Dr. Will Mayo had no way of knowing his assessment of the group medical practice would also perfectly describe a 21st century Mayo initiative, this one involving joint research to improve patient care. The Minnesota Partnership for Biotechnology and Medical Genomics is one of those ventures that fits well into the Mayo concept that one can accomplish more with others than one can alone. The Minnesota Partnership is a formal research collaboration between Mayo Clinic, the University of Minnesota and the State to improve health care using the most recent breakthroughs in medical technology. By joining forces in the Partnership, the these two renown institutions hope to achieve goals that neither could alone.

How It All Began

The Partnership stems from a request by then Governor-Elect Tim Pawlenty, who wanted to know whether clinic and university could collaborate in some way to foster biotechnology in the state and better position Minnesota for economic growth. Now, after three years of progress, the Partnership is promising long-term possibilities for both - critical breakthroughs in medical research and significant economic impact for Minnesota. Overall economic impact is estimated to range from $64 million to over one billion dollars annually after ten years, depending on the level of support.

In 2001 lawmakers wanted to make sure that these two organizations could work together to launch an effective program. By 2003, there was no doubt. Research, administrative and legal staff from both institutions resolved issues, made compromises and reached agreements on everything from communications to intellectual property. Joint planning teams were set up, a Web site and newsletter were launched, and leaders were named. Providing leadership are Hugh Smith, M.D., Chair, Mayo Clinic Board of Governors, and Frank Cerra, M.D., Senior Vice President for Health Sciences, University of Minnesota. Science coordinators for the Partnership are Eric Wieben, Ph.D., Director of Mayo's Genomics Research Center, and Mark Paller, Ph.D., Assistant Vice President for Research at the university's academic health center.

Initial funding from the Minnesota legislature, Mayo Clinic, and the University has made possible the Partnership's first research awards. In early 2003 the leadership asked for collaborative research proposals from their investigators. The proposals were required to be true collaborations by investigators from both institutions and involve research that could not be conducted by either organization alone. Projects had to advance understanding of a disease and generate outside funding, presumably from the National Institutes of Health. Applicants were strongly encouraged to involve some form of genomics or biotechnology in their proposal.

Response from researchers was overwhelming. Thirty-four collaborative proposals were received from 128 investigators from 12 colleges at the University and 121 investigators from Mayo Clinic, for a total of $21.8 million in requested funds. The applicants were hailed for their interest and enthusiasm and the overall quality of the science proposed was called "superb." Clearly, the interest exceeded available funding. The field was narrowed and the final selection was made by an independent team of nationally recognized scientists from across the country. Four proposals were chosen to share the $3 million in direct funding. They included research on obesity, heart disease, Alzheimer's disease, and prostate cancer. The four projects were announced at a State capitol news conference in January 2004.

Future Partnership plans include an initiative to increase laboratories for medical genomics in Rochester and a request for a five-year commitment from the Minnesota legislature for $70 million in research support.

Minnesota Partnership Research Projects

Two of the Partnership investigators are seeking to understand the genomic origins of atherosclerosis. It's clear that some individuals have a greater susceptibility to arterial plaque and vascular dysfunction. Basing their research on the recently mapped human genome, Amir Lerman, M.D., from Mayo and Robert Hebbel, M.D., from the University of Minnesota, hope to pinpoint the genetic factors that place patients at greater risk for "hardening of the arteries" and subsequent vascular disease and heart attacks.

Their investigation builds upon each institution's respective discoveries and expertise. University researchers have previously devised a method for propagating the endothelial cells from a simple blood sample. Dr. Hebbel and his team will try to understand the functioning of the cells that line the vascular system. Those cells harbor the clues that could lead to a new drug or treatment.

At Mayo Clinic, researchers have already developed a clinical test to identify atherosclerosis. Dr. Lerman's group will continue to study patients with the condition, along with the cells. This team is particularly interested in inflammation signals in the vascular system and how they correspond to the biologic behavior of the endothelial cells. They will compare those cellular behaviors to the known vascular conditions of study volunteers. Their goal is to discover a means of earlier and more accurate identification of heart disease risks. Ultimately, the hope is for a new drug to control coronary artery disease as part of a broad-ranging therapy.

Another pair of investigators is tackling the growing obesity problem by studying how brain function affects weight. Mayo's James Levine, M.D., and the University's Catherine Kotz, Ph.D., are aware that some individuals have a greater resistance to weight gain and obesity - a characteristic that cannot be totally explained by exercise, eating habits and or a person's metabolism.

Again, foundational discoveries by each organization lay the groundwork for this study. The Mayo team has identified a fourth factor in weight loss -- the calories burned not by exercise, but during regular, daily activities. They've termed this factor "non-exercise physical activity thermogenesis" or NEAT. University researchers have identified mechanisms within the brain that are likely players in the regulation of NEAT in the body. Not unlike switches or thermostats, these mechanisms control how much energy a person burns for each type of activity. Some people are more efficient in using and burning energy in this way and the collaborative team wants to discover why. With that knowledge, researchers may be able to initiate or increase the factor in individuals prone to obesity.

Alzheimer's disease is an increasing focus of medical research as the Baby Boom generation ages. There is no cure or effective treatment, only therapies designed to slow the progress of dementia. It is known that the therapies are most effective when intervention is early. Again, because Alzheimer's is traditionally diagnosed by accumulated observable symptoms (physical and behavioral) it is difficult to identify in the very early stages when the culprit amyloid plaques and neural tangles associated with the disease begin to form in the brain. MRI or PET scans are helpful, but at this point their precision is insufficient. There is no laboratory test and no way to make a definitive diagnosis, much less an early one.

A collaborative team headed by Michael Garwood, Ph.D., of the University of Minnesota and Joseph Poduslo, Ph.D. and Clifford Jack, M.D., of Mayo Clinic, hope to develop a special probe, a "smart molecule" that could navigate through the blood-brain barrier and attach itself to amyloid plaques. This molecule would be chemically marked to make it easily identifiable with MRI. If successful, the method would be tested in animal models, and hopefully lead to a means of early diagnosis of Alzheimer's in humans.

The fourth collaborative project funded by the Partnership seeks to find a biomarker for aggressive forms of prostate cancer. Currently, tests can indicate the presence of cancer, but not its likelihood of progression, a critical factor in deciding on treatment among older patients. George Klee, M.D., Ph.D., at Mayo and Donald Connelly, M.D., at the University are co-investigators. Blood or biopsy tissue samples collected at Mayo Clinic will be tested using microarray technology and results will be cross-indexed against genes and known biomarkers being studied at both institutions. So much genomic data is expected that it will take the computing and analytical power of both organizations to handle the bioinformatics workload. Specialized software programs developed by the University will be used to help identify biomarkers. Mayo researchers will use the data to develop automated systems to measure the biomarkers. Knowing what to look for in blood or tissue and how to measure it, can lead researchers from the laboratory to clinical trials in testing prospective methodologies for prostate cancer screens. The goal is a specific chemical or genetic test that will identify the more aggressive forms of the cancer, allowing timely and equally aggressive treatment.

The Minnesota Partnership has inspired additional collaborations and discussions between the two institutions. Collaborative medical training on genomics is planned and cost savings are already being realized through bulk purchasing of microarray chips and supplies.

To keep up to date on the Minnesota Partnership for Biotechnology and Medical Genomics, visit the Partnership web site, http://minnesotapartnership.info.