions of a new paradigm have been either very young or very new to the field whose paradigm they change.”2

Indeed, many paradigm-shifting discoveries have been made by scientists in their 20s and 30s, says Nobel Prize winner Thomas R. Cech, PhD, in a 2005 commentary published in the Journal of the American Medical Association.3 And yet the median age for investigators to be awarded their first independent research grant from the National Institutes of Health (NIH) is 42. Almost half of first-time applications are rejected with commonly cited reasons including that the researcher was too ambitious, Cech explains, or that more preliminary results that attest to the project's feasibility need to be submitted before approval. In this environment, Cech points out, Marshall Nirenberg would get his Nobel Prize before he received his first NIH grant.

Cech argues that principal investigators and postdoctoral fellows need to be empowered—and given time free from other administrative duties—to carry out innovative, high-risk/high reward research. Clinical research physicians and patient-oriented physician-scientists must be nurtured throughout their careers, he adds.

A fresh look at a scientific field from a different perspective also fuels innovation, as Kuhn suggested. If he is correct, more scientific meetings should be re-engineered to facilitate the cross-pollination of ideas. Howard Alper, PhD, Chair of the Science Technology and Innovation Council of Canada, says multidisciplinary groups should tackle problems jointly, and rules should be established to enable participants to communicate in a common vernacular.4 In neurosurgery, for example, chemists, immunologists, and biomedical engineers would routinely gather with clinicians to exchange ideas and seek new, potentially curative approaches for the most allusive diseases like glioblastoma. Although expanding neurosurgery meetings to include more invited non-neurosurgeon experts for interactive sessions may require additional resources, the investment would be money well spent.

The American academic research culture has not evolved to encourage innovation, Cech suggests. Rather than fostering “productive collisions” between scientists of different disciplines by establishing collaborative institutes, most universities create departmental silos.

In this environment, he writes, “discovery, creativity, and innovation are particularly imperiled. In the absence of a concerted effort to reset funding mechanisms and priorities, translation of basic science into clinical outcomes will continue, but the ability to capitalize on deeper insights into disease processes to enhance prevention, diagnosis, and treatment may be compromised.”

The experience of surgeon Judah Folkman, MD, is a prime example of delayed progress due to entrenched bias. In 1971, Folkman began to promote the concept that tumors must induce the body to build the blood vessels that feed them. As Nicholas Wade reported in his profile of Folkman in The New York Times, the scientist was routinely turned down for funding and was ridiculed by medical students and criticized by skeptical biochemists.5 It is a period that Folkman liked to call the “valley of death of good ideas.”

Folkman persevered, and after years of attempting to prove the concept, his theory of angiogenesis is now well accepted, and hundreds of laboratories around the world use it in developing new drugs against cancer, heart disease, blindness and other conditions.

In his speech to the Congress of Neurological Surgeons in 2006, Folkman suggested that the huge volume of criticism he received from the larger research establishment might have been an indication that his was a meritorious idea.6

Another factor in the genesis of innovation may be crisis, Kuhn argues. For example, when an explosion aboard Apollo 13 forced the mission to abort, a combination of leadership, teamwork and ingenuity saved the lives of all three astronauts, who fashioned a CO2 converter from odds and ends found on the spacecraft.

Cuberules contributor, Scott Herrick says business leaders could learn a lot from the Apollo 13 example. Among things to consider, he asks: “How often are we to simply solve a problem without explanation of the constraints that limit our options—and increase our creativity?”7

A more recent example of innovation through crisis—and perhaps universal fear —is AIDS. The worldwide epidemic was a virtual death sentence until well-funded research collaborations yielded the discovery of the human immunodeficiency retrovirus as the causative agent and the development of reverse transcriptase inhibitors, which today have made the virus more of a manageable chronic disease.8

Why more medical challenges are not tackled in this way was explored in the May 15, 2010 issue of Newsweek. “Desperately Seeking Cures,” by Mary Carmichael and Sharon Begley, described how the return on investment of tax dollars to the NIH had been dismal for many years.9

They argue that the system of honors, grants and tenure rewards basic discoveries, and not the work that turns them into real cures. Scientists spend years trying to identify individual mutated genes that cause disease, for example, but rarely do academic labs take those discoveries to the next level.

The authors cite "the chasm between a scientific discovery and the doctor's office," a valley of death. They discuss why competitive research laboratories are not rewarded for sharing data, and opt for safer projects that yield more publications and career advancement rather than taking on high-risk, potentially novel projects which may fail or take years to complete and publish. Other obstacles to taking scientific discoveries to the next level are patents that prevent transparency or use of important knowledge and the withholding of preliminary but important data until added studies make it attractive to a higher-quality journal.

The well-articulated concerns and suggestions made in the past several years seem to have been taken to heart at the NIH, where several new grant opportunities have come on line, and in the private sector, where new models of innovation are replacing less effective methods for discovery.

Begley and Carmichael cite private groups such as the Michael J. Fox Foundation for Parkinson's Research for “managing and directing scientists more closely, requiring them to share data before it is published, cooperate and do the non-sexy development work required after a discovery is made.”9

Some drug companies are shifting gears, as well. Sanofi Pasteur is moving to stimulate innovation by shifting its research and development to smaller companies.

In a March 6, 2009 article in the Wall Street Journal, Jacob Goldstein reported that Sanofi CEO Chris Veihbacker planned to cut his company's internal budget for early-stage research in half. Veihbacker observed that small biotech and pharma startups which must prove the value of their ideas or perish from lack of funding, may be more effective at novel drug development. That, Goldstein writes, “often yields more promising candidates than internal research programs at big pharma shops like Sanofi, where bureaucratic fiefdoms may keep unworthy ideas alive.”10

At the World Economic Forum in Davos, January 25, 2011, Veihbacker said he was decreasing internal research and development funding in favor of collaboration with smaller companies because big institutions are not conducive environments for breakthrough research.

Some theorists suggest when researchers interact with Nobel laureates they are more likely to themselves be Nobel Prize winners. But studies show this so-called “cluster effect” is only moderately significant.11

In fact, individuals from 85 US institutions have been awarded Nobel Prizes in science since the beginning of the program; in that time 41 institutions had only one laureate and 44 had two or more, suggesting that prize winners are well-dispersed throughout the academic world.12

What may be more influential are environments in which creative people are nurtured. As Charles B. Wilson, MD, then UCSF Chairman of Neurosurgery once told his fellows, “We can't teach people to innovate; we can only influence the field they choose.”

At Apple, for example, the so-called “creatives” work free from outside distractions and interference, in glass-enclosed sanctuaries with music playing in the background.

Funding, however, cannot be overlooked as a key driver of innovation.

Fortunately, the NIH seems to have listened to concerns such as those raised by Cech, responding with many new kinds of grants that break the mold. NIH's new leader, Francis Collins, MD, PhD, is leading the way with a commitment to translational research designed to hasten the time it takes to get a new discovery from the laboratory into the clinic for patients. At Davos, Collins discussed ways NIH is working to stimulate breakthrough research, including encouraging shorter post-doctoral fellowships, identifying younger, highly innovative investigators, and taking more funding risks.13

A commentary by Richard Aragon in Science Translational Medicine, published in February 11, 2011, describes how the NIH's new funding paradigm promotes non-hypothesis-driven research and supports development of high-risk technologies that have the potential to empower research.14

What's different, Aragon explains, is that the new grants, such as the New Innovator Award, make creative early-stage investigators with highly innovative ideas eligible for funding even if they don't have preliminary data as is normally required for an RO1 grant. Even more remarkable is the fact that these kinds of grants reward individual researchers—not organizations or infrastructure.

Other new grants include the Exploratory/Developmental Grant to fund “breakthrough research,” and the Transformative RO1 (T-RO1) supporting “exceptionally innovative, high-risk, original and/or unconventional research projects that have the potential to create or overturn fundamental paradigms.”

The NIH's Clinical and Translational Science Awards support a consortium of Clinical Translational Science Institutes (CTSI) that are working to improve the way biomedical research is conducted nationwide. Consortium members share a common vision to reduce the time it takes for laboratory discoveries to become treatments for patients, to engage communities in clinical research efforts and to train clinical and translational researchers.

“NIH is looking for ways to rethink how they drive innovative science,” says USC Executive CTSI Director, Susan A. Autry, MBA. “They are funding CTSI's to foster collaborative research and to make administrative systems more efficient rather than a barrier.”

Neurosurgeons are contributing to new paradigms. Douglas Kondziolka, MD, Professor and Vice-Chairman of Neurological Surgery at the University of Pittsburgh, has launched World Science, a Web-based network in which scientists more expediently collaborate, write and publish basic science, clinical research, case reports, and reviews, with the opportunity to provide and share data with researchers throughout the world.

Their goal is to increase the credibility and impact of science and facilitate manuscript creation - breaking down as many barriers to the process as possible, while allowing authors to maintain copyright, all within an interactive environment.15

There are many reasons for optimism. As we have learned from businesses like Apple, and crises such as Apollo 13 and the AIDS epidemic, innovation can be engineered and hardwired. With funding to incentivize creative thinking, interdisciplinary problem-solving and flattened management structures that encourage and reward researchers with breakthrough ideas, we will bridge Folkman's valley of death.

Edie E. Zusman

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1. Morrison C. How to Innovate Like Apple. Interactive Business Network. August, 2010. []
2. Kuhn, TS. The Structure of Scientific Revolutions. Chicago: University of Chicago Press, 1962.
3. Benderly BL. Not your father's postdoc. Science. 2005;308(5722):717-718.
4. Alper, H. 2011, “Science, Discovery and Controversy.” World Economic Forum 2011 Annual Meeting, Davos-Klosters, Switzerland.
5. Wade N. Scientist at Work: Judah Folkman; A Lonely Warrior Against Cancer. New York Times. December 9, 1997.
6. Folkman, J. 2006,“Angiogenesis and the Role of Surgeons as Scientists”. Congress of Neurological Surgeons 2006 Annual Meeting, Chicago, Illinois.
7. Herrick S.Apollo 13 and the Lessons of Leadership. Job Performance. October 3, 2007.
8. HIV/AIDS: Lessons for the Future, January 27, 2011. World Economic Forum 2011 Annual Meeting, Davos-Klosters, Switzerland.
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11. Ham, JC, Weinberg, BA. Geography and Innovation: Evidence from Nobel Laureates, Dec 2007.
12. The Official Web Site of the Nobel Prize, March 27, 2011.
13. Collins FS. January 26, 2011, “Science, Discovery and Controversy”. World Economic Forum 2011 Annual Meeting, Davos-Klosters, Switzerland.
14. Aragon R. Thinking outside the box: fostering innovation and non-hypothesis-driven research at NIH. Sci Transl Med. 2011;3(70):70cm5.
15. Kondziolka, D. World Science Website.
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