Scientific Report 2007
is my pleasure to report on another extraordinary year at The Scripps Research Institute.
In 2007, construction began on the permanent Scripps Florida campus in Jupiter,
Palm Beach County; scientists at the institute continued to push the boundaries
of discovery; and new collaborations positioned Scripps Research to thrive in the
In March, Scripps
Research officially dedicated its Florida campus in Jupiter to "increasing
human knowledge, advancing biomedical science, educating the researchers of the
future, and improving the health of humanity." At the ceremony before some
400 Scripps Florida employees and guests at the construction site on the Jupiter
campus of Florida Atlantic University, I had the opportunity to again thank the
people and leaders of Palm Beach County and the State of Florida for their contributions
to the establishment of Scripps Florida.
We were honored
to have with us to share in this celebration Palm Beach County Commission Chair
Addie Greene, former Governor Jeb Bush, and Governor Charlie Crist. Each has been
instrumental in bringing Scripps Florida to where it is today and in establishing
its future positive impact on the community, science, and human health.
on the first phase, 3 buildings totaling 350,000 square feet of laboratory and administrative
space, is proceeding according to schedule. The buildings are expected to be ready
for occupancy in early 2009. About 220 researchers, technicians, and administrative
staff are already at work in 2 temporary buildings and several trailers adjacent
to the construction site. The buildings will be turned over to Florida Atlantic
University when the new permanent facilities open.
In 2007, we
welcomed 2 new students to our graduate program in Florida. We were also proud to
have chemistry student Porino Va become our first graduate from the Florida campus.
Dr. Va marched down the aisle with 26 of his California colleagues to receive his
doctorate of science as part of the Kellogg School of Science and Technology commencement
We have continued
to expand our education outreach efforts in Florida. The summer internship at Scripps
Florida, modeled on the California program and now in its third year, hosted 9 students
and 3 high school teachers, thanks to support from the William R. Kenan, Jr., Charitable
Trust. The Science Saturday program gave more than 300 Palm Beach County high school
students an opportunity to use modern biotechnology tools. The hands-on Introduction
to Science lesson has provided information to middle schools on what the world is
made of and how it fits together. In addition, work has begun on a permanent exhibit
at the South Florida Science Museum, illustrating how bioscience is shaping our
lives and our future.
Breakthroughs of 2007
innovative science is central to our mission as a leading biomedical research institution,
so I am delighted to highlight a few of our researchers' many scientific accomplishments.
In 2007, Scripps Research investigators did the following:
professors Anette Schneemann and Marianne Manchester and their colleagues developed
a new and highly effective agent that provides protection against anthrax by combining
a fast-acting inhibitor of anthrax toxin with a vaccine in a single compound. The
immune response generated in rats protects against exposure to lethal toxin after
only a single injection and is faster and stronger than any currently available
Sydney Brenner, Tobin J. Dickerson, and other colleagues, I developed a breakthrough
method that can be used to rapidly predict how viruses such as avian influenza virus
H5N1, a dangerous strain that causes "bird flu," will mutate in response
to attacks by the immune system. The new approach, dubbed "checkmate analysis,"
may also be useful in predicting which antibodies or small-molecule therapeutic
agents will best neutralize these viral mutations before the viruses can result
in global epidemics. Because of its simplicity and low cost, this innovative approach
will be accessible to scientists around the world.
Mark Yeager, research associate Barbie Ganser-Pornillos, and colleagues published
a detailed molecular model of the full-length HIV capsid protein, a viral protein
that forms a cone-shaped shell around the genome of HIV. This structure reveals
a never-before-seen molecular interaction that may be a weakness at the core of
professor Phil Baran and colleagues developed new techniques that dramatically reduce
the time, complexity, and cost of synthesizing natural products with pharmaceutical
potential. The work dislodges previously entrenched beliefs in organic chemistry
about how such products must be produced and could help advance and expand the use
of natural products in drug discovery programs.
Corinne Lasmézas and colleagues showed for the for the first time that small
clumps of abnormal prion proteins called oligomers cause the widespread death of
In contrast, much larger prion aggregates known as fibrils are far
less toxic. The findings suggest that small protein aggregates play a central role
in prion diseases, such as bovine spongiform encephalitis (mad cow disease)
Creutzfeldt-Jakob disease; similar mechanisms have been proposed for the so-called
amyloid neurodegenerative diseases, including Alzheimer's disease.
Martin Friedlander and colleagues completely inhibited the growth of new blood vessels
in animal models of a highly vascular brain tumor and of neovascular eye diseases
with little or no effect on normal tissue vasculature. This combination therapy
provides a new range of treatment options for patients with neovascular diseases.
Ulrich Müller and colleagues showed that 2 key proteins join at the precise
location where energy of motion is turned into electrical impulses in the ear. These
proteins, cadherin 23 and protocadherin 15, are part of a complex of proteins called
"tip links" on hair cells in the inner ear.
Kim Janda and colleagues developed a new monoclonal antibody that destroys the highly
addictive drug methamphetamine. The new antibody, called YX1-40H10, converts methamphetamine
into a benign substance, pointing to an entirely new way to treat the global epidemic
of substance abuse.
Koob, chair of the Committee on the Neurobiology of Addictive Disorders, research
associate Olivier George, and colleagues identified a neurobiological mechanism
that contributes to nicotine dependence, and to the anxiety and craving experienced
upon withdrawal. The findings may lead to drugs that could help smokers quit.
Rebek, a professor at Scripps Research and the director of The Skaggs Institute
for Chemical Biology, and colleagues described a new chemical tool that effectively
pauses the formation of certain intermediate products never before seen, allowing
them to be identified and studied. The technique will improve basic understanding
of chemical processes and may aid in biosynthesis studies, drug development, and
detection of pollutants.
L. Cleveland, professor and chair of the Department of Cancer Biology, and colleagues
showed that targeting the autophagy pathway (an ancient cell survival pathway that
cells use to survive conditions of metabolic stress) can prevent and cure cancer
in mouse models of malignant lymphoma and leukemia.
professor Peiqing Sun, professor Jiahuai Han, and colleagues discovered a surprising
new function of a well-known protein kinase signaling pathway. When activated, the
pathway can inhibit tumor growth. This finding may lead to the development of drugs
that can be used to effectively treat cancer by artificially activating this pathway
in tumor cells.
Paul Wentworth, Jr., and colleagues furthered the ongoing search for better treatments
for devastating parasitic diseases such as Chagas' disease and African sleeping
sickness. The group now understands better a critical DNA-protein binding event
that if blocked can kill the parasites that cause the diseases. The researchers
are already working to screen drugs that will block this mechanism.
professor Sheng Ding and colleagues generated a new type of embryonic stem cell
and developed a chemical method to "reprogram" adult mouse somatic cells
to become embryonic stem cells, thus opening up new research avenues. The results
shed light on the detailed mechanisms that control how stem cells choose their specialized
fate and how specialized cells can unwind that choice.
professor Mark Mayford and colleagues unlocked one of the secrets of how memory
is formed. Working with a unique breed of transgenic mice, the researchers found
that the same neurons activated during fear conditioning are reactivated during
memory retrieval. The findings could help uncover precisely how drugs such as antidepressants
work in the brain, allowing clinicians to better evaluate treatment options.
Tamas Bartfai, research associate Manuel Sánchez-Alavez, and colleagues discovered
a pathway that appears to play a critical role in the onset of obesity. The team
showed that mice genetically altered to lack a molecule known as the EP3 receptor
tend to be more active during the animals' normal sleep cycle and to eat more.
Further research could lead to better understanding of obesity and to new treatments.
New Grants for Research
of their potential for future breakthroughs, Scripps Research scientists received
a number of new grants this year. In addition to support for individual research
programs, the grants included funding for several consortiums and other notable
A $17 million,
5-year grant from the National Eye Institute will support the development of the
use of adult stem cells as a therapy for treating the most common types of vision
loss, including diabetic retinopathy, age-related macular degeneration, glaucoma,
and retinitis pigmentosa. The team, led by Dr. Friedlander and scientists in the
research groups of Laura Crisa, Glen Nemerow, Wolfram Ruf, Gary Siuzdak, Bruce Torbett,
and William Balch, will conduct the extensive and detailed preclinical work necessary
for moving the potential therapy forward.
A $51 million,
5-year contract from the National Institute of Allergy and Infectious Diseases will
support the study of innate and adaptive immune responses to a number of dangerous
pathogens, including those that cause influenza, smallpox, and anthrax. The project
scientists, led by Richard Ulevitch, professor and chairman of the Department of
Immunology at Scripps Research, and including researchers at the Institute for Systems
Biology, Seattle, Washington; the Australian National University, Canberra, Australia;
and Stanford University, Palo Alto, California, will develop innovative approaches
to improving vaccines and immunotherapeutics.
10-year MERIT grant to associate professor Cindy Ehlers from the National Institute
on Alcohol Abuse and Alcoholism will support research on risk and protective factors
for alcoholism in Southwest California Indians. Southwest California Indians have
a 5-fold greater risk than the general population for alcohol dependency. In work
funded by a separate 3-year, $1.5 million grant from the National Institute on Alcohol
Abuse and Alcoholism and the National Center on Minority Health and Health Disparities,
Dr. Ehlers will help design, implement, and evaluate a program to build services
and to prevent underage drinking in Native American young people.
to government-sponsored grants and our corporate partners, we are grateful for the
generosity of our many donors, whose gifts accelerate the progress of research on
our campuses and leave a powerful legacy for future generations.
is the ongoing gift from Aline and Sam Skaggs through the Skaggs Institute for Research
and their family foundation, the ALSAM Foundation. Their commitment of $100 million
created the The Skaggs Institute for Chemical Biology to improve human health by
supporting research at the interface of chemistry and biology.
In 2007, philanthropist
and entrepreneur Mark Pearson gave $3 million to establish the Pearson Family Chair,
an endowed position in alcohol and addiction research; the first recipient will
be Professor Barbara Mason. The Pearson Family Chair builds on Pearson's previous
gift of $3 million in 2003, which created the Pearson Center for Alcoholism and
Addiction Research. The center, codirected by Dr. Mason and Professor George Koob,
combines the latest biomedical research with new clinical treatments to fight the
devastating, costly, and deadly diseases of alcohol and drug addiction.
another far-reaching act of generosity, in 2007 we received the final payment from
the estate of Norma and Frank Sugg, a California couple who included Scripps Research
as a beneficiary of their will. The $1.6 million gift from proceeds of the sale
of the Suggs' home and other assets will support research on leukemia.
Research friend and supporter Daniel Koshland, Jr., gave $100,000 to the Scripps
Research Kellogg School of Science and Technology this year, forming the basis for
a new student fellowship, the Koshland Graduate Fellowship in Enzyme Biochemistry.
Sadly, Dr. Koshland passed away in July at the age of 87. An original thinker whose
work changed the field of biochemistry, he will be remembered not only for his exemplary
science but also for his deep commitment to the next generation.
New Corporate Collaboration
The year 2007
marked the first full year of our new research collaboration with Pfizer Global
Research and Development. Under the terms of the agreement, Pfizer will pay Scripps
Research $100 million over a 5-year period. During that time, scientists from Pfizer
and Scripps Research will work together to identify and perform specific projects
of mutual interest. The goal of the agreement is to advance scientific knowledge
of uncured diseases and novel ways to treat the diseases, making full use of emerging
technologies and resident talent from both organizations. In a separate initiative,
Pfizer is funding 8 postdoctoral fellowships in chemistry at Scripps Research.
Awards and Honors
In 2007, Scripps
Research investigators, postdoctoral fellows, and graduate students were again lauded
by numerous awards. To mention only a few, this year's honors include the following:
Beutler, chair of the Department of Genetics, was awarded the prestigious Balzan
Prize for his work with Jules Hoffmann of the Academie des Sciences in Paris. The
International Balzan Prize Foundation of Italy and Switzerland cited the researchers
for "their discovery of the genetic mechanisms responsible for innate immunity."
Drs. Beutler and Hoffmann have collaborated to develop a new vision, across a wide
evolutionary spectrum, of the molecular defense strategy deployed by animals against
infectious agents. The results of the research have led to promising medical applications.
June, I received an honorary doctor of science degree from the University of Oxford
for my research on catalytic antibodies. The studies indicate that antibodies can
be used as enzymes and are relevant for conditions such as atherosclerosis and Alzheimer's
Benjamin Cravatt was elected a fellow of the American Association for the Advancement
of Science "for the development of innovative chemical proteomic technologies
to annotate enzymatic pathways in mammalian systems." Dr. Cravatt also won
the 2007 Young Investigator Award from the Linda and Jack Gill Center at Indiana
University in Bloomington.
Chi-Huey Wong was the recipient of a Humboldt Research Award from the Alexander
von Humboldt Foundation in recognition of lifetime achievements in research. In
addition, in 2007 Dr. Wong received the F.A. Cotton Medal from Texas A&M, an
honorary degree from Technion-Israel Institute of Technology, and an honorary fellowship
from the Chemical Research Society of India.
Francis Chisari won the Distinguished Scientist Award of the Hepatitis B Foundation
for his "seminal work in the immunopathology of hepatitis B, which has contributed
significantly to the current understanding of the disease and advanced medical research
towards finding a cure."
William Roush, executive director of Medicinal Chemistry and associate dean of Scripps
Florida graduate studies, was named Scientist of the Year by the South Florida Science
Museum in the first of the museum's annual series of awards.
Linda Curtiss received the Distinguished Achievement Award from the American Heart
Association Council on Arteriosclerosis, Thrombosis, and Vascular Biology for "immense
contributions to the council for many years."
Dale Boger won the Ernest Guenther Award in the Chemistry of Natural Products from
the American Chemical Society. The award was given "in recognition of contributions
to the total synthesis of complex biologically active natural products and key analogs
used to define their mode of action."
professor Dorian McGavern won a prestigious award from the Burroughs Wellcome Fund,
which named him 1 of 15 new Investigators in Pathogenesis of Infectious Disease.
These highly competitive awards are given to scientists during the early years of
the scientists' career.
professor Kristin K. Baldwin was 1 of 20 exceptional researchers selected as 2007
Pew Scholars in the Biomedical Sciences by the Pew Charitable Trusts and the University
of California, San Francisco.
I extend my
sincerest thanks to trustees, donors, friends, faculty, staff, postdoctoral fellows,
and students for their efforts in making 2007 another exemplary year at The Scripps