Caltech Researchers Join Global GEM4 Initiative

PASADENA, Calif.—Researchers at the California Institute of Technology have joined a global medical effort to address a number of diseases through innovative, multi-institutional, multidisciplinary approaches. The initiative, the Global Enterprise for Micromechanics and Molecular Medicine (GEM4), is centered at MIT's Department of Materials Science and Engineering, and was officially launched October 12 at an MIT campus ceremony.

According to Mory Gharib, who is the Liepmann Professor of Aeronautics and Bioengineering at Caltech, the participation of Caltech researchers will concentrate on the micromechanics of cells and tissues related to certain diseases.

"In the past, researchers have always looked at the biological and chemical aspects of diseases like malaria," says Gharib. "So this is a novel approach. The idea is that, by looking at the ways certain mechanical properties of the cell change with the disease, you could have new and ideally faster technical devices for doing diagnoses."

An end result might be a microfluidic device, for example, that would use a hairpin needle for doing in situ examinations of cells passing by. The sensor, by utilizing the laws of physics, would be able to tell the percentage of infected cells.

Such a device could also be used for screening, Gharib says. "Millions and millions of cells could be screened, with no need for determining their chemical or spectral behavior."

Another Caltech researcher who will be closely involved in the GEM4 effort is Ares Rosakis, who is director of the Graduate Aeronautical Laboratories (GALCIT) and the von Kármán Professor of Aeronautics and Mechanical Engineering. According to Rosakis, a $750,000 gift from Joe and Edwina Charyk to GALCIT will go to facilitating Caltech's participation in GEM4. Specifically, the Charyk gift will be used for the creation of the Charyk Biomechanics Laboratory, which will be part of the existing GALCIT complex.

According to MIT's announcement, GEM4 is "a new paradigm in global interactions among leading institutions to work together seamlessly across the boundaries of science, engineering, technology, medicine, and public health, with an emphasis on biomechanics at the microscopic and molecular levels."

Among GEM4's goals are the bringing together of institutions globally, the creation of new models for interdisciplinary partnerships, and the fostering of a global forum to address and explore huge challenges for the future. The diseases and conditions to be addressed include metastatic cancer, cardiovascular diseases, inflammatory diseases, and infectious diseases such as malaria.

"The initial emphasis will include (but will not be limited to) molecular, subcellular, and cellular mechanics applied to major problems in biomedicine," the MIT announcement continues, "where a single investigator or institution is not likely to have the full spectrum of expertise, infrastructure, or resources available to span fundamental molecular science all the way to clinical practice and societal implications."

Professor Subra Suresh, who is the GEM4 director, is the Ford Professor of Engineering and head of the Department of Materials Science and Engineering at MIT. At Caltech he held the Clark Millikan Visiting Professor Chair in Aeronautics and was also a Moore Visiting Scholar.

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Baltimore to Retire as Caltech President; Will Remain at Institute as Biology Professor

PASADENA, Calif.- David Baltimore, the seventh president of the California Institute of Technology, will retire on June 30, 2006, after nearly nine years in the post. He will remain at the Institute, where he intends to focus on his scientific work and teaching.

"This is not a decision that I have made easily," Baltimore announced to the Caltech trustees, faculty, staff, and students, "but I am convinced that the interests of the Institute will be best served by a presidential transition at this particular time in its history. By next summer we will be well along in the process of implementing our plans to strengthen the financial foundation of the Institute. Although our $1.4 billion campaign is not scheduled for completion until the end of 2007, we have made remarkable progress, and successful attainment of its audacious goals will remain my highest priority. As these important endeavors near their final stages, it will be time for the Institute to once again turn to the future, guided most effectively by the revitalizing vision and leadership of a new president."

He has agreed to remain in the position until a successor is named.

"David Baltimore's articulate advocacy of the Institute's mission has played a huge role in raising the public's awareness of Caltech as a unique national treasure. Our task ahead is to find our next president to carry this vision of excellence into the future," said Kent Kresa, the chairman of the Caltech Board of Trustees.

Baltimore, 67, assumed the presidency on October 15, 1997. His tenure saw many significant events at Caltech. Early on, he oversaw the completion of a fund-raising initiative for the biological sciences, marked by the construction and dedication of the Broad Center for the Biological Sciences. He launched the current $1.4 billion capital campaign, which has included receipt of the largest gift to higher education, $600 million from Gordon and Betty Moore and the Gordon and Betty Moore Foundation. The campaign still has two years to run, but has already raised almost $1.1 billion. An important aspect of Caltech is its stewardship of the Jet Propulsion Laboratory, supported by NASA. Baltimore's presidency has seen many spectacular JPL successes, notably the Mars Exploration Rovers, as well as the appointment of a new director, Dr. Charles Elachi.

"David Baltimore will go down in history as not only a great scientist, but also as one of the great presidents of Caltech," said Eli Broad, a trustee of, and major donor to, the Institute. "It is rare to find someone of his intelligence, integrity, and leadership who can relate so well to people both within and outside the world of science. It was David who inspired Edye and me to become interested in science. We had no background in the field, but he made us feel comfortable. We are fortunate that he will continue his research at Caltech."

Other events during his term have been Caltech's acquisition of the former St. Luke Medical Center in northeast Pasadena; the funding of the design-development phase of the Thirty Meter Telescope; and the establishment of the Information Science and Technology (IST) initiative. Baltimore championed contemporary architecture, chosing James Freed of Pei, Cobb, Freed for the Broad Center, Thom Mayne of Morphosis for the new Cahill Center for Astronomy and Astrophysics, and Rem Koolhaas for the new Walter and Leonore Annenberg Center for Information Science and Technology. The latter two buildings are still in the design phase. Baltimore worked toward increasing diversity at Caltech, particularly by bringing more women into administrative roles. He also was concerned about the quality of undergraduate life, appointing the first full-time vice president for student affairs and starting a $3 million fund for enhancing student life. During the last year, an important activity for him has been his membership on the Independent Citizens Oversight Committee for the California stem cell initiative.

"David Baltimore is an incisive and articulate leader who has strengthened Caltech's core commitments to excellence in research and teaching and has led several initiatives that have ensured promising avenues of research can be pursued at the Institute," said Paul Jennings, Caltech's provost. In a written announcement to the campus and its trustees, Baltimore said, "It has been a privilege to serve as president of Caltech and a pleasure to work with the dedicated and remarkable Caltech faculty, staff, students, trustees, and alumni. The administration in place at Caltech is an extraordinary group, and I will retire with full confidence in their abilities to effect a smooth transition. During my time in the president's office, I have worked to keep Caltech the unique and highly effective university that was imagined into existence by George Ellery Hale almost 100 years ago. Its dedication to excellence has been undiminished, requiring that it continually be in flux, reaching for the altering frontiers of knowledge. The great gift from Gordon and Betty Moore has provided the resources for maintaining our momentum and was truly a defining event of my time as Caltech's president."

Baltimore will remain at Caltech as a professor of biology. In June he was awarded a grant of $13.9 million by the Grand Challenges in Global Health initiative for his proposal "Engineering Immunity Against HIV and Other Dangerous Pathogens," which promises to address the challenge of creating immunological methods to deal with chronic diseases. This grant was awarded by the Bill & Melinda Gates Foundation.

"David has been a wonderful Caltech president," said Caltech faculty chair Henry Lester, the Bren Professor of Biology. "His energy, articulate intelligence, and vision have resulted in a stronger, more interesting, and more diverse Caltech. Speaking also as a Caltech biologist, I'm delighted that he will remain on campus to contribute to our research and teaching programs."

Baltimore, who received a Nobel Prize for his work on the genetic mechanisms of viruses in 1975 at the age of 37, has contributed widely to the understanding of cancer, AIDS, and the molecular basis of the immune response. He has continued to operate his research lab while president and has announced many important findings while at Caltech, including establishing a new methodology to help fight cancer, developing a new gene therapy that is highly effective in preventing HIV from infecting individual cells in the immune system, and creating a new methodology for producing transgenic mice. He has also joined with others in proposing a new global effort to create an HIV vaccine. He received the National Medal of Science in 1999 from President Bill Clinton and the Warren Alpert Foundation Scientific Prize in 2001 for pioneering work leading to cancer therapy.

Not only has Baltimore been prolific in writing about his findings in scientific journals, but he also raised Caltech's visibility by contributing opinion pieces to general interest media on such subjects as the value of stem cell research, the unnecessary public panic that arose during the SARS epidemic, science research under the Bush administration, and maintaining the scientific workforce in the U.S.

"Throughout my years as a Caltech trustee, I have been repeatedly impressed by David's skill at communicating the importance of Caltech to a wide range of constituencies, from the scientific community to potential donors to readers of daily newspapers," said Kresa, the chairman of the Caltech Board of Trustees.

Baltimore has several outstanding administrative and public policy achievements to his credit. In the mid-1970s, he played an important role in creating a consensus on national science policy regarding recombinant DNA research. He served as founding director of the Whitehead Institute for Biomedical Research at MIT from 1982 until 1990, and was president of Rockefeller University in 1990-91. An early advocate of federal AIDS research, he cochaired the 1986 National Academy of Sciences Committee on a National Strategy for AIDS and was appointed in 1996 to head the National Institutes of Health AIDS Vaccine Research Committee.

Feynman Professor and Professor of Theoretical Physics Kip Thorne, who chaired the faculty search committee that selected Baltimore, feels Baltimore has accomplished what the search committee hoped he would. "We attracted David to Caltech to provide leadership in a period of change-changing relations to the federal government, changing ties to the private sector, and a growth in biological sciences at Caltech-while maintaining our traditional strengths. He has led us through this superbly well, and has been a remarkable intellectual force on campus. His presidential shoes will be hard to fill, but I'm tremendously pleased he will remain as a professor, liberated to contribute more strongly to the intellectual life of the Caltech community," Thorne said.

Walter Weisman, trustee chairman of the Caltech capital campaign, has worked closely with Baltimore since its kickoff in 2002, and is pleased with the impact Baltimore has had. "David Baltimore has made an enormous contribution to our campaign success. I am delighted that he will continue to assist the Institute with the campaign as he moves to full-time research. His legacy at Caltech will be felt for years to come, thanks in no small part to his fund-raising achievements as president of the Institute."

Gordon Moore-a Caltech alumnus who was trustee chairman when Baltimore was hired-said, "David's leadership over the last nine years has significantly strengthened Caltech in many important ways. His impact will be felt for decades."

Ben Rosen, also an alumnus and former trustee chairman, said, "During his years of leadership at Caltech, David Baltimore elevated the already considerable reputation and strengths of the Institute. The faculty is stronger than it has ever been. The students are smarter, more diverse, and better rounded. The facilities have been substantially augmented to meet the growing needs of leading-edge research. JPL has achieved triumph after triumph. And the ambitious capital campaign that began during his period in office, and led by his energetic fund-raising skills, will assure that future Caltech needs are met and our goals achieved. Sometime next year, David will begin doing research full time in his biology lab, and a new president will lead Caltech. But because David will remain on campus, we'll still be lucky enough to share with him his myriad interests outside of science, a small sample of which would include art, fly-fishing, music, architecture, travel, literature, and politics."

Caltech's Board of Trustees will immediately initiate the search process for a new president.

Baltimore is the seventh person to lead "modern day" Caltech, his predecessors being James A. B. Scherer, Robert A. Millikan, Lee A. DuBridge, Harold Brown, Marvin L. Goldberger, and Thomas E. Everhart.

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Caltech Stem Cell Biology Training Program Awarded $2.3 Million

PASADENA, Calif. - At a historic meeting today in Sacramento, a three-year, $2.3 million grant was earmarked for the creation of the Caltech Stem-Cell Training Program at the California Institute of Technology. The grant is part of the first round of funding resulting from the passage by California voters of Proposition 71, the California Stem Cell Research and Cures Initiative, in November 2004. The controversial bond measure provides $3 billion over the next ten years to support human embryonic stem-cell research at California universities and research institutions.

The new program, an independently funded collaboration with the Keck School of Medicine at the University of Southern California and Children's Hospital Los Angeles, will provide cross-disciplinary education to postdoctoral scholars on the potential medical uses for stem-cell research, as well as training in the social, ethical, and legal issues surrounding such research. It will be directed by Paul H. Patterson, Anne P. and Benjamin F. Biaggini Professor of Biological Sciences, who currently studies stem cells in the adult brains of mice and their potential usefulness in the treatment of Alzheimer's disease.

The program will support ten postdoctoral students, drawn from different disciplines on campus, for three years.

"This will allow us to bring people into stem-cell research that might otherwise have gone in different directions, providing new expertise and research ideas to the field," Patterson says. "A physicist will look at a problem in a way that a biologist might not have."

A key feature of the program will be newly developed courses in bioethics, and a unique tri-institutional stem-cell biology lecture course, taught in conjunction with the USC Keck School of Medicine and Children's Hospital, that will train students in cutting-edge gene-transfer technology applications in the clinic, medical applications, and current stem-cell research.

The collaboration with the Keck School of Medicine and Children's Hospital "will bring a new medical, preclinical, and clinical outlook to Caltech's work," says Patterson. The university is a world leader in basic stem-cell research. Recently, Caltech researchers uncovered crucial mechanisms regulating the fate of stem cells, and provided unprecedented views of the movement of stem cells through living embryos. Other work has demonstrated the ability to manipulate the genes of stem cells.

The allocation of funds was recommended at a meeting of the Independent Citizens' Oversight Committee of the California Institute for Regenerative Medicine (CIRM). In subsequent awards, CIRM will provide the funds to construct new research facilities and to support individual research programs.

"This is the first fruit of Proposition 71, an initiative that was overwhelmingly voted in by the people of California to support stem-cell research. Caltech will luckily be part of that effort," said Caltech president and Nobel laureate David Baltimore. "This training grant will allow us to use our expertise to develop a pool of new talent to conduct stem-cell research," he adds. Baltimore is on the 29-member CIRM oversight committee. Committee members do not vote on applications in which they have a conflict of interest.

"This is just the beginning," Patterson says. "It's part of a comprehensive approach that is unique to California, and we hope to participate in all aspects of this at Caltech."

Caltech Media Relations contacts: Kathy Svitil (626) 395-8022 ksvitil@caltech.edu

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Authority on the Brains and Behavior of Owls and Songbirds Wins Neuroscience Prize

PASADENA, Calif.-Masakazu "Mark" Konishi, a California Institute of Technology neuroscientist renowned for his work on the neural wiring that allows owls to swoop in on their prey in darkness and songbirds to sing, and his former postdoctoral researcher Eric Knudsen, who is now chair of the neurobiology department at Stanford University, have been awarded this year's Peter Gruber Foundation Neuroscience Prize.

Konishi, who is the Bing Professor of Behavioral Biology at Caltech, and Knudsen received the prize for their work on the brain mechanisms of sound localization in barn owls, which Konishi has worked on since the mid-1970s. The two will receive an unrestricted cash prize of $200,000, a gold medal, and a citation for their contributions to neuroscience. The award was established in 2004 and is given each year to "to honor the most distinguished work in the field of the brain, nervous system and the spinal cord."

Konishi has worked extensively for two decades on the auditory systems of barn owls, which can use their acute hearing to home in on mice on the ground, even in total darkness. The research has led to a good understanding of how the owl's brain manages to "compute" precise locations in two dimensions, and how the neural pathways and circuits are involved.

One of their noteworthy collaborative accomplishments was their work on the auditory physiology of owls in which they used "free-field" speakers that could be moved around the owls' heads. This method allowed them to find the "space-specific" neurons that respond to sounds coming from particular directions. As they plotted the directions and the brain-recording sites, it became clear to them that the neurons involved formed a map of auditory space.

The neurobiology of birdsongs is also of interest to Konishi because several areas of the bird's brain are involved, and because the interaction between the neural wiring and the birds' behavior is of interest to those who strive to better understand the vertebrate brain. Young birds select the song of their own species out of many alien songs in their environment, and they do so because of the way they memorize a "tutor song" at an early stage of development and then produce a copy of it at maturity.

Konishi's work has implications for better understanding the human brain and perhaps even for future interventions in certain neurological disorders.

For example, his group in the past has focused on the death of a special group of nerve cells during a particular developmental period in songbirds, and on the hormonal means of preventing cell death. The problem of the biologically programmed death of nerve cells may have long-term implications for understanding human disorders such as Alzheimer's and Parkinson's diseases.

The Peter Gruber Foundation was founded in 1993 and established a record of charitable giving principally in the U.S. Virgin Islands, where it is located. In recent years the foundation has expanded its focus to a series of international awards recognizing discoveries and achievements that produce fundamental shifts in human knowledge and culture. In addition to the Neuroscience Prize, the foundation presents awards in the fields of cosmology, genetics, justice, and women's rights. Further information about the Peter Gruber Foundation and its awards is available from www.petergruberfoundation.org.

Last year, Seymour Benzer, who is Caltech's Boswell Professor of Neuroscience, Emeritus, became the first recipient of the Neuroscience Prize.

 

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Robert Tindol
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Baltimore Offered $13.9 Million from Grand Challenges in Global Health Initiative for AIDS Research

PASADENA, Calif.- The Grand Challenges in Global Health initiative, a major effort to achieve scientific breakthroughs against diseases that kill millions of people each year in the world's poorest countries, today offered 43 grants totaling $436.6 million for a broad range of innovative research projects involving scientists in 33 countries, including David Baltimore, president of the California Institute of Technology. The ultimate goal of the initiative is to create "deliverable technologies"--health tools that are not only effective, but also inexpensive to produce, easy to distribute, and simple to use in developing countries.

The initiative is supported by a $450 million commitment from the Bill & Melinda Gates Foundation, as well as from two new funding commitments: $27.1 million from the Wellcome Trust, and $4.5 million from the Canadian Institutes of Health Research (CIHR). The initiative is managed by global health experts at the Foundation for the National Institutes of Health (FNIH), the Gates Foundation, the Wellcome Trust, and CIHR. Additional proposed Grand Challenges projects are under review and may be awarded grants later this year.

Baltimore's grant is to address Grand Challenge #12: Create immunological methods that can cure latent infection. He has been offered a grant of $13.9 million for his proposal "Engineering Immunity Against HIV and Other Dangerous Pathogens."

Baltimore's team will explore a fundamentally new way of stimulating the immune system to fight off infectious diseases, focusing on HIV as a test of the concept. The premise of this project is that for some infections, including HIV, the immune system's natural responses are inherently inadequate, and therefore the traditional approach of using vaccines to stimulate and boost these responses is likely to be ineffective. As an alternative, Baltimore and his colleagues propose to genetically engineer immune cells that can produce adequate responses. Their work is intended to lead eventually to immunotherapy for people who are infected with HIV. It could also lead to new ways to prevent HIV infection.

"This grant offers me and Pamela Bjorkman, my collaborator, the opportunity to bring a new concept into the fight against infectious diseases. We are deeply grateful to the Grand Challenges initiative for giving us this opportunity and look forward to turning our dream into a reality," said Baltimore.

The Grand Challenges initiative was launched by the Gates Foundation in 2003, in partnership with the National Institutes of Health, with a $200 million grant to the FNIH to help apply innovation in science and technology to the greatest health problems of the developing world. Of the billions spent each year on research into life-saving medicines, only a small fraction is focused on discovering and developing new tools to fight the diseases that cause millions of deaths each year in developing countries.

"It's shocking how little research is directed toward the diseases of the world's poorest countries," said Bill Gates, co-founder of the Bill & Melinda Gates Foundation. "By harnessing the world's capacity for scientific innovation, I believe we can transform health in the developing world and save millions of lives."

Following the publication of the Grand Challenges in October 2003, more than 1,500 research projects were proposed by scientists in 75 countries.

"We were overwhelmed by the scientific community's response to the Grand Challenges. Clearly, there's tremendous untapped potential among the world's scientists to address diseases of the developing world," said Nobel Laureate Dr. Harold Varmus, chair of the international scientific board that guides the Grand Challenges initiative. Varmus is president of Memorial Sloan-Kettering Cancer Center, and former director of the National Institutes of Health.

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Contact: Jill Perry (626) 395-3226 jperry@caltech.edu

Visit the Caltech Media Relations Web site at http://pr.caltech.edu/media

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Single-Cell Recognition: A Halle Berry Brain Cell

Embargoed for release at 10 a.m., PDT, June 22, 2005

PASADENA, Calif. - World travelers can instantly identify the architectural sails of the Sydney Opera House, while movie aficionados can immediately I.D. Oscar-winning actress Halle Berry beneath her Catwoman costume or even in an artist's caricature. But how does the human brain instantly translate varied and abstract visual images into a single and consistently recognizable concept?

Now a research team of neuroscientists from the California Institute of Technology and UCLA has found that a single neuron can recognize people, landmarks, and objects--even letter strings of names ("H-A-L-L-E-B-E-R-R-Y"). The findings, reported in the current issue of the journal Nature, suggest that a consistent, sparse, and explicit code may play a role in transforming complex visual representations into long-term and more abstract memories.

"This new understanding of individual neurons as 'thinking cells' is an important step toward cracking the brain's cognition code," says co-senior investigator Itzhak Fried, a professor of neurosurgery at the David Geffen School of Medicine at UCLA, and a professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior, also at UCLA. "As our understanding grows, we one day may be able to build cognitive prostheses to replace functions lost due to brain injury or disease, perhaps even for memory."

"Our findings fly in the face of conventional thinking about how brain cells function," adds Christof Koch, the Lois and Victor Troendle Professor of Cognitive and Behavioral Biology and professor of computation and neural systems at Caltech, and the other co-senior investigator. "Conventional wisdom views individual brain cells as simple switches or relays. In fact, we are finding that neurons are able to function more like a sophisticated computer."

The study is an example of the power of neurobiological research using data drawn directly from inside a living human brain. Most neurobiological research involves animals, postmortem tissue, or functional brain imaging in magnetic scanners. In contrast, these researchers draw data directly from the brains of eight consenting clinical patients with epilepsy at the UCLA Medical Center, wiring them with intracranial electrodes to identify the seizure origin for potential surgical treatment.

The team recorded responses from the medial temporal lobe, which plays a major role in human memory and is one of the first regions affected in patients with Alzheimer's disease. Responses by individual neurons appeared on a computer screen as spikes on a graph.

In the initial recording session, subjects viewed a large number of images of famous people, landmark buildings, animals, objects, and other images chosen after an interview. To keep the subjects focused, researchers asked them to push a computer key to indicate whether the image was a person. After determining which images prompted a significant response in at least one neuron, additional sessions tested response to three to eight variations of each of those images.

Responses varied with the person and stimulus. For example, a single neuron in the left posterior hippocampus of one subject responded to 30 out of 87 images. It fired in response to all pictures of actress Jennifer Aniston, but not at all, or only very weakly, to other famous and non-famous faces, landmarks, animals, or objects. The neuron also (and wisely, it turns out) did not respond to pictures of Jennifer Aniston together with actor Brad Pitt.

In another patient, pictures of Halle Berry activated a neuron in the right anterior hippocampus, as did a caricature of the actress, images of her in the lead role of the film Catwoman, and a letter sequence spelling her name. In a third subject, a neuron in the left anterior hippocampus responded to pictures of the landmark Sydney Opera House and Baha'í Temple, and also to the letter string "Sydney Opera," but not to other letter strings, such as "Eiffel Tower."

In addition to Koch and Fried, the research team included Rodrigo Quian-Quiroga of Caltech and UCLA, Leila Reddy of Caltech, and Gabriel Kreiman of the Massachusetts Institute of Technology.

The research was funded by grants from the National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, the National Science Foundation, the Defense Advanced Research Projects Agency, the Office of Naval Research, the W. M. Keck Foundation Fund for Discovery in Basic Medical Research, a Whiteman fellowship, the Gordon Moore Foundation, the Sloan Foundation, and the Swartz Foundation for Computational Neuroscience.

MEDIA CONTACTS: Mark Wheeler, Caltech (626) 395-8733 wheel@caltech.edu

Dan Page, UCLA (310) 794-2265 dpage@mednet.ucla.edu

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Norman Horowitz Dies; Conducted Experiment with Viking Lander to Search for Life on Mars

PASADENA, Calif.--Norman Horowitz, a geneticist best known for his work on the "one-gene, one-enzyme" hypothesis and the experiments aboard the Viking lander to search for life on Mars in 1976, died on Wednesday, June 1, at his home in Pasadena. He was 90.

A pioneer of the study of evolution through biochemical synthesis, Horowitz was a professor of biology at the California Institute of Technology for many years. After a distinguished career studying the genetics of the red bread-mold Neurospora crassa, he began collaborating with the Jet Propulsion Laboratory in 1965 after becoming interested in the biochemical evolution of life and its possible applications to the search for life on other worlds. He spent five years as chief of JPL's bioscience section.

Horowitz was a member of the scientific teams for both the Mariner and Viking missions to Mars. On the Viking mission, he and two collaborators designed an instrument capable of detecting any biochemical evidence of life on the planet. The results of the experiment were negative at the two Viking sites, but this information in itself was a robust scientific result that continues to inform current efforts in astrobiology to this day.

Horowitz is most renowned in the field of biochemistry for his 1945 thought experiment on biochemical evolution. The paper, published in the Proceedings of the National Academy of Sciences, is today considered the origin of the study of evolution at the molecular level. Horowitz also performed a seminal experiment that led to the widespread acceptance of the one-gene, one-enzyme hypothesis that, until the early 1950s, was considered a radical theory of the way that life carries on its chemistry. Horowitz and a colleague used mutations to disprove an alternative interpretation that was gaining credence at the time, thereby indirectly strengthening the one-gene, one-enzyme hypothesis.

A native of Pittsburgh, Horowitz earned his bachelor's degree at the University of Pittsburgh, and then came to Caltech in 1936 for graduate study in the comparatively new division of biology, founded by famed geneticist Thomas Hunt Morgan. After completing his doctorate in 1939 under embryologist Albert Tyler, Horowitz became a postdoctoral researcher at Stanford University, in the laboratory of George W. Beadle.

When Beadle became chair of the Caltech biology division in 1946, Horowitz returned to his alma mater as a faculty member, and stayed at the Institute for the remainder of his career. He was the biology division chair from 1977 to 1980, and became a professor emeritus in 1982. His contributions to the division also included the endowment of the Horowitz Lecture Series.

He was a member of the National Academy of Sciences and the American Academy of Arts and Sciences. His honors included a 1998 medal from the Genetics Society of America. He was also the author of a 1986 book titled To Utopia and Back: The Search for Life in the Solar System.

Horowitz is survived by a daughter, Elizabeth Horowitz of Berkeley, and a son, Joel Horowitz of Iowa City, Iowa and Evanston, Illinois. He has two grandchildren, Katharine of Minneapolis, Minnesota, and Daniel of Davis, California. He was married to Pearl (née Shykin) Horowitz, who died in 1985. Horowitz funded the Pearl S. Horowitz Book Fund at Caltech in her honor.

 

 

 

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Caltech Neuroscientists Unlock Secrets of How the Brain Is Wired for Sex

PASADENA--There are two brain structures that a mouse just can't do without when it comes to hooking up with the mate of its dreams--and trying to stay off the lunch menu of the neighborhood cat. These are the amygdala, which is involved in the initial response to cues that signal love or war, and the hypothalamus, which coordinates the innate reproductive or defensive behaviors triggered by these cues.

Now, neuroscientists have traced out the wiring between the amygdala and hypothalamus, and think they may have identified the genes involved in laying down the wiring itself. The researchers have also made inroads in understanding how the circuitry works to make behavioral decisions, such as when a mouse is confronted simultaneously with an opportunity to reproduce and an imminent threat.

Reporting in the May 19 issue of the journal Neuron, David Anderson, Caltech's Roger W. Sperry Professor of Biology and a Howard Hughes Medical Institute investigator, his graduate student Gloria Choi, and their colleagues describe their discovery that the neural pathway between the amygdala and hypothalamus thought to govern reproductive behaviors is marked by a gene with the rather unromantic name of Lhx6.

For a confirmation that their work was on track, the researchers checked to see what the suspected neurons were doing when the mice were sexually aroused. In male mice, the smell of female mouse urine containing pheromones was already known to be a sexual stimulus, evoking such behaviors as ultrasonic vocalization, a sort of "courtship song." Therefore, the detection of neural activity in the pathway when the mouse smelled the pheromones was the giveaway.

The idea that Lhx6 actually specifies the wiring of the pathway is still based on inference, because when the researchers knocked out the gene, the mutation caused mouse embryos to die of other causes too early to detect an effect on brain wiring. But the Lhx6 gene encodes a transcription factor in a family of genes whose members are known to control the pathfinding of axons, which are tiny wires that jut out from neurons and send messages to other neurons.

The pathway between the amygdala and hypothalamus that is involved in danger avoidance appears to be marked by other genes in the same family, called Lhx9 and Lhx5. However, the function of the circuits marked by these factors is not as clear, because a test involving smells to confirm the pathways was more ambiguous than the one involving sexual attraction. The smell of a cat did not clearly light up Lhx9- or Lhx5-positive cells. Nevertheless, the fact that those cells are found in brain regions implicated in defensive behaviors suggests they might be involved in other forms of behaviors, such as aggression between male mice.

The researchers also succeeded in locating the part of the mouse brain where a circuit-overriding mechanism exists when a mouse is both exposed to a potential mate and perceives danger. This wiring is a place in the hypothalamus where the pathways involved in reproduction and danger avoidance converge. The details of the way the axons are laid down shows that a mouse is clearly hard-wired to get out of harm's way, even though a mating opportunity simultaneously presents itself.

"We also have a behavioral confirmation, because it is known that male mice 'sing' in an ultrasonic frequency when they're sexually attracted," Anderson explains. "But when they're exposed to danger signals like predator odors, they freeze or hide.

"When we exposed the mice to both cat odor and female urine simultaneously, the male mice stopped their singing, as we predicted from the wiring diagram," he says. "So the asymmetry in the cross-talk suggests that the system is prioritized for survival first, mating second."

The inevitable question is whether this applies to humans as well. Anderson's answer is that similarities are likely, and that the same genes may even be involved.

"The brains of mice and humans have both of these structures, and we, like mice, are likely to have some hard-wired circuits for reproductive behavior and for defense," he says. "So it's not unreasonable to assume that some of the genes involved in these behaviors in mice are also involved in humans."

However, humans can also make conscious decisions and override the hard-wired circuitry. For example, two teenagers locked in an amorous embrace in a theater can ignore a horrid monster on the screen and continue with the activity at hand. In real-life circumstances, they would be more inclined to postpone the groping until they were out of danger.

"We obviously have the conscious ability to interrupt the circuit-overriding mechanism, to see if the threat is really important," Anderson says.

Gloria Choi, a doctoral student in biology, did most of the lab work involved in the study. The other collaborators are Hongwei Dong and Larry Swanson, a professor at USC who in the past has comprehensively mapped the neural wiring of the rat brain, and Andrew Murphy, David Valenzuela, and George Yancopoulos at Regeneron Pharmaceuticals, in Tarrytown, New York, who generated the genetically modified mice using a new high-throughput system that they developed, called Velocigene.

 

 

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Robert Tindol
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Four from Caltech Named to National Academy of Sciences

PASADENA-Three members at the California Institute of Technology faculty and one former faculty who is now a visiting associate are among the 72 new members and 18 foreign associates being named to the National Academy of Sciences today. The election was announced during the 142nd annual meeting of the Academy in Washington, D.C.

Caltech's newest members are Richard Andersen, the Boswell Professor of Neuroscience; James Eisenstein, the Roshek Professor of Physics; and Wallace Sargent, the Bowen Professor of Astronomy. Roger Blandford, a former Caltech faculty member and current visiting associate in physics, is also among the electees.

Membership in the National Academy of Sciences is considered one of the most important honors that a scientist can achieve. In addition to the 1,976 active members of the academy following today's election, 360 foreign associates are also listed in the organization's roster as nonvoting members.

The National Academy of Sciences is a private organization of scientists and engineers dedicated to the furtherance of science and its use for the general welfare. It was established in 1863 by a congressional act of incorporation signed by Abraham Lincoln that calls on the Academy to act as an official adviser to the federal government, upon request, in any matter of science or technology.

Andersen is a neuroscientist who has garnered considerable attention in recent years for his progress toward the goal of controlling prosthetic devices with brain signals. Much of his current work focuses on severely paralyzed human patients who can think about making movements, but due to brain lesions from trauma, stroke, or peripheral neuropathies, can no longer make movements. His approach is to create brain-implant technology that will act as an interface between a patient's thoughts for movement and artificial limbs, computers, or other devices, that would "read out" the patient's desires.

Eisenstein is a specialist in condensed-matter physics, which involves the exploration of the fundamental laws of nature as they apply to atoms and molecules that comprise solid matter. His most significant research accomplishment in the last year has been his demonstration that unusual particles known as "excitons" can inhabit solid semiconductor materials in such a way that each exciton loses its individual identity and, in certain ways, a large collection of excitons becomes a single quantum entity.

Sargent is particularly well-known in the astrophysical community for his work in spectroscopy. His research in extragalactic spectroscopy provided the first evidence for a black hole in galaxy M87, and his work on intergalactic gas has led to new insights on the primeval materials of the early universe. His work in the stellar spectroscopy of A-type stars led to the discovery of the He3 isotope in the star 3 Centauri.

Blandford is a former faculty member in the Division of Physics, Mathematics and Astronomy at Caltech. He is currently a visiting associate in physics at Caltech and the Pehong and Adele Chen Professor of Physics and Stanford Linear Accelerator Center at Stanford University, where he is also director of the Kavli Institute for Astrophysics and Cosmology.

Today's election brings the total number of Caltech faculty members of the National Academy of Sciences to 70.

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Five from Caltech Faculty Elected to American Academy of Arts and Sciences

PASADENA, Calif.-Five faculty members at the California Institute of Technology are among this year's newly elected fellows of the American Academy of Arts and Sciences. They join 191 other Americans and 17 foreign honorees as the 225th class of fellows of the prestigious institution that was cofounded in 1780 by John Adams.

This year's new Caltech inductees are Barry Barish, the Linde Professor of Physics and director of the Laser Interferometer Gravitational-Wave Observatory (LIGO); Andrew Lange, the Goldberger Professor of Physics; Barry Simon, the IBM Professor of Mathematics and Theoretical Physics; David Tirrell, chair of the Division of Chemistry and Chemical Engineering and McCollum-Corcoran Professor and professor of chemistry and chemical engineering; and William Bridges, the Braun Professor of Engineering, Emeritus.

The five from Caltech join an illustrious list of fellows, both past and present. Other inductees in the 225th class include Supreme Court Chief Justice William Rehnquist, Angels in America author Tony Kushner, Academy Award-winning actor Sidney Poitier, former NBC Nightly News anchor Tom Brokaw, Washington Post CEO Donald Graham, and Pulitzer Prize-winning cartoonist Art Spiegelman. Past fellows have included George Washington, Benjamin Franklin, Ralph Waldo Emerson, Albert Einstein, and Winston Churchill.

According to the academy's president, Patricia Meyer Spacks, the fellows were chosen "through a highly competitive process that recognizes individuals who have made preeminent contributions to their disciplines and to society at large."

"Throughout its history, the Academy has convened the leading thinkers of the day, from diverse perspectives, to participate in projects and studies that advance the public good," said Executive Officer Leslie Berlowitz.

The academy is an independent policy research center that focuses on complex and emerging problems such as scientific issues, global security, social policy, the humanities and culture, and education.

The new fellows and foreign honorary members will be formally recognized at the annual induction ceremony on October 8 at the academy's headquarters in Cambridge, Massachusetts.

 

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