Walter Gilbert ForMemRS | |
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Born | Boston, Massachusetts, U.S. | March 21, 1932
Education | |
Known for | DNA sequencing |
Spouse | Celia Stone (m. 1953) |
Children | 2 [1] |
Awards |
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Scientific career | |
Fields | |
Institutions | Harvard University |
Thesis | On generalised dispersion relations and meson-nucleon scattering (1958) |
Doctoral advisor | Abdus Salam |
Doctoral students | |
Website | www |
Walter Gilbert (born March 21, 1932) is an American biochemist, physicist, molecular biology pioneer, and Nobel laureate. [1] [4] [5]
Walter Gilbert was born in Boston, Massachusetts, on March 21, 1932, into a Jewish family, [6] the son of Emma (Cohen), a child psychologist, and Richard V. Gilbert, an economist. [4] [7]
When Gilbert was seven years old, the family moved to the Washington D.C. area so his father could work under Harry Hopkins on the New Deal brain trust. While living in Washington the family became friends with the family of I.F. Stone and Wally met Stone's oldest daughter, Celia, when they were both 8. They later married at age 21. [8]
He was educated at the Sidwell Friends School, and attended Harvard University for undergraduate and graduate studies, earning a baccalaureate in chemistry and physics in 1953 and a master's degree in physics in 1954. [4] He studied for his doctorate at the University of Cambridge, where he earned a PhD in physics supervised by the Nobel laureate Abdus Salam in 1957. [4] [9]
Gilbert returned to Harvard in 1956 and was appointed assistant professor of physics in 1959. [4] Gilbert's wife Celia worked for James Watson, leading Gilbert to become interested in molecular biology. Watson and Gilbert ran their laboratory jointly through most of the 1960s, until Watson left for Cold Spring Harbor Laboratory. [10] In 1964 he was promoted to associate professor of biophysics and promoted again in 1968 to professor of biochemistry. [4]
Gilbert is a co-founder of the biotech start-up companies Biogen, with Kenneth Murray, Phillip Sharp and Charles Weissman [11] and Myriad Genetics with Dr. Mark Skolnick and Kevin Kimberlin [12] [13] where he was the first chairman on their respective boards of directors. Gilbert left his position at Harvard to run Biogen as CEO, but was later asked to resign by the company's board of directors. [14] He is a member of the Board of Scientific Governors at The Scripps Research Institute. Gilbert has served as the chairman of the Harvard Society of Fellows.
In 1996, Gilbert and Stuart B. Levy founded Paratek Pharmaceuticals. Gilbert served as chairman until 2014. [15]
Gilbert was an early proponent of sequencing the human genome. At a March 1986 meeting in Santa Fe New Mexico he proclaimed "The total human sequence is the grail of human genetics". In 1987, he proposed starting a company called Genome Corporation to sequence the genome and sell access to the information. [14] In an opinion piece in Nature in 1991, he envisioned completion of the human genome sequence transforming biology into a field in which computer databases would be as essential as laboratory reagents [16]
Gilbert returned to Harvard in 1985. [17] Gilbert was an outspoken critic of David Baltimore in the handling of the scientific fraud accusations against Thereza Imanishi-Kari. [18] Gilbert also joined the early controversy over the cause of AIDS. [19] In 1962, Gilbert's physics PhD student Gerald Guralnik extended Gilbert's work on massless particles; Guralnik's work is widely recognized as an important thread in the discovery of the Higgs Boson. [20]
With his PhD student Benno Müller-Hill, Gilbert was the first to purify the lac repressor, [21] just beating out Mark Ptashne for purifying the first gene regulatory protein. [22]
Together with Allan Maxam, Gilbert developed a new DNA sequencing method, Maxam–Gilbert sequencing, [23] [24] using chemical methods developed by Andrei Mirzabekov. His approach to the first synthesis of insulin via recombinant DNA [25] lost out to Genentech's approach which used genes built up from the nucleotides rather than from natural sources. Gilbert's effort was hampered by a temporary moratorium on recombinant DNA work in Cambridge, Massachusetts, forcing his group to move their work to an English biological weapons site. [26]
Gilbert first proposed the terms introns (intragenic regions) and exons (expressed regions) in reference to recently discovered phenomenon of splicing [27] and suggested explanation for the evolution of introns in a seminal 1978 "News and Views" correspondence to Nature titled "why genes in pieces?". [28] In 1986, Gilbert proposed the RNA world hypothesis for the origin of life, [29] based on a concept first proposed by Carl Woese in 1967.
In 1969, Gilbert was awarded Harvard's Ledlie Prize. [4] In 1972 he was named American Cancer Society Professor of Molecular Biology. [4] In 1979, Gilbert was awarded the Louisa Gross Horwitz Prize from Columbia University together with Frederick Sanger. [4] [30] That year he was also awarded the Gairdner Prize and the Albert Lasker Award for Basic Medical Research. [4]
Gilbert was awarded the 1980 Nobel Prize in Chemistry, shared with Frederick Sanger and Paul Berg. Gilbert and Sanger were recognized for their pioneering work in devising methods for determining the sequence of nucleotides in a nucleic acid.
Gilbert has also been honored by the National Academy of Sciences (US Steel Foundation Award, 1968); Massachusetts General Hospital (Warren Triennial Prize, 1977); [31] the New York Academy of Sciences; (Louis and Bert Freedman Foundation Award, 1977), the Académie des Sciences of France (Prix Charles-Leopold Mayer Award, 1977). [4] Gilbert was elected a Foreign Member of the Royal Society (ForMemRS) in 1987. [4] [32] [33]
In 2002, he received the Biotechnology Heritage Award, from the Biotechnology Industry Organization (BIO) and the Chemical Heritage Foundation. [34] [35]
Allan Maxam and Walter Gilbert's 1977 paper "A new method for sequencing DNA" was honored by a Citation for Chemical Breakthrough Award from the Division of History of Chemistry of the American Chemical Society for 2017. It was presented to the Department of Molecular & Cellular Biology, Harvard University. [36] [24]
Gilbert married Celia Stone, the daughter of I. F. Stone, in 1953 and has two children. [1] After retiring from Harvard in 2001, Gilbert has launched an artistic career to combine art and science. His art format is centered on digital photography. [17] [37]
An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word intron is derived from the term intragenic region, i.e., a region inside a gene. The term intron refers to both the DNA sequence within a gene and the corresponding RNA sequence in RNA transcripts. The non-intron sequences that become joined by this RNA processing to form the mature RNA are called exons.
Genomics is an interdisciplinary field of molecular biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dimensional structural configuration. In contrast to genetics, which refers to the study of individual genes and their roles in inheritance, genomics aims at the collective characterization and quantification of all of an organism's genes, their interrelations and influence on the organism. Genes may direct the production of proteins with the assistance of enzymes and messenger molecules. In turn, proteins make up body structures such as organs and tissues as well as control chemical reactions and carry signals between cells. Genomics also involves the sequencing and analysis of genomes through uses of high throughput DNA sequencing and bioinformatics to assemble and analyze the function and structure of entire genomes. Advances in genomics have triggered a revolution in discovery-based research and systems biology to facilitate understanding of even the most complex biological systems such as the brain.
Frederick Sanger was a British biochemist who received the Nobel Prize in Chemistry twice.
Renato Dulbecco was an Italian–American virologist who won the 1975 Nobel Prize in Physiology or Medicine for his work on oncoviruses, which are viruses that can cause cancer when they infect animal cells. He studied at the University of Turin under Giuseppe Levi, along with fellow students Salvador Luria and Rita Levi-Montalcini, who also moved to the U.S. with him and won Nobel prizes. He was drafted into the Italian army in World War II, but later joined the resistance.
DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. The advent of rapid DNA sequencing methods has greatly accelerated biological and medical research and discovery.
Robert G. Roeder is an American biochemist. He is known as a pioneer scientist in eukaryotic transcription. He discovered three distinct nuclear RNA polymerases in 1969 and characterized many proteins involved in the regulation of transcription, including basic transcription factors and the first mammalian gene-specific activator over five decades of research. He is the recipient of the Gairdner Foundation International Award in 2000, the Albert Lasker Award for Basic Medical Research in 2003, and the Kyoto Prize in 2021. He currently serves as Arnold and Mabel Beckman Professor and Head of the Laboratory of Biochemical and Molecular Biology at The Rockefeller University.
Chemical biology is a scientific discipline between the fields of chemistry and biology. The discipline involves the application of chemical techniques, analysis, and often small molecules produced through synthetic chemistry, to the study and manipulation of biological systems. Although often confused with biochemistry, which studies the chemistry of biomolecules and regulation of biochemical pathways within and between cells, chemical biology remains distinct by focusing on the application of chemical tools to address biological questions.
Dideoxynucleotides are chain-elongating inhibitors of DNA polymerase, used in the Sanger method for DNA sequencing. They are also known as 2',3' because both the 2' and 3' positions on the ribose lack hydroxyl groups, and are abbreviated as ddNTPs.
George McDonald Church is an American geneticist, molecular engineer, chemist, serial entrepreneur, and pioneer in personal genomics and synthetic biology. He is the Robert Winthrop Professor of Genetics at Harvard Medical School, Professor of Health Sciences and Technology at Harvard University and Massachusetts Institute of Technology, and a founding member of the Wyss Institute for Biologically Inspired Engineering at Harvard University.
DNA footprinting is a method of investigating the sequence specificity of DNA-binding proteins in vitro. This technique can be used to study protein-DNA interactions both outside and within cells.
Allan Maxam is one of the pioneers of molecular genetics. He was one of the contributors to develop a DNA sequencing method at Harvard University, while working as a student in the laboratory of Walter Gilbert.
Peter B. Dervan is the Bren Professor of Chemistry at the California Institute of Technology. The primary focus of his research is the development and study of small organic molecules that can sequence-specifically recognize DNA, a field in which he is an internationally recognized authority. The most important of these small molecules are pyrrole–imidazole polyamides. Dervan is credited with influencing "the course of research in organic chemistry through his studies at the interface of chemistry and biology" as a result of his work on "the chemical principles involved in sequence-specific recognition of double helical DNA". He is the recipient of many awards, including the National Medal of Science (2006).
Ray Jui Wu was a Chinese-born American geneticist and served as Liberty Hyde Bailey Professor of Molecular Genetics and Biology at Cornell University.
Cancer genome sequencing is the whole genome sequencing of a single, homogeneous or heterogeneous group of cancer cells. It is a biochemical laboratory method for the characterization and identification of the DNA or RNA sequences of cancer cell(s).
The history of genetics can be represented on a timeline of events from the earliest work in the 1850s, to the DNA era starting in the 1940s, and the genomics era beginning in the 1970s.
Julian Edmund Davies is a British-born microbiologist and Professor Emeritus in the Department of Microbiology and Immunology at the University of British Columbia.
Maxam–Gilbert sequencing is a method of DNA sequencing developed by Allan Maxam and Walter Gilbert in 1976–1977. This method is based on nucleobase-specific partial chemical modification of DNA and subsequent cleavage of the DNA backbone at sites adjacent to the modified nucleotides.
Microbial phylogenetics is the study of the manner in which various groups of microorganisms are genetically related. This helps to trace their evolution. To study these relationships biologists rely on comparative genomics, as physiology and comparative anatomy are not possible methods.
David Ruchien Liu is an American molecular biologist and chemist. He is Richard Merkin Professor, Director of the Merkin Institute of Transformative Technologies in Healthcare, and Vice-Chair of the Faculty at the Broad Institute of Harvard University and the Massachusetts Institute of Technology.
Anthony R. Cashmore is a biochemist and plant molecular biologist, best known for identifying cryptochrome photoreceptor proteins. These specialized proteins are critical for plant development and play an essential role in circadian rhythms of plants and animals. A Professor emeritus in the Department of Biology at the University of Pennsylvania, Cashmore led the Plant Science Institute from the time of his appointment in 1986 until his retirement in 2011. He was elected to the National Academy of Sciences in 2003.