Personalized medicine will transform how the world confronts disease. The collaborations that usher in personalized medicine will transform Arizona.
That vision took a step closer to becoming reality in October, with the unveiling of the Partnership for Personalized Medicine, a new effort that will unite premier researchers from the Translational Genomics Research Institute (TGen), the Biodesign Institute at Arizona State University, and other experts in the state with a world leader in the field, Nobel laureate Lee Hartwell.
The birth of the Partnership is the latest in a string of developments that together are reshaping the bioscience landscape across Arizona, from the construction of new research facilities and the recruitment of key scientists, to the founding of new biotech firms and increased attention to quality K-12 science and math education. Together, the advances represent dramatic progress on Arizona’s Bioscience Roadmap, a ten-year strategy that has now reached its midpoint.
A Unique Partnership
When Hartwell’s discoveries of key regulators of the cell cycle were recognized with the 2001 Nobel Prize in Physiology or Medicine, virtually no one could have imagined that the Partnership would one day take shape, much less that Arizona would serve as its home. Hartwell, president and director of the Seattle-based Fred Hutchinson Cancer Research Center, would acknowledge as much at the announcement of the Partnership’s formation: “Five years ago, I would never have thought my path would bring me here to Phoenix.”
But as the Nobel Assembly at Korlinska Institutet honored Hartwell in Sweden, the groundwork was being laid in Arizona: The previous November, voters had approved Prop. 301, a sales-tax initiative that includes 20 years of dedicated funding for scientific research at the three state universities—an estimated $1 billion. At the University of Arizona, the creation of the BIO5 Institute—then known as the Institute for Biomedical Science and Biotechnology—introduced a new model for interdisciplinary bioscience research to tackle real-world problems. And Jeffrey Trent of the National Institutes of Health (NIH), while immersed in mapping the human genome, was considering a move to Arizona, a development that would take place in 2002 as TGen was being born.
Today, more pieces of the puzzle have been laid in place. The Biodesign Institute was established in 2003, with world-renowned pharmacologist George Poste recruited as its director. A facility housing both TGen and the International Genomics Consortium was built to anchor the downtown Phoenix Biomedical Campus, an extraordinary example of multi-institution collaboration that includes the UA College of Medicine-Phoenix, in partnership with ASU. A legislative appropriation of $440 million for university research facilities gave scientists and entrepreneurs added confidence that the public sector was serious about supporting their endeavors; last year’s formation of Science Foundation Arizona (SFAz) gave that belief greater credence.
Two years ago, eager to tap Hartwell’s expertise and ability to assess opportunities, Poste recruited him as a member of Biodesign’s scientific advisory board. “I think during his visits to Arizona since then,” Poste says, “Dr. Hartwell developed a keen sense of the pace of research expansion here, the excitement of building a team-oriented, multidisciplinary approach to science directed at solving urgent societal problems, and wanted to be a key leader in that effort.”
To launch the Partnership, the Virginia G. Piper Charitable Trust committed $35 million, and the Flinn Foundation granted $10 million. The two philanthropies’ contributions will support the development, testing, and validation of new molecular diagnostic tools and the approval and distribution of these tools for widespread clinical use. In addition to drawing on existing TGen and Biodesign resources, new researchers will be recruited, and a high-throughput proteomics production facility will be assembled for their use. (Proteomics goes a step further than genomics, to study proteins and their functions in the body.)
One component of the Partnership, the Flinn Fund for Arizona Proteomics Research, will be used to encourage cooperation and will support use of the Partnership’s facility by researchers from institutions throughout Arizona. “While many areas around the country are building research capacity centered on proteomics and diagnostics, what makes Arizona rise to the top is the close cooperation among our private and state institutions,” Poste says. “The level and degree of cooperation is imperative to our success, since other regions have had a generational head start to build upon their bioscience research strengths.”
“We want to diagnose disease more precisely, in a more individualized manner,” Hartwell said at the announcement of the Partnership. That goal articulates the essence of personalized medicine, which applies advances in genomics and pharmacogenomics—and now, proteomics—to the development of individually targeted patient treatments. Knowing which patients will respond to which therapies should deliver a huge payoff: improved health outcomes at reduced cost.
It is in the powerful, enticing economics of health care, Hartwell believes, that potential exists for the new venture to involve researchers, pharmaceutical companies, insurers, and governments from around the world.
“Our secret weapon is partnerships—between TGen and Biodesign, between Piper and Flinn, between research institutions throughout the state and the world,” Hartwell said. “I can’t tell you how excited I am to get started on this and to be part of this community.”
The establishment of the Partnership for Personalized Medicine provides the latest evidence that Arizona’s most distinctive bioscience undertakings are having a spillover effect—the expansion of existing initiatives, the attraction of new scientists and their innovative lines of research, the translation of research discoveries into new products and spinoff firms.
Research discoveries announced by Phoenix-based TGen include: a gene that appears to increase a person’s risk of developing Alzheimer’s disease; a recurring mutation in breast, colorectal, and ovarian cancers; a set of more than 50 genetic abnormalities in people with Lou Gehrig’s disease; and a genetic marker linked to greater incidence of prostate cancer in African American men. And these findings have all come in just in the past six months.
TGen aims to translate such findings into new diagnostics, prognostics, and therapies as rapidly as possible. To do so, it has initiated collaborative efforts involving all three state universities, independent research institutes, various hospital networks, and industrial partners. Its ventures include several spinoff firms, most notably Molecular Profiling Institute Inc., a for-profit spinoff that turns TGen’s research discoveries into diagnostic tests; a collaborative cancer-research facility for Mayo Clinic and TGen scientists on Mayo’s Scottsdale campus; and TGen North, which opened in Flagstaff earlier this year and concentrates on pathogen genomics.
The Tucson-based Critical Path Institute, launched in 2005, occupies another unique niche in the biosciences, as a neutral third party working with the Food and Drug Administration and the industries it regulates in order to achieve quicker, safer development of more-effective medical products. Demonstrating a cooperative spirit like the drive toward partnership that Hartwell describes, C-Path last year facilitated an agreement between five of the largest U.S. pharmaceutical companies to share with each other and the FDA their internal methods for predicting the safety of treatments before they enter human clinical trials—an unheard of practice in this competitive industry. That five-firm agreement has now become a 16-firm agreement.
“Because of C-Path, the FDA created a new application process for the review of these methods and is now considering new testing methods that should replace tests that are decades old and ones that are far less sensitive and specific,” says Ray Woosley, President and CEO of C-Path. “Because of this project, the drugs that enter human testing and those that reach the market will be more safe than ever before.”
Another collaborative C-Path project, announced in October, will address how to assess and evaluate biomarkers and other diagnostic tools used to test the safety and effectiveness of drugs under development. Under a two-year, $2.1 million grant from SFAz, C-Path will work with a private-sector partner, Ventana Medical Systems Inc. of Tucson, to design a set of standards for the FDA to employ when it evaluates diagnostic tools used in conjunction with drug therapies. Currently, the FDA has no defined procedure for how it assesses diagnostics; consequently, diagnostics receive approval far too slowly, and no structure exists for co-submitting drugs and their companion diagnostics for FDA approval.
Establishing improved methods for evaluating drugs under development will provide a major impetus for the development of personalized medicine, which significantly relies on diagnostic testing to match patients and treatments, and will even more prominently put C-Path on the map. That, in turn, will strengthen the state’s competitiveness in its pursuit of more bioscience experts like Woosley, inspiring the kind of enthusiasm he caught when he first visited to interview at UA.
“I heard a commitment to science, technology, and improved health from the leaders in the community, the universities, and the state and local government,” Woosley says. “The passage of Prop. 301 and the outstanding science base at the University of Arizona gave me confidence that the base was sound and the commitment to a high-tech knowledge economy was genuine.”
Silo Mentality Ends
While C-Path breaks down barriers to new treatments and facilitates industry-government cooperation, cross-disciplinary endeavors like BIO5 at UA and the Biodesign Institute at ASU—and scientific collaborations underway between the two institutes—have broken down the silos that traditionally isolate university departments and even individual researchers from each other. In both cases, thanks to the Legislature’s 2003 facilities appropriation, major new buildings have opened to house their investigations. These facilities fill an important infrastructure gap, and at the same time symbolize the institutions’ commitment to collaboration. Both BIO5 and Biodesign have assembled scientists representing distinct areas of expertise who are eager to confront complex, real-world problems as a team.
“BIO5 is catalyzing a number of cross-disciplinary research and training programs and we are beginning to see great results,” says Vicki Chandler, BIO5 director. “For example, UA researchers from nine departments have been working for the past three years to move a potential cure for valley fever forward. The drug now is in clinical trials and the genome of the bacteria that produces the drug is being sequenced.”
As another example, Chandler cites the Center for Complex Disease, in which BIO5 researchers are working to understand how genes and environment can influence diseases such as asthma, colon cancer, and cardiovascular disease. More recently, BIO5 researchers from engineering, computer science, neurobiology, and pharmacy have begun developing a rapid screen for drugs that impact nerve function, with eventual applications for treating autism and mental retardation. And BIO5 is a contributor to an even broader interdisciplinary entity at UA, the Arizona Mass Spectrometry Consortium, led by renowned proteomics experts Vicki Wysocki and Serrine Lau.
At Biodesign, one of the most recently announced initiatives is one of the most ambitiously collaborative. Supported by SFAz and petroleum giant BP, the project—nicknamed “Tubes in the Desert”—seeks to use photosynthetic bacteria grown in clear tubes to produce biodiesel. Biodesign has recruited scientists from across the university to participate in the project, including scientists from the Fulton School of Engineering working to optimize the bioreactor for bacterial growth and geneticists from the School of Life Science who are genetically engineering the bacteria to produce more high energy fat to use as biodiesel.
Poste notes another team of researchers, who refer to their early-stage project as “Doc in a Box.” This endeavor, initiated by Stephen Johnston, director of the Center for Innovations in Medicine, intends to develop a diagnostic platform that could measure up to 10,000 distinct biomarkers from a single drop of blood.
“It involves researchers from four different centers at Biodesign, drawing from expertise in diverse fields including cell biology, high-throughput genomics and proteomics, microfluidics, and electrical engineering,” Poste says. “This type of project would not have been possible in a traditionally-oriented biosciences department.”
The innovative projects that Chandler and Poste are leading have helped Arizona to accelerate dramatically its overall base of research funding. When Battelle, a national leader in positioning regions to excel in technology and the sciences, presented Arizona’s Bioscience Roadmap in 2002, it suggested that Arizona greatly increase its NIH research funding—considered the gold standard of biomedical research excellence. Specifically, Arizona’s growth in NIH grants should meet that of the top 10 states by 2007. This was met—and exceeded—two years early.
Building on Existing Strengths
The 2002 Roadmap also recommended that, to achieve the greatest impact in the biosciences, Arizona should make investments in selective bioscience disciplines—cancer research, neurosciences, and bioengineering—where it had already achieved excellence. All three of the state’s universities are engaged in significant research in these disciplines, as are private research institutes and hospitals, such as Banner Alzheimer’s Institute, Barrow Neurological Institute, Mayo Clinic, Scottsdale Healthcare, and Sun Health Research Institute.
In northern Arizona, two institutions that stand outside those core bioscience disciplines have nevertheless achieved particular reputations for excellence: W. L. Gore & Associates Inc., and TGen North. The former is well-established in the region, the latter a new arrival on the scene.
Gore is an unusual member of Arizona’s bioscience community, its presence the result of company founder Bill Gore visiting Flagstaff and being captivated by northern Arizona’s natural beauty. Today, Gore’s Flagstaff facility is the company’s headquarters for high-tech medical products, from vascular grafts to cast linings. Gore, which recently celebrated 40 years in Flagstaff, is the city’s largest private employer, and is substantially responsible for the region’s unusually high concentration of high-paying biotech jobs.
According to Eve Ross, Gore’s corporate counsel and the former chair of the Greater Flagstaff Economic Council, the firm intends to maintain its regional standing while expanding to the Phoenix area.
“We just opened our largest medical plant anywhere, in Flagstaff, with a ribbon cutting ceremony in August,” Ross says, “and we still have about 100 acres in Flagstaff for future growth. But we have announced that we will grow next in the north Phoenix area to take advantage of the labor force in the Valley of the Sun.”
That expansion, announced this summer, could eventually employ 800 scientists and technicians. It will give Arizona a new opportunity, as exists in northern Arizona, for complementary economic development like the establishment of medical-device firms that could function as Gore’s supply-chain partners. And Gore’s expansion indicates the state’s growing capacity—intellectually and financially—to support major new bioscience firms that may soon arrive.
A prime example of how Arizona is building on existing strengths is TGen North, which specializes in the study of pathogens such as influenza, valley fever, drug-resistant staphylococcus, and pneumonia. Paul Keim, the research center’s director, earned his undergraduate degree from Northern Arizona University and has served on NAU’s faculty since 1989. He achieved international recognition for his research on anthrax, and besides TGen North, he directs NAU’s Center for Microbial Genomics and Genetics.
Keim says that TGen North has the potential to be an economic engine by sustaining high-quality research. “My NAU efforts have resulted in patents and licensed IP in the past and we will continue this in the future,” he says. “TGen North is just a year old; as we mature at TGen North, commercialization will be more common. In the short term, we just try to do good science with an eye towards commercialization.”
As these efforts mature, they will form a new foundation for the state’s further growth, with innovative research spinning off new firms and growing firms engendering new opportunities for collaborative and collateral development.
At the announcement of the Partnership for Personalized Medicine, Poste spoke of that initiative’s potential to radically improve healthcare. But he could have been speaking more broadly about the bioscience sector’s potential to radically strengthen Arizona’s economy and the quality of life its citizens enjoy.
“This is something that—if we do it right—will burgeon nationally and internationally,” Poste said. “The charge is formidable, but we’ve been given a great opportunity to be in the vanguard.”
The Next Five Years
By most measures, the five years since the introduction of Arizona’s Bioscience Roadmap have seen admirable progress. Arizona BioIndustry Association president and CEO Bob Eaton, a recent arrival from Maryland, says that the state has emerged rapidly on the national scene.
“I had heard for several years about the significant investments being made in the bioscience research infrastructure in Arizona, and had seen some of it firsthand during a visit in 2005,” he says. “I think it will be an exciting time to be part of the bioscience community here.”
Over the next five years, though, as the state’s success stories mature, sustained attention and investment will be necessary to keep afloat projects like the Partnership for Personalized Medicine while finding and nurturing the next W. L. Gore or Ventana Medical Systems—today the target of a takeover bid by pharmaceutical giant Roche. Many bioscience leaders argue that in the next several years, both public and private investments will need to expand.
“Arizona has markedly stepped up its investment in bioscience research, with TGen, Biodesign, BIO5, and others,” says Richard Love, one of the original senior administrators of TGen. “These investments are bearing fruit in commercialization opportunities. More than three dozen new bioscience companies have been formed in the recent past. More are coming.”
Vicki Chandler of BIO5 says that by facilitating connections between BIO5 researchers and private industry, her institute has played a part in 11 start-up companies, 118 inventions, 45 patents, and 18 licenses. “We have had hundreds of facility-access agreements, which enable small companies to access leading-edge technologies,” she says.
Need for Venture Capital
Love advises, though, that growth that relies solely on public-sector and university support will not necessarily last. “We must also encourage the development of a venture capital community that is knowledgeable and competent in bioscience investing,” he says. “I firmly believe that, unless these companies have access to local venture capital, many of these emerging companies will leave Arizona.”
The challenge, says Paul Keim of NAU and TGen North, lies in assuring venture capitalists that Arizona bioscience is a good bet. “The private sector is risk-averse and is most willing to fund the ‘end game’ in product development,” he says. “The early stages of the scientific endeavor have to be done by government or private foundations.”
To help bridge the gap, Keim says, TGen is employing the concept of “accelerator companies,” which can for-profit or non-profit and focus on fundraising and the final product development effort so that the commercial sector can recognize its potential.
Going forward, such technology commercialization will be the mandate of Arizona’s bioscience enterprise. Based on existing excellence and progress to date, Battelle is recommending that Arizona focus its commercialization efforts on three signature opportunities: molecular therapies, vaccines, and diagnostics evolving from research in genomics and proteomics; advanced medical technologies leveraging the convergence of the biosciences with such fields as imaging, information technology, and nanotechnology; and sustainable bio-related technologies that yield new material resources, energy, and products without damaging the environment.
Across Arizona, projects well aligned with Battelle’s recommendations, such as the Partnership for Personalized Medicine, are beginning to emerge with greater frequency, indicating the state’s readiness to take this next big step.
Stronger K-12 Education
Still, while calling for new investment on the commercialization front, bioscience leaders also urge the state to keep working to strengthen K-12 education, particularly its STEM (science, technology, engineering, and math) curriculum. Eaton acknowledges the challenge in developing the particular educational programs to match biotech companies’ emerging workforce needs, and the challenge to build students’ awareness of the opportunities for them in the biosciences.
Chandler has pushed to make science education and outreach a priority at BIO5, providing curricula and training to teachers, as well as hosting summer camps and internship programs for students. “It is absolutely clear that the economic health of our state and nation depends on technology, and we must increase the number of American students interested in science, math, and engineering if our economic vitality is going to continue,” she says.
Gore’s Eve Ross links Arizona’s willingness to strengthen education to the retention of existing scientists and technicians, too. “People who have Ph.D.’s, who met their spouse in graduate school, want their kids to be going to good schools,” she says. “In Flagstaff, we’re lucky to have some good charter-school options and some new programming from the school district that I know has helped us retain Associates who might otherwise be dissatisfied with the education system here.”
C-Path’s Ray Woosley agrees, and broadens the appeal for enhancing education. “The state that makes the greatest commitment to education—at all levels—will have the greatest prosperity,” he says.