Matthew Meselson

Matthew Meselson
Born 24 May 1930
Denver, Colorado, USA
Citizenship USA
Fields Genetics, Molecular Biology
Institutions Harvard University
Alma mater University of Chicago (Ph.B., 1951)
California Institute of Technology (Ph.D., 1957)
Doctoral advisor Linus Pauling
Doctoral students Mark Ptashne 1968, Susan Lindquist 1976, Steven Henikoff 1977

Matthew Stanley Meselson (born May 24, 1930) is a Harvard geneticist and molecular biologist who has investigated how DNA replicates, recombines, and is repaired in cells and how cells recognize and destroy foreign DNA. In the famous Meselson–Stahl experiment he showed that DNA is replicated semi-conservatively [1] In addition, he, François Jacob, and Sydney Brenner were largely responsible for discovering the existence of messenger RNA. He also has an interest in chemical and biological weapons disarmament.

Biography

Youth and education

Meselson was born in Denver, Colorado, on May 24, 1930 and attended elementary and high-school in Los Angeles, California. He was an undergraduate in liberal arts at the University of Chicago (1946-1950) and a graduate student of Linus Pauling in chemistry at the California Institute of Technology (1953-1957). His doctoral dissertation was on equilibrium density gradient centrifugation and on x-ray crystallography. He was Assistant Professor of Physical Chemistry and then Senior Research Fellow at CalTech until he joined the Harvard faculty in 1960 where he conducts research and has taught undergraduate genetics for many years.

Research

In 1957, Meselson and Franklin Stahl (as part of the Phage group) showed that DNA replicates semi-conservatively.[2] In order to test hypotheses for how DNA replicates, Meselson and Stahl, together with Jerome Vinograd, invented a method that separates macromolecules according to their buoyant density.[3] The method, equilibrium density gradient centrifugation, was sufficiently sensitive that Meselson and Stahl were able to separate DNA containing the heavy isotope of nitrogen, 15N, from DNA made of the lighter isotope, 14N. In their classic experiment, described and analyzed in a book by science historian Frederic L. Holmes,[4] they grew the bacterium Escherichia coli for many generations in medium containing 15N as the only nitrogen source and then switched the bacteria to growth medium containing 14N instead. They extracted DNA from bacteria prior to switching and, at intervals, for several generations thereafter. After one generation of growth, all the DNA was seen to have a density half way between that of 15N DNA and 14N DNA. In successive generations, the fraction of DNA that was “half-heavy” fell by a factor of ½, as the total amount of DNA increased two-fold. When the half-heavy DNA was made single stranded by heating, it separated into two density species, one heavy (containing only 15N) and one light (containing only 14N). The experiment implied that, upon replication, the two complementary strands of the bacterial DNA separate, and that each of the single strands directs the synthesis of a new, complementary strand, a result that verified the suggestion for DNA replication put forward five years earlier by James Watson and Francis Crick [5] and lent important early support for the Watson-Crick model of the DNA molecule.

In collaboration with Jean Weigle, Meselson then applied the density gradient method to studies of genetic recombination in the bacteriophage Lambda.[6] The question was whether such recombination involved breakage of the recombining DNA molecules or cooperative synthesis of new molecules. The question could be answered by examining phage particles derived from co-infection of bacteria with genetically marked Lambda phages that were labeled with heavy isotopes (13C and 15N). The density-gradient method allowed individual progeny phages to be characterized for their inheritance of parental DNA and of parental genetic makers. Meselson’s initial demonstration of breakage-associated, replication-independent recombination was later found to reflect the activity of a special system that can recombine Lambda DNA at only one spot, normally used by the phage to insert itself into the chromosome of a host cell. Subsequently, variations of the experiment by Franklin Stahl revealed reciprocal dependencies between DNA replication and most genetic recombination.[7] With Charles Radding, Meselson developed a model for recombination between DNA duplexes that guided research in the field for the decade from 1973 to 1983.[8]

In 1961, Sydney Brenner, François Jacob and Meselson used the density-gradient method to demonstrate the existence of messenger RNA.[9][10] In subsequent work, Meselson and his students demonstrated the enzymatic basis of host-directed restriction,[11] a process by which cells recognize and destroy foreign DNA and then demonstrated methyl-directed mismatch repair,[12][13][14] a process that enables cells to correct mistakes in replicating DNA. Meselson’s current research is aimed at understanding the advantage of sexual reproduction in evolution.

The Meselson Effect

The "Meselson effect” is the process by which the two alleles, or copies of a gene, in an asexual diploid organism evolve independently of each other, becoming increasingly different over time. In sexual organisms the processes of recombination and independent assortment allow both of the alleles within an individual to descend from a recent single ancestral allele. Without recombination or independent assortment alleles cannot descend from a recent ancestral allele. Instead the alleles share a last common allelic ancestor at or just preceding the loss of meiotic recombination.[15] A striking example of this effect was described in bdelloid rotifers where the two alleles of the lea gene have diverged into two different genes which work together to preserve the organism during periods of dehydration.[16] The Meselson effect should cause entire copies of an organism's genome to diverge from each other, effectively reducing all anciently asexual organisms to a haploid state, in a process similar to the diploidization following whole genome duplication.

However, gene conversion, a form of recombination common in asexual organisms, may prevent the Meselson effect from occurring in young asexual organisms [17] and may limit the effect in Bdelloid rotifers.[18] Moreover, a number of putative examples of the Meselson effect remain controversial because other biological process, such as hybridation, can mimic the Meselson effect.[19][20][21][22][23]

Chemical and biological weapons defense and disarmament

In 1963 Meselson served as a resident consultant in the US Arms Control and Disarmament Agency, where he became interested in chemical and biological weapons programs and policies. Since then he has been involved in chemical and biological weapons defense and disarmament matters as a consultant to various US government agencies and through the Harvard Sussex Program, an academic research organization based at Harvard and at the University of Sussex in the UK of which he and Julian Perry Robinson in the UK are co-directors.

Concluding that biological weapons served no substantial military purpose for the US and that their proliferation would pose a serious threat and that, in years ahead, the exploitation of advanced biology for hostile purposes would be inimical to society generally, he worked to persuade members of the Executive Branch, the Congress and the public that the US had no need for such weapons and that there would be benefits in renouncing them and working for worldwide prohibition. After President Richard Nixon in 1969 canceled the US BW offensive program and endorsed a UK proposal for an international ban, Meselson was among those who successfully advocated international agreements to ban biological and then chemical weapons, leading to the Biological Weapons Convention of 1972 and the Chemical Weapons Convention of 1993. Meselson and his colleagues have undertaken three on-site investigations with implications for chemical and biological weapons arms control. During August and September 1970, on behalf of the American Association for the Advancement of Science, Meselson led a team in the Republic of Vietnam in a pilot study of the ecological and health effects of the military use of herbicides.[24][25] Upon returning to Harvard, he and Robert Baughman developed an advanced mass-spectrometric method for analysis of the toxic herbicide contaminant dioxin and applied it to environmental and biomedical samples from the Vietnam and the US. In December 1970, President Richard Nixon ordered a "rapid but orderly" phase-out of herbicide operations in Vietnam.[26]

During the 1980s, Meselson investigated allegations that "yellow rain" was a Soviet toxin weapon being used against Hmong tribespeople in Laos. Citing the physical appearance and high pollen content of samples of the alleged agent; the resemblance of the alleged attacks to showers of feces from swarms of honeybees that he and entomologist Thomas Seeley documented during a 1983 field study in Thailand; the inability of US and UK government laboratories to corroborate initial reports of the presence of trichothecene mycotoxins in samples of the alleged agent and in biomedical samples from alleged victims; the lack of any supporting evidence from extensive interviews with Vietnamese military defectors and prisoners; and other considerations, Meselson and his colleagues argued that the allegations were mistaken.[27][28][29][30]

In April 1980 Meselson served as a resident consultant to the CIA investigating a major outbreak of anthrax among people in the Soviet city of Sverdlovsk. He concluded that on the basis of available evidence the official Soviet explanation that the outbreak was caused by consumption of meat from infected cattle was plausible but that there should be an independent on-site investigation. After the collapse of the Soviet Union, he was allowed to bring a team to Sverdlovsk in 1992 and again in 1993. Their reports conclusively showed that the official Soviet explanation was wrong and that the outbreak was caused by the release of an anthrax aerosol at a military biological facility in the city.[31][32]

Professor Meselson is a member of the U.S. National Academy of Sciences, the American Academy of Arts and Sciences, the American Philosophical Society, the Académie des Sciences (Paris), the Royal Society (London) and the Russian Academy of Sciences and has received numerous awards and honors in the field of science and in public affairs. He has served on the Council of the National Academy of Sciences, the Council of the Smithsonian Institution, the Arms Control and Non-Proliferation Advisory Board to the US Secretary of State and the Committee on International Security and Arms Control of the US National Academy of Sciences. He is past President of the Federation of American Scientists, and presently is Co-director of the Harvard Sussex Program on Chemical and Biological Weapons, a member of the Steering Committee of the Pugwash Study Group on the Implementation of the Chemical and Biological Weapons Conventions and a member of the Board of Directors of the Belfer Center for Science and International Affairs at the John F. Kennedy School of Government at Harvard University.

Selected Awards

Honorary Doctoral Degrees

References

  1. ↑ Meselson, Stahl, and the Replication of DNA. A History of "The Most Beautiful Experiment in Biology", Frederic Lawrence Holmes, Yale University Press (2001). ISBN 0300085400
  2. ↑ Meselson, M. and F. Stahl 1958. The Replication of DNA in E. coli. Proceedings of the National Academy of Sciences USA 44: 671-682
  3. ↑ Meselson, M., F. Stahl, and J. Vinograd 1957. Equilibrium Sedimentation of Macromolecules in Density Gradients. Proceedings of the National Academy of Sciences USA 43: 581-588
  4. ↑ Meselson, Stahl, and the Replication of DNA. A History of "The Most Beautiful Experiment in Biology", Frederic Lawrence Holmes, Yale University Press (2001). ISBN 0300085400
  5. ↑ Watson, J. D., and F. H. C. Crick Nature May 1953. Genetical Implications of the Structure of Deoxyribonucleic Acid. Nature 171: 964-967 doi:10.1038/171964a0
  6. ↑ M Meselson, M. and J. Weigle 1961. Chromosome Breakage Accompanying Genetic Recombination in Bacteriophage. Proceedings of the National Academy of Sciences USA 47: 857-868
  7. ↑ Stahl, F. W. (1998) Recombination in phage λ: one geneticist's historical perspective. Gene 223: 95-102 10.1016/S0378-1119(98)00246-7
  8. ↑ Meselson, M. and C. Radding 1975. A General Model for Genetic Recombination. Proceedings of the National Academy of Sciences USA 72: 358-361
  9. ↑ Brenner, S., F. Jacob, and M. Meselson 1961. An Unstable Intermediate Carrying Information from Genes to Ribosomes for Protein Synthesis. Nature 190: 576-581 doi:10.1038/190576a0
  10. ↑ Meselson, M. 2014. François and X. Research in Microbiology 165: 313-135 DOI: 10.1016/j.resmic.2014.05.004
  11. ↑ Meselson, M. and R. Yuan 1968. DNA Restriction Enzyme from E. coli. Nature 217: 1110-1114 doi:10.1038/2171110a0
  12. ↑ Wagner, R., Jr., and M. Meselson 1976. Repair Tracts in Mismatch DNA Heteroduplexes Proceedings of the National Academy of Sciences USA 73: 4135-4139
  13. ↑ Radman, M., R.E. Wagner, Jr., B.W. Glickman, and M. Meselson 1980. DNA Methylation, Mismatch Correction and Genetic Stability. in Progress in Environmental Mutagenesis ed. M. Alacevic. Amsterdam, Elsevier/ North Holland Biomedical Press, pp. 121-130 ISBN 044480241X
  14. ↑ Pukkila, P.J., J. Peterson, G. Herman, P. Modrich, and M. Meselson 1983. Effects of High Levels of DNA Adenine Methylation on Methyl-Directed Mismatch Repair in E. coli. Genetics 104: 571-582
  15. ↑ Butlin, R. (2002). "OPINION — EVOLUTION OF SEXThe costs and benefits of sex: New insights from old asexual lineages". Nature Reviews Genetics 3 (4): 311–317. doi:10.1038/nrg749. PMID 11967555.
  16. ↑ Pouchkina-Stantcheva, N. N.; McGee, B. M.; Boschetti, C.; Tolleter, D.; Chakrabortee, S.; Popova, A. V.; Meersman, F.; Macherel, D.; Hincha, D. K.; Tunnacliffe, A. (2007). "Functional Divergence of Former Alleles in an Ancient Asexual Invertebrate". Science 318 (5848): 268–271. doi:10.1126/science.1144363. PMID 17932297.
  17. ↑ Tucker AE, Ackerman MA, Eads BD, Xu S, Lynch M. (2013) Population-genomic insights into the evolutionary origin and fate of obligately asexual Daphnia pulex. PNAS. 110:15740.
  18. ↑ Flot J-F, Hespeels B, Li X, Noel B, Arkhipova I, Danchin EGJ, Hejnol A, Henrissat B, Koszul R, Aury JM, Barbe V, Barthélémy RM, et al. (2013)
  19. ↑ Schön I, Martens K, Dijk P (2009) Lost Sex: The Evolutionary Biology of Parthenogenesis. The Netherlands: Springer. 615 p. (chapter 13)
  20. ↑ SCHAEFER, I., DOMES, K., HEETHOFF, M., SCHNEIDER, K., SCHÖN, I., NORTON, R. A., SCHEU, S. and MARAUN, M. (2006), No evidence for the ‘Meselson effect’ in parthenogenetic oribatid mites (Oribatida, Acari). Journal of Evolutionary Biology, 19: 184–193. doi: 10.1111/j.1420-9101.2005.00975.x
  21. ↑ David B. Mark Welch, Jessica L. Mark Welch and Matthew Meselson. Evidence for degenerate tetraploidy in bdelloid rotifers PNAS 2008 105 (13) 5145-5149; published ahead of print March 24, 2008, doi:10.1073/pnas.0800972105
  22. ↑ Jae H. Hur,Karine Van Doninck,Morgan L. Mandigo and Matthew Meselson. Degenerate Tetraploidy Was Established Before Bdelloid Rotifer Families Diverged Mol Biol Evol (2009) 26 (2): 375-383 first published online November 7, 2008 doi:10.1093/molbev/msn260
  23. ↑ Stoeckel S, Masson J-P (2014) The Exact Distributions of FIS under Partial Asexuality in Small Finite Populations with Mutation. PLoS ONE 9(1): e85228. doi: 10.1371/journal.pone.0085228
  24. ↑ Meselson, M. and Constable J. "The Ecological Impact of Large Scale Defoliation in Vietnam", Sierra Club Bulletin, April 1971, Vol. 56, pp 4-9
  25. ↑ Statement at hearing: Chemical and Biological Warfare, Committee on Foreign Relations, U.S. Senate, secret hearing held 30 April 1969, sanitized and printed 23 June 1969, 50 pp. SUDOC: Y4.F76/2:W23/2
  26. ↑ Richard Lyons, New York Times, December 26, 1970 “Military to Curb Use of Herbicides” http://query.nytimes.com/mem/archive/pdf?res=9B00E3D6163FE43BBC4F51DFB467838B669EDE
  27. ↑ Nowicke, J. and M. Meselson 1984. Yellow Rain: A Palynological Analysis. Nature 309: 205-206 doi:10.1038/309205a0
  28. ↑ Seeley, T.D., J.W. Nowicke, M. Meselson, J. Guillemin and P. Akratanakul 1985. Yellow Rain. Scientific American 253: 128-137
  29. ↑ Meselson, M. and J.P. Robinson 2008. The Yellow Rain Affair: Lessons from a Discredited Allegation. Chapter 4 in Terrorism, War or Disease? Unraveling the Use of Biological Weapons. eds. S. Clunan, P. Levoy, S. Martin. Stanford University Press pp 72-96 ISBN 9780804759762
  30. ↑ Merle L. Pribbenow, "'Yellow Rain': Lessons from an Earlier WMD Controversy," International Journal of Intelligence and Counterintelligence, 19 (2006): 737–745
  31. ↑ Meselson, M., J. Guillemin, M. Hugh-Jones, A. Langmuir, I. Popova, A. Shelokov, and O. Yampolskaya 1994. The Sverdlovsk Anthrax Outbreak of 1979. Science 266: 1202-1208 DOI:10.1126/science.7973702
  32. ↑ Guillemin, J. 2001. Anthrax, investigation of a deadly outbreak. University of California Press. ISBN 9780520229174

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