JONES, WALTER JENNINGS

(b. Baltimore. Maryland, 28 April 1865; d. Baltimore, 28 February 1935)

biochemistry.

The thirteenth child of Levin Jones, a successful ship’s chandler, and of Zeanette jane Bohnen, Walter grew up in a devout and wealthy Methodist family. Educated at Baltimore City College and at Johns Hopkins University (A.B., 1888; Ph.D., 1891), he married Grace Crary Clarke on i September 1891; they had one daughter, Marion. After teaching at Wittenberg College in Springfield, Ohio (1891–1892) and at Purdue University (1892–1895), he began his lifelong professional association with Johns Hopkins. Ill health caused him to retire in 1927.

The major figure who determined Jones’s choice of research topics was Albrecht Kossel, an authority on nucleoproteins, under whom he worked during a seven-month period of study at Marburg in 1899. There, too, he came to know the nucleic acid chemist P. A. Levene, who was to become his rival and the acknowledged leader in his field in the United States.

In the 1890’s the relation of the nucleins (nucleoproteins) to other organophosphorus compounds and to the proteins was still unclear. Kossel hoped that the study of the breakdown products of the nucleins would furnish clarification. Among these products he had recognized the amino-purine bases adenine and guanine, and the corresponding oxypurine bases hypoxanthine and xanthine. He traced their source to the nucleic acid component of nuclein, as he did the pyrimidine bases thymine and cytosine. His conception of nucleic acid structure, however, was vague, and the precise identity of thymine uncertain. By the preparation of a bromine derivative of thymine, Jones, working in Marburg, was able to confirm Kossel’s opinion that it was distinct from the known 4-methyl uracil, with which it shared the same empirical formula.

After returning to Baltimore. Jones taught physiological chemistry and toxicology under the pharmacologist John Abel. From the establishment of the John Hopkins medical department in 1893 on, the importance of chemistry in the curriculum had been recognized. When physiological chemistry was established as an independent department in 1908, Jones became full professor. The confusion in the subject of nucleic acid chemistry and physiology attracted and held him in this field. His mission was to bring clarification, and this he did, though his claim in 1914 that “the nucleic acids constitute what is possibly the best understood field of Physiological Chemistry” was surely an overstatement. Levene at the Rockefeller Institute certainly considered that Jones had also added some confusion.

Jones’s chief contributions to physiological chemistry concerned the enzymatic and hydrolytic breakdown of the nucleic acids. It was by such studies that the nucleic acids. It was by such studies that the nucleic acids were shown to be built from four different nitrogenous bases—two purines and two pyrimidines—each base being attached to a sugar to constitute a “Nucleoside,” and each nucleoside being phosphorylated to constitute a “nucleotide”; all four were linked to produce a “tetranucleotide.” Although subsequent research showed that the nucleic acids were much larger than a tetranucleotide, this structure did embody the correct constituents in the right arrangement. Before the tetranucleotide was established, controversy continued as to whether the nucleic acids were mixtures of different mononucleotides or “polymers” of all of them (what we would call oligonucleotides). As a result of such controversy. much of the literature seems very confused to the modern reader.

Jones’s first contribution to clarification concerned the purine products of nucleic acid decomposition. He showed that the tissues contain deaminating enzymes that convert the guanine and adenine bases in nucleic acids into their corresponding oxypurines, xanthine and hypoxanthine. These bases were therefore secondary products of the degradation and not present as such in the nucleic acids. Jones’s next contribution concerned the products of the partial breakdown of yeast nucleic acid. He demonstrated the production of dinucleotides and of guanylic and adenylic acids. These acids were therefore constituent nucleotides of yeast nucleic acid. Guanylic acid was not an independent nucleic acid. These results supported Leven and Jacob’s opinion that the constituents of nucleic acid were nucleotides, the structure of each of which corresponded to that of inosinic acid. They showed that in the latter the phosphoric acid and the purine base hypoxanthine were linked through the pentose sugar ribose.

The manner of linkage of the nucleotides to each other in the nucleic acid molecule of yeast remained a subject of dispute until the late 1930’s. Levene, Robert Feulgen, and Jones supported different structures. The linkages involved were either (1) ribose-ribose, (2) phosphoric acid-phosphoric acid, or (3)phosphoric acid-ribose. In 1919 Leven concluded that all the links were between phosphoric acid and ribose, as in the structure accepted today. Jones, however, presented evidence first in favor of only ribose-ribose links, and later (in 1923) in favor of both ribose-ribose and ribose-phosphoric acid links (a structure that Levene had suggested in 1912 but later rejected). Testily, Levene wrote:

During the period when Jones believed in the existence of the cytosine-uracil dinucleotide, this formulation might have been warranted, but after Levene had shown in 1917 that the dinucleotide of Jones and Read consisted of a mixture of two mononucleotides….there was much less justification for referring to a structural scheme that had been abandoned earlier. (Nucleic Acids, pp. 274–275).

Perhaps the most intriguing of Jones’s enzymatic studies was that indicating the presence of an enzyme in an extract of pig pancreas that cleaved internucleotide bonds. Although Levene failed to confirm this observation, René Dubos and R. H. S. Thompson succeeded when they described an RNA depolymerase (RNase) in 1938.

The two most popular sources of nucleic acid were the thymus gland and yeast, hence the names for the two fundamental types: thymonucleic acid (DNA) and yeast nucleic acid (RNA). Jones, in common with other authorities, believed the former to be confined to animal tissues and the latter to plants. His study of the β nucleoprotein of the pancreas, however, caused him to change his opinion and conclude: “It thus seems more than probable that the distinction between animal and plant nucleic acids will in the future not be so definitely drawn.”

Jones accepted the identification of the sugar in thymonucleic acid as a hexose and in yeast nucleic acid as ribose. At one time he doubted that guanylic acid was present in thymonucleic acid, and he retained a skeptical view on the uracil found in yeast nucleic acid, for he suspected it was the product of the deamination of cytosine. But he accepted Levene’s assertion that both nucleic acids were constructed on the same general plan.

The state of analytical chemistry and the knowledge of extractive procedures in Jones’s day made the study of nucleic acid chemistry a difficult one. Jones was at times hasty and overconfident. Levene’s frequent criticisms of his work were to be expected. Always forthright, a gifted conversationalist, and an enthusiastic controversialist, Jones won wide respect. He was a member of the National Academy of Sciences and twice president of the American Society of Biological Chemists.

BIBLIOGRAPHY

I. Original Works. Jones and his co-workers published sixty-eight articles, the majority of them in the Journal of Biological Chemistry. Among them is “The Occurrence of Plant Nucleotides in Animal Tissue.” in Journal of Biological Chemistry, 62 (1924–1925), 291–300. with M. E. Perkins. As well as contributing to the literature of toxicology in his early days, Jones wrote Nucleic Acids: Their Chemical Properties and Physiological Conduct (London. 1914: 2nd ed., 1920).

II. Secondary Literature. The fullest account of Jones, with portrait and bibiography is William Mansfield Clark, “Walter (Jennings) Jones, 1865–1935.” in Biographical Memoirs, National Academy of Sciences, 20 (1939), 79–139. Clark also wrote an obituary of Jones in Science, n.s. 81 (1935), 307–308. His work is criticized in P. A. Levene, Nucleic Acids (New York. 1931).

Robert Olby