December 2009

Retrospective: Mahlon Hoagland (1921–2009)

At the Worcester Foundation, Mahlon turned his attention to writing and speaking to lay audiences about the importance of basic research. The terms “curiosity driven” and “unfettered” were among his favorites, and readers and audiences reacted warmly. They did so, in part, because Mahlon possessed an unassuming, modest style and an almost childlike excitement about the discovery process. In the mid-1970s, Mahlon catalyzed a group including James Watson, Arthur Kornberg, George Palade, Lewis Thomas and others to form the Delegation for Basic Biomedical Research. The group went to Washington and brought a new cogency to the view that fundamental research can predict no outcomes. The group was an overnight sensation and soon was widely imitated.

After retiring in 1985, Mahlon authored or co-authored six books that conveyed his unique talent for expressing science to a general readership. He was a longtime member of the American Society for Biochemistry and Molecular Biology, a member of the American Academy of Arts and Sciences and the U.S. National Academy of Sciences and received numerous other honors and awards, including the Franklin Medal (1976) and the 1982 and 1996 book awards from the American Medical Writers Association. He and Zamecnik were nominated for the Nobel Prize more than once.

Having made two seminal discoveries as a young investigator, Mahlon spent the last part of his career leading and reforming the Worcester Foundation and inspiring lay audiences to understand what makes science happen. It is a matter of subjectivity as to the arena in which he made his most enduring contribution: as a biochemist or as an eloquent statesman-spokesman for basic research. Maybe it’s a tie. He was a gifted biochemist over short quanta of everlasting discoveries, a gracious, modest man and an eternal optimist for science.

We offer our deepest sympathy to Mahlon’s family. Below are reflections by his colleagues.

To do my work, I climbed onto the shoulders of Mahlon Hoagland, who was a great trailblazer and who laid the foundation and basic framework for the grand world of aminoacyl tRNA synthetases. These ancient, universal proteins, which appeared at the base of the tree of life in conjunction with the development of the genetic code, embody so many mysteries yet to be solved. Little did any of us know that Hoagland’s early work would guide those like me into a land filled with surprise and meaning— from the role of tRNA synthetases in the evolution of the tree of life to their development of expanded functions that are critical for wellness and homeostasis and that have applications to human diseases.

Paul R. Schimmel
Ernest and Jean Hahn Professor
The Scripps Research Institute

***

I encountered and spoke with Mahlon occasionally during the ’60s. What struck me most was the modesty and the quiet demeanor of such a highly accomplished scientist. The impression I got was of an urbane, sophisticated and broadly educated individual. Quite recently, in preparation for historical talks at some meetings, I have had the occasion to read and re-read some of Mahlon’s classical papers and reviews, and one cannot but be impressed with the clarity and precision of his writings. In scientific publications and in books, Mahlon had the tremendous gift of taking the reader along with him and conveying the sense of excitement that he felt about science.

In describing experiments showing that aminoacyl sRNAs were the intermediates in protein synthesis, Mahlon writes, “It was night by the time the samples were dried, stacked and ready to move automatically under the counter tube. I still can clearly see the dark windows of the lab, smell the organic solvents, hear the buzzing of a defective fluorescent lamp in the next room. In front of me were the transfixing flashing lights of the Geiger counter as the samples began to be counted… Those little numbers caused a shiver to go down my spine: Amino acids had left the RNA and entered protein!” (7) As someone who started working with radio isotopes using what was likely the same type of gas flow counter that Mahlon was describing, I read these lines and could sense the excitement that he must have felt as he saw the flashing lights of the counter indicate to him that the number of counts in sRNA were going down and those in the protein were going up. This was scientific writing at its best, and Mahlon was a master at that. 

Uttam L. RajBhandary
Lester Wolfe professor of molecular biology,
The Massachusetts Institute of Technology

References

1. Hoagland, M. B. (1955) An enzymatic mechanism for amino acid activation in animal tissues. Biochim. Biophys. Acta 16, 288—289.
2. Hoagland, M. B., Keller, E. B., and Zamecnik, P. C. (1956) Enzymatic carboxyl activation of amino acids. J. Biol. Chem. 218, 345—358.
3. Kresge, N., Simoni, R. D., and Hill, R. L. (2009) The mechanism of amino acid activation: the work of Mahlon Hoagland. J. Biol. Chem. 284, e7—e8.
4. Hoagland, M. B., Stephenson, M. L., Scott, J. F., Hecht, L. I., and Zamecnik, P. C. (1958) A soluble ribonucleic acid intermediate in protein synthesis. J. Biol. Chem. 231, 241—256.
5. Hoagland, M. Toward the Habit of Truth: A Life in Science. W. W. Norton, 1990.
6. Hoagland, M. (2004) Enter transfer RNA. Nature 431, 249.
7. Hoagland, M. (1996) Biochemistry or Molecular Biology? The discovery of “soluble RNA.” TIBS 21, 77—80. 

Thoru Pederson (Thoru.Pederson@umassmed.edu) is the Vitold Arnett professor in the department of biochemistry and molecular pharmacology at the University of Massachusetts Medical School.


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