From creativity and collaboration, Arizona has given birth to what might be the next great wave in biotechnology. Hallmarks of the state’s growth include nearly $500m in research infrastructure brought online in 2004; identification of 1.5 million square feet in convertible clean room space; more than $1m in state job training funds to 10 bioscience companies during 2004 with more allocated so far this year; and upwards of $100m has been allocated for workforce development in secondary schools and community colleges.
In March, the christening of the Translational Genomics Research Institute (TGen) took place in downtown Phoenix, Arizona. Against all odds, this miracle baby survived birth and incubation and has emerged as Arizona’s new golden child – both scientifically and economically.
Beginning in 2002, a public-private partnership raised more than $100m to launch TGen. Land, office space and building contraction was completed in less than 18 months, creating the catalyst for explosive development and attracting some of the most talented researchers in the world.
The public face and scientific soul of TGen is Dr Jeffrey Trent. Raised in Phoenix with masters and doctoral degrees in genetics from the University of Arizona in Tucson, he served as scientific director of the National Human Genome Research Institute at the National Institutes of Health in Washington, DC. He was, in essence, lead investigator on the US team, working with scientists worldwide to map the human genome. From Dr Trent’s perspective, a global revolution is afoot. “I think all of medicine will be recorded by what we knew before the human genome project and what we have learned since its completion,” he told Arizona-based TechConnect magazine.
When he accepted the post of president and chief scientific director of TGen, Dr Trent made it clear that his goal was to move discoveries and information into the marketplace as quickly as possible. Saying that the genome map results in a “better parts list”, he works toward a vision of customised treatment for individual patients. He insisted that this “bench to bedside” or translational approach be at the centre of TGen’s mission.
This new chapter in genetic research is aptly called “translational research”. It is a relatively new field and employs innovative advances, including genome-wide array technology and the burgeoning field of computational biology, to provide the data and tools necessary to identify genes that play a role in hereditary susceptibility to disease. Genetic changes that contribute to disease or the resistance to treatment can also be identified with these technologies.
Effective treatment for cancer depends on identifying specific targets: molecular vulnerabilities that differentiate cancer cells from healthy cells. Once a target is identified, rapid screening of potential compounds determines their ability to treat the vulnerabilities. DNA micro-arrays, which can scan hundreds of gene mutations at once, are central to this process.
TGen’s genomics group uses another new technology called synthetic lethal screening to locate a tumour’s weakness – the target for treatment. Then, with the rapid testing technologies in full gear, the most promising therapies to combat cancer cells advance to human trials and ultimately the marketplace.
The process of moving quickly from bench to bedside is working. In 2004, researchers at the fledgling institute located the gene associated with Sudden Infant Death Syndrome (SIDS). It used to take hundreds of scientists years to discover specific genes associated with specific maladies but with today’s technology, four scientists at TGen unlocked SIDS’ genetic secret in just seven days.
Among those joining Dr Trent in Arizona is R & D Magazine’s 2004 Scientist of the Year, Dr George Poste, who was appointed in May 2003 as director of The Biodesign Institute at Arizona State University. This is a major new initiative combining research groups in biotechnology, nanotechnology, materials science, advanced computing and neuromorphic engineering. In addition to his academic post, Dr Poste serves as chief executive of consulting company, Health Technology Networks, which specialises in the application of genomic technologies and computing in healthcare. He is also chairman of Orchid Biosciences, the leading company in DNA forensic analysis, and serves on the board of directors of Monsanto and Exelixis.
Dr Poste is a Fellow of the Royal Society, and of the UK Academy of Medicine, a Distinguished Fellow at the Hoover Institution, Stanford University and a member of the Council for Foreign Relations. He is a member of the Defense Science Board of the US Department of Defense. And he serves as a member of the National Academy Sciences Working Group on Biological Weapons; the Forum on Microbial Threats of the Institute of Medicine Board on Global Health; and the Institute of Medicine Committee on Advances in Technology and New Generation Biowarfare Threats.
Like Dr Trent, Dr Poste leads initiatives born of collaboration. To optimise the management of the research agenda in specific focus areas, the institute is organised into several networked and overlapping research centres. Each centre is composed of a group of researchers collaborating to address defined problems or needs of major societal importance. Innovative solutions are sought that leverage the emerging discoveries in related fields, such as the biosciences, biotechnology, and nanotechnology and integrating disciplines such as genomics and bioinformatics. These centres are organised to be flexible, adaptable and responsive, thus allowing the institute to keep pace with the accelerating advances in science and society’s increasing demands for new technology.
Door to discovery
The ability to study and construct systems at nanoscale – 1000 times smaller than a human hair – has unlocked a door to discovery. To accelerate these discoveries and translate them into useful applications, the Biodesign Institute is taking a bold, integrated approach. Inside the institute, the lines between biotechnology, biomedicine, nanotechnology, information technology and cognitive science will become increasingly blurred. Biologists, engineers and computer scientists work side-by-side, bringing highly specialised expertise into an environment where glass walls and flexible laboratory designs stimulate collaboration.
The BIO5 Institute for Collaborative Bioresearch, which is located at the University of Arizona (UA), is named in recognition of the strength to be found in collaboration. Five disciplines – science, agriculture, medicine, pharmacy and engineering – combine to solve complex biological problems. BIO5 creates science, education and industry partnerships to disseminate knowledge and apply the knowledge gained to treat disease, feed humanity and preserve livable environments.
Launched with funds from a voter-approved tax in 2001, the institute is designed to fuel economic development by pursuing state-of-the-art biological research, by creating new products and processes, by encouraging productive research interactions between faculty and industrial scientists, and by training a bioindustry workforce and enhancing science literacy.
BIO5 has expanded the multidisciplinary approach to solving complex scientific problems of medical importance, by partnering with the UA’s Biomedical Engineering (BME) Program. Stuart K Williams, head of the BME program, says: “BIO5 is part of the biology revolution that is rapidly incorporating engineering analysis and synthesis design approaches. As engineers, we work through a ‘measure, model, manipulate’ paradigm. As molecular components become easier to manipulate, our approach will be invaluable in understanding and predicting the effects of these manipulations. Quantitative methods now permeate all of biology.”
The BME Program’s areas of expertise include imaging technologies and materials science. It has established an international reputation in regenerative medicine, an emerging field that focuses on the repair or replacement of damaged tissues and organs. Another example from UA’s efforts resulted in top billing for one of Arizona’s star medical devices earlier this year when Bill Wohl, who owes his life to the CardioWest artificial heart (named the top advance in cardiac medicine last year by the American Heart Association), was featured on the cover of LIFE magazine.
Pipeline to application
Arizona’s seamless pipeline from laboratory research to clinical applications extends beyond the pristine laboratory space of its two Research 1 Universities. For example, Barrow Neurological Institute is gaining leadership in neural engineering – the interface between the nervous system and artificial devices that replace lost senses or missing limbs. Here emerging technologies include cutting edge advances such as: direct brain control of a motor prosthesis, spinal cord microstimulation, and development of bioactive coatings for implantable devices.
In response to the Food and Drug Administration’s (FDA) call for research to develop and validate new tools and methods for the development of safe new medicines, The Critical Path to Accelerate Therapies Institute (C-Path) was established in Tucson early this year. With the award of a $400,000 grant from the Arizona Department of Commerce, this non-profit corporation is getting off the ground and starting to conduct the educational and research programmes that will enable the FDA and the pharmaceutical industry to accelerate drug development.
The C-Path institute is affiliated with three founding partners: the UA, SRI International (formerly Stanford Research Institute) and the FDA. UA will serve as home for the institute’s educational and research programmes and provide an environment of innovation and inquiry. The participating FDA scientists will provide the first-hand knowledge of the regulatory process and a wealth of experience in modern pharmaceutical development, scientific expertise and a track record of commercialising innovations.
Arizona’s well-established and growing optics cluster offers unique capabilities to provide new imaging modalities as well as the use of lasers in regenerative medicine that is modifying healing response. One breakthrough technology in the diode laser (also known as an injection laser) for tissue removal could have a great impact on tissue remodeling and cancer treatments.
Other milestones being reached in Arizona include: a big role for the Mayo Clinic in Scottsdale in a four-pronged brain cancer research grant from the Specialized Programs of Research Excellence division of the National Cancer Institute. The grant, worth $10.8m over five years, will be used to seek new research therapies and to reduce deaths caused by a specific type of brain cancer.
The International Genomics Consortium’s (IGC) Expression Project for Oncology (expO) has released clinically-annotated gene expression profiles for 60 tumour specimens, completing the initial phase of the nation’s first and eventually largest public database dedicated to standardised gene expression data. The clinically-annotated dataset is available in the public domain through the National Center for Biotechnology Information website at www.ncbi.nlm.nih.gov/geo/.
The goal of expO and its consortium supporters is to procure tissue samples under standard conditions and perform gene expression analyses on a clinically annotated set of de-identified tumour samples, updated with clinical outcomes, and release all data into the public domain without intellectual property restriction.
“This publicly-accessible gene expression clinical database of patient specimens will fuel and accelerate clinically-meaningful and scientifically-valid research into better prognostic tests, new diagnostics, targeted therapies, predictive therapeutic strategies and potentially preventative modalities for patients,” said IGC founder Daniel Von Hoff.
In Arizona, expO is just one of the projects that helps to demonstrate this new translational wave of biotechnology. True translational research begins with the scientists collaborating in the search for ideas and answers. Moving their results quickly into clinical practice – from bench to bedside – is the first part of translation. Now, with expO’s results coming online, the potential of translation can begin to be realised. As physicians and practitioners (by the bedside) begin to return their observations and findings to the laboratory, they close the loop and help to focus ongoing scientific activity, thereby accelerating access to improved diagnostics and treatments.
This article was written by Jami McFerren, director of communications at the Arizona Department of Commerce. An award-winning journalist, Ms McFerren joined the agency in May 2000