Rollin Hotchkiss
Encyclopedia
Rollin Douglas Hotchkiss (1911 – December 12, 2004) was an American biochemist who helped to establish the role of DNA
as the genetic material and contributed to the isolation and purification of the first antibiotics. His work on bacterial transformation helped lay the groundwork for the field of molecular genetics
.
, Connecticut
. The son of factory workers, he attended Yale University
after scoring the highest in the nation on an achievement test
. Hotchkiss earned a B.S. in chemistry in 1932, and remained at Yale for a Ph.D. in organic chemistry. After completing his doctoral work in 1935, Hotchkiss became a fellow of the Rockefeller Institute of Medical Research, where he would remain until retirement in 1982.
and Walter Goebel, and was encouraged to learn more biology at a summer courses at the Marine Biological Laboratory
. His early work isolating and synthesizing derivatives of glucoronic acid led to the identification of one of the specific polysaccharide
s in the capsule of type III pneumococci. Hotchkiss spent the 1937-1938 academic year in the lab of Heinz Holter and Kaj Linderstrøm-Lang at Carlsberg Laboratory
learning protein analysis techniques. In 1938, he began collaborating with René Dubos
to isolate and study antibiotics produced by soil bacteria. Their work on gramicidin
and tyrocidine
led to the first commercial antibiotics, and with Fritz Lipmann they found that the antibiotics include D-amino acids.
During the late 1930s, Hotchkiss was also strongly critical of the Bergann-Niemann hypothesis of protein structure, the proposal by fellow Rockefeller biochemists Max Bergmann
and Carl Niemann
that protein structures always consist of multiples of 288 amino acids. (This would also be a feature of Dorothy Wrinch's cyclol
hypothesis of protein structure).
In 1946, in the wake of the Avery-MacLeod-McCarty experiment
showing that DNA, not protein, had the power to transform bacteria from one type to another, Hotchkiss rejoined Avery's lab. His work on protein analysis helped answer Avery's critics who argued that the experiment was not sufficiently rigorous to rule out protein contamination (and thus the possibility that protein was the transforming factor). Hotchkiss found that virtually all the detected nitrogen in the purified DNA used in for the transformation experiments came from glycine
, a breakdown product of the nucleotide base adenine
, and estimated that undetected protein contamination was at most .02%, although he did not publish this result until 1952 (the year of the Hershey-Chase experiment
). In 1948 Hotchkiss used paper chromatography
to quantify the base composition of DNA and, independently of Erwin Chargaff
, found that the base ratios differed from species to species.
In 1951, Hotchkiss showed that purified bacterial DNA could be used to transfer penicillin
resistance
from one strain of bacteria to another without changing the capsule type (the main identifying feature of different types of the same bacterial species). His subsequent worked helped establish the basics of bacterial genetics, showing that many features of classical genetics (including genetic linkage
) have parallels in bacteria, despite their lack of chromosome
s. Hotchkiss continued working in molecular genetics until his retirement in 1982, including significant collaborations with Julius Marmur
, Maurice Fox, Alexander Tomasz, Joan Kent, Sanford Lacks, Elena Ottolenghi, and his wife Magda Gabor-Hotchkiss.
In the mid-1960s, Hotchkiss became interested in the potential dangers of genetic engineering
(a term he helped to popularize). Through the early 1970s he articulated many of the concerns that led to the 1975 Asilomar Conference on Recombinant DNA
.
Hotchkiss was a member of the American Academy of Arts and Sciences
and the National Academy of Sciences
(elected in 1961), and served as president of the Genetics Society of America
from 1971 to 1972. After leaving Rockefeller University in 1982, he worked as a research professor at the University at Albany, SUNY
until retiring to Lenox
, Massachusetts in 1986. Hotchkiss died December 12, 2004 of congestive heart failure.
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
as the genetic material and contributed to the isolation and purification of the first antibiotics. His work on bacterial transformation helped lay the groundwork for the field of molecular genetics
Molecular genetics
Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...
.
Education
Hotchkiss was born in South BritainSouth Britain
South Britain is a term which was occasionally used in the 17th and 18th centuries, for England and Wales in relation to their position in the southern half of the island of Great Britain...
, Connecticut
Connecticut
Connecticut is a state in the New England region of the northeastern United States. It is bordered by Rhode Island to the east, Massachusetts to the north, and the state of New York to the west and the south .Connecticut is named for the Connecticut River, the major U.S. river that approximately...
. The son of factory workers, he attended Yale University
Yale University
Yale University is a private, Ivy League university located in New Haven, Connecticut, United States. Founded in 1701 in the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States...
after scoring the highest in the nation on an achievement test
Achievement test
An achievement test is a test of developed skill or knowledge. The most common type of achievement test is a standardized test developed to measure skills and knowledge learned in a given grade level, usually through planned instruction, such as training or classroom instruction...
. Hotchkiss earned a B.S. in chemistry in 1932, and remained at Yale for a Ph.D. in organic chemistry. After completing his doctoral work in 1935, Hotchkiss became a fellow of the Rockefeller Institute of Medical Research, where he would remain until retirement in 1982.
Research career
At the Rockefeller Institute, Hotchkiss initially worked as an assistant to Oswald AveryOswald Avery
Oswald Theodore Avery ForMemRS was a Canadian-born American physician and medical researcher. The major part of his career was spent at the Rockefeller University Hospital in New York City...
and Walter Goebel, and was encouraged to learn more biology at a summer courses at the Marine Biological Laboratory
Marine Biological Laboratory
The Marine Biological Laboratory is an international center for research and education in biology, biomedicine and ecology. Founded in 1888, the MBL is the oldest independent marine laboratory in the Americas, taking advantage of a coastal setting in the Cape Cod village of Woods Hole, Massachusetts...
. His early work isolating and synthesizing derivatives of glucoronic acid led to the identification of one of the specific polysaccharide
Polysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
s in the capsule of type III pneumococci. Hotchkiss spent the 1937-1938 academic year in the lab of Heinz Holter and Kaj Linderstrøm-Lang at Carlsberg Laboratory
Carlsberg Laboratory
The Carlsberg Laboratory in Copenhagen, Denmark was created in 1875 by J. C. Jacobsen, the founder of the Carlsberg brewery, for the sake of advancing biochemical knowledge, especially relating to brewing. It featured a Department of Chemistry and a Department of Physiology...
learning protein analysis techniques. In 1938, he began collaborating with René Dubos
René Dubos
René Jules Dubos was a French-born American microbiologist, experimental pathologist, environmentalist, humanist, and winner of the Pulitzer Prize for General Non-Fiction for his book So Human An Animal. He is credited as an author of a maxim "Think globally, act locally"...
to isolate and study antibiotics produced by soil bacteria. Their work on gramicidin
Gramicidin
Gramicidin is a heterogeneous mixture of six antibiotic compounds, gramicidins A, B and C, making up 80%, 6%,and 14% respectively, all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramicidin D are linear pentadecapeptides; that is...
and tyrocidine
Tyrocidine
Tyrocidine is a mixture of cyclic decapeptides produced by the bacteria Bacillus brevis found in soil. It can be composed of 4 different amino acid sequences, giving tyrocidine A–D . Tyrocidine is the major constituent of tyrothricin, which also contains gramicidin...
led to the first commercial antibiotics, and with Fritz Lipmann they found that the antibiotics include D-amino acids.
During the late 1930s, Hotchkiss was also strongly critical of the Bergann-Niemann hypothesis of protein structure, the proposal by fellow Rockefeller biochemists Max Bergmann
Max Bergmann
Max Bergmann was a Jewish-German biochemist. He was the first to use the Carboxybenzyl protecting group for the synthesis of oligopeptides.-Life and work:Bergmann was born in Fürth, Bavaria, Germany on February 12, 1886....
and Carl Niemann
Carl Niemann
Carl George Niemann was an American biochemist who worked extensively on the chemistry and structure of proteins, publishing over 260 research papers...
that protein structures always consist of multiples of 288 amino acids. (This would also be a feature of Dorothy Wrinch's cyclol
Cyclol
The cyclol hypothesis is the first structural model of a folded, globular protein. It was developed by Dorothy Wrinch in the late 1930s, and was based on three assumptions. Firstly, the hypothesis assumes that two peptide groups can be crosslinked by a cyclol reaction ; these crosslinks are...
hypothesis of protein structure).
In 1946, in the wake of the Avery-MacLeod-McCarty experiment
Avery-MacLeod-McCarty experiment
The Avery–MacLeod–McCarty experiment was an experimental demonstration, reported in 1944 by Oswald Avery, Colin MacLeod, and Maclyn McCarty, that DNA is the substance that causes bacterial transformation...
showing that DNA, not protein, had the power to transform bacteria from one type to another, Hotchkiss rejoined Avery's lab. His work on protein analysis helped answer Avery's critics who argued that the experiment was not sufficiently rigorous to rule out protein contamination (and thus the possibility that protein was the transforming factor). Hotchkiss found that virtually all the detected nitrogen in the purified DNA used in for the transformation experiments came from glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
, a breakdown product of the nucleotide base adenine
Adenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
, and estimated that undetected protein contamination was at most .02%, although he did not publish this result until 1952 (the year of the Hershey-Chase experiment
Hershey-Chase experiment
The Hershey–Chase experiments were a series of experiments conducted in 1952 by Alfred Hershey and Martha Chase, which helped to confirm that DNA was the genetic material. While DNA had been known to biologists since 1869, a few scientists still assumed at the time that proteins carried the...
). In 1948 Hotchkiss used paper chromatography
Paper chromatography
Paper chromatography is an analytical chemistry technique for separating and identifying mixtures that are or can be colored, especially pigments. This can also be used in secondary or primary colors in ink experiments. This method has been largely replaced by thin layer chromatography, however it...
to quantify the base composition of DNA and, independently of Erwin Chargaff
Erwin Chargaff
Erwin Chargaff was an American biochemist who emigrated to the United States during the Nazi era. Through careful experimentation, Chargaff discovered two rules that helped lead to the discovery of the double helix structure of DNA...
, found that the base ratios differed from species to species.
In 1951, Hotchkiss showed that purified bacterial DNA could be used to transfer penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...
from one strain of bacteria to another without changing the capsule type (the main identifying feature of different types of the same bacterial species). His subsequent worked helped establish the basics of bacterial genetics, showing that many features of classical genetics (including genetic linkage
Genetic linkage
Genetic linkage is the tendency of certain loci or alleles to be inherited together. Genetic loci that are physically close to one another on the same chromosome tend to stay together during meiosis, and are thus genetically linked.-Background:...
) have parallels in bacteria, despite their lack of chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s. Hotchkiss continued working in molecular genetics until his retirement in 1982, including significant collaborations with Julius Marmur
Julius Marmur
Julius Marmur was an American molecular biologist who made significant contributions to DNA research. His discovery, while working in the laboratory of Paul Doty at Harvard University, that the denaturation of DNA was reversible and depended on salt- and GC-content, had a major impact on how...
, Maurice Fox, Alexander Tomasz, Joan Kent, Sanford Lacks, Elena Ottolenghi, and his wife Magda Gabor-Hotchkiss.
In the mid-1960s, Hotchkiss became interested in the potential dangers of genetic engineering
Genetic engineering
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...
(a term he helped to popularize). Through the early 1970s he articulated many of the concerns that led to the 1975 Asilomar Conference on Recombinant DNA
Asilomar Conference on Recombinant DNA
The Asilomar Conference on Recombinant DNA was an influential conference organized by Paul Berg discussing the potential biohazards and regulation of biotechnology held in February 1975 at a conference center Asilomar State Beach...
.
Hotchkiss was a member of the American Academy of Arts and Sciences
American Academy of Arts and Sciences
The American Academy of Arts and Sciences is an independent policy research center that conducts multidisciplinary studies of complex and emerging problems. The Academy’s elected members are leaders in the academic disciplines, the arts, business, and public affairs.James Bowdoin, John Adams, and...
and the National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
(elected in 1961), and served as president of the Genetics Society of America
Genetics Society of America
The Genetics Society of America is a scholarly membership society of more than 4000 genetics researchers and educators, established in 1931...
from 1971 to 1972. After leaving Rockefeller University in 1982, he worked as a research professor at the University at Albany, SUNY
University at Albany, SUNY
The State University of New York at Albany, also known as University at Albany, State University of New York, SUNY Albany or simply UAlbany, is a public university located in Albany, Guilderland, and East Greenbush, New York, United States; is the senior campus of the State University of New York ...
until retiring to Lenox
Lenox, Massachusetts
Lenox is a town in Berkshire County, Massachusetts, United States. Set in Western Massachusetts, it is part of the Pittsfield, Massachusetts Metropolitan Statistical Area. The population was 5,077 at the 2000 census. Where the town has a border with Stockbridge is the site of Tanglewood, summer...
, Massachusetts in 1986. Hotchkiss died December 12, 2004 of congestive heart failure.