Centerline Fall/Winter 2003

Research Highlights

Deep brain stimulation treats Parkinson's Disease

Erwin Montgomery Jr., Neurology, is researching how the brain controls movement and what goes wrong in the brain with Parkinson's Disease.

One approach is studying how the brain responses to deep brain stimulation (DBS) as a method for treating symptoms of Parkinson's Disease. DBS is proving effective in reversing the symptoms of Parkinson's Disease in some, but not all patients.

The therapy involves implanting a modified electronic cardiac pacemaker into the chest, and connecting this stimulator to electrodes implanted deep within the brain. However, researchers are not certain why it works in some people and not in others.

More knowledge gained from nonhuman primate studies using this electrical, versus pharmaceutical approach to treating Parkinson's may help doctors help more patients with this and other neurological conditions in the future.

References:

Baker KB, Montgomery EB Jr, Rezai AR, Burgess R, Luders HO. Subthalamic nucleus deep brain stimulus evoked potentials: physiological and therapeutic implications. Mov Disord. 2002 Sep;17(5):969-83.

Montgomery EB Jr. Two advances in the management of Parkinson disease. Cleve Clin J Med. 2002 Aug;69(8):639-43. Review.

High Vitamin A levels enlarge liver cells in rhesus macaques

Sherry Tanumihardjo and Kristina Penniston, Nutritional Sciences Dept., recently found that liver vitamin A concentrations in rhesus monkeys were elevated, and that their liver cells were enlarged. While marmoset livers studied were also high in vitamin A, they did not show cell irregularities.

The monkeys ate widely used commercial diets. The researchers found that the diets contained vitamin A concentrations as great as four times higher than National Research Council recommendations for human vitamin A intake.

To further characterize the effects of high dietary vitamin A from preformed sources, the researchers analyzed serum from both rhesus and marmoset monkeys for vitamin A metabolites. They found total serum vitamin A within expected limits for both monkey species, but high serum vitamin A esters in both species. Normal serum vitamin A concentrations were found for both monkeys when compared with published normal values.

References:

Penniston KL, Thayer JC, Tanumihardjo SA. Serum vitamin A esters are high in captive rhesus (Macaca mulatta) and marmoset (Callithrix jacchus) monkeys. J. Nutr. 2003 (In press).

Penniston KL, Tanumihardjo SA. Subtoxic hepatic vitamin A concentrations in captive Rhesus monkeys (Macaca mulatta). J. Nutr. 2001. 131: 2904-2909.

Thomson heads new National Stem Cell Center

By Emily Carlson, UW News and Public Affairs

The WiCell Research Institute (WiCell), a non-profit subsidiary of the Wisconsin Alumni Research Foundation (WARF), has been named as one of three Exploratory Centers for Human Embryonic Stem Cell Research in the nation by the National Institute of General Medical Sciences. With the designation comes a three-year $1.7 million grant that WiCell will use to further the study of human embryonic stem cells.

James Thomson, National Primate Research Center, University of Wisconsin-Madison, and WiCell scientific director, is the lead researcher on the grant. The funds will allow WiCell's central core facility to provide cell-culture support to scientists studying human embryonic stem cells at both WiCell and the UW-Madison. In addition, three pilot projects are planned to study questions in basic biology that are important for further stem cell discoveries.

"This grant will enable WiCell and the University of Wisconsin-Madison to continue their leadership roles in human embryonic stem cell research. It is a significant tribute to Dr. Thomson, his collaborators and the entire stem cell team," says Carl Gulbrandsen, president of WiCell's Board of Directors.

WiCell is a private, non-profit organization that supports UW-Madison. A scientific advisory board made up of UW-Madison faculty members is responsible for the scientific direction of the institute. WiCell's centralized facility, which is adjacent to the UW-Madison campus, provides a laboratory space where researchers from diverse disciplines and far-flung campus locations can collaborate on human embryonic stem cell research while maintaining primary laboratories in their own departments.

"The heart and soul of stem cell research is here at the University of Wisconsin. This award reiterates the important role we play at the national level," says R. Timothy Mulcahy, Graduate School associate dean for the biological sciences.

WARF and UW-Madison established WiCell in 1999. The university and WiCell operate under a collaboration agreement that ensures that the expertise of both entities will be available to advance research relating to human embryonic stem cells. WiCell's mission is two fold: 1) to provide human embryonic stem cells and training for research purposes to academic scientists all over the world, and 2) to engage in research utilizing the expertise of the UW-Madison scientific community.

"To date, WiCell has provided human embryonic stem cells to more than 125 research groups and also provides training at its Madison facility to researchers all over the world," says Nancy Block, WiCell general manager. "This grant will help us continue the progress of stem cell research - not just on this campus - but throughout the entire scientific community."

The two other grants for Exploratory Centers for Human Embryonic Stem Cell Research were awarded to the University of Michigan Medical School in Ann Arbor and the Fred Hutchinson Cancer Research Center at the University of Washington in Seattle.

Thomson receives Annunzio, MacArthur awards

The Christopher Columbus Fellowship Foundation awarded its 2003 Frank Annunzio Award to embryonic stem cell pioneer James Thomson Oct. 13 in Washington, D.C. The science and technology award for "cutting edge" innovation recognizes one American who is improving the world through ingenuity and innovation. The $50,000 award also provides incentive for continuing research and/or a specific project. The Frank Annunzio Award is named for the late congressman from Illinois. It is given in recognition of the "visionary spirit and pioneering heritage of Christopher Columbus."

Earlier this year, Thomson was named a John D. MacArthur Professor. The July 1, 2003, appointment carries with it a five-year award for research and scholarly work. The chair was established by a grant from the John D. and Catherine T. MacArthur Foundation. MacArthur purchased Bankers Life and Casualty in 1935 and built it into a highly successful company. He died in 1978, establishing a foundation that has awarded substantial grants to individuals and liberal arts colleges, as well as research institutions.

Thomson was the first to isolate and culture nonhuman primate embryonic stem cells (PNAS 1995), and human ES cells (Science 1998). He aims to use these cells to improve knowledge of basic reproductive biology, and to explore new treatments for degenerative diseases such as diabetes, heart disease, leukemia and Parkinson's. He has published more than 30 scientific papers on reproductive biology and embryonic stem cells. He has also testified in support of ES cell research to both the Wisconsin and U.S. Congresses.

Thomson is a UW professor of anatomy, Director of Stem Cell Resources, National Primate Research Center at UW-Madison, and Director of the National Stem Cell Center at WiCell in Madison. He earned his advanced degrees in veterinary medicine and molecular biology at the University of Pennsylvania, Philadelphia. He is board certified in veterinary pathology.

Primate Center shares in egg quality grant — Does excess insulin damage oocytes?

The National Institute of Child Health and Development on Sept. 1 awarded Daniel Dumesic at the Mayo Clinic a $1.2 million, four-year grant to determine whether excessive circulating insulin in women and monkeys with polycystic ovary syndrome (PCOS) causes infertility by damaging eggs.

Leading the monkey studies is David Abbott, National Primate Research Center, University of Wisconsin-Madison. Primate Center scientists will attempt to reverse detrimental insulin elevation by putting PCOS monkeys on a calorie-restricted diet that will lower circulating insulin levels and potentially normalize egg quality, according to Abbott.

"The monkey model for PCOS affords us a unique look at egg quality and early embryo defects in primates, since human embryo work is not ethically possible for these studies," Abbott said. Primate Center researchers will compare their egg quality findings with those related to eggs obtained from both PCOS-afflicted and normal women undergoing in vitro fertilization at the Mayo Clinic in Rochester, Minnesota.

Primate Center scientists Ricki Colman and R. Dee Schramm are two other coinvestigators on the grant. Collaborators include Lisa Forrest, Wisconsin School of Veterinary Medicine; Michael Diamond, Wayne State University; Cheryl Conover, Michael Jensen and Wilma Lingle, Mayo Clinic; Jerome F. Strauss III, University of Pennsylvania Medical Center, and Dagan Wells, St. Barnabus Medical Center.

Cynthia Robinson is new chief librarian

Cynthia Robinson began Aug. 1 as the new director of the Primate Center's internationally recognized Library and Information Services. She succeeds Larry Jacobsen, who retired in April. Cynthia comes to us from the University of Minnesota, Minneapolis, where she served as associate director of Public Services in the Bio-Medical Library. She brings to her new position a wealth of experience in reference, instructional, and outreach services.

Before her University of Minnesota position, Cynthia was manager for Library Services at Allina Health System in Minnesota. In her "past lives," she was also assistant director for Collection Services and acting co-director for Technical Services, Claude Moore Health Sciences Library, University of Virginia. Before that, she served as head of education at the McGoogan Library of Medicine, University of Nebraska Medical Center.

Cynthia also completed a one-year post-graduate program as an associate fellow at the National Library of Medicine, Bethesda, Maryland. She found this job shortly after completing her masters degree at the University of Wisconsin-Madison.

"In many ways, I feel as if I have come full-circle, with my return to Madison," Cynthia said. "Larry's retirement is certainly a big change here at the library, but I know the wonderful staff will continue to offer top notch services and resources. I have been enjoying getting to know everyone and working with them."

Librarian Larry Jacobsen retires after 30 challenging years

A gentle, yet persuasive style, coupled with a strong vision of what an international resource in primatology should be, were hallmarks of Larry Jacobsen's dynamic work ethic. Over the past 30 years, Larry tirelessly worked with hundreds of primatologists, students, librarians and others who shared his passion for sharing knowledge and learning about primates.

Larry was raised in Chicago and earned his masters in library science at the UW-Madison. In 1973, he joined the Wisconsin Regional Primate Research Center as a UW special librarian. From there, he created one of the most specialized libraries in the world, housing the largest collection of nonhuman primate books and articles. Additionally, as anyone knows who has been to the library, collections of rare primate books, video and audiotapes, and primate art add to the special quality of this unique resource.

Larry may have been based on the UW-Madison campus, but in reality, he was a man without boundaries. Primate library services and outreach were simply redefined under Larry Jacobsen. The library he founded is today one of the most comprehensive resources in the field of primatology. Its flagship service is Primate Info Net and the many resources it promotes - The International Directory of Primatology, The World Directory of Primatologists, AskPrimate, PrimateJobs, Careers in Primatology, Primate-Science, and the Callicam. These resources receive more than 8 million hits every year from people all over the world.

Larry retired as Director of Library Information Services on April 30, 2003; however, his impact on all primates was far too great to warrant a quiet exit. Larry's retirement was marked with numerous milestone articles in colleagues' newsletters. Well-wishers' notes and e-mails poured in from all over the country and beyond (see sidebar). A memorable retirement party attracted Larry's colleagues and friends on April 24 at the UW-Madison University Club. On that mild, sunny afternoon, Joe Kemnitz, Chuck Snowdon, Steve Shelton, Deborah Blum, Toni Ziegler, Virginia Kruse and others lauded Larry for his enthusiasm, hard work, and infectious passion for the field. Larry, in turn, thanked his hard-working staff, Joanne Brown, Ray Hamel and Matt Hoffman.

"We had a unique blend of talents that enabled us to make the most of the changing terrain in library science and to be innovative in our approach to providing outreach services," Larry said.

He also praised the many UW students and graduates of the UW School for Library and Information studies. Every day, these students greet visitors to the Primate Center Library at 1220 Capitol Court. They provide the backbone of support that allows the library to provide document delivery, updated Internet resources, and personalized attention to library patrons.

Many other milestones marked Larry's career at the Primate Center. On the UW campus, he instituted the first document delivery service and was a key organizer of the Special Purpose Libraries Group. This group brought funding and recognition for the role of specialized libraries on the UW campus.

In 1995, the Wisconsin Library Association named the Primate Center Library its Library of the Year. In 1996, he curated the Primates in Art and Illustration exhibit at the joint IPS/ASP Meetings in Madison. In 1997, he organized the Friends of the Primate Center Library with Gabriel Lubach, assistant scientist in psychology. This nonprofit fundraising group continues to help support the library's information and education programs. Also in 1997, Larry received the Distinguished Service Award from the American Society of Primatologists, becoming the first librarian ever to achieve this honor.

One of Larry's main interests was using the internet to make information available to people in countries where primates are endemic and resources are often in short supply. In his words, "The Internet provided unique and exciting opportunities to store images, newsletters and a host of other useful information. At the Primate Center, we were able, in fact, to create a second, easily accessible electronic library."

To cap his long career, the American Society of Primatologists awarded him a five-year membership and the International Primatological Society a lifetime membership. The IPS also unveiled the Lawrence Jacobsen Education Development Award this past spring. Anne Savage, IPS vice-president writes, "This award will now carry Larry's name to recognize his outstanding contribution to the field of education and career development."

For his part, Larry says, "I have had a long, enjoyable and productive run, and I am delighted to have had the opportunity to work with so many fine people in the primate community. I feel very lucky!"

Invited Talks

David Abbott

• “Metabolic and Reproductive Consequences of Prenatal Testosterone Exposure,” Clinical/Translational Symposium: Behavioral and Reproductive Consequences of Prenatal Androgen Exposure, S34-1, ENDO 2003, Philadelphia, PA, June.
• “Neuroendocrine and Behavioral Mechanisms Regulate Female Fertility in Marmoset Monkeys,” Seminar Series, College of Medicine, University of Alabama, Mobile, AL, October.

Ted Golos

• Symposium on Frontiers in Human Embryonic Stem Cells, Pittsburgh Development Center, University of Pittsburgh, PA, May.
• NIH Symposium and Workshop on Progress with Human Embryonic Stem Cells, NIH, June.
• Third International Meeting on HLA-G, HLA-E and Stem Cells, Paris, July.
• Fourth Conference on Transgenic Animal Models, Lake Tahoe, CA, August.

Matt Hoffman

• “Putting Primates in the Classroom,” American Society of Primatologists K-12 Teachers Workshop, Calgary, Canada, July/August.
• “Accessing the Primate Information Highway,” focusing on internet resources in primate medicine. Association of Primate Veterinarians Workshop, Tacoma, WA, October.

David O'Connor

• “SIVmac239 Control in Animals Expressing Mamu-A*01, -B*17, and -B*29: Every Silver Lining's Got a Touch of Grey.” Mid-Atlantic SIV Research Group Meeting on Lentiviral Long-Term Non-Progression. Frederick, MD, February.

R. Dee Schramm

• “Strategies for Production of Genetically Identical Monkeys Using Blastomere Separation,” NIH meeting on development of SPF monkey colonies, Tulane National Primate Research Center, Covington, LA, January.

James Thomson

• “Human ES Cells and Parkinson's Disease,” Michael J. Fox Foundation workshop on Parkinson's disease, Menlo Park, CA, March.
• “Genetic Modification of Human ES Cells,” Keystone Symposium, “From Stem Cells to Therapy”, Steamboat Springs, CO, March.
• “Hope or Hype: Human ES Cell Research,” The Wisconsin Alumni Association International Meeting, Oslo, Norway, June.

Ei Terasawa

• “Mechanisms of Pulsatile LHRH Release: Role of ATP in Synchronization of Ca2+ Oscillations,” Molecular Mechanisms of Cellular Feedback and Pulsatility in Neuroendocrine Systems symposium, 36th Winter Conference on Brain Research, Snowbird, UT, January.

David Watkins

• “SIV Diversity and Cellular Immune Responses,” Keystone Symposia, “Twenty Years of HIV Research: From Discovery to Understanding,” Banff, Alberta, Canada, March.
• Talk on HIV pathogenesis with Ron DesRosiers, New England National Primate Research Center, Cancer Research Institute 2003 Palm Springs Symposium on HIV/AIDS, University of California, Irvine, CA, March.
• “Immunogenetics of HIV/AIDS,” British Society for Immunology Congress, Harrogate, UK, December.

Richard Weindruch

• “New Mechanistic Pathways of Caloric Restriction Suggested by Gene Expression Profiles,” Pennington Center Symposium­Mechanisms and Retardation of Aging, Baton Rouge, Louisiana, May.
• “A Nutrigenomic Approach to Study the Aging Process.” Wisconsin Symposium III: From DNA to Molecular Medicine, Madison, WI, May.
• “Caloric Restriction, Gene Expression and Aging.” 2nd International Conference on Senescence: The SAM Model, Sapporo, Japan, July.
• “The Retardation of Aging by Caloric Restriction.” 2003 NAASO Annual Scientific Meeting, Ft. Lauderdale, FL, October.

Toni Ziegler

• “Chemical Cues of Ovulation Mediate Androgen Production in Marmosets (Callithrix jacchus) and Tamarins (Saguinus oedipus)”. American Society of Primatology, Calgary, Canada, August.

Thomas Zwaka

• “Gene Targeting of Oct4 in Human ES Cells Reveals that Both Self-Renewal and Differentiation Occurs through Symmetric Cell Division.” Keystone Symposium, “From Stem Cells to Therapy,” Steamboat Springs, CO, March.

Research Support expands services

By Jennifer Lambert-Newman

Members of the Reproductive Research Services Unit are under new leadership within Veterinary Services. Dr. Kevin Brunner is heading the new and improved unit, Research Support Services (RSS), consisting of Michele Schotzko, Eric Peterson, and Jennifer Lambert-Newman.

As a more generalized research unit, RSS members are broadening their horizons to include technical support for a wider range of research needs. Project areas already underway include cardiology, virology, and nutritional sciences, in addition to providing reproductive services as in the past. Anyone who thinks they (or another investigator) would find this new resource useful is encouraged to contact Kevin to discuss specific needs.

The unit members are excited to get their feet wet in new areas and are eager to expand on the skills they currently possess. Please try to solicit our services as far in advance as possible. We will do our best to accommodate your needs.

Gleanings

In the news

Director Joe Kemnitz interviewed with free-lance science journalist Harvey Black this spring. Black's article on rhesus monkey shortages in biomedical research appeared July 28 in The Scientist. His piece was the impetus for several original stories in the mainstream media, including The Boston Globe, The Wired, and the Atlanta Journal Constitution. (The AP picked up the Globe story and it ran nationwide in August.) Kemnitz also described the Primate Center's research and animal care in an Oct. 3 Daily Cardinal feature story, "Primates used for medical gains."

Stem cell research continued to be a hot topic in 2003, five years after James Thomson's famous ES cell paper in Science. "From a groundbreaking discovery come many advances: Stem cell research thrives at Wisconsin" was the cover story in this Fall's UW Medical School magazine, Quarterly. The article overviewed why Wisconsin is a leader in stem cell research. The piece focused on the advances of scientists James Thomson, Tim Kamp, Su-Chun Zhang, Dan Kaufman, Clive Svendsen and Jon Odorico. A sidebar listed stem cell researchers with MS affiliations. Kamp's news on growing heart cells from ES cells went national this year. Zhang spoke with US News and World Report on his neural ES cell derivations. Thomson, John Gearhart (Johns Hopkins), and actor Christopher Reeve spoke Oct. 27 at a National Press Club briefing in Washington, D.C. The event marked the fifth anniversary of the successful isolation and culture of human embryonic stem and germ cells. The three urged federal policy makers to ease restrictions and lend more support to human embryonic stem cell research. At a same-day Coalition for the Advancement of Medical Research meeting, Thomson and Gearhart were recognized for their research discoveries.

Others in touch with mainstream audiences in 2003 included:

• Steve Shelton, Racine Journal-Times, primate brain differences.
• Nancy Wilson, BBC World Service radio, importance of condom use to prevent HIV transmission.
• Richard Weindruch, Milwaukee Journal-Sentinel, obesity, caloric restriction and aging; Washington Post, enzymes and the aging process.
• David Abbott, Baltimore Sun, mating and reproduction.

New resources

The Caribbean Primate Research Center

Recent Primate News clips is now on Primate-Science.

Vervets arrive

The Primate Center now has two new species for use in expanding research opportunities and alleviating monkey shortages. Sixty cynomolgous macaques (Macaca fascicularis) are now out of quarantine and available for research. Twenty vervets, also know as African green monkeys (Cercopithecus aethiops), arrived Oct. 1.

New Database on Biomarkers of Aging

The National Institute on Aging has awarded the Primate Center a contract to develop and manage the Primate Aging Database (PAD). PAD is a new multi-center, relational database of biological variables in aging, captive nonhuman primates. The NIA, National Center for Research Resources (NCRR), and National Primate Research Center, University of Wisconsin-Madison, have already organized more than 400,000 data points on 17 species at nine facilities. An invaluable research, veterinary and clinical resource, PAD now features biomarkers on body weight, blood chemistry and hematology. This will grow in terms of numbers of animals and biological endpoints, using support from the new contract. For more information, contact Dr. Joe Kemnitz, principal investigator.

This is the text-only, electronic version of Centerline, which is published twice per year by the Wisconsin Primate Research Center, 1220 Capitol Court, Madison, WI 53715-1299. This newsletter provides updates on scientific research and supporting activities funded by the National Institutes of Health, National Center for Research Resources. We welcome enquiries about our research programs in primate biomedicine and conservation. We can also provide references for scientific papers or other information concerning topics addressed in this newsletter. Please send correspondence to:

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, Senior Editor
Wisconsin Primate Research Center
1220 Capitol Court
Madison, WI 53715-1299
Telephone (608)263-7024
FAX (608)263-3524