San Diego’s Nobel Pride

On Oct. 3, 2011, Dr. Bruce Beutler checked his voicemail in the middle of the night and noticed an email with “Nobel Prize” in the subject line.

“It said that I had won the Nobel Prize. I was thrilled and a little disbelieving,” Beutler stated in an Oct. 3, 2011 interview with Adam Smith of the Nobel Foundation. “So I went to Google News, and in a few minutes I saw my name there, so I knew it was real.”

Every year, the Nobel Foundation in Stockholm, Sweden awards prizes for achievements in physics, chemistry, physiology or medicine, literature and peace. These categories were established by Alfred Nobel, a Swedish chemist and engineer best known for inventing dynamite, when he died in December of 1896. The first prizes were awarded in 1901.

Beutler, 54, is the latest in a line of 18 UCSD-affiliated Nobel laureates. He graduated from UCSD in 1976 with a bachelor’s degree in biology. Afterward, Beutler completed medical research in Chicago, New York and Dallas, where he made discoveries about the innate immune system, also referenced as the body’s non-specific “first line” of defense against pathogens, which includes the skin and white blood cells. The Nobel Foundation awarded him the Nobel Prize for Medicine because of his work with the innate immune system.

Beutler is most known for his characterization of “toll-like” receptors — specialized proteins on the surface of non-specific immune cells that he calls “the eyes of the immune system.” Beutler discovered these receptors over decades of microbial research. The first toll-like receptor Beutler isolated was tumor necrosis factor-alpha (TNF-?) in mice. He performed a series of experiments to determine its function, ultimately discovering a signaling pathway that is responsible for neutralizing endotoxins, which are released by certain species of bacteria.

In these infections, TNF-? actually acts against the body’s defenses to destroy healthy human cells. Most of the symptoms of cytotoxic bacterial infections, Beutler discovered, are caused by the action of TNF-? and a close cousin, called lipopolysaccharides. Beutler then invented a recombinant molecule to neutralize TNF-? and began experimenting to confirm that blocking TNF-? in mice stopped them from expressing high levels of cytosolic LPS, a precursor to cell death. This discovery earned him the Robert Koche Prize in 2004.

He found that blocking TNF-? did indeed stop mice from expressing high levels of cytosolic LPS, a finding that received a great deal of attention from the scientific community when his paper, “TNF, Apoptosis and Autoimmunity: A Common Thread?” was published in Blood Cells, Molecules and Diseases in 1998.

In the process of linking the necrotic factor to LPS and cell death, he found that TNF-? worked by binding to a class of receptors that had never been thoroughly characterized before — toll-like receptors. He found that toll-like receptors start a signaling cascade that result in the inflammation of internal organs in mice, a process that had never been fully understood before the publication of his research.

Through these experiments, which initially appeared to have unrelated results, Beutler came to the work that eventually led to understanding this class of previously uncharacterized receptors’ actions. This work in turn led him to map out the pathways that are crucial to innate immunity.

After working for 14 years at University of Texas Southwestern and the Howard Hughes Medical Institute in Dallas, Beutler moved with his laboratory to La Jolla in 2000 to work at the Scripps Research Institute as a professor of immunology for over a decade.

Beutler was still teaching at UCSD when he received his Nobel Prize last year. Beutler now serves as a professor of the University of Texas, though he recently returned to UCSD on Nov. 8 to talk about his research and career options for current undergraduates.

Although Beutler left La Jolla for Texas last year, five other Nobel laureates currently work at UCSD.

Harry M. Markowitz

Harry M. Markowitz, 85, who received the Nobel Prize in Economics in 1990, currently serves as an adjunct professor at UCSD’s Rady School of Management. The Nobel Foundation cited his “pioneering work in the theory of financial economics” in a press release on Oct. 16, 1990.

After graduating from University of Chicago, Markowitz didn’t know what to study for his master’s right away. He decided to continue at the same university for a master’s in economics, researching the application of math techniques to the stock market. He was one of the first economists to analyze the patterns in which investors optimize their returns in his paper on “Portfolio Selection,” published in The Journal of Finance in March 1952.

As Markowitz notes in his Nobel speech, he was interested in the “economics of uncertainty,” the role of risk taking in economic investment.

Up to this point, economics had been analyzed in terms of the overall movements of producers and consumers rather than the decision making of individuals. Markowitz realized that the uncertainty of an individual’s actions must be incorporated into mathematical models of investment for them to be reflective of reality. Once he had incorporated uncertainty into his calculations, he realized there were huge opportunities to develop better ways to diversify an investor’s portfolio.

In his autobiography for the 1990 edition of the Nobel Foundation’s yearbook Les Prix Nobel, Markowitz discusses how he continued to work on “the application of mathematical or computer techniques to practical problems, particularly problems of business decisions under uncertainty,” which opened the doors to others to understand portfolio risk assessment.

These days, in addition to teaching at the Rady School of Management, Markowitz operates a consulting firm out of San Diego.

In his autobiography, he acknowledges the people he’s worked with over the years by saying, “As each of these people knows, I often consider work to be play and derived great joy from our collaboration.”

Mario J. Molina

Two of the three winners of the Nobel Prize in Chemistry 1995 currently work at UCSD. The first, Mario J. Molina, earned a Nobel Prize for discovering the effect of man-made chemicals on the atmosphere.

Growing up in Mexico City as a son of a diplomat, Molina became interested in chemistry at a young age. In his autobiography, he recounts setting up a rudimentary laboratory in the bathroom of his house. When his aunt, a chemist, discovered his experimentation, she brought him to her laboratory and let him carry out college-level experiments there. By the time he moved to Switzerland at 11 for boarding school, he had already decided to become a research chemist.

Molina studied chemical engineering at the National Autonomous University of Mexico, which he states in his autobiography was the closest thing to physical chemistry that was offered by the university in 1960. He went on to graduate school at the University of Freiburg in Germany. There, he did research in kinetics and polymerizations before deciding to explore other research areas. He returned to UNAM as an assistant professor for a short time before going to study physical chemistry at UC Berkeley in 1968.

After graduating, he moved to UC Irvine for some post-doctorate study researching a class of inert industrial chemicals, chlorofuorocarbons, which had been accumulating in the atmosphere since the wide spread of refrigeration in the 1930s. With his mentor, Professor Sherwood Rowland, Molina developed the “CFC-ozone depletion theory” the now widely known theory, which posits that as these man-made chemicals rise up in the atmosphere, they decompose upon contact with solar radiation, releasing chlorine radicals that convert ozone into diatomic oxygen.

They published their findings in 1974, calling on policy makers and news media to bring attention to the dangers of CFC-ozone depletion. In his Nobel lecture in 1995, Molina described the chemical process, pointing to later studies by other scientists observing the ozone depletion over the Antarctic as further proof that his theory was correct. In 1989, Molina moved to the Massachusetts Institute of Technology to teach graduate students and continue research on “global atmospheric chemistry issues.” He was working at MIT the time he received the Nobel Prize.

Molina moved to UCSD in 2006, where he now works with a research group investigating the chemical properties of atmospheric particles in order to better understand their effect on climate.

Paul J. Crutzen

The other 1995 Nobel laureate working at UCSD also received an award for his research in the role that NXOY molecules play in ozone depletion.

Paul J. Crutzen, 78, wasn’t very interested in chemistry as a teenager in the Netherlands. He trained as a civil engineer after finishing school because he didn’t qualify for a university stipend. After several years as a civil engineer, Crutzen felt he wasn’t being intellectually stimulated and decided he wanted a career in academia.

He went to work at the International Meteorological Institute of Stockholm University in 1958 as a computer programmer, even though he did not have “the slightest bit of experience in this subject,” as he said in his Nobel Prize acceptance speech. Taking this risk allowed him to attend classes at the university while working full time to support his wife and child.

While researching for his filosofie licentiat (the Netherlands’ equivalent of a Ph.D. thesis) around 1965, Crutzen was asked to help develop a model of oxygen distribution in the atmosphere. In this way, Crutzen was introduced to the study of atmospheric chemistry.

During his post-doctorate studies at Oxford in 1969, Crutzen published a paper on “catalytic ozone destruction” by nitric oxide (NO) and nitrogen dioxide (NO2), stating that the concentration of these potentially destructive molecules in the atmosphere was directly proportional to emissions of nitrous oxide (N2O) from the use of nitrogen fertilizers in agriculture. The imbalance of NXOY molecules, Crutzen hypothesized, contributed to climate change by increasing sun radiation in the atmosphere. For confirming this through his research, the Nobel Foundation awarded Crutzen the Nobel Prize in Chemistry in 1995.

Crutzen currently works as an environmental researcher at the Scripps Institution of Oceanography at UCSD.

Robert Engle III

In 2003, Robert Engle III, 69, received the Nobel Prize in Economics for the invention of the ARCH model, which extrapolates economic trends in market prices and interest rates — which are normally very difficult to predict — with a high degree of accuracy.

Engle noted that economic trends tend to be heteroskedastic, conditional in the sense that the trends change due to different variables over time. Heteroskedasticity is a statistical term for a collection of variables in which one set of data has different variables than the rest. Engle applied regression analysis, a technique for estimating relationships among variables, to analyze the trends. With these ideas, he developed the ARCH model, short for autoregressive conditional heteroskedasticity model, to map financial statistics in order to predict future market values.

Engle wasn’t always sure about what he wanted to do.

He graduated from Cornell University in 1966 with a bachelor’s degree in physics, but he became interested in economics during an introductory course that he took during his senior year. He went on to get a doctorate in economics from the Cornell in 1969, and he worked as a research professor at the Massachusetts Institute of Technology from 1969 to 1977. In 1975, he began to teach and research at UCSD, where he conducted the research that earned him the Nobel Prize. He has retired from teaching at UCSD and is now a professor emeritus in the economics department.

Roger Tsien

The most recent Nobel Prize winner at UCSD is Roger Tsien, who received the Nobel Prize in Chemistry in 2008 for “the discovery and development of the green fluorescent protein, GFP,” according to the Nobel Foundation’s press release.

Tsien, 60, wrote in his autobiography that he developed an interest in chemistry in elementary school, during which time he studied by copying down experimental procedures from books in the school library.

Tsien’s favorite experiments when he was young were those in which the addition of a reagent caused a common chemical or protein to change color. In one experiment, he made a deep purple-colored solution change into a brilliant green hue, an experiment that “reflects an early and long-lasting obsession with pretty colors.”

However, he found his chemistry classes at Harvard University so “distasteful” that he abandoned the subject and majored in neurobiology for a while. Eventually he graduated with degrees in chemistry and physics and went on to get a doctorate in physiology at the University Cambridge.

After the fellowship ended, Tsien had a difficult time finding a job because he couldn’t be neatly categorized as a biologist or a chemist.

“Biology departments considered me a chemist,” he stated in his “Prix Nobel” autobiography. “But chemistry departments rejected me as a biologist.”

Tsien ultimately found a position at UC Berkeley, but had to leave when a financial crisis in the mid-’80s caused his lab’s budget to be cut. In 1989, Tsien came to UCSD, where he began work on fluorescent proteins, and his work continues to this day.

While at UCSD, Tsien discovered green fluorescent protein, which is now used to observe chemical changes within cells. In the mid-’90s, Tsien figured out how to attach these fluorescent genes to proteins in the cell in order to track these proteins for study. Tsien’s techniques are now “ubiquitous,” according to the Nobel Foundation, in research facilities around the world.

Tsien continues to teach in the chemistry department at UCSD.

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