Meselson, Matthew Stanley (1930- )

American molecular biologist

Matthew Meselson, in collaboration with biologist Franklin W. Stahl, showed experimentally that the replication of deoxyribonucleic acid (DNA ) in bacteria is semiconservative. Semiconservative replication occurs in a double stranded DNA molecule when the two strands are separated and a new strand is copied from the parental strand to produce two new double stranded DNA molecules. The new double stranded DNA molecule is semiconservative because only one strand is conserved from the parent; the other strand is a new copy. (Conservative replication occurs when one offspring of a molecule contains both parent strands and the other molecule offspring contains newly replicated strands) The classical experiment revealing semiconservative replication in bacteria was central to the understanding of the living cell and to modern molecular biology .

Matthew Stanley Meselson was born May 24, 1930, in Denver, Colorado. After graduating in 1951 with a Ph.D. in liberal arts from the University of Chicago, he continued his education with graduate studies at the California Institute of Technology in the field of chemistry. Meselson graduated with a Ph.D. in 1957, and remained at Cal Tech as a research fellow. He acquired the position of assistant professor of chemistry at Cal Tech in 1958. In 1960, Meselson moved to Cambridge, Massachusetts to fill the position of associate professor of natural sciences at Harvard University. In 1964, he was awarded professor of biology, which he held until 1976. He was appointed the title of Thomas Dudley Cabot professor of natural sciences in 1976. From that time on, Meselson held a concurrent appointment on the council of the Smithsonian Institute in Washington, DC.

After graduating from the University of Chicago, Meselson continued his education in chemistry at the California Institute of Technology. It was during his final year at Cal Tech that Meselson collaborated with Franklin Stahl on the classical experiment of semiconservative replication of DNA. Meselson and Stahl wanted to design and perform an experiment that would show the nature of DNA replication from parent to offspring using the bacteriophage T4 (a virus that destroys other cells, also called a phage). The idea was to use an isotope to mark the cells and centrifuge to separate particles that could be identified by their DNA and measure changes in the new generations of DNA. Meselson, Stahl, and Jerome Vinograd originally designed this technique of isolating phage samples. The phage samples isolated would contain various amounts of the isotope based on the rate of DNA replication. The amount of isotope incorporated in the new DNA strands, they hoped, would be large enough to determine quantitatively. The experiments, however, were not successful. After further contemplation, Meselson and Stahl decided to abandon the use of bacteriophage T4 and the isotope and use instead the bacteria Escherichia coli (E. coli ) and the heavy nitrogen isotope 15N as the labeling substance. This time when the same experimental steps were repeated, the analysis showed three distinct types of bacterial DNA, two from the original parent strands and one from the offspring. Analysis of this offspring showed each strand of DNA came from a different parent. Thus the theory of semiconservative replication of DNA had been proven. With this notable start to his scientific career Meselson embarked on another collaboration, this time with biologists Sydney Brenner , from the Medical Research Council's Division of Molecular Biology in Cambridge, England, and François Jacob from the Pasteur Institute Laboratories in Paris, France. Together, Meselson, Brenner, and Jacob performed a series of experiments in which they showed that when the bacteriophage T4 enters a bacterial cell, the phage DNA incorporates into the cellular DNA and causes the release of messenger RNA . Messenger RNA instructs the cell to manufacture phage proteins instead of the bacterial cell proteins that are normally produced. These experiments led to the discovery of the role of messenger RNA as the instructions that the bacterial cell reads to produce the desired protein products. These experiments also showed that the bacterial cell could produce proteins from messenger RNA that are not native to the cell in which it occurs.

In his own laboratory at Harvard University, Meselson and a postdoctoral fellow, Robert Yuan, were developing and purifying one of the first of many known restriction enzymes commonly used in molecular biological analyses. Restriction enzymes are developed by cultivating bacterial strains with phages. Bacterial strains that have the ability to restrict foreign DNA produce a protein called an enzyme that actually chews up or degrades the foreign DNA. This enzyme is able to break up the foreign DNA sequences into a number of small segments by breaking the double stranded DNA at particular locations. Purification of these enzymes allowed mapping of various DNA sequences to be accomplished. The use of purified restriction enzymes became a common practice in the field of molecular biology to map and determine contents of many DNA sequences.

After many years working with the bacteria E. coli, Meselson decided to investigate the fundamentals of DNA replication and repair in other organisms. He chose to work on the fruit fly called Drosophila melanogaster. Meselson discovered that the fruit fly contained particular DNA sequences that would be transcribed only when induced by heat shock or stress conditions. These particular heat shock genes required a specific setup of DNA bases upstream of the initiation site in order for transcription to occur. If the number of bases was increased or reduced from what was required, the gene would not be transcribed. Meselson also found that there were particular DNA sequences that could be recombined or moved around within the entire chromosome of DNA. These moveable segments are termed transposons . Transposons, when inserted into particular sites within the sequence, can either turn on or turn off expression of the gene that is near it, causing mutations within the fly. These studies contributed to the identity of particular regulatory and structural features of the fruit fly as well as to the overall understanding of the properties of DNA.

Throughout his career as a scientist, Meselson has written over 50 papers published in major scientific journals and received many honors and awards for his contributions to the field of molecular biology. In 1963, Meselson received the National Academy of Science Prize for Molecular Biology, followed by the Eli Lilly Award for Microbiology and Immunology in 1964. He was awarded the Lehman Award in 1975 and the Presidential award in 1983, both from the New York Academy of Sciences. In 1990, Meselson received the Science Freedom and Responsibility Award from the American Association for the Advancement of Science. Meselson has also delved into political issues, particularly on government proposals for worldwide chemical and biological weapon disarmament.

See also Microbial genetics; Transposition