In the early 1980s, Sidney Altman discovered that ribonucleic acid (RNA) molecules can act as enzymes. This disclosure, independently and concurrently made by Thomas R. Cech of the University of Colorado, broadened scientists' understanding of the origins of life. Before this discovery, it was believed that all enzymes were made of protein and that primitive cells, therefore, used proteins to catalyze biochemical processes. Altman's research showed that RNA appears to have acted as a catalyst. Altman and Cech's work has not only had a "conceptual influence on basic natural sciences", according to the Royal Swedish Academy of Sciences, but in addition, "the discovery of catalytic RNA will probably provide a new tool for gene technology, with potential to create a new defense against viral infections." As a result of their findings, Altman and Cech were jointly awarded the 1989 Nobel Prize for chemistry.
Altman was born in Montreal, Quebec, the second son of Victor Altman, an immigrant grocer, and Ray Arlin, who worked in a textile mill before marriage. Altman attended West Hill High School in Montreal, then the Massachusetts Institute of Technology, where he graduated with a bachelor of science degree in physics in 1960. From 1960-1962, Altman was a teaching assistant in the department of physics at Columbia University, while he waited for a position in a lab. During this time, Altman switched from physics to the newly emerging interdisciplinary field of molecular biology. Altman moved to the University of Colorado in Boulder in late 1962 to work as a research assistant, where he was mainly preoccupied with studying the replication of the T4 bacteriophage, a substance that infects bacterial cells in much the same way as a virus infects human cells. Altman received his Ph.D. in biophysics in 1967.
After graduation, Altman briefly worked as a research assistant in molecular biology at Vanderbilt University before winning a grant from the Damon Runyon Memorial Foundation for Cancer Research. This grant permitted him to work as a research fellow in molecular biology at Harvard University. From 1967 to 1969, working under the biochemist Matthew Meselson, Altman continued his research into the genetic structure of the T4 bacteriophage. His receipt of the Anna Fuller Foundation Fellowship in 1969 enabled Altman to transfer to Cambridge, England, where he worked with pioneering molecular biologists Sydney Brenner and Francis Crick. The latter, in partnership with James D. Watson, discovered DNA's double-helix structure in 1954.
By the 1970s, it was clear to scientists that genetic information is carried by DNA (deoxyribonucleic acid) into a cell's nucleus. In the cytoplasm (the substance inside the cell wall, surrounding the nucleus), the genetic code is copied into RNA. It is then converted into proteins, which are built of chains of amino acids. Altman originally intended to study the three-dimensional structure of transfer RNA (tRNA), which is a small component of RNA that transfers amino acids onto a growing polypeptide chain as proteins are made. Much of the breakthrough work in this area had already been accomplished, however, so Altman decided to switch his attention to the transcription of tRNA from DNA. He found that the DNA from which tRNA is produced is not directly copied into tRNA but first undergoes an intermediary stage when it becomes a long strand of precursor RNA. Precursor RNA is composed of a strand of tRNA with additional genetic sequences at each end that are somehow later removed before it becomes tRNA.
While working at Cambridge, Altman studied the tRNA genes of the Escherichia coli (E. coli) bacterium, to which he added toxic chemicals. Subsequent mutations in the tRNA enabled him to isolate precursor tRNA from bacterial cells. Altman discovered that the additional sequences at each end of the strand of precursor tRNA were removed by something in the cells of the bacteria, probably an enzyme. The scientists found that the enzyme, named ribonuclease P (RNase P), would only cut off the extra sequences at a precise point.
Returning to the United States in 1971, Altman joined Yale University's biology department as an assistant professor. Altman was promoted to associate professor in 1975. In 1978, he published the results of an experiment carried out by one of his graduate students, Benjamin Stark. It demonstrated that RNase P was at least partially composed of RNA, which meant that RNA itself played an integral part in the activity of the enzyme. This finding was highly unorthodox, as it was then presumed that enzymes are made of protein, not nucleic acids.
In 1980, Altman attained a full professorship of biology at Yale. The following year, Cech at the University of Colorado published independent results similar to Altman's. Cech discovered that the precursor RNA from the protozoan Tetrahymena were reduced to their final size as tRNA without the assistance of protein, and suggested that the precursor RNA catalyzed this itself. Cech's findings gave weight to Altman's. Cech's use of the word "catalyst" to describe the action of the RNA was questioned, however, because rather than just speeding up a reaction, it used itself up in the process.
Three years later, by which time Altman had become chairman of Yale's biology department, his colleague, Cecilia Guerrier-Takada, tested the catalytic activity of RNase P. She discovered catalysis even in the control experiments that used the RNA subunit of RNase P (the M1 RNA) but which contained no protein. Altman was able to prove that the M1 RNA demonstrated all the classical properties of a catalyst, especially as, unlike that studied by Cech, it remained unchanged by the reaction. This removed the last shadow of a doubt that RNA could act as an enzyme.
In 1984, Altman became a naturalized American, but retained his Canadian citizenship. From 1985 until 1989, as the dean of Yale College, Altman established a greater role for scientific education in all of Yale's curriculums. In 1989, Altman and Cech jointly received the Nobel Prize for chemistry for their discovery of RNA's catalytic ability. Their work put an end to the conundrum regarding proteins and nucleic acids which had long mystified scientists. They had been unable to discover which came first in the development of life, proteins or nucleic acids. Proteins catalyze biological reactions, whereas nucleic acids, such as RNA, transport the genetic codes that create the proteins. Altman and Cech proved that nucleic acids were the building blocks of life, acting as both codes and enzymes.
High hopes exist for the practical applications of their discovery, which was described by the Nobel Academy as one of "the two most important and outstanding discoveries in the biological sciences in the past 40 years," the other being Crick and Watson's discovery of DNA's double helix structure. If RNA enzymes are able to cut additional sequences of tRNA from a strand of precursor tRNA, scientists could possibly use RNA enzymes to cut infectious RNA from the genetic system of a person with an infectious viral disease. Research into this field is ongoing and, if fruitful, could contain key elements leading to cures for viral infections and certain cancers.
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