Hot Topics in Life Sciences
Fifty Years of the Genetic Code: Honoring the Legacy of Marshall Nirenberg
Posted October 14, 2014
On July 31, 2014, in partnership with the International Union of Biochemistry and Molecular Biology, the Academy held a Hot Topics in Life Sciences symposium celebrating Fifty Years of the Genetic Code. The event occurred exactly 50 years after Marshall Nirenberg's 1964 talk in New York to what was then the International Union of Biochemistry. Nirenberg described the basic unit of the genetic code, which maps a group of three nucleotides to an amino protein. The identification of the 64 codons in the genetic code opened the door for further discoveries; as Gregory A. Petsko of Weill Cornell Medical College told the audience, "The most important moment in breaking a code is when you realize it can be broken."
Speakers described both the history of the genetic code and the myriad ways in which its implications continue to guide and inspire biologists. Topics included the complex machinery of code translation in the ribosome, work to manipulate this process to create new proteins, and modern sequencing capabilities. The talks also revealed how the genetics revolution is transforming medical treatment through applications such as individual gene sequencing and safer, more effective gene therapy. Of course, as Nirenberg himself stressed decades ago, these capabilities raise many ethical and social issues, which were touched on during a panel discussion at the end of the symposium.
Use the tabs above to find a meeting report and multimedia from this event.
Presentations available from:
C. Thomas Caskey, MD (Baylor College of Medicine)
Ronald G. Crystal, MD (Weill Cornell Medical College)
Philipp Holliger, PhD (MRC Laboratory of Molecular Biology, UK)
Gregory A. Petsko, DPhil (Weill Cornell Medical College)
Frank Portugal, PhD (The Catholic University of America)
Venki Ramakrishnan, PhD (MRC Laboratory of Molecular Biology, UK)
Lei Wang, PhD (Salk Institute for Biological Studies)
Jonathan Weissman, PhD (University of California, San Francisco)
Huanming Yang, PhD (BGI–China)
Moderator: Robert B. Darnell, MD, PhD (New York Genome Center)
Mission Partner support for the Frontiers of Science program provided by
C. Thomas Caskey
Caskey CT, Gonzalez-Garay ML, Pereira S, McGuire AL. Adult genetic risk screening. Annu Rev Med. 2014;65:1-17.
Marshall RE, Caskey CT, Nirenberg M. Fine structure of RNA codewords recognized by bacterial, amphibian, and mammalian transfer RNA. Science. 1967;155:820-6.
Ronald G. Crystal
Crystal RG, McElvaney NG, Rosenfeld MA, et al. Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. Nat Genet. 1994;8:42-51.
Hicks MJ, Rosenberg JB, De BP, et al. AAV-directed persistent expression of a gene encoding anti-nicotine antibody for smoking cessation. Sci Transl Med. 2012;4:140ra87.
O'Reilly M, Federoff HJ, Fong Y, et al. Gene therapy: charting a future course — summary of a National Institutes of Health Workshop, April 12, 2013. Hum Gene Ther. 2014;25:488-97.
Attwater J, Wochner A, Holliger P. In-ice evolution of RNA polymerase ribozyme activity. Nat Chem. 2013;5:1011-8.
Cozens C, Pinheiro VB, Vaisman A, et al. A short adaptive path from DNA to RNA polymerases. Proc Natl Acad Sci U S A. 2012;109:8067-72.
Pinheiro VB, Taylor AI, Cozens C, et al. Synthetic genetic polymers capable of heredity and evolution. Science. 2012;336:341-44.
Pinheiro VB, Holliger P. The XNA world: progress towards replication and evolution of synthetic genetic polymers. Curr Opin Chem Biol. 2012;16:245-52.
Wochner A, Attwater J, Coulson A, Holliger P. Ribozyme-catalyzed transcription of an active ribozyme. Science. 2011;332:209-12.
Schmeing TM, Voorhees RM, Kelley AC, et al. The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA. Science. 2009;326:688-94.
Voorhees RM, Schmeing TM, Kelley AC, Ramakrishnan V. The mechanism for activation of GTP hydrolysis on the ribosome. Science. 2010;330:835-8.
Chen XH, Xiang Z, Hu YS, et al. Genetically encoding an electrophilic amino acid for protein stapling and covalent binding to native receptors. ACS Chem Biol. 2014. [Epub ahead of print]
Coin I, Katritch V, Sun T, et al. Genetically encoded chemical probes in cells reveal the binding path of urocortin-I to CRF class B GPCR. Cell. 2013;155:1258-69.
Hoppmann C, Lacey VK, Louie GV, et al. Genetically encoding photoswitchable click amino acids in Escherichia coli and mammalian cells. Angew Chem Int Ed Engl. 2014;53:3932-6.
Kang JY, Kawaguchi D, Coin I, et al. In vivo expression of a light-activatable potassium channel using unnatural amino acids. Neuron. 201;80:358-70.
Xiang Z, Lacey VK, Ren H, et al. Proximity-enabled protein crosslinking through genetically encoding haloalkane unnatural amino acids. Angew Chem Int Ed Engl. 2014;53:2190-3.
Ingolia NT, Brar GA, Rouskin S, et al. Genome-wide annotation and quantitation of translation by ribosome profiling. Curr Protoc Mol Biol. 2013 Jul; Chapter 4: Unit 4.18.
Li GW, Burkhardt D, Gross C, Weissman JS. Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources. Cell. 2014;157:624-35.
Nirenberg MW. Will society be prepared? Science. 1967;157:633.
National Institutes of Health. Deciphering the Genetic Code: Marshall Nirenberg. 2010.
Nirenberg M. The genetic code. Nobel Lecture, December 12, 1968.
Click here to access the full list of articles by Marshall Nirenberg in the PubMed database.
C. Thomas Caskey, MD
C. Thomas Caskey is a professor of molecular and human genetics at Baylor College of Medicine. He has over 35 years of experience in molecular genetics, holding positions as CEO of the Brown Foundation Institute of Molecular Medicine at the University of Texas Health Science Center at Houston, senior vice president of human genetics and vaccines discovery at Merck Research Laboratories, and president of Merck Genome Research Institute. Caskey's research identified the genetic basis of 15 heritable diseases and clarified the understanding of "anticipation" in triplet repeat diseases (Fragile X, myotonic dystrophy, and over 30 others). His personal identification patent is the basis of worldwide application for forensic science, and he is a consultant to the FBI in forensic science. He is an editor of the Annual Reviews of Medicine. His recent publications address the usefulness of genome-wide sequencing to prevent adult-onset diseases, and his current research focuses on the genetic basis of schizophrenia and autism.
Brian Clark, PhD, ScD
University of Aarhus, Denmark
Brian Clark was Professor Emeritus of Biostructural Chemistry at the University of Aarhus in Denmark. Early in his career, he was a visiting fellow at the NIH in Marshall Nirenberg's group and a scientific staff member of the MRC Laboratory of Molecular Biology in the Division of Molecular Genetics coheaded by Francis Crick and Sydney Brenner. He worked on decoding the initiation of protein synthesis, the first crystallization of a nucleic acid molecule (tRNA), the structural elucidation of transfer RNA, the discovery of the initiation codon for protein synthesis, and the determination of the first structure of a GTP-binding domain. His later research focused on functional genomics. He was past vice chairman of the European Molecular Biology Organization Council (EMBO), past chairman of the Federation of European Biochemical Societies (FEBS), and past president of the International Union of Biochemistry and Molecular Biology (IUBMB). He was chairman of the Task Group on International Relations (TGIR), vice president of the European Federation of Biotechnology (EFB), chief scientist of PhytAge Aps, chairman of the EU Expert Advisory Group in International Cooperation for Science, Information and Technology, coordinator of the Proteomage EU Integrated Project, and a member of the King's College 1441 Foundation. Dr. Clark passed away on October 6, 2014.
Gregory A. Petsko, DPhil
Gregory A. Petsko is a professor of neurology at Weill Cornell Medical College and Tauber Professor of Biochemistry and Chemistry, Emeritus, at Brandeis University. He was a professor of chemistry at MIT before moving to Brandeis University to serve as director of the Rosenstiel Basic Medical Sciences Research Center. His awards include the Pfizer Award in Enzyme Chemistry of the American Chemical Society and the Max Planck Prize, shared with Prof. Roger Goody. He is immediate past president of the American Society for Biochemistry and Molecular Biology and is president-elect of the International Union of Biochemistry and Molecular Biology. His research interests include protein structure and function and the development of methods to treat age-related neurodegenerative diseases, including ALS (Lou Gehrig's), Alzheimer's disease, and Parkinson's disease. His public lectures on the aging of the population and its implications for human health have attracted a wide audience. For the past 12 years he has also written a column on science and society, the first 10 years of which have just appeared in book form.
Jennifer Henry, PhD
The New York Academy of Sciences
Jennifer Henry is the former director of Life Sciences at the New York Academy of Sciences. Before joining the Academy, she was a publishing manager in the Academic Journals division at Nature Publishing Group. She also served for eight years as editor of Functional Plant Biology for CSIRO Publishing in Australia. She received her PhD in plant molecular biology from the University of Melbourne, specializing in the genetic engineering of transgenic crops. As director of Life Sciences, she developed scientific symposia across a range of life sciences, including biochemical pharmacology, neuroscience, systems biology, genome integrity, infectious diseases and microbiology. She also generated alliances with organizations interested in developing programmatic content.
C. Thomas Caskey, MD
Ronald G. Crystal, MD
Ronald G. Crystal is professor and chairman of the Department of Genetic Medicine at New York Presbyterian Hospital–Weill Cornell Medical College, where he is also Bruce Webster Professor of Internal Medicine. After earning an MS in physics and an MD from the University of Pennsylvania, Crystal served as chief of the Pulmonary Branch of the National Heart, Lung and Blood Institute. In 1993 he joined the faculty at Weill Cornell, initially focusing on the pathogenesis and therapy of inflammatory diseases of the lung. His work formed the basis of the current understanding of the pathogenesis of lung fibrosis and the hereditary form of emphysema associated with alpha 1-antitrypsin deficiency, a disease for which he developed the FDA-approved therapy now in use. In the late 1980s, Crystal shifted his focus to gene therapy. He was the first to use a recombinant virus as a vehicle for in vivo gene therapy and has carried out human trials of gene therapy for cystic fibrosis, cardiac ischemia, cancer, and central nervous system disorders. Recent studies from his laboratory have focused on using viral gene transfer vectors as platform strategies for vaccines against addiction.
Philipp Holliger, PhD
Philipp Holliger is a program leader at the MRC Laboratory of Molecular Biology (MRC-LMB) in Cambridge, UK. He earned a PhD with Sir Greg Winter at the Cambridge Centre for Protein Engineering (CPE), where he stayed for his postdoctoral studies. He became a tenured program leader in 2005. Holliger's research spans chemical biology, synthetic biology, and in vitro evolution. His recent work on synthetic genetic polymers was featured in Scientific American's 10 World Changing Ideas. The Holliger group is focused on the chemical logic and origins of the genetic apparatus shared by all life on Earth. His laboratory has shown that the fundamental function of DNA and RNA in biology—the capacity for genetic information storage, propagation, and evolution—is shared by a range of alternative nucleic acid scaffolds (XNAs) not found in nature. The researchers are also interested in RNA self-replication and the role that structured media such as water ice may have played in its emergence, a process closely connected to the origin of life.
Gregory A. Petsko, DPhil
Frank Portugal, PhD
Frank Portugal received his PhD in biochemistry from the University of Illinois. He did his postdoctoral work with Marshall Nirenberg at the National Institutes of Health and then moved to the scientific staff of the National Cancer Institute. Portugal is now a clinical associate professor of biology and director of the MS in Biotechnology Program in the Department of Biology at the Catholic University of America. He is on the editorial boards of the online journals American Journal of Biochemistry, Journal of Biochemical and Pharmacological Research, and Journal of Immunology and Infectious Diseases. Portugal is coauthor of A Century of DNA (MIT Press) and author of a forthcoming book on Marshall Nirenberg to be published by MIT Press this year.
Venki Ramakrishnan, PhD
Venkatraman "Venki" Ramakrishnan holds a PhD in physics from Ohio University and is a group leader at the MRC Laboratory of Molecular Biology in Cambridge, UK. He has a long-standing interest in ribosome structure and function. In 2000, his laboratory determined the atomic structure of the 30S ribosomal subunit and its complexes with ligands and antibiotics. This work led to insights into how the ribosome "reads" the genetic code, as well as into various aspects of antibiotic function. Recently, Ramakrishnan's laboratory has determined the high-resolution structures of functional complexes of the entire ribosome at various stages along the translation pathway, which has led to insights into its role in protein synthesis during decoding, peptidyl transfer, translocation, and termination. With Drs. Thomas A. Steitz and Ada E. Yonath, he won the Nobel Prize in Chemistry in 2009 for his work on the structure and function of the ribosome.
Lei Wang, PhD
Lei Wang received his PhD from the University of California, Berkeley. His graduate research resulted in the first expansion of the genetic code to include unnatural amino acids (Uaas), for which he was awarded the Young Scientist Award by Science. Wang started his group at the Salk Institute in 2005, where he is the Frederick B. Rentschler Associate Professor. His group has developed new methods for the expansion of the genetic code in several cells and model organisms, including mammalian cells, stem cells, C. elegans, and recently embryonic mice. Wang discovered that release factor one is nonessential in E. coli, and engineered autonomous bacteria capable of incorporating Uaas at multiple sites with high efficiency. By proposing the concept of proximity-enabled bioreactivity, Wang designed and demonstrated that a new class of Uaas, the bioreactive Uaas, can be genetically encoded in live systems. These bioreactive Uaas enable bioreactivities, inaccessible to proteins before, to be specifically introduced into biosystems, opening the door for new protein engineering and biological research in vivo. Wang is a Beckman Young Investigator, a Searle Scholar, and NIH Director's New Innovator awardee.
Jonathan Weissman, PhD
Jonathan Weissman is a Howard Hughes Medical Institute investigator and professor of cellular and molecular pharmacology and of biochemistry and biophysics at the University of California, San Francisco. After obtaining a PhD in physics from Massachusetts Institute of Technology, he pursued postdoctoral fellowship training at Yale University School of Medicine. Weissman's laboratory focuses on understanding the mechanisms of protein folding and the role of protein misfolding in disease and normal physiology. His group also develops novel experimental and analytical approaches for exploring the organizational principles of biological systems. The lab recently described a ribosome-profiling approach, based on deep sequencing of ribosome-protected mRNA fragments, that enables genome-wide investigation of protein translation with a speed, depth, and precision that rivals the best microarray experiments. Such technologies, in addition to the lab's experience in using genetic interaction maps to gain biological insights, enable his group to obtain a holistic understanding of complex biological systems.
Huanming Yang, PhD
Huanming Yang is cofounder and president of BGI–China, one of the major genomics centers in the world. He and partners have contributed to the International Human Genome Project, the HapMap Project, the 1000 Genomes Project, and other human 'omics research, and to the sequencing and analysis of the genomes of many other animals, plants, and microorganisms. Yang obtained his PhD from University of Copenhagen in Denmark and completed postdoctoral training in France and the U.S. He is an elected foreign member of the European Molecular Biology Organization (EMBO), an academician of the Chinese Academy of Sciences, a fellow of the Third World Academy of Sciences, a foreign academician of the Indian National Science Academy, and a member of both the German National Academy of Sciences and the U.S. National Academy of Sciences.
Robert B. Darnell, MD, PhD
Robert B. Darnell earned his MD and PhD from Washington University School of Medicine in St. Louis, where he specialized in molecular biology. Darnell trained in internal medicine at Mount Sinai School of Medicine and in neurology at Weill Cornell Medical College, where he was chief neurology resident. Darnell joined The Rockefeller University as assistant professor and associate physician at the university hospital. In 2002 he was appointed investigator at the Howard Hughes Medical Institute and named Heilbrunn Professor at Rockefeller. He is also an attending neurologist at Memorial Sloan-Kettering Cancer Center, associate professor at Weill Cornell, and president of the New York Genome Center. Darnell's awards include the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research, the Derek Denny-Brown Young Neurological Scholar Award, and the Irma T. Hirschl Trust Career Scientist Award. He is an elected member of the Institute of Medicine of the National Academies and the Association of American Physicians and a fellow of the American Association for the Advancement of Science.
Arthur L. Caplan, PhD
Arthur L. Caplan is the Drs. William F. and Virginia Connolly Mitty Professor and founding head of the Division of Bioethics at New York University Langone Medical Center. Before joining NYU he was the Sidney D. Caplan Professor of Bioethics at the University of Pennsylvania Perelman School of Medicine, where he created the Center for Bioethics and the Department of Medical Ethics. Caplan has also taught at the University of Minnesota, where he founded the Center for Biomedical Ethics, as well as at the University of Pittsburgh and Columbia University. He was the associate director of the Hastings Center from 1984 to 1987. Caplan's most recent books are Contemporary Debates in Bioethics and Ethics in Mental Healthcare: A Reader. Caplan writes a regular column on bioethics for NBC.com. He is a monthly commentator on bioethics and health care issues for WebMD/Medscape. He appears as a guest and commentator on various national and international media outlets.
Jane M. Love, JD, PhD
Jane M. Love, co-vice chair of WilmerHale's Intellectual Property Department, is a patent attorney with a practice focused on life sciences. Love advises corporations, biotech and pharmaceutical start-ups, universities, and research institutions in the fields of biotechnology, molecular biology, biology, biochemistry, immunology, nanotechnology, and chemistry. Her practice encompasses ANDA litigation, biologics litigation, advice related to biosimilars, post-grant proceedings under the AIA, and global coordination of prosecution and enforcement of patent rights. Love prepares and prosecutes patent applications and manages portfolios in the U.S. and internationally. She has obtained IP protection on innovations such as gene and protein therapeutics, molecular diagnostics, vaccines, treatment methods, pharmaceutical compounds, and formulations.
Alan N. Schechter, MD
National Institute of Diabetes and Digestive and Kidney Diseases, NIH
website | publications
Alan N. Schechter is chief of the Molecular Medicine Branch of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. He received his MD from the Columbia University College of Physicians and Surgeons. Since 2004 he has been on the Council of the NIH Assembly of Scientists, which he chaired for five years. He serves, or has served, on multiple scientific review committees for the NIH, the Food and Drug Administration, the National Science Foundation, and the Howard Hughes Medical Institute. For more than 30 years he has been an officer of the Foundation for Advanced Education in the Sciences (FAES) at NIH. He has held teaching faculty positions at FAES, Johns Hopkins University, and George Washington University School of Medicine. He has also served as coeditor of Perspectives in Biology and Medicine, published by Johns Hopkins University Press. He is coauthor of the NIH Guidelines for the Conduct of Research and NIH Guide for Training and Mentoring.
Don Monroe is a science writer based in Murray Hill, New Jersey. After getting a PhD in physics from MIT, he spent more than fifteen years doing research in physics and electronics technology at Bell Labs. He writes on physics, technology, and biology.