Panel V
New Initiatives and Best Practices in Innovation
Moderator:
Chris Fall
Office of Naval Research
Tim Persons
Government Accountability Office
Dr. Persons reminded his audience that the name of the GAO was changed in 2004 from General Accounting Office to Government Accountability Office. This reflected a change in policy, which began in 1970, toward more performance audits of “value for money,” he said, especially studies done at the request of Congress. A major feature of the GAO, which publishes some 1,000 reports a year, has remained its political independence, which permits neither political appointees nor linkages with the executive branch. Similarly, the structure of the GAO, whose director is appointed to a term of 15 years, is designed to disentangle its work from the cycles of political elections. The long term itself is intended to expand the GAO’s institutional memory, which, along with its independence, gives it credibility for one of its central functions—including that of advising new presidential administrations on federal matters.
He said that he was participating at the conference both because “so much of the federal sector is very scientific in its endeavors,” and because the GAO is both an evaluator of technological change and government responses to it. Disruptive technologies, he said, are becoming as important to the federal enterprise as they have been to industry and to society at large.
He began with a brief narration of U.S. roots of innovation, as depicted in the famed “Apotheosis of Washington” (1865), the large fresco painting in the U.S. Capitol dome by Greek artist Constantino Brumidi. “This is one of the most sacred places in the United States government,” he said. “But the importance is not just what’s in the middle—it’s what happens around the ring.”
There, he said, were numerous examples of “disruptive technologies,” which is in the “U.S. DNA.” They begin in the era of Abraham Lincoln, he said, and include Greek gods and goddesses pointing to such innovations as a hand-cranked generator of electricity; a snake-like black shape portraying the laying of the first transatlantic cable; the first “ironsides” warships, the Monitor and the Merrimac; the use of advanced steel to construct railroad locomotives; Cyrus McCormick’s reaper; and many others. If Brumidi had painted the fresco it today, he said, he might have continued with other American inventions: the telegraph, light bulb, airplane, xerography, nuclear fission, transistor, integrated circuits, ARPAnet, email, personal computer, DOS, Internet search, map of the human genome, and the iPhone. A current example of the power of disruption, he said, is digital photography, which helped hasten the end for Eastman Kodak, a 135-year-old company whose name was long synonymous with photography. Kodak filed for bankruptcy in 2012.
It is easier, he said, to recognize innovations of the past than to summon them up for what he called the “wicked” problems of the present, such as the need for renewable energy and responses to climate change. He associated this challenge “innovation gaps,” such as the gap between some predictions about global warming and the ability of current models to verify these predictions. “We’re pretty good at predicting weather,” he said, “but how do we get from that to climate?”
How do disruptive technologies arise? he went on. As an example, he cited the increased power and use of graphics processing units (GPUs) for high-powered computation. Once confined to special designs for computer graphics, and difficult to program for other uses, today’s GPUs are general-purpose parallel processors with support for a variety of functions, especially when hybridized with a general-process central processing unit, or CPU, the traditional processing hardware.47
Dr. Persons recalled giving a talk in 2010 when he discussed (what was then) the world’s fastest supercomputer: the Jaguar installation by Cray at Oak Ridge National Laboratory. To his surprise, he recalled, within a matter of weeks the Chinese supercomputer Tianhe 1-A had jumped into the #1 spot to displace the Cray. This upgrade had achieved its speed by using Nvidia GPUs. ”What was disruptive,” he said, “was that graphics processing units had advanced rapidly to meet the demands of other markets, like X-Boxes and Playstations, that used parallel processing in magnificent ways. The standard architectures were not able to keep up, and the Chinese were very smart in seeing that and leveraging this GPU technology for another purpose.”48
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47The GPU-CPU hybrid has quickly become the industry standard, achieving 10 to 100 times as much power as older architectures while consuming about the same amount of energy. In a hybrid, the CPU consists of only a few cores optimized for serial processing, while GPUs consist of thousands of smaller, more efficient cores designed for parallel performance. <http://www.nvidia.com/object/what-is-gpu-computing.html>; <http://gpgpu.org>.
48As mentioned earlier, the ranking of the top supercomputers changes as fast as the technologies driving them. Tianhe 1-A held the top spot only until July 2011, when it was replaced by the
He said that the possibility of an even more disruptive innovation was presented by the concept of quantum computation. “Think about Turing computability,” he said, “and then let’s try to think about quantum Turing computability, what that means.49 If you can hold any number 2n in an integer register, in quantum computing you can hold all 2n numbers simultaneously in the quantum register.” He attributed current advances to scientists at the University of Innsbruck, and to others at the NIST Quantum Information Program in Boulder, Colorado, where researchers are working with individual calcium ions—“shifting them around, passing light through them, entangling them, doing computations with them. That is what the marriage of materials science and computational science has brought us.”
In the energy sector, he pointed to “small, modular nuclear reactors” as a potentially disruptive technology. “Why do we need to build Three-Mile-Island-size footprints? Why not build a reactor small enough to bury underground and carry on an 18-wheeler?” he said. This is the goal of a partnership between Hyperion Power Generation and Savannah River National Laboratory in Georgia, using technology developed at Los Alamos National Laboratory. A first installation is designed to produce 25 megawatts of electricity; the power module will be replaced after a 10-year lifespan. “If we are going to find scalable zero-carbon-emission-based energy in the near term, it has to be nuclear. We do have the key issue of waste management, which this doesn’t solve, but it brings tremendous potential as a disruptive technology.”50
He said that research into genetic engineering is another area where technological disruption is likely. For example, in the case of biofuels, “the key lesson we have learned is the mistake of being penny wise and pound foolish,” he said. “We’re using corn, but that is a petroleum intensive fuel. It needs a lot of fertilizer, and to get the fertilizer we use petroleum, so how much do we save? We’re learning how to bioengineer the energy feed stocks. We’re at the tip of the iceberg.”
In genetic engineering, he said, we are learning how to sequence more and more data. “But that’s not the metric we want. We need the information out of that data. A real breakthrough would be a ‘Google’ to search across these things as we sequence them.”
Another area ripe for a disruption is laser fusion. One possibility he said, is the National Ignition Facility (NIF), a three-story sphere at Lawrence Livermore National Laboratory. Engineers are using 192 high-energy lasers of about 1.8 million joules to strike peppercorn-sized deuterium-tritium spheres suspended in thimble-sized chambers with just the right geometry to cause fusion. “They need to get the right geometry,” he said, “so that the energy
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Fujitsu’s K Computer in Japan, which was in turn surpassed by Lawrence Livermore’s Sequoia in 2012. <http://www.top500.org>.
49Turing computability, named after Alan Turing, refers to computations that can be made on a “Turing machine,” an early means of simulating the logic of a computer algorithm.
coming out is greater than the energy going in. This would last on the order of 10 picoseconds, and at its hottest point be about 100 million degrees C, hotter than center of sun. It is very technical, very bold, and very controversial, a very big bet. It could certainly be disruptive.”
He concluded by mentioning several recent publications of potential value to attendees. The first, completed in 2007, is the “GAO Cost Estimating and Assessment Guide: Best Practices for Developing and Managing Capital Program Costs.” Also, the GAO had just released the “GAO Schedule Assessment Guide: Best Practices for Project Schedules,” published in 2012. The GAO was in the process of writing a guide for technology insertion and risk management.
“We try to be Hippocratic: we don’t want to do harm to any innovation system,” he said in closing. “This is not a bureaucratic process. But there have to be some metrics to measure goodness or how well things work, and that’s also our domain.”
INNOVATIVE APPROACHES IN ONCOLOGY:
PHYSICAL SCIENCES PERSPECTIVES
Larry A. Nagahara
Office of Physical Sciences-Oncology
National Cancer Institute
Dr. Nagahara noted that he works closely with Dr. Lee of the National Cancer Institute (NCI), who spoke the previous day. Dr. Lee heads the Center for Strategic Scientific initiatives (CSSI), formed a decade ago by the NIH to pursue innovative approaches to the causes and potential cures for cancer. A central part of the CSSI is the Office of Physical Sciences-Oncology (OPSO), directed by Dr. Nagahara. “The idea of OPSO,” he said, “is to invited researchers in the physical sciences to work in the cancer domain. These researchers bring a whole new approach to the questions of how cancer initiates and progresses.”
Started in 2008, the OPSO met with researchers in the physical sciences and engineering, as well as clinicians, to discuss the directions from which physical scientists would approach a family of diseases as complex as cancer. From the workshops emerged four main themes, he said:
• Physics (the physical laws and principles) of cancer.
• Evolution and evolutionary theory of cancer.
• Information coding, decoding, transfer, and translation in cancer.
• “De-convoluting” cancer’s complexity.
Since then, the OPSO has reaffirmed its strategy of “asking big questions.” Accordingly, they challenge these new partners to do the following:
• Generate new knowledge, which may emerge from new areas.
• Pursue science that is not just better, but paradigm shifting. “That is,” he said, we don’t want just better sequencing tools; we want tools that are completely new.”
• Build trans-disciplinary teams and infrastructure to better understand and control cancer.
He reviewed the OPSO’s challenge from the point of view of the traditional “translation pipeline”—the imaginary spectrum from basic research to concept and design, prototyping, feasibility, testing, clinical trials, and finally standard of care. While such a pipeline may be useful for some purposes, he said, “innovation cannot be defined as one color or one definition.”
Instead, he continued, creating an “innovation environment” within the physical sciences-oncology centers (PS-OC) network requires new approaches. These include:
• Building a team of innovators.
• Creating an innovation culture.
• Facilitation innovation leadership.
• Setting strategic direction for the long term.
Ground rules for the PS-OC network, he said, began with “lending a helping hand to each other.” In other words, scientific definitions, culture, and “DNA” are so different between the physical and life sciences that communication between the two can succeed only when both sides make the effort to understand the language and values of the other.
The PS-OC network itself is now built, and funded, and it is quite large. There are 12 “virtual” centers, each of which has a principal investigator who is a physical scientist by training and a senior scientific investigator from the life sciences.51 Over 110 institutions are represented—83 domestic and 32 foreign. More than 770 investigators and 550 trainees participate. Senior leadership is divided almost equally between physical scientists and cancer biology or clinical researchers.
Dr. Nagahara said that there is a notable precedent for what he is trying to do in the form of the “quintessential” physicist-biologist, Max Delbrück. His physical science credentials were impeccable, as he earned a PhD at Gottingen in theoretical physics and trained in quantum mechanics with Nils Bohr. Ironically, Bohr interested him in biology, where he foresaw applications of quantum theory. After the coming of the war prompted his move to the United States, where he taught at Vanderbilt University, he formed a research partnership with Salvador Luria, then at the University of Indiana. Together they
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51One of the 12 centers is located at Northwestern University.
were instrumental in establishing the field of molecular biology.52 There, said Dr. Nagahara, it was the physical sciences that proved “disruptive” to traditional biology.
He also offered a more modern instance of exposing experts in one field to a problem in another. Biologists had been stumped for 15 years in trying to decipher the enzyme structure of an AIDS-causing monkey retrovirus known as the Mason-Pfizer monkey virus. Players of an online puzzle video game called Foldit were invited to try their hand at unlocking the protein structure.53 While the puzzle was available to play for a period of three weeks, players produced an accurate 3D model of the enzyme in just ten days.54
As exercise in bridging disciplines, the PS-OC invited a group of physical scientists who had never looked at cancer to team up with people who had spent their careers studying cancer. “An analogy is the blind men and the elephant,” he said. “People from different backgrounds are going to have to learn to communicate. How do they start? Their knowledge means nothing because they don’t trust each other’s data. Each observes a different part of the elephant. The ability to communicate begins with respect for different perspectives. We asked the teams at every center to look at the same two cell lines, outline a research protocol, and report back. Because they were all doing the same thing, they could begin to learn a common language. And this builds trust.”
Another exercise was intended to facilitate interactions among young investigators. “We gave them funds and told them they could distribute the funding in their own way. They didn’t know each other, and we invited them all into the same big room, had them line up in a row, and start interviewing each other. It was like ‘speed dating’ for science. After that they told us whose ideas they found interesting, and they started writing a joint proposal with that person. They had a week to do that, and then we would fund it.”
Five percent of the annual budget is devoted to pilot projects, he said, that enable centers to fund their own research ideas. “One complaint we always hear is, ‘I sent my proposal to NIH; it got reviewed; I didn’t score, but I don’t know why.’ This is their opportunity to think freely. For example, one student was looking at the disparity in the incidence of breast cancer in African-American and Caucasian populations in North Carolina. Rather than doing normal genomics or proteomics, we suggested, could you look at what causes
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52They also shared, with Alfred D. Hershey, the Nobel Prize for Physiology or Medicine in 1969 for discovering that bacteria become resistant to viruses (phages) through the mechanism of genetic mutation. <http://www.nobelprize.org/nobel_prizes/medicine/laureates/1969/delbruck-bio.html>.
53The game is part of a research project at the University of Washington’s Center for Game Science in collaboration with the Department of Biochemistry. The objective of the game is to fold the structure of selected proteins to the best of the player's ability, using various tools provided within the game. The highest scoring solutions are analyzed by researchers, who determine whether or not there is a native structural configuration (or native state) that can be applied to the relevant proteins in the “real world.” Scientists can then use such solutions to solve real-world problems by targeting and eradicating diseases and creating biological innovations. <http://fold.it/portal>.
this. They found that a certain part of population had a very accelerated rate of development between onset and symptoms. They thought it might be based on a cause in physical science. They proposed taking tissue samples, making various measurements on those samples, and looking for a physical basis.”
He closed by touching on the topic of evaluating the new PS-OC approach. “What principles do you use to show that a new community is doing something valuable? We’re trying figure out the metrics for that. One way is to see if there are collaborations, a mix of teams. We can even quantify this by using some familiar numbers: cross-disciplinary publications, numbers of grant proposals. It’s the blending of skills, viewpoints, and sectors that we’re after.”
NEW INITIATIVES AT THE UNIVERSITY OF ILLINOIS
Caralynn Nowinski
University of Illinois
Dr. Nowinski began by saying that she had been at her position for less than a year, but that her colleagues in the technology transfer office and research park had created innovative programs with strong momentum that “she had the privilege to share with the conference.”
She said that these programs fell under three of the themes she had noted over the past day and half. The first is to bring companies to the point “where they’re actually venture fundable.” She noted the debate about whether funding is adequate, given the economic climate, but said that “we need the talented people who create good companies before we start thinking about the funding or lack of it.” Doing this was possible through “establishing these collisions across the sectors” and “bringing the players together in unique ways.” The third theme was to foster talent development, which “goes full circle back to the first point. If we’re going to create fundable ventures,” she said, “we need the talent that can do that.”
The outcome of innovation, she said, is “new products or processes that ultimately change the way we do things, or live.” And the goal is to get those into the market place. “What are we doing to make this happen?” she asked. “If President Lincoln didn’t make it clear enough in 1862 when he signed the Morrill Act, our state legislature made it very clear in 2000 when they established economic development as the fourth mission of the University of Illinois. It truly is our mandate as a public research university to strengthen our state’s economy.”55
She said that she looks at the economic development portion of the mission “comprehensively.” The university tries to enable research, transfer it into people’s daily lives, incubate young companies that grow out of research,
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55According to the university’s web site, “The University of Illinois is among the preeminent public universities of the nation and strives constantly to sustain and enhance its quality in teaching, research, public service and economic development.” <http://www.uillinois.edu/about/mission.cfm>.
and invest in those companies. She said she would focus mostly on the “entrepreneurial pieces”—technology transfer and infrastructure.
She began with “STEM ed,” the idea of training pre-schoolers through grad students and even incumbent workers in the areas of science, technology, engineering and math. “How are we thinking about creating a workforce that is skilled enough for knowledge-based jobs? We know those jobs are increasing, while lower-skill jobs are on the decline.” One university program is I-STEM, which brings in public funding for pre-school education, middle and high school education, and experiences for college and graduate students. The state has nearly doubled its investment in STEM education over the last few years, “but we have a long way to go to keep up with the increase in STEM-based jobs.”
She said Illinois also needs to teach students how to apply STEM learning to entrepreneurial experiences. “Various groups on our campuses are trying to provide that experience to students.” This includes units such as the Technology Entrepreneur Center in the College of Engineering in Urbana and the Institute for Entrepreneurial Studies in the College of Business in Chicago. A more innovative initiative is the Innovation Living Learning Community, or Innovation LLC, a dorm with 130 students from different disciplines who are interested in entrepreneurship. It has a garage where they can work on prototyping, a 3-D printer, and programs to encourage interaction and provide them with mentorship and a classroom curriculum to nurture the development of ideas.
The university has held a variety of Business Plan Competitions, she said, that have been successful in rewarding students and in providing state funding for their companies. The program introduces students with business skills to students with engineering and science skills and helps them combine skill sets and potentially find a commercial application. For example, the Tech Ventures Program in the UIC Liautaud Graduate School of Business enables students from the business school to partner with the tech transfer office, create a business plan, and try to identify a commercial application for new technologies. A winner of the first Concept Venture competition in 2006, a company called OrthoAccel Technologies, ultimately found funding, spun out from the university, and created a real management team. In 2011 the company got FDA clearance for a medical device designed to accelerate the orthodontic process, which she called “braces on steroids.”
She also highlighted a program called ThinkChicago, a partnership between the University of Illinois, the City of Chicago, and Chicago Ideas Week. It brings 100 college students from across Midwest to Chicago to learn about technology entrepreneurship and see firsthand how companies function. “Hopefully,” she said, “other universities in Illinois will encourage students to participate in this as well. We need to bring the talent here and show them we have a vibrant community if we want them to stay here.”
“Our obligation goes beyond our students,” she continued, “to programs for the faculty. Our tech transfer office has nearly doubled its royalties in the last five years, and in the last year we generated a record number of start-
up companies. We’re on pace to do it again this year. We try in many ways to stimulate company formation, starting with informal conversations about IP called IP Coffee Breaks, where faculty and grad students talk about protecting IP, making disclosures, and getting help to form a company.” There are also more formalized programs, such as the Proof of Concept programs in Urbana and Chicago. This provides up to $75,000 to faculty entrepreneur teams to try to fill a portion of the start-up funding gap and aims to prepare companies to file an SBIR application.
The Chicago Innovation Mentors (CIM) Program was founded by UIC, Northwestern, University of Chicago and iBIO Propel last year to link faculty entrepreneurs with mentorship teams that can help them vet market potential and develop appropriate milestones. This program will soon expand to Argonne and the Urbana campus.
It isn’t enough to support people, she said; they also need “a place and a process.” She showed an illustration of the incubator in Urbana, called EnterpriseWorks, which is part of the University of Illinois Research Park. The incubator offers SBIR consultation and a Mobile Development Center, among other support services. “When I came to the U of I,” she said, “I had no idea we had that going on in Urbana. The research park has worked with 140 start-ups in the last 10 years, and in the last several years has helped to raise over $400 million in venture capital.”
Other programs within the research park that have contributed to this success include the Entrepreneurs-in-Residence program, which pairs serial entrepreneurs, VCs, or industry executives with early-stage companies. The entrepreneurs help the companies adapt to the commercial world—to learn, for example, that the milestones that are useful in the lab are typically not the same as those that are useful in the world of venture capital or seed funding. Similarly, the I-Start Professional Launch Program is designed to help entrepreneurs avoid the distraction of all the professional services they need. It delivers those services in a suite so the entrepreneur can focus on running the company. Finally, the SBIR Consultation program has helped the university find funding for early technology ventures. In the last 10 years, 18 percent of SBIR funding that has been received in Illinois has gone to Champaign County, which has only 1.6 percent of the state’s population. In the last six years, $35 million in SBIR funding has gone to companies in the Research Park.
More seed funding is needed, she said, and Illinois Ventures was established by the legislature to help. “This has been a real success story,” she said. “The seed funding program gets companies to next level, and we have had follow-on investments of nearly 13 to 1. This is capital really needed to fill the gap. We have a venture fund that invests 80 percent of its capital in Illinois, compared to the 4 percent across the nation that is invested in Illinois. This is not sufficient, but we are clearly addressing the more fundamental problem: how do we create the most venture fundable businesses.”
Her favorite topics, she concluded, “are the things we’re looking to do next”—how to bring university technologies to industry, how to extend our reach to the Chicago area, how to reach out to other institutions.
To present U of I technologies to industry, she said, a successful technology showcase called Share the Vision was held in April 2012 on the Urbana campus. It was attended by almost 40 faculty and more than 50 venture capital and business development executives. Faculty and students from 30 start-ups presented their stories over the two days, and plans for the next Share the Vision are already underway.
She said that a next step would be to “bring some of the success we’ve seen in the research park and on our campus in central Illinois up to Chicago.” One motivation is the increasing concentration of innovation in urban areas. EnterpriseWorks Chicago, a new incubator near the UIC campus, will open in spring 2013 not only for the U of I community but for the broader Chicagoland entrepreneurial community. She referred again to ThinkChicago, whose goals are to bring students from all of the university campuses and connect them to the entrepreneurial community in Chicago, including the activity at 1871, the technology incubator based in the Merchandise Mart.
Finally, she said, she wanted to use some of the program’s physical locations as places where new business interactions could happen. She mentioned intercampus initiatives in health care and manufacturing, and expressed plans to expand both “not just on our academic campuses but on others as well. We are really excited. We hope to have great initiatives to announce over the next year or so, and we’ve set up a variety of communications media over the last year to tell people what we are doing.”
UNIVERSITY TECHNOLOGY TRANSFER:
LESSONS LEARNED FROM Lyrica™
Richard B. Silverman
Department of Chemistry
Northwestern University
Dr. Silverman, a chemist who discovered a drug called Lyrica that is effective in blocking epilepsy and other neurological disorders, said he would discuss his personal experience in shepherding this discovery through the many stages of technology transfer, including proof of concept, patenting, licensing, testing, commercialization, and ultimately marketing. From the point of view of an experimental scientist, he said, the experience was a sobering one for which his own professional training did not prepare him.
His story began with an enzyme called GABA aminotransferase, which seemed to be implicated in epileptic seizures. “We wanted to understand how it works,” he said, “and we also wanted to block its activity because the blocking could be a potential treatment for epilepsy.”
He noted that epilepsy was an important concern for health scientists, and had been since it was recorded in Babylonia some 4,000 years ago. “It’s not just a single condition,” he said. “It’s a family of disorders, like cancer, with a lot of etiologies. Defined broadly, it is any disease that’s characterized by recurring convulsive seizures.” About 1 to 2 percent of the world population experiences some form of epilepsy, and of these, about 30 to 40 percent could not be treated by any known therapy. “So even 1 percent of 30 percent is a huge number, and a huge unmet need.”
During the 1980s, he began to study GABA aminotransferase in his laboratory, and gradually discovered a series of compounds that seemed to produce the effect he wanted. On the basis of enzyme studies in vitro, they seemed to do this through a new pathway, but this needed to be confirmed in animal studies. Despite this promising situation, he had little success at interesting drug companies to test the series of compounds. “There did seem to be a bias against academic discoveries,” he said. “In the view of the companies, they were the experts. What could an academic scientist contribute that we couldn’t do better? This has changed in last 10 years, but in the late 1980s that’s the way it was.”
“So I tried the university’s tech transfer office (TTO),” he continued. “Our office was quite small, and not well established.” He filled out an invention disclosure form, listing what it was he had invented and why he thought it was important. He suggested some companies that might be interested; the TTO added some others and contacted all of them.
“Only two companies were interested, he said—Parke-Davis and Upjohn. We sent letters—the old-fashioned kind, with mailboxes. It took months to get answers. Eventually we heard from them. Upjohn wanted only the ‘best’ compound: ‘Just send us one, we’ll look at it.’ Parke-Davis, on the other hand, wanted to test the entire set.”
So Dr. Silverman signed a material transfer agreement with Parke-Davis to do anti-convulsant tests in mice. When the results came back, the company reported that one of the compounds was “off the charts” in activity, “the most potent we have ever tested.” The rest were only weak anticonvulsants. Eventually Upjohn tested the “best” compound, in 1990, and found it only weakly active. “The most potent one was not the one we sent to Upjohn,” he said. “The ‘best’ compound was best for what we were screening it for, and that may not have been related to how it actually worked. It turned out 10 years later they found out how it does work, and it works by a different mechanism than what we were screening it for.”
In November of 1990 a license agreement was signed with Parke-Davis and a patent applied for. In December of 1991 a patent option agreement was signed between Warner Lambert, the parent company of Parke-Davis, and Northwestern University.
“At this point,” he said, “the compound was in the hands of Parke-Davis, who did all the pharmacokinetic and metabolism studies over a period of six months in 1992. Then it took another 24 months to do chemical synthesis on
single enantiomer56 and animal toxicology. Finally, in 1995 the compound was ready for filing with the FDA as an investigational new drug.57
Phase I clinical trials were performed in 1996, and Phases II and III took from 1999 to 2003. “This was one of the largest sets of clinical trials ever done for a central nervous system drug,” he said, with 10,000 patients. That was because by then Parke-Davis had realized there are other indications for this molecule than just epilepsy, including neuropathic pains (diabetic neuropathy and postherpetic neuralgia). So Lyrica went into clinical trials for several indications, and then also for fibromyalgia and generalized anxiety. It was found to be very effective for epilepsy, neuropathic pains, fibromyalgia, and generalized anxiety, and just this last week was also approved for pain from spinal cord injury.” The process continued beyond the United States with filing for use in Europe in 2003, where it was approved in 2004 and also in Asia.
Lyrica finally reached the U.S. market in 2005, and in its first full year of sales (2006) it reached the $1 billion “blockbuster” status by achieving $1.2 billion in revenue. “It was a very much-needed drug,” said Dr. Silverman. “It had no counterpart at that point.”
He said that among the many lessons he learned during this process of commercialization was a particularly painful one. In the beginning of development, when Parke-Davis was doing its testing, he was able to keep in close touch with events. “I had friends there,” he said. “I would call periodically for updates, and they would tell me what was going on. As a scientist that’s what you crave: scholarship, trying to understand the unknown, bringing clarity. The most rewarding thing you can do is to discuss experiments and interact with the experimenters.” However, when Pfizer bought Warner Lambert and Parke-Davis in 2000, during the clinical trials, the leadership of the new company decided that the Pfizer scientists should no longer talk to anybody outside the company about the project. “This was the most frustrating thing that could happen,” he said. “When they told me that, I said, even the inventor? They said yes, even the inventor. I didn’t hear another word for five years until this thing reached the market.”
Since that time, he said, things have changed at Northwestern. The Tech Transfer Office is now called the Innovation and New Ventures Office, or INVO, and INVO makes it clear that license agreements must include two-way collaboration with full data sharing. “Now they make it clear,” he said, “that if you want to work with our scientists, you have to treat them like scientists. And you can’t delay publication and oral public dissemination of results. We say you get about a month to decide if you want to patent anything in there. Of course during that month we’re savvy enough to not talk about it to anyone outside because we know that then it would lose all its value.”
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56An enantiomer is one of two chemical isomers that are mirror images of one another but not identical, like right and left hands. Different enantiomers may have different effects as drugs.
57The FDA’s IND, or investigational new drug, program serves as a safety screen for compounds before they can enter Phase I clinical testing on humans.
Since Lyrica, he said in closing, he has collaborated with three start-up companies, all good experiences. Collaboration has become part of the fabric, he said, certainly at Northwestern. “The folks at INVO are tremendous,” he said. “They go out there and try to make marriages between industry and Northwestern. We’re connecting with a lot more companies. Of course we don’t want to stifle innovation and scholarship along the way, but this is the direction we all have to go. So that’s what I learned from Lyrica.”
Dr. Tirrell discussed innovation of a very different kind—innovation at the institutional level. He said his talk would concern “a very local story that’s just emerging. It is a story about building a new engineering program from scratch across the boundaries of two very large institutions—University of Chicago and Argonne National Laboratory.”
The most innovative aspect of his program, he said, is to “create a new model for an engineering program that transcends disciplinary boundaries from the outset.” The institute is being established as an autonomous academic unit of approximately departmental size. It is called an institute because it has the character of an interdisciplinary research institute, but also the autonomy and authority of an academic unit to hire its own faculty.
The name Institute for Molecular Engineering, he said, is meant to describe engineering “from the molecular level up.” This is also to give “some indication of what we’re not doing: we’re not training people to design 787s or bridges or dams. We’ll focus at the nanoscale. We want to create leading programs that couple with UC science on one hand, Argonne science and engineering on the other, and fit into this ecosystem we’ve been talking about. It will build on a unique structure I’ll try to get across.”
One feature of the Institute, he said, is to “add a new aspect to the University of Chicago (UC), which has a rich reputation for rigor and depth in science. You know that science is about nature and discovery, while engineering is about something else—invention, design, and doing things that nature never did. We don’t say that one is more interesting than the other. But the idea of molecular engineering is to connect with molecular-level science and to develop solutions to problems that society cares about in energy, information, environment, and health care.”
Construction of the Institute’s new building has begun, he said, on the “corner of 57th and Ellis,” so that the Institute can be housed in a single,
common location. It will also have a significant physical presence at Argonne, with a suite of offices and lab space.
To begin an engineering program from scratch, in a non-traditional way, he said, the Institute would bypass the traditional departmental structure. “Our target size for the initial development phase is 25 faculty,” he said, “so it would be crazy to create little sections with administrative boundaries.” Instead, he said he would begin by imagining the kinds of skills needed to do engineering at the molecular level. “Researchers would need to know how to make new materials—organic, inorganic, biological. Engineers are never satisfied with the rates of reactions, so catalysis will be important. They will need to know how to manipulate biology, so we will need biological engineering, including synthetic biology and both bio-inspired and bio-derived materials. We’ll need to see at the molecular scale, using imaging and structure. We’ll want functional assemblies to process and develop molecular systems, scaling up from the molecular level: photonic, micro-mechanical/robotic, membranes. And finally we’ll need computation and modeling.”
He said that this was the format he used the previous fall when he sought to recruit senior faculty. “We want to fill in as many of these skills as we can, and we’re working on that through a rich planning process.” He has tried to supplant the structure of departments with one of themes, and look for talent under each of those themes. Some themes suggested during the planning process, he said, were:
• Energy conversion, transport, and storage at molecular level.
• Photonic materials and systems.
• Molecular electronics and devices.
• Smart and adaptive materials.
• Bio-inspired materials and machines.
• Engineering of complex systems.
• Molecular imaging.
• Bioengineering of membranes and their applications.
• Engineering of evolvable systems.
• Molecular therapeutics.
“The only way I could plan our hiring,” he said, “was to hire the best people I could find and let them create their own themes. We will probably have between three and five.” He said he expected to build up the faculty over the next few years, spanning a range of technological expertise. Developing graduate and eventually undergraduate programs would follow the arrival of faculty, with the first classes forming in three to five years.
A major new strategy, he said, would be a more cooperative research relationship with industry, with incentives and collaborations to develop technological innovations with commercial promise. “We want to be a better
partner across the whole spectrum of activities we’ve been talking about at this conference,” he said.
He emphasized the advantage of good local resources at both the university and at Argonne. “Collaboration with the local institutions will be very important,” he said, “and we are eager to do that. Our aspirations are to create inventions from discovery, and create industrial impact and new ventures from inventions. Another goal is to make the Chicago area a magnet or destination for people to come to study, work, and form companies. “That is the case in California,” he said, “where I spent the last 12 years. We want to do the same.”
In conclusion, he acknowledged that in creating this new institute he was entering a competitive environment. “If we tried to create a traditional engineering school,” he said, “with departments like those already established elsewhere, we’d be playing catch-up for many years. What we are attempting is innovation on the academic side, and it is risky. We won’t worry much about what we call our engineering disciplines, but we do worry about what they can do. Hopefully we can compete alongside and complement other styles of engineering.”
He closed by saying the institute had announced its first three faculty hires just a few days before the conference. “So it’s no longer just me,” he said. “Faculty meetings will be different; I’ll have someone to talk to.” The three pioneers are David Awschalom of the University of California at Santa Barbara, a physicist and engineer in quantum information: and chemical engineers Juan de Pablo and Paul Nealey, both from the University of Wisconsin at Madison. “All of them, like me, have joint appointments at Argonne. Among them they have more than 50 patents, with emerging, overlapping themes in organic materials, electronic materials and devices, and bioengineering; all have active relationships with 10-plus multinational corporations. And a key point: they are all people from outside Illinois. I believe they will begin to make this region a destination very soon.”
Discussion
Dr. Peterson asked Dr. Tirrell how he and his colleagues at the institutes would keep their research programs going if graduate students would not arrive for three or four years. Dr. Tirrell said that he had made explicit agreements with chemistry, physics, and biology programs for the short term, and would be advertising for students who could work for molecular engineering faculty. “It’s not a perfect solution. But new faculty are also bringing interim students from programs where they are now.”
Dr. Fall said he saw some similarity between the interdisciplinary programs of Dr. Nagahara at NCI and Dr. Tirrell in terms of nurturing careers and placing people. Dr. Tirrell agree that the new model of breaking down silos would also challenge people in finding their way as they work in teams and find good opportunities for professional placement.
Dr. Fall asked whether universities were thinking about how best to collaborate with other sectors in the technology clusters. Dr. Nowinski said that this was a high priority for the University of Illinois, which was learning “how to reach into industry” at the levels of both small and large companies. The university is also collaborating with multiple institutions to build a nanotechnology work force.
