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President's Introduction
Leadership
is about many things: a passionate commitment to pursuing your goals, a vision for the future and
staying the course, a record of solid performance and achievement, and a spirit of innovation and
creativity. I think that as an organization, The Scripps Research Institute has firmly established
its leadership in the international scientific community by remaining true to these basic tenets;
by continuing to promulgate a record of outstanding scientific achievements; by attracting extraordinarily
talented scientific faculty, staff, students, and board members; and by extending the reach of
its capabilities with the development of our major new initiative in Florida. Simply stated, it
has been an exceptional year for Scripps Research.
Scripps Florida Moves Forward
Substantial progress has been made in shaping
the scientific scope of the Scripps Florida enterprise and in recruiting a strong roster of scientific
faculty and administrative management. Our first announcement early this year was the recruitment
of internationally renowned scientist Charles W. Weissman, a pioneer in modern biomedical research
and molecular biology. Formerly a senior research scientist in the Department of Neurodegenerative
Diseases at University College London, London, England, he heads the Scripps Florida Department
of Infectology. Among Dr. Weissmann’s research interests are the pathogens that cause malaria
and tuberculosis and such prion diseases as mad cow disease.
More recently, we announced the recruitment
of noted chemist William R. Roush as professor of chemistry, executive director of medicinal chemistry,
and associate dean of the Florida graduate programs. Currently the Warner Lambert/Parke Davis
Professor of Chemistry and chair of the Department of Chemistry at the University of Michigan,
Ann Arbor, Michigan, he will begin work at Scripps Florida in early 2005. Dr. Roush is recognized
for his groundbreaking research in the analysis, structural determination, and synthesis of
complex, biologically active, natural products that may lead to the development of new drugs.
Further, he has been a mentor to two generations of chemists, a role he will continue with Scripps
Florida graduate students and postdoctoral fellows.
We have created the framework for the scientific
research that will be undertaken at Scripps Florida, including developing leading-edge technologies
to enable scientists to examine the basic biology of human health and find new and better treatments
for a variety of devastating human diseases. These programs have been specifically designed to
answer the most important questions in biology and medicine and will address such diseases as AIDS,
cancer, diabetes, obesity, prion diseases, Parkinson’s disease, and schizophrenia. The
new research programs encompass scientific inquiry in genetic disease informatics, cancer biology,
infectology, the genetics of complex diseases, proteomics, nuclear hormone receptors, drug
metabolism and pharmacokinetics, diabetes and obesity, medicinal chemistry, cell-based screening,
and HIV therapeutics. We have recruited more than 20 highly accomplished scientists who will carry
out much of the research in these new programs. They have previously held positions and appointments
at many of the finest academic institutions and private companies in the world, and we are pleased
that they have made the commitment to join us at the inception of our research efforts in Florida.
Executive management expertise is critical
to the efficient operation of research activities. To this end, we have appointed Harry W. Orf as
vice president of scientific operations for Scripps Florida to oversee the administration and
management of scientific services that will support biomedical research there. For the past 21
years, he has served as director of the molecular biology laboratories at Massachusetts General
Hospital in Boston; he also is a principal associate in genetics at Harvard Medical School, Boston,
Massachusetts. His management and administrative experience includes memberships on the boards
of directors of several biotechnology companies.
We also appointed Will E. Ray, Ph.D., to
our team as director of external affairs for Scripps Florida and as vice president for development
for all of Scripps Research. Dr. Ray comes to us from the Palm Beach County Cultural Council, Palm
Beach, Florida, where he was president and chief executive officer for more than 20 years.
New Members to the Board of Trustees
At no time in the history of the organization
has strong leadership from the board of trustees been more important in making decisions that will
leave an indelible mark on the future of Scripps Research. This year we have been fortunate in recruiting
5 distinguished and accomplished individuals to our board. Alexander W. Dreyfoos owns and directs
the Dreyfoos Group, a private capital management firm that grew out of his previous ventures, including
Photo Electronics Corporation and WPEC-TV, the CBS network affiliate in West Palm Beach, Florida.
Andrew J. Viterbi is head of Viterbi Group, L.L.C., a firm he cofounded to advise and invest in start-up
companies. He also is the cofounder of Qualcomm, a leading developer and manufacturer of mobile
satellite communications and digital wireless telephony, and professor emeritus at the University
of California, San Diego, California.
Phillip Frost is a clinical professor of
dermatology at the University of Miami School of Medicine, Miami, Florida. He also has served in
leadership positions with many corporations and organizations and is currently a director of
Northrop Grumman Corporation, a governor of the American Stock Exchange, chairman of the board
and chief executive officer of IVAX Corporation, and chairman of the board of trustees at the University
of Miami. J. Michael Cook, retired chairman and chief executive officer of Deloitte & Touche
L.L.P, is also chair of the Deloitte & Touche Foundation and a member of the board of Deloitte
& Touche Tohmatsu. Mr. Cook has been a leader in his profession, serving as immediate past chairman
and president of the board of trustees of the Financial Accounting Foundation, and is active as
a member of the board of such companies as the Dow Chemical Company, Northrop Grumman Corporation,
and Fidelity Group Mutual Funds. Lawrence F. De George is chairman and chief executive officer
of LPL Investment, Inc., and LPL Group, Inc., in West Palm Beach, Florida. He also is founder and
chairman of CompleTel L.L.C., a competitive local exchange carrier in Amsterdam and Paris; director
of United Global Communications, Inc.; founder and chairman of Cervalis; and founder and director
of Advanced Display Technologies.
Significant Research Discoveries
Peter Schultz and his group continue their
prolific efforts on a variety of research fronts. Dr. Schultz has directed a group of scientists
at Scripps Research and the Genomics Institute of the Novartis Research Foundation in identifying
a small synthetic molecule that can control the fate of embryonic stem cells. The compound, cardiogenol
C, causes mouse embryonic stem cells to selectively differentiate into cardiomyocytes, or heart
muscle cells, an important step on the road to developing new therapies for repairing damaged heart
tissue. Stem cells have huge potential in medicine because they can differentiate into many different
cell types, potentially replacing cells that have been permanently lost by a patient. Dr. Schultz
and his group continue their work toward an understanding of the exact biochemical mechanism whereby
cardiogenol C causes the cells to differentiate into cardiomyocytes and are attempting to increase
the efficiency of the process.
In another study, a Schultz research team
achieved the simultaneous incorporation of 2 unnatural amino acids into the same polypeptide
in Escherichia coli, showing that the genetic code is amenable to expansion to 22 amino
acids. For years, scientists have created proteins with such unnatural amino acids, but until
Dr. Schultz and his colleagues began their work several years ago, no one had ever found a way to get
unnatural amino acids into the genetic code. This latest result opens the door for making proteins
within the context of living cells with 3, 4, or more additional amino acids at once. The discovery
has implications in medicine, because many proteins used therapeutically must be modified with
chemical groups such as polymers, cross-linking agents, and cytotoxic molecules.
Dr. Schultz and Chi-Huey Wong, professor
in the Department of Chemistry and The Skaggs Institute for Chemical Biology, have developed a
new way of making glycoproteins, proteins with carbohydrates attached. Methods for making these
proteins are important not only to scientists who want to understand the role of carbohydrates
in protein structure and function but also to physicians, because pharmaceuticals are often heavily
glycosylated proteins. The new strategy, which avoids some of the bottlenecks of previous methods,
is scalable and should be less expensive than other current methods.
Kim Janda, who holds the Ely R. Callaway
Chair in Chemistry and is an investigator in the Skaggs Institute, has designed a potentially valuable
tool for treating cocaine addiction by creating a modified “phage” virus that soaks
up the drug inside the brain. His research group coated the virus with an antibody that binds to molecules
of cocaine and helps clear the drug from the brain, a situation that could suppress the positive
reinforcing aspects of the drug by eliminating the cocaine “high.” Phage particles,
like many types of viruses, can enter the brain through the internasal passageway. The scientists
used this passageway to deliver their antibody into the CNS, thereby reducing one effect of cocaine
in rodent models. Although this technique could be useful as a general strategy of delivering therapeutic
agents into the brain, the approach has not yet been tested clinically in humans.
A group of scientists led by Nora Sarvetnick,
a professor in the Department of Immunology, has found a connection between poor T-cell survival
and the development of autoimmunity. Because of this linkage, they have proposed a new hypothesis
of the cause of autoimmunity, asserting the need for a certain level of immune stimulation to fill
the body with immune cells. An understimulated immune system results in too few T cells, and the
body tries to correct this state by inducing a vigorous expansion of the remaining T cells, creating
a more autoreactive population of cells. These findings provide a new way for thinking about how
to make autoimmune diseases more preventable. The scientists postulate that the key to decreasing
the chances that autoimmunity will develop may be to stimulate the immune system by priming people
with germs.
Ian Wilson, a professor in the Department
of Molecular Biology and a member of the Skaggs Institute, and his colleagues have elucidated the
structure of a protein from the deadly 1918 “Spanish flu” virus, a virus that took more
lives than World War I and resulted in the largest and deadliest influenza outbreak in recorded
history. Seeking to discover why the outbreak was so devastating, the team described the structure
of a protein called hemagglutinin, the first structure of this extinct virus to be solved. This
structure has features found primarily in avian viruses and reveals details that may be crucial
to understanding the outbreak. Avian-to-human transmission is rare and thus has the potential
to be more deadly than human-to-human transmission. Because the surface proteins of the virus
differed from those of other flu viruses, people’s immune systems were unaccustomed to the
proteins and could not fight off the Spanish flu.
A team of researchers led by Martin Friedlander
has been able to preserve visual function in mice genetically predisposed to retinitis pigmentosa,
a profound degenerative eye disease. When eyes of these mice were injected at an appropriate stage
of development with stem cells derived from the bone marrow of adult mice or humans, the mice had
a completely normal retinal vasculature and significantly improved retinal tissue. They also
responded to light. This approach could potentially be used to treat disorders of the retina that
involve vascular and neuronal degeneration. More than 100,000 persons in the United States have
retinitis pigmentosa, which is caused by more than 100 different genetic mutations. Currently,
no intervention exists to treat or even slow the course of the disease.
Grant Establishes Pearson
Center for Alcoholism and Addiction Research
In early 2004, Scripps Research received
a gift of $3 million to establish the Pearson Center for Alcoholism and Addiction Research, which
combines biomedical research with clinical applications to fight these deadly and costly diseases.
In leading the center, George F. Koob, who directs the Division of Psychopharmacology in the Department
of Neuropharmacology, collaborates with Barbara J. Mason, who heads the department’s Division
of Clinical Pharmacology. Of particular interest to the scientists are the physiologic changes
in the brain that compel excessive drinking and create vulnerability to relapse. These researchers
study the practicality of using new compounds, designed at Scripps Research and elsewhere, to
modulate the neurologic effects of alcohol and reduce excessive intake and/or relapse. Scripps
Research received the grant from an anonymous donor on behalf of family and friends who have experienced
the devastating consequences of alcoholism and addiction. Farewells
Few men are worthy of being known as gentlemen
and scholars, but this description was an entirely apt one of our colleague, friend, and Scripps
Research medical scientist Bernard M. Babior, who died this year after a long battle with prostate
cancer. For the past 18 years, he was a professor and the head of the Division of Biochemistry at Scripps
Research and a staff physician at Scripps Clinic. Dr. Babior was noted for his groundbreaking insights
into human biochemistry, particularly the body’s defenses against infection. He contributed
so much during his long tenure not only through his valuable research that has enriched the scientific
community but also through his humanity and his sense of serving those with whom he interacted.
We miss him dearly.
In a lasting tribute to a former colleague
and one of the original scientists at Scripps, William O. Weigle, a sculpture entitled Oak Cairn,
by renowned British artist Andy Goldsworthy, was installed on the La Jolla campus. Dr. Weigle,
who died in 2001, was one of the immunologists who came from Pittsburgh in 1961 to establish the Division
of Experimental Pathology at Scripps Clinic and Research Foundation. The work of this group attracted
others, and the research program flourished and diversified, forming the basis of the modern-day
Scripps Research. Dr. Weigle leaves a permanent legacy of seminal contributions to immunology
and contributions to the lives of those he trained and colleagues with whom he worked for 40 years
at Scripps and throughout the world.
The past year was another period of extraordinary
effort on the part of our scientists, board members, donors to and friends of the institute, students,
and technical and administrative support staff. It was a year in which the collective contributions
of those involved in the Scripps Research enterprise elevated the organization to a new level.
I am proud and honored to work side by side with our colleagues in La Jolla and in Florida as we create
a new vision for the future of Scripps Research and position the institute to assume an even greater
role in the scientific community in the years ahead.
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