Leroy Hood

Leroy Hood was born on October 10, 1938 in Missoula, Montana to Thomas Edward Hood and Myrtle Evylan Wadsworth. His father was an electrical engineer, and his mother had a degree in home economics. Hood had a sister and two brothers, one of whom had Down syndrome. One of his grandfathers had a ranch and ran a summer geology camp for university students, which Hood attended as a high school student. Hood excelled in math and science, being one of forty students nationally to win a Westinghouse Science Talent Search.

Hood received his undergraduate education from the California Institute of Technology (Caltech), where he had teachers such as Richard Feynman and Linus Pauling. Hood received an M.D. from Johns Hopkins School of Medicine in 1964 and a Ph.D. from Caltech in 1968, where he worked with William J. Dreyer on antibody diversity. Dreyer is credited with giving Hood two important pieces of advice: “If you want to practice biology, do it on the leading edge, and if you want to be on the leading edge, invent new tools for deciphering biological information.”

In 1967 Hood joined the Public Health Service, working in the Immunology Branch of the National Cancer Institute at NIH as a Senior Investigator.

In 1970 he returned to Caltech as an Assistant Professor. He was promoted to associate professor in 1973, full professor in 1975, and became Bowles Professor of Biology in 1977. He served as Chairman of the Division of Biology from 1980-1989, and took on the Directorship of Caltech's Special Cancer Center in 1981. In 1989 he stepped down as Chairman to assume the Directorship of a newly funded NSF Science and Technology Center at Caltech. The NSF Center for the Development of an Integrated Protein and Nucleic Acid Biotechnology became one of the founding research centers of the Beckman Institute at Caltech in 1989.

In October 1991, Hood announced that he would move to Seattle, to found and direct the first cross-disciplinary biology department, the Department of Molecular Biotechnology (MBT) at the University of Washington Medical School. The new department was financed by a $12-million gift from Bill Gates, who shared Hood's interest in combining biological research and computer technology and applying them to medical research. Hood and other scientists from Caltech's NSF center moved to the University of Washington during 1992-1994, where they received renewed support from the NSF as the Center for Molecular Biotechnology. (The Department of Molecular Biotechnology and the Genetics department at UW would later reorganize to form the Department of Genome Sciences, in 2001.)

In 2000 Hood resigned his position at the University of Washington to become co-founder and president of the non-profit Institute for Systems Biology, possibly the first independent systems biology organization. His co-founders were protein chemist Ruedi Aebersold and immunologist Alan Aderem. Hood is still an affiliate professor at the University of Washington in Computer Science, Bioengineering and Immunology. Hood will be succeeded as president of ISB as of January 2018, but will continue to lead his research group at ISB, and will remain on ISB's board of directors.

Hood believes that a combination of big data and systems biology has the potential to revolutionize healthcare and create a proactive medical approach focused on maximizing wellness. He coined the term "P4 medicine" in 2003. In 2010 ISB partnered with the Ohio State University Wexner Medical Center in Columbus, Ohio to establish the nonprofit P4 Medicine Institute (P4MI). Its goal was stated as being "to lead the transformation of healthcare from a reactive system to one that predicts and prevents disease, tailors diagnosis and therapy to the individual consumer and engages patients in the active pursuit of a quantified understanding of wellness; i.e. one that is predictive, preventive, personalized and participatory (P4)." In 2012, P4 Medical Institute established an agreement with its first community health partner, PeaceHealth. PeaceHealth is a not-for-profit Catholic health care system, operating in a variety of communities in Alaska, Washington and Oregon. In 2016, ISB affiliated with Providence Health & Services, and Hood became the senior vice president of Providence St. Joseph Health and its chief science officer.

Hood has published more than 700 peer-reviewed papers, received 36 patents, and co-authored textbooks in biochemistry, immunology, molecular biology, and genetics. In addition, he co-authored, with Dan Keveles, The Code of Codes, a popular book on the sequencing of the human genome.

He has been instrumental in founding 15 biotechnology companies, including Amgen, Applied Biosystems, Systemix, Darwin, Rosetta Inpharmatics, Integrated Diagnostics, and Accelerator Corporation.

Genomics and proteomics

At Caltech, Hood and his colleagues created the technological foundation for the study of genomics and proteomics by developing five groundbreaking instruments (the protein sequencer, the protein synthesizer, the DNA synthesizer, the automated DNA sequencer and later the ink-jet DNA synthesizer). Hood's instruments incorporated concepts of high throughput data accumulation through automation and parallelization. When applied to the study of protein and DNA chemistries, these ideas were essential to the rapid deciphering of biological information.

The protein sequencer and automated peptide synthesizer had a tremendous impact on the emerging field of proteomics. The gas-liquid phase protein sequencer, developed with Michael W. Hunkapiller, built upon the Edman degradation of Pehr Edman. Edman and Begg's 1967 design placed a protein or peptide sample into a spinning cup in a temperature controlled chamber. Reagents were added to cleave the protein, followed by solvents to allow extraction of reagents and byproducts. A series of analysis cycles had to be performed to identify a sequence. Hood and Hunkapiller made a number of modifications to improve effectiveness and automate further steps in the analysis. By applying reagents in the gas phase instead of the liquid phase, the retention of the sample during the analysis and the sensitivity of the instrument were increased. Polybrene was used as a substrate coating to better anchor proteins and peptides, and the purification of reagents was improved. HPLC analysis techniques were used to reduce analysis times and extend the technique's applicable range. This allowed scientists to determine partial amino acid sequences of proteins that had not previously been accessible, resulting in the characterization of a series of new proteins whose genes could then be cloned and analyzed. The amount of protein required for an analysis decreased, from 10-100 nanomoles for Edman and Begg's protein sequencer, to the low picomole range, a revolutionary increase in the sensitivity of the technology. These discoveries led to significant ramifications for biology, medicine, and pharmacology.

The automated peptide synthesizer allowed for the synthetic synthesis of peptides and small proteins in sufficient quantities to begin characterizing their functions.

The DNA synthesizer was developed by Hood and Marvin H. Caruthers, based on Caruthers' work on phosphoramidite oligonucleotide synthesis chemistry. This led to commercialization of the first phosphoramidite DNA synthesizer. Revolutionizing the field of molecular biology, it enabled biologists to synthesize DNA fragments for cloning and other genetic manipulations. The DNA synthesizer played a critical role in the identification of many important genes and in the discovery of the polymerase chain reaction (PCR), the critical technique that allowed any segment of DNA to be amplified a million-fold.

Hood had a strong interest in commercial development, actively filing patents and seeking private funding. Applied Biosystems, Inc. (initially named GeneCo.) was formed in 1981 in Foster City, CA to commercialize instruments developed by Hood, Hunkapiller, Caruthers, and others in Hood's lab. The company was supported by venture capitalist William K. Bowes, who brought in Sam H. Eletr and Andre Marion as president and vice-president of the new company. The company shipped the first Model 4790A gas phase protein sequencer in August 1982. The 380 DNA synthesizer appeared in 1983, the 430A peptide synthesizer in 1984, and the 370A DNA sequencing system in 1986.

The most notable of Hood's inventions, the automated DNA sequencer made possible high-speed sequencing of human genomes and was the key technology enabling the Human Genome Project. Hood was involved with the Human Genome Project from its first meeting at the University of California, Santa Cruz in 1985. Hood became an enthusiastic advocate for The Human Genome Project. Hood directed the Human Genome Center’s sequencing of portions of human chromosomes 14 and 15.

At the University of Washington in the early 1990s, Hood and his colleagues developed the ink-jet DNA synthesis technology for creating DNA arrays with tens of thousands of gene fragments. The ink-jet DNA synthesizer created one of the first DNA array chips, which enabled measuring of expression levels of 10,000s of genes. This instrument has transformed genomics, biology, and medicine.

The protein sequencer, peptide synthesizer, DNA sequencer and DNA synthesizer were commercialized by Applied Biosystems, Inc. and the ink-jet technology was commercialized by Agilent Technologies.

Immunology and neurobiology

Hood also made generative discoveries in the field of molecular immunology. His studies of the amino acid sequences of immunoglobulins (also known as antibodies) helped to fuel the 1970s’ debate regarding the generation of immune diversity and supported the hypothesis advanced by William J. Dreyer that immunoglobulin (antibody) chains are encoded by two separate genes (a constant and a variable gene). He (and others) conducted pioneering studies on the structure and diversity of the antibody genes. This research led to verification of the "two genes, one polypeptide" hypothesis and insights into the mechanisms responsible for the diversification of the immunoglobulin variable genes. Hood shared the Lasker Award in 1987 for these studies.

Additionally, Hood was among the first to study, at the gene level, the MHC (major histocompatibility complex) gene family and the T-cell receptor gene families as well as the being among first to demonstrate that alternative RNA splicing was a fundamental mechanism for generating alternative forms of antibodies. He showed that RNA splicing is the mechanism for generating the membrane bound and the secreted forms of antibodies.

In neurobiology, Hood and his colleagues were the first researcher to clone and study the myelin basic protein (MBP) gene. The MBP is a central component in the sheath that wraps and protects neurons. He demonstrated that disease called "shiverer mouse" arose from a defect in the MBP gene. Hood's research group corrected the neurological defect in mice (the shiverer defect) by transferring a normal MBP gene into the fertilized egg of the shiverer mouse. These discoveries led to extensive studies of MBP and its biology.

Systems biology

In the 1990s, Hood began to focus more on cross-disciplinary biology and systems biology. In 1992, with support from Bill Gates, he moved to the University of Washington, where he was the founder and chairman of the Molecular Biotechnology Department, the first cross-disciplinary biology department. In 2000, he co-founded the Institute for Systems Biology (ISB) in Seattle, Washington, with Ruedi Aebersold and Alan Aderem. The institute is an independent, nonprofit organization that develops strategies and technologies for systems approaches to biology and medicine. Hood pioneered the systems biology concept of looking at human biology as a "network of networks." In this model, to understand how systems functions, one needs to know (1) all the components of each network (including genetic, molecular, cellular, organ networks), (2) how these networks inter and intra-connect, (3) how the networks change over time and with perturbations, and (4) how function is achieved within these networks. At the ISB under Hood's direction, genomic, transcriptomic, metabolomic and proteomic technologies are used to understand the "network of networks" and are focused on diverse biological systems (e.g. yeast, mice and humans).

Systems medicine and "P4 medicine"

After the founding of the Institute for Systems Biology, Hood began exploring the idea of systems medicine (the application systems biology to study disease), specifically focusing on cancer and neurodegeneration in mice and humans. His paper on a systems approach to prion disease in 2009 was one of the first to thoroughly explore the use of systems biology to interrogate the dynamic network changes in disease models. These studies are the first to explain the dynamics of diseased-perturbed networks and have now expanded to include frontal temporal dementia and Huntington's disease. Hood is also studying glioblastoma in mice and humans from the systems viewpoint. Hood has established several practices in the burgeoning field of systems medicine:

• The use of family genome sequencing, integrating genetics and genomics, to identify genetic variants associated with health and disease
• The use of targeted proteomics and a systems approach to biomarker discovery (particularly the use of blood as a window into health and disease). He has pioneered the discovery of biomarker panels for lung cancer and posttraumatic stress syndrome.
• The use of systems biology to stratify disease into its different subtypes allowing for more effective treatment.
• The use of systems strategies to identify new types of drug targets to greatly facilitate and speed up the drug discovery process.

In 2002 Hood began progressing in his vision of the future of medicine: first focusing on predictive and preventive (2P) Medicine, then predictive, preventive and personalized (3P) Medicine and finally predictive, preventive, personalized and participatory which led to the current concept of P4 Medicine. Hood states that P4 Medicine is the convergence of systems medicine (see above), big data and patient (consumer) driven healthcare and social networks.

Hood's vision is that in 10 years each individual will be surrounded by a virtual cloud of billions of data points and that we will have the computational tools to analyze this data and produce simple hypotheses about how to optimize wellness and minimize disease for each individual. The patient's demand for better healthcare will be the real driving force for the acceptance of P4 Medicine by the medical community. This driving force is exemplified by the movement known as the quantified self, which used digital devices to monitor self-parameters such as weight, activity, sleep, diet, etc. His view is that P4 Medicine will transform the practice of medicine over the next decade, moving it from a largely reactive, disease-care to a proactive P4 approach that is predictive, preventive, personalized and participatory.

The promise of Predictive, Preventive, Personalized and Participatory (P4) Medicine led Hood in 2010 to co-found the P4 Medicine institute (P4Mi), dedicated to bringing P4 Medicine to society. Through demonstration projects integrating systems biology, consumer driven healthcare management and the current healthcare institutions the P4Mi is introducing a new healthcare system to society. His view is that P4 Medicine will improve healthcare, decrease the cost of healthcare and promote innovation.

Leroy Hood, 2008 Pittcon Heritage Award recipient

Leroy Hood is a member of the National Academy of Sciences (NAS, 1982), the National Academy of Engineering (2007), and the National Academy of Medicine (formerly the Institute of Medicine, 2003). He is one of only 15 scientists ever elected to all three national academies. He is also a member of the American Academy of Arts and Sciences (1982), a member of the American Philosophical Society (2000), a fellow of the American Society for Microbiology, and a charter fellow of the National Academy of Inventors (2012).He has received 17 honorary degrees from institutions including Johns Hopkins and Yale.

In 1987 Hood shared the Albert Lasker Award for Basic Medical Research with Philip Leder and Susumu Tonegawa for studies of the mechanism of immune diversity. This was followed by winning the Dickson Prize in 1988. He won the 2002 Kyoto Prize for Advanced Technology for developing automated technologies for analyzing proteins and genes; the 2003 Lemelson-MIT Prize for Innovation and Invention for inventing "four instruments that have unlocked much of the mystery of human biology" by helping decode the genome; the 2004 Biotechnology Heritage Award; the 2006 Heinz Award in Technology, the Economy and Employment, for breakthroughs in biomedical science on the genetic level; inclusion in the 2007 Inventors Hall of Fame for the automated DNA sequencer; the 2008 Pittcon Heritage Award for helping to transform the biotechnology industry; and the 2010 Kistler Prize for contributions to genetics that have increased knowledge of the human genome and its relationship to society . Leroy Hood won the 2011 Fritz J. and Dolores H. Russ Prize "for automating DNA sequencing that revolutionized biomedicine and forensic science"; the 2011 National Medal of Science, presented at a White House ceremony by President Obama in early 2013; the IEEE Medal for Innovations in Healthcare Technology in 2014, and the 2016 Ellis Island Medal of Honor.

In 2017 he received the NAS Award for Chemistry in Service to Society.