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Constant Focus on the Future

Tue, 11/16/2004 - 4:45am

R&D's 2004 Scientist of the Year uses his strong interdisciplinary research background to build new paradigms for future academic growth.

When George Poste left SmithKline Beecham in late-1999 after nearly 20 years of running many of their R&D operations, he thought that his future commuting route would be a lot different than his nearly weekly trips between SmithKline's headquarters in Philadelphia and its offices in Europe. "I had what I called my three-S triangle—Scottsdale (Ariz.), San Francisco, and San Diego," he explains. "That was going to be my commuting triangle and I would interact with a series of biotech companies in those cities and have more time to explore the landscape of Arizona."

It turns out that his commuting schedule is even shorter now, just cross-town from Scottsdale to Tempe, the site of the brand new Biodesign Institute at Arizona State Univ. (ASU), where he is now the Director. But the intensity of his involvement is assuredly greater than he had initially envisioned as he works to chart the course for a new standard in education and multidisciplinary life science research.

George Poste
Current Position
• Director, Biodesign Institute at Arizona State
University, Tempe
• Del E. Webb Distinguished Professor of Biology
Academic Affiliations
• Distinguished Visiting Fellow, Hoover Institution, Stanford University
• William Pitt Fellow, Pembroke College, University of Cambridge, England
Education and Honors
• Doctor of Veterinary Medicine, University of
Bristol, England
• PhD in Virology, University of Bristol
• Membership, Royal College of Pathologists,
London
• D.Sc., University of Bristol
• Fellow, Royal College of Veterinary Surgeons, London
• Fellow, Royal College of Pathologists, London
• Fellow, Royal College of Physicians, London
• Fellow, Royal Society of Arts, Manufacturers,
and Commerce, London
• Fellow, The Royal Society, London
• Fellow, The Academy of Medical Sciences,
London
• Fellow (Hon.), University College London
• LLD (Hon.), University of Bristol, England
• LLD (Hon.), University of Dundee,
Scotland
• CBE, Commander of the Order of the British Empire, Honours List, H.M. Queen
• Member of the U.S. Council on Foreign Relations
Experience
• Research Fellow and Lecturer, University of London
• Professor, Dept. of Cell and Molecular Biology, SUNY Buffalo
• Principal Cancer Research Scientist, Roswell Park Memorial Institute
• VP/Director of Research, Smith-Kline & French Laboratories
• VP, Worldwide Research and Preclinical Development, SmithKline & French Laboratories
• President, R&D, SmithKline & French Laboratories
• EVP, R&D, SmithKline Beecham Pharmaceuticals
• President, R&D, SmithKline Beecham Pharmaceuticals
• Chief Science and Technology Officer, SmithKline Beecham
• Research Professor,
University of Pennsylvania
Executive Boards
• SmithKline Beecham
• Illumina
• Maxygen
• diaDexus (Chairman)
• Structural GenomiX (Chairman)
• Advance PCS
• Orchid Biosciences (Chairman)
• Monsanto
• Exelixis
• Health Technology Networks (Chief Executive)
Current Memberships
• Defense Science Board, U.S. Dept. of Defense
• Threat Reduction Committee, U.S. Dept. of Defense
• Advisory Committee on International Economic Policy, U.S. State Department
• Biological Weapons Working Group, National Academy of Sciences
• Committee on Advances in Technology and
Next Generation Biowarfare Threats, Institute
of Medicine
• Governing Board, Beckman Center for Molecular and Genetic Medicine, Stanford University
• Editorial Board, Nature Bio/Technology
• Advisor, Burrill and Company
• Advisor, Bank of America
Other
• 350+ published scientific papers
• Co-edited 15 books on cancer, biotechnology, and infectious diseases
• Chaired the Task Force on Bioterrorism for the U.S. Dept. of Defense

For his background and accomplishments in academic, industrial, and government research and for his initial work and charge as Director of the Biodesign Institute at ASU, the editors of R&D Magazine are proud to name Dr. George Poste as our 39th Scientist of the Year. Poste follows in the footsteps of previous R&D Scientists of the Year Eric Lander (Human Genome mapper, 2003), Craig Venter (genome sequencing pioneer, 1998), Tim Berners-Lee (World Wide Web developer, 1996), Kary Mullis (Nobel Prize winning developer of PCR, 1993), John Bardeen (Nobel Prize winning developer of the transistor, 1976) and Wehner Von Braun (German-U.S. rocket pioneer, 1969), among others. Poste is the eighth Scientist of the Year in the past 15 years to work in the life science arena.

Few researchers have attained the level of recognition that Dr. Poste has received, let alone across the full breadth of the R&D environment—from academia, industry, and government circles. He has been at the pinnacle of prominence in all sectors, heading the R&D operations for SmithKline from the time it was Smith-Kline French to after it became SmithKline Beecham. He's been Chair of the U.S. Dept. of Defense's Task Force on Bioterrorism following the Sept. 11th and anthrax attacks on the U.S. And in the academic world, Poste has gone full circle from working as a lecturer at the Universities of London and Bristol, following his English education, to his current position at ASU.

Along the way he wrote more than 350 research papers, was involved in the successful registration of 29 drugs and vaccines, and was awarded the rank of Commander of the British Empire by Queen Elizabeth II for services to medicine and for the advancement of biotechnology.

The road to Tempe
Poste grew up in the English countryside of Sussex, just south of London. "Growing up in a rural environment, the local veterinarian had a very dramatic role within the fabric of the agricultural economy, which essentially steered me more toward veterinary medicine rather than conventional medicine," says Poste. By the time he went to college, he found the area of molecular biology to be far more attractive than the rough and tumble life of a country veterinarian.

When the time came around, Poste chose to get his PhD in virology, which was just emerging as an independent science from the prevailing microbiology arena. "Virology was beginning to emerge, not only by a better understanding of the role that viruses had in infectious disease, but also by virtue of their ability to modulate processes within a living cell. They were also found to be very powerful tools for dissecting cellular function and that's how I came to be interested in virus-cell interactions. That then led to my looking at the use of viruses as tools for analyzing cell function, and eventually to my involvement in cancer research."

Following a series of academic positions at the Universities of London and Bristol, Poste was attracted to the Roswell Park Cancer Institute, Buffalo, N.Y., and the State University of N.Y., Buffalo, because the "most dramatic state-of-the-art cancer research was going on there at the time." The research was centered around three main researchers, James Holland, Leonard Weiss, and George Moore, the Director of the Institute. "Holland pioneered all the work in childhood leukemia, Weiss developed an understanding of the circuits of the cell in guiding the metastatic behavior of cancer cells, and Moore, who was ahead of his time, pioneered work in large-scale cell cultivation techniques."

Improving Upon the Standard of Excellence

R&D's Scientist of the Year George Poste was hired in early-2003 as Director of the Biodesign Institute at Arizona State Univ. (ASU) by Michael Crow, President of ASU. Crow had been hired in mid-2002 and in his first inaugural address, he outlined a program targeted at creating a new Gold Standard of American universities at ASU. Crow noted that American research universities, with more than a century of experience, have established themselves as the finest institutions in the world. Universities with names like Harvard, Stanford, MIT, Princeton, Johns Hopkins, and Chicago are the Gold Standards of current educational research institutions and have been responsible for successive generations of leaders in government, business, and industry.
But Crow sees many of these universities as being static and not responding fast enough to educational, technological, and social changes. Crow sees ASU as "poised to become a new American university that can break the mold of the current model for the American research university, and serve as a bellwether in its reconceptualization."
To create this new research model, Crow stated eight design imperatives that he is putting in place at ASU. They include:
1. ASU must embrace its cultural, socioeconomic, and physical setting and dedicate part of its energy, insight, and wisdom back to the place they're trying to build.
2. ASU must become an integral part of the community and a lifelong presence in the lives of its alumni and the general citizenry.
3. ASU must explore the entrepreneurial potential of university teaching and research and expedite the transfer of knowledge and technology to the commercial sector. The Biodesign Institute at ASU is one part of this imperative.
4. ASU must involve itself in the social outcome of its research and be aware of the large contributions that that research may make to society.
5. ASU must focus on the individual student, making use of new media tools, new technologies, and collaborative procedures. The university must make the excitement of discovery, the craft of scholarly writing, and the appreciation for scientific method an embedded part of the learning process. As part of this process, ASU is creating a Polytechnic version of itself and a "New College" with an interdisciplinary approach to education.
6. ASU should foster teaching and research that is interdisciplinary, multidisciplinary, and transdisciplinary. Crow recommends the convergence of disciplines where appropriate, a practice he calls "intellectual fusion."
7. The university must take the lead in addressing a multitude of social problems, from those in the local primary educational system to global technological problems. ASU has a responsibility to consider not only the value and relevance of its research, but also the outcome of this research. ASU must strive to embed education and research into the fabric of society.
8. While ASU is currently underpowered in resources that are related to global engagements, the university must devote resources to expanding the global emphasis of its programs, as well as expanding its global engagement dialogue.

Following these researchers' lead, Poste became a full professor at SUNY-Buffalo, when in 1981, he was approached by Bryce Douglas, president of SmithKline & French Laboratories (SKF) in Philadelphia, asking Poste to become VP and Director of Research at SKF.
At the time, Poste had not contemplated leaving academia. "I had a very comfortable existence, I was a full professor at an early age, and I was well funded," he says. "But there was the incestuous element of academia in terms of the usual cycle of the same conferences with the same people. And in the early 1980s, biotechnology was just beginning to get off the ground in a very dramatic way."

"It was a very exciting time with the establishment of new biotech companies like Cetus and Genentech, and even though SKF was a large pharmaceutical company, as opposed to a fledgling biotech company, they could see the impact of biotech on their industry, well ahead of most others," says Poste.

Industrial metastasis
Douglas realized that he needed to build a biotech capability at SKF and so recruited Poste to recruit others. At the time, SKF was benefiting from the success of their anti-ulcer drug Tagamid—their first billion-dollar drug—and so their R&D coffers were flush with the revenue from that drug. Poste saw the SKF offer as a great opportunity and accepted a position that was to last nearly two decades.

"The one thing that stunned me about moving to industry, and still resonates with me today, is how difficult it is to make a drug or vaccine," says Poste. "I'm amazed that any drug ever makes it, frankly." He believes that, not because of the ineptitude of some developers, but because of the technical complexity of the process. "It is intellectually complex at the scientific level, logistically complex at the development level, and commercially complex at the regulatory level. I am in awe of the talent of the teams who manage to get a successful drug registration."

While at SmithKline (in its various M&A transformations through the 1980s and 1990s), Poste was able to help create the teams that successfully processed 29 drug and vaccine registrations.

"Two things that I recall as being the most seminal during those years at SmithKline were 1) staying in the vaccine business in the 1980s when everyone else was dropping out because of low margins and high liabilities, and 2) SmithKline's entry into genomics in the early 1990s, where we led the entire biotech and pharmaceutical industries at the time."

In the vaccine business, Poste argued and won the case that recombinant DNA technology was going to radically transform the commercial landscape for the vaccine industry. "I recruited Martin Rosenberg from the National Institutes of Health in the early 1980s and he led the team that developed Engerix-B, the first recombinant hepatitis vaccine," says Poste. "Not only did it become a billion dollar a year business for SmithKline, but it also immunized several hundred thousand people."

Pharmaceutical technology went through several significant changes during Poste's tenure at SmithKline. "In the early 1980s, we went from cellular pharmacology and molecular pharmacology to embrace recombinant technology driven by advances in gene isolation and gene splicing," says Poste. "And then in the 1990s our researchers moved to large-scale methods with the full sequencing of the human genome, large-scale combinatorial chemistry, advanced robotics, high-throughput screening, and bioinformatics."

The First Eight Centers

The Biodesign Institute at Arizona State Univ. (ASU) is an interdisciplinary center that focuses on the integration of nanoscience, biotechnology, advanced computing, materials science, and neuromorphic engineering to develop real-world applications. The Institute is being built in four phases, with four interconnected buildings containing 74 km2 of total advanced research space. The first phase, a $69 million building, contains 16 km2 of research space and is schedule to open in late 2004. Phase two, which is already under construction, is scheduled to open in the fall of 2005, and the remaining two phases are planned for completion between 2005 and 2007, depending upon approval of additional state funding.
Four overarching principles were chosen when the design for the Biodesign Institute was initiated: 1) fitness for use, 2) flexibility, 3) enhance communication and collaboration, and 4) serving as a hub. These principles were used to design the overall structures in terms of providing for future growth, minimizing the effects of technology obsolescence, and maximizing the physical and technical collaborative capabilities of other technology centers on the ASU campus. The labs themselves are constructed to be open, flexible configurations to enhance the tone of the overall interdisciplinary research. And adaptability features in the labs include overhead service carriers for a utility infrastructure.
More than 20 advanced research centers are expected to be housed within the Biodesign Institute when it's completed. Eight centers already reside there, including:
• Applied NanoBioscience
• BioOptical Nanotechnology
• Evolutionary Functional Genomics
• Infectious Diseases and Vaccinology
• Neural Interface Design
• Protein and Peptide Therapeutics
• Rehabilitation Neuroscience and Rehabilitation Engineering
• Single Molecule Biophysics
Each of these centers has a world-class research director in place with numerous actively funded research programs. Most of these directors have been there since the Biodesign Institute was founded in 2002, when it was know as the Arizona Biodesign Institute, or AzBio. The name was modified slightly in 2003 to its current wording.
In addition, research and technology development research in the institute will focus on the following areas that the administrators feel offer the highest potential for industrial and clinical applications:
• Systems Biology
• Biomimetic Materials and Smart Devices
• Sensors, Sensor Networks, and Imaging Technologies
• Neural Interface Engineering and Brain-Machine Interactions
The Biodesign Institute also has numerous partnerships and research collaborations, many with Arizona-based clinical and industrial organizations. Two of these include the ASU - Univ. of Arizona Biomedical Collaborative and the Translational Genomics Institute (TGen), both based in Phoenix. These particular relationships are expected to provide invaluable resources for local, regional, and national technical, legislative, and public audiences. Additional partnerships in the life sciences include those with the Mayo Clinic, Scottsdale, Barrow Neurological Institute, the Carl T. Hayden VA Medical Center, and others. The Institute also has industrial partnerships with Intel, Motorola, Pfizer, Lockheed-Martin, Medtronic, and others.
Additionally, the southwestern geographical location of the Biodesign Institute portends future relationships with academia in Latin America. The first example of this was an agreement signed in October 2003 with the Instituto Technologico de Estudios Superiores de Monterrey, Mexico, commonly known as Tec de Monterrey, for research and teaching collaborations in engineering, biotechnology, and agriculture. The non-profit Tec de Monterrey university system has an enrollment of 95,000 full-time students and a faculty of 7,600 professors.

Since he left SmithKline in late-1999, Poste has seen relatively few changes in the technological area. "We still have this quartet of genomics, combinatorial chemistry, high-throughput screening, and bioinformatics. They're clearly being refined very successfully, but I don't think that there's anything that you can point to that has been a radical change."

On the other side of the coin, there are a number of areas that have not changed at all in the past 20 years. "Even though we've gotten better at identifying new targets for drug discovery, the ADME-Tox (absorption-distribution-metabolism-excretion-toxicity) relationships are still pretty much a black box. So you can have a superb drug target and you can have a chemical that interacts superbly with that molecule, but then we're literally flying blind in understanding how that chemical will be absorbed, where it will go in the body, how it will be metabolized, or how it will be excreted. Even the toxicology is still pretty much a lottery, and if you have a significant toxicity, you can kiss a drug goodbye and all its earlier, very expensive, development efforts."

These limitations in drug development research have not been lost on Poste. He has carried them over to his position at the Biodesign Institute.

Back to academia
Poste decided to leave Smith-Kline at the end of 1999. He had informed SmithKline Beecham CEO Jan Leschley in 1996 of his intention to leave so a succession plan could be conveniently be put into place. Coincidentally, Leschley left SmithKline Beecham in April 2000 to clear the way for the merger with Glaxo Wellcome to become GlaxoSmithKline.

In May 2003, Poste was recruited by the new president of ASU, Michael Crow, to become the Director of the Biodesign Institute.

Crow came to ASU in 2002 as its new president and immediately set about to transform the university from a very good school for providing a four-yr education to the children of the residents of the state to a school that is one of the premier centers of research excellence. "Even though ASU has the fifth largest campus in the nation with 58,000 students, you could never claim that it was in the same research league like the Univ. of California-San Francisco or the Univ. of California-San Diego, or better yet, the current top tier Gold Standards of UC-Berkeley, Stanford, Harvard, Yale, Duke, or Columbia," says Poste.


Linda Lopez is a Research Associate Professor in the School of Life Sciences at Arizona State Univ., and a research team member in the Center for Infectious Diseases and Vaccinology at the Biodesign Institute. Lopez's research involves communication between living cells and the outside world, which is mediated by complex sugars attached to the proteins and lipids that coat all cells. "My research is focused on post-translational modifications of biomolecules and the discovery and development of protein-based therapeutics for clinical applications," says Lopez. Her group has made significant progress in the engineering of plants to produce recombinant proteins with human glycosylation patterns. Eventually, they hope to develop plants that produce both stable and efficacious therapeutic glycoprotein drugs. Lopez also is George Poste's wife.

"And so the Biodesign Institute has become the flagship entity that's being targeted to accomplish that," says Poste. "It had its origins not only in Michael Crow's vision, but the Arizona state legislature passed a research infrastructure bill that provided nearly a half billion dollars to create the building and physical infrastructure." Poste's job is to "build the Biodesign Institute in what [he believes] is the next conceptual shift in the evolution of the life sciences—the convergence of biology, computing, and engineering, or bio, info, and nano."

The gating of the four-phase physical structure that will become the Biodesign Institute paces the recruitment effort that Poste is charged with implementing. At present, there are eight research centers for the one building that is in place. Creation and staffing of the other 15 or so research centers that are planned will be spread out over the next three years as the other construction phases are completed.

"We successfully recruited Roy Curtiss from Washington Univ. in St. Louis earlier this year to co-direct the Center for Infectious Diseases and Vaccinology with Charles Arntzen," says Poste. Curtiss is one of the leading microbial virulence experts in the nation and a member of the National Academy of Sciences. He represents the caliber of the people that Poste hopes to attract to the Biodesign Institute for the other research centers that will be created.

Included in Poste's charge is the implementation and acceptance of a true interdisciplinary research condition per President Crow's strategic plan as opposed to the conventional siloed research procedures. In terms of interdisciplinary overlaps, "If I were to characterize how the bio-info-nano technology focus of the Biodesign Institute breaks down, I think that we need to focus our efforts in four major areas: 1) molecular profiling of disease, 2) sensor networks, 3) bionics, and 4) biosustainability."

Molecular profiling or the creation of bio-signatures in terms of genomic, proteomic, or metabolomic characteristics is needed to define new opportunities for drug discovery and to work out the pathways for biological control in any given cell system, or, in other words, a systems biology approach. The union of engineering with this comes about through biosensors and directed molecular assembly. "I think one of the great momentums in the coming decade will be the ability to combine the cognitive capacity of biological molecules to recognize any other class of biological molecules and to link those into miniature devices," says Poste.

The development of bionics is linked to that same theme, in terms of interfacing engineering in the area of smart prostheses and rehabilitation engineering. The final concept, biosustainability, is embedded in how to adopt biological processes that do not deplete natural resources to create products that are currently manufactured by industrial processes that do deplete natural resources.

The industrial connection


Editor in Chief Tim Studt (l) and Publisher Hal Avery (r) present Scientist of the Year Geoge Poste (center) with his award at R&D Magazine's Gala Awards Banquet in Chicago on October 14th.

Poste has been integrally involved in the creation and support of industrial start-up companies through his previous and ongoing participation in various boards of directors. "This effort has taught me how to make tough decisions on how to build an organization," he says. "Technology advances are largely driven by industry and how these are accomplished is vital to leading a university-based research organization. And while there are different roles in companies and universities, it has been important to learn how to survive and how to introduce new products."

Poste's experience at SmithKline also has helped him look at what biotechnology areas are likely to be explored and developed in the future. "Only 10% of the drugs developed by pharmaceutical companies actually are commercial successes. That is unacceptable," he says. Patient segmentation and developing the right drug for the right patient is needed to create an economically feasible health care system. This will require the union of drug development with computing as a start.

Poste's prospects


Charles Arntzen is Co-Director of the Center for Infectious
Diseases and Vaccinology at the Biodesign Institute. Arntzen served as Founding Director of the Institute until George Poste assumed the position in May 2003. Arntzen's primary research interests are in plant molecular biology and protein engineering. He is a recognized pioneer in the development of plant-based vaccines for disease prevention in humans and animal agriculture. With the recent national emphasis on bioterrorism, Arntzen's research has been extended to include creation of effective vaccines and therapeutics to reduce the threat of biowarfare agents.

Stuart Lindsay is the Director of the Center for Single Molecule Biophysics at the Biodesign Institute. Lindsay's research focuses on the structural changes within DNA involved in turning genes on and off. With the assistance of a company he co-founded, Molecular Imaging Corp. in Tempe, Ariz., Lindsay builds specialized scanning probe microscopes to study the DNA, along with the electron transfers in single molecules, such as photosynthesis. Lindsay continues to be a technology advisor to Molecular Imaging, where he was VP of R&D from 1994 to 2000. Lindsay's research team at ASU also was instrumental in the design and development of Molecular Imaging's PicoTREC Topography and RECognition system that won a 2004 R&D 100 award.

There is a lot of promise and a lot of potential disruptions in the future of life science research. Bioterrorism is a low probability, but a high consequence issue that is probably not at the top of his list at this point in time. "Bioterrorism in the agricultural sector may be a more likely target. In ten years, however, the wide availability of things like biological circuit disruptors may create an entirely different, and potentially more hazardous scenario than we currently have," adds Poste.

One of Poste's pet peeves is the growing issue of antibiotic immunity. "Society is asleep at the wheel and within this decade, the effects of not having any new antibiotic drugs in the pipeline will be profound."

The future of new pharmaceutical development will involve "the five horsemen of the medical apocalypse—genomics, informatics, economics, ethics, and politics," says Poste. "Over the next 20 years there will also be a shift from the current reactive role to a more predictive and preemptive relationship." Looking at the future, Poste also sees that globalization is inevitable and will permeate every element of life. "The world may be unstable for some length of time and politically volatile. One of the stabilizing or destabilizing effects to this future will be the ubiquity of access to health care."

Poste expects to do his part to make that future as stable as possible through the development and availability of ever newer and more effective life science technologies.

--Tim Studt

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