Alexander R. Todd
Chemist Alexander Todd researched the chemistry of nucleotides and was influential in synthesizing vitamins for commercial applications. For his work on nucleotides, he was awarded the 1957 Nobel Prize in chemistry.
Alexander Todd was awarded the 1957 Nobel Prize in chemistry for his work on the chemistry of nucleotides. He was also influential in synthesizing vitamins for commercial application. In addition, he invesitgated active ingredients in cannabis and hashish and helped develop efficient means of producing chemical weapons.
Alexander Robertus Todd was born in Glasgow, Scotland, on October 2, 1907, to Alexander and Jane Lowrie Todd. The family, consisting of Todd, his parents, his older sister and younger brother, was not well-to-do. Todd's autobiography, A Time to Remember, recalls how through hard work his parents rose to the lower middle class despite having no more than an elementary education, and how determined they were that their children should have an education at any cost.
In 1918 Todd gained admission to the Allan Glen's School in Glasgow, a science high school; his interest in chemistry, which first arose when he was given a chemistry set at the age of eight or nine, developed rapidly. On graduation, six years later, he at once entered the University of Glasgow instead of taking a recommended additional year at Allan Glen's. His father refused to sign an application for scholastic aid, saying it would be accepting charity; because of superior academic performance during the first year, though, Todd received a scholarship for the rest of course. In his final year at university, Todd did a thesis on the reaction of phosphorus pentachloride with ethyl tartrate and its diacetyl derivative under the direction of T. E. Patterson, resulting in his first publication.
After receiving his B.Sc. degree in chemistry with first-class honors in 1928, Todd was awarded a Carnegie research scholarship and stayed on for another year working for Patterson on optical rotatory dispersion. Deciding that this line of research was neither to his taste nor likely to be fruitful, he went to Germany to do graduate work at the University of Frankfurt am Main under Walther Borsche, studying natural products. Todd says that he preferred Jöns Berzelius's definition of organic chemistry as the chemistry of substances found in living organisms to Gmelin's definition of it as the chemistry of carbon compounds.
At Frankfurt he studied the chemistry of apocholic acid, one of the bile acids (compounds produced in the liver and having a structure related to that of cholesterol and the steroids). In 1931 he returned to England with his doctorate. He applied for and received an 1851 Exhibition Senior Studentship which allowed him to enter Oxford University to work under Robert Robinson, who would receive the Nobel Prize in chemistry in 1947. In order to ease some administrative difficulties, Todd enrolled in the doctoral program, which had only a research requirement; he received his D.Phil. from Oxford in 1934. His research at Oxford dealt first with the synthesis of several anthocyanins, the coloring matter of flowers, and then with a study of the red pigments from some molds.
After leaving Oxford, Todd went to the University of Edinburgh on a Medical Research Council grant to study the structure of vitamin B1 (thiamine, or the anti-beriberi vitamin). The appointment came about when George Barger, professor of medical chemistry at Edinburgh, sought Robinson's advice about working with B1. At that time, only a few milligrams of the substance were available, and Robinson suggested Todd because of his interest in natural products and his knowledge of microchemical techniques acquired in Germany. Although Todd and his team were beaten in the race to synthesize B1 by competing German and American groups, their synthesis was more elegant and better suited for industrial application. It was at Edinburgh that Todd met and became engaged to Alison Dale— daughter of Nobel Prize laureate Henry Hallett Dale —who was doing postgraduate research in the pharmacology department; they were married in January of 1937, shortly after Todd had moved to the Lister Institute where he was reader (or lecturer) in biochemistry. For the first time in his career, Todd was salaried and not dependent on grants or scholarships. In 1939 the Todds' son, Alexander, was born. Their first daughter, Helen, was born in 1941, and the second, Hilary, in 1945.
Toward the end of his stay at Edinburgh, Todd had begun to investigate the chemistry of vitamin E (a group of related compounds called tocopherols), which is an antioxidant—that is, it inhibits loss of electrons. He continued this line of research at the Lister Institute and also started an investigation of the active ingredients of the Cannabis sativa plant (marijuana) that showed that cannabinol, the major product isolated from the plant resin, was pharmacologically inactive.
In March of 1938, Todd and his wife made a long visit to the United States to investigate the offer of a position at California Institute of Technology. On returning to England with the idea that he would move to California, Todd was offered a professorship at Manchester which he accepted, becoming Sir Samuel Hall Professor of Chemistry and director of the chemical laboratories of the University of Manchester. At Manchester, Todd was able to continue his research with little interruption. During his first year there, he finished the work on vitamin E with the total synthesis of alpha-tocopherol and its analogs. Attempts to isolate and identify the active ingredients in cannabis resin failed because the separation procedures available at the time were inadequate; however, Todd's synthesis of cannabinol involved an intermediate, tetrahydrocannabinol (THC), that had an effect much like that of hashish on rabbits and suggested to him that the effects of hashish were due to one of the isomeric tetrahydrocannabinols. This view was later proven correct, but by others, because the outbreak of World War II forced Todd to abandon this line of research for work more directly related to the war.
As a member, and then chair, of the Chemical Committee, which was responsible for developing and producing chemical warfare agents, Todd developed an efficient method of producing diphenylamine chloroarsine (a sneeze gas), and designed a pilot plant for producing nitrogen mustards (blistering agents). He also had a group working on penicillin research and another trying to isolate and identify the "hatching factor" of the potato eelworm, a parasite that attacks potatoes.
Late in 1943 Todd was offered the chair in biochemistry at Cambridge University, which he refused. Shortly thereafter he was offered the chair in organic chemistry, which he accepted, choosing to affiliate with Christ's College. From 1963 to 1978, he served as master of the college. As professor of organic chemistry at Cambridge, Todd reorganized and revitalized the department and oversaw the modernization of the laboratories (they were still lighted by gas in 1944) and, eventually, the construction of a new laboratory building.
Before the war, his interest in vitamins and their mode of action had led Todd to start work on nucleosides and nucleotides. Nucleosides are compounds made up of a sugar (ribose or deoxyribose) linked to one of four heterocyclic (that is, containing rings with more than one kind of atom) nitrogen compounds derived either from purine (adenine and guanine) or pyrimidine (uracil and cytosine). When a phosphate group is attached to the sugar portion of the molecule, a nucleoside becomes a nucleotide. The nucleic acids (DNA and RNA), found in cell nuclei as constituents of the chromosomes, are chains of nucleotides. While still at Manchester, Todd had worked out techniques for synthesizing nucleosides and then attaching the phosphate group to them (a process called phosphorylating) to form nucleotides; later, at Cambridge, he worked out the structures of the nucleotides obtained by the degradation of nucleic acid and synthesized them. This information was a necessary prerequisite to James Watson and Francis Crick's formulation of the double-helix structure of DNA two years later.
Todd had found the nucleoside adenosine in some coenzymes, relatively small molecules that combine with a protein to form an enzyme, which can act as a catalyst for a particular biochemical process. He knew from his work with the B vitamins that B1 (thiamine), B 2 (riboflavin) and B3 (niacin) were essential components of coenzymes involved in respiration and oxygen utilization. By 1949 he had succeeded in synthesizing adenosine—a triumph in itself— and had gone on to synthesize adenosine di-and triphosphate (ADP and ATP). These compounds are nucleotides responsible for energy production and energy storage in muscles and in plants. In 1952, he established the structure of flavin adenine dinucleotide (FAD), a coenzyme involved in breaking down carbohydrates so that they can be oxidized, releasing energy for an organism to use. For his pioneering work on nucleotides and nucleotide enzymes, Todd was awarded the 1957 Nobel Prize in chemistry.
Todd collaborated with Dorothy Crowfoot Hodgkin in determining the structure of vitamin B12, the antipernicious anemia factor, which is necessary for the formation of red blood cells. Todd's chemical studies of the degradation products of B12 were crucial to Hodgkin's X-ray determination of the structure in 1955.
Another major field of research at Cambridge was the chemistry of the pigments in aphids. While at Oxford and working on the coloring matter from some fungi, Todd observed that although the pigments from fungi and from higher plants were all anthraquinone derivatives, the pattern of substitution around the anthraquinone ring differed in the two cases. Pigment from two different insects seemed to be of the fungal pattern and Todd wondered if these were derived from the insect or from symbiotic fungi they contained. At Cambridge he isolated several pigments from different kinds of aphids and found that they were complex quinones unrelated to anthraquinone. It was found, however, that they are probably the products of symbiotic fungi in the aphid.
In 1952 Todd became chairman of the advisory council on scientific policy to the British government, a post he held until 1964. He was knighted in 1954 by Queen Elizabeth II for distinguished service to the government. Named Baron Todd of Trumpington in 1962, he was made a member of the Order of Merit in 1977. In 1955 he became a foreign associate of the United States' National Academy of Sciences. He has traveled extensively and been a visiting professor at the University of Sydney (Australia), the California Institute of Technology, the Massachusetts Institute of Technology, the University of Chicago, and Notre Dame University.
A Fellow of the Royal Society since 1942, Todd served as its resident from 1975 to 1980. He increased the role of the society in advising the government on the scientific aspects of policy and strengthened its international relations. Extracts from his five anniversary addresses to the society dealing with these concerns are given as appendices to his autobiography. In the forward to his autobiography, Todd reports that in preparing biographical sketches of a number of members of the Royal Society he was struck by the lack of information available about their lives and careers and that this, in part, led him to write A Time to Remember.
Current Biography, H. W. Wilson, 1958, pp. 437-439.
Nobel Lectures Including Presentation Speeches and Laureate's Biographies—Chemistry: 1942-1962, Elsevier, 1964, pp. 519-538. □
Alexander R. Todd was born in Glasgow on October 2, 1907. His father was a businessman. Young Todd was educated at the Allan Glen School and Glasgow University. There he earned a B.S. and in 1928 left for the University of Frankfurt-am-Main, where he earned a Ph.D. in 1931 for his work on bile acids with W. Borsche. He returned to England that same year to study with Sir Robert Robinson; it was during this period that he completed very successful work on the colored materials of fruits, the anthocyanins. Todd journeyed home to Scotland in 1934 to join the staff of Edinburgh University. In 1938 he was appointed Sir Samuel Hall Professor of Chemistry and director of the Chemical Laboratories at the University of Manchester, posts he held until 1944. He then accepted a position as professor of organic chemistry at Cambridge University and became a fellow of Christ's College. He was named chancellor of the University of Strathclyde in 1975 and was a visiting professor at Hatfield Polytechnic until 1986.
The anthocyanin dyes that Todd researched while working with Robinson are important substances because they are part of the mechanism for protecting the plants' DNA from the deleterious effects of UV radiation during pollination and act as insect attractants during the pollination season. The structure for the red substance of cranberries is given in Figure 1.
While at Manchester, Todd began his work on nucleotides. These compounds are the structural units of the nucleic acids DNA and RNA . In 1949, while at Cambridge, he synthesized adenosine triphosphate (ATP; Figure 2) and later that same year flavin adenine dinucleotide (FAD). These nucleotides are the molecules that carry and transfer energy in virtually all living organisms. These discoveries are not only important in the elucidation of the energy transfer mechanisms, but they also set a precedent for the synthesis of nucleotides and the precursors of DNA and RNA. These accomplishments required the utmost skill in the art of organic synthesis because nucleotides are very difficult substances to prepare and characterize.
Todd also did significant work on the structure and synthesis of vitamin B12, vitamin E, and a number of alkaloids . The most noteworthy of these contributions was the elucidation of the structure of tetrahydrocannabinol (THC), the active component of marijuana.
Todd was named president of the Royal Academy in 1975. He was also a member of the National Academy of Sciences (USA), the American Academy of Arts and Sciences, and several prestigious European societies. Todd served as the chairman of the British government's advisory committee on scientific policy from 1952 until 1964. He was awarded the Nobel Prize in chemistry in 1957 for his work on nucleotides and nucleotide coenzyme studies. He was knighted in 1954 and died in 1997.
see also Nucleotide.
Lawrence H. Brannigan
Moore, Ruth (1961). The Coil of Life. New York: Knopf.