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DR. LEROY HOOD — 2003 WINNER OF THE $500,000 LEMELSON-MIT PRIZE FOR INVENTION AND INNOVATION

“My prediction is that in 10-15 years, we will have identified hundreds of genes that predispose humans to virtually all of the common, late-onset diseases such as cancer, cardiovascular disease, neurological diseases, and the like. We will be able to take a blood sample, interrogate the possibility of defects in hundreds of genes, and write out a probabilistic future health history of what is likely to happen to individuals. This is the predictive approach to medicine,” states the 64-year-old Leroy (Lee) Hood, M.D., Ph.D., 2003 winner of the $500,000 Lemelson-MIT Prize.

Once an individual's health history has been predicted, Hood further explains, “…we can say, 'Here is a course of action, which, if you follow, will delay, if not prevent, the onset of predicted disease and extend your life span.'”

Prior to 1990, this was inconceivable. Hood's achievements in molecular biotechnology and genomics, most specifically his invention of the DNA sequencer—which made possible the decoding of the human genome (Human Genome Project)—have laid the groundwork for the new field of predictive and preventive medicine.

Early on, while a graduate student at the California Institute of Technology (Caltech) working under his mentor and advisor, William Dreyer, Hood realized the transforming role technology could play within the field of biology. This vision, unpopular among most biologists, motivated the Missoula, MT native to become a driving force in the integration of biology and technology, which resulted in four extraordinary inventions that form the technical foundation of modern molecular biology. Among Hood's long list of patents and inventions are the protein sequencer and synthesizer, which uncovered significant details about the structure and functions of proteins, and, the DNA synthesizer and sequencer.

Hood's parents—an electrical engineer and stay-at-home mom—instilled in him the importance of excelling in school and fostered Hood's penchant for math and science. His growing interest in biology and genetics was partly influenced by having a younger brother born with Down's Syndrome. While a senior in high school, Hood was asked to help teach the sophomore biology class. It was while reviewing articles from Scientific American (in preparation for a lecture) that he learned, for example, about the 1953 discovery of the structure of DNA. The excitement and potential of biology fascinated him to the point that he decided to pursue a career in this discipline.

In 1956, Hood moved from the small town of Shelby, MT to the Los Angeles, CA area to begin his college career at Caltech. As he was finishing his undergraduate work, Hood realized his true passion for studying human biology and continued his studies at the Johns Hopkins University School of Medicine, where he earned a M.D. in three years. Here, he became captivated by the immune system's operations and thus focused on this area. Afterward, he returned to Caltech to pursue his Ph.D. in biochemistry.

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Inventions that Form the Cornerstone of Modern Molecular Biology

In the 1970s, as a faculty member at Caltech, Hood assembled a team of biologists and technologists to invent prototypes of instruments that would open new horizons in biology. “Lee's work went beyond the scientific issues to encompass the technology of modern biology. Because his scientific interests led Lee to be concerned with gene families, he saw with a clarity that no one else displayed, the need for new tools to gather the data on molecular diversity,” explains David Baltimore, president, California Institute of Technology, in a letter of recommendation. “…It is not hyperbole to say that Lee's laboratory provided tools that have changed the way molecular biology is done and which provided the impetus for the Human Genome Project.”

The first tool, a protein sequencer, took nearly a decade to develop. The powerful chemicals used to sequence the proteins wrought havoc on the valves through which they flowed. After several frustrating attempts to replace the leaky valves, Hood and his team decided to develop their own valves that could withstand the acidic material. The resulting protein sequencer invention, 100 times more sensitive than its predecessors, is the most powerful machine to “read” the order of amino acid sub-units of the protein. This machine made it possible to read and analyze proteins that had previously been invisible to scientists, allowing for the discovery of six new proteins, which effectively introduced six new fields of biology.

The first protein sequenced with the new machine, the platelet-derived growth factor, led to an understanding of how oncogenes cause cancer. In 1982, Hoodís team determined the sequence of the hormone erythropoietin, which stimulates the production of red blood cells. This led to the creation of Epogen—the first billion-dollar-a-year drug used to treat anemia in dialysis patients—and to the founding of Amgen, today's most successful biotech company. Hood and his colleagues also unearthed the prion protein, which explains in part how Mad Cow disease is caused; colony stimulating factors, which provided an understanding of key hormones in the development of blood cells; interferons, which helped to introduce effective drugs for dealing with certain types of cancers; and acetycholine receptors, which opened the path for studying receptors of the nervous system.

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After successfully commercializing his protein sequencer through Applied Biosystems, a company he founded after 19 companies declined the opportunity, Hood proceeded to develop his second invention, the protein synthesizer. This instrument produced proteins in high, consistent quantities so scientists could run experiments on them. It enabled the study of the HIV protease molecule. This work led to the creation of an effective and highly successful AIDS drug, the protease inhibitor.

During the same timeframe, Hood and his colleagues were working on a machine that could automate the process for synthesizing DNA, ignoring those who believed such a machine was unnecessary. Hood's DNA synthesizer strings together fragments of genes to manufacture DNA for use in DNA mapping and gene cloning, making possible new strategies for molecular biology.

In the late 1970s, Hood and his colleagues began to think about automating DNA sequencing. After years of exploring initially unsuccessful possibilities, they realized how it should be done. It took another three years to work step by step through the chemistry, engineering and biological challenges. Hood finally succeeded in developing such a tool in 1986. The DNA sequencer used four fluorescent dyes to tag each of the four letters across the 24 strings of DNA. A laser makes the DNA chemicals glow in red, green, blue or orange, then computer software reads the fluorescent coding to decipher DNA sequences. This machine became the engine of the Human Genome Project, which has enabled the “reading” of the entire human genetic code, DNA letter by DNA letter.

As one of the first scientists to champion the Human Genome Project, Hood understood that there was a need to drive forward the development of new tools and analytical strategies on a larger scale. With financial backing from Microsoft's Bill Gates, and approval from the University of Washington's Dean of the School of Medicine, Hood brought together chemists, engineers, computer scientists, applied physicists, and biologists to create the cross-disciplinary Department of Molecular Biotechnology at the University of Washington. This department was responsible for a range of scientific firsts, including the study of the genomics of prostate cancer and the launch of proteomics, which studied and analyzed protein structure and function. Hood explains, “The department was successful beyond my wildest expectations, but a striking new opportunity that I had been thinking about since 1990 or so began to emerge—systems biology.”

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The New Frontier: Systems Biology

In 2000, Hood co-founded the Institute for Systems Biology in Seattle, WA. Systems biology requires the integration of biology, medicine, computation and technology to analyze all of the elements in a biological system rather than one gene or protein at a time. The Institute, 170 employees strong, has been successfully using the systems approach to study the biological systems of bacteria, yeast, sea urchins and mice to reveal important findings about the interactions and complexities of systems. Hood and his colleagues believe the systems approach will allow for the exploration of previously uncharted regions in biology and medicine, such as the ability to predict and prevent disease and administer personalized medicine. Hood states, “It is my conviction that systems approaches to biology and medicine will dominate the 21st century.”

In addition to his overwhelming contributions to biology and medicine, one of his foremost goals is bringing hands-on, inquiry-based science to the classroom. In collaboration with the Seattle School District, Hood has implemented a systemic science education reform, a paragon for science programs across the nation. The reform requires that all Seattle school district teachers receive professional training and that all students, grades K-12, participate in the program. To date, elementary (K-5) and middle school (6-8) science programs are in place, and the Institute is working on a high school program.

Since 1960, Hood has received nearly 60 academic and professional honors, including the 1987 Albert Lasker Award for Studies of Immune Diversity and the 2002 Kyoto Prize in Advanced Technology. He is the founder or co-founder of more than ten biotechnology companies, including Applied Biosystems, Inc. (ABI), Amgen, Darwin, Rosetta and MacroGenics.

 

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