The Clayton Foundation Biochemical Institute
A Short History by Roger J. Williams

Published by The University of Texas at Austin, 1966
Cover and illustrations by Pauline G. West
(Edited by Donald R. Davis and Marvin L. Hackert, April 2001)

 

I

Introduction

This Institute, integrated with the Chemistry Department of The University of Texas, is of the date of this writing (1965) an association of eight principal investigators along with a substantial number of semi-independent and cooperative investigators and a large number of graduate and undergraduate students, technicians, secretaries and others who contribute in many diverse ways. The role of graduate students is important and the Institute accordingly performs a considerable educational as well as investigational function. The total present staff includes something less than 100 individuals.

The principal investigators are: David J. Cox, Ph.D. (1960) Pennsylvania; Robert E. Eakin, Ph.D. (1942) Texas; Boyd A. Hardesty, Ph.D. (1961) Cal. Tech.; Lester J. Reed, Ph.D. (1946) Illinois; William Shive, Ph.D. (1941) Texas; Alfred Taylor, Ph.D. (1935) Oregon State University (retiring Sept. 1965); Roger J. Williams, Ph.D. (1919) Chicago; and Daniel Ziegler, Ph.D. (1955) Loyola.

The principal investigators in the Institute are autonomous with respect to their own research activities. Since they have been selected on the basis of the appropriateness of their interests, they are free to operate as they wish; there is no disposition to guide or direct their efforts or to curtail or modify their thinking or the expression of their thoughts and opinions. By encouraging each investigator to make his own contributions and earn his own reputation, it has been possible to attract and keep able and highly productive individuals on the staff.

Each of the principal investigators, except Dr. Alfred Taylor whose training was primarily in zoology (physiology), has a professorial appointment in the Chemistry Department. One of the principal investigators, William Shive, is Chairman of the Chemistry Department. In addition to the tie with the Chemistry Department, the Institute has always enjoyed cordial cooperative relations with all related departments and schools in the University.

The policy of helping each independent investigator develop his own program has been successful in promoting their individual advancement. A notable example is one who is no longer on the staff, namely Professor Esmond E. Snell. He gained sufficient eminence in the Institute (1939-45 and 1951-56) to be given a professorship in his Alma Mater, Wisconsin, and later to be made chairman of the Department of Biochemistry at the University of California (Berkeley).

When I first came to the University of Texas in 1939, my research had temporary Rockefeller Foundation support. On Friday, September 13, 1940, Clayton Foundation support was received; the operation was designated an Institute and I served as director, with continuous Clayton Foundation support, from that time until September 1, 1963. This support has been given in a most satisfactory manner; members of the Institute have been able to devote the maximum of their effort to the work that interests them and a minimum to administrative details.

In September 1963, Lester J. Reed became in name and in fact director of the Institute. It is at his instigation and suggestion that this brief story of the Institute and its contributions is being written. It will perhaps serve as a 25-year report to the Clayton Foundation and to inform others of the nature of our objectives and past contributions.

The deepest roots of the Institute go back to the joint interest of Mr. Benjamin Clayton and myself in the fundamentals of the cancer problem. Fortunately there has never been a disagreement between the two of us with respect to (1) our mutual interest in the cancer problem (2) our recognition that the road to success in the cancer field may be a long one and (3) the paramount importance of a fundamental approach.

The situation with respect to cancer research may be compared to an imaginary one in which an unlettered inexperienced novice (or group of novices) sets out to repair a complex malfunctioning machine—a watch, an automobile, a radio or a television set. There are two general courses open: (1) to tinker with the machine, make changes here or there with little or no basic understanding, in the hope of stumbling quickly upon the cause of the malfunction; or (2) to take a longer and seemingly less direct course, that of first making a careful scientific study of the machinery in all its parts, before concentrating on a solution to the difficulty.

Cancer being as deep-seated as it is, and the machinery of living matter being as complicated as it is, we have been inclined, justifiably, to take the latter course. We have worked in the direction of learning more and more about the machinery considered to be "in order," as well as that which is obviously out of order, before seriously attempting to correct the malfunctioning involved in malignancy.

The analogy of repairing a malfunctioning machine is satisfactory as far as it goes, but a human organism is incomparably more complicated than any man-made machine. Even a single cell (our bodies are made up of trillions of these) is so complex, particularly as revealed in recent years by electron microscope studies, that it is quite impossible as yet even to name and describe all the working parts. At one time it was supposed that cancer was purely a cellular derangement and that the secret of malignancy lies embedded in the functioning of "the living cell." Now it seems certain that the obscure influences which control differentiation and the interrelationships between cells—the coordination of their activities—are involved.

It has become increasingly evident during the years while the Institute has been in operation that cancer is indeed a most fundamental disease process and not one that could be expected to yield to blind or nearly blind tinkering. A vast amount of background information was and still is essential to an intelligent approach to the disease. From this point of view a fundamental attack on the cancer problem is, in effect, an exploration in fundamental biochemistry.

Of course everyone concerned with the cancer problem would like to see a quick and happy solution, but without more basic understanding this is not likely to happen. There has never been exhibited in this Institute an impatient desire to get at the matter of an immediate cancer cure nor has there ever been a failure to recognize that any fundamental contribution to biochemistry and nutrition (which is, of course, one of the basic aspects of biochemistry) would inevitably be something of a step toward the ultimate solution of the cancer problem.

The approach we have followed has several advantages. First, we believe it will ultimately lead to treatment and prevention of cancer; second, it has made and now is making possible many other discoveries which may be of far-reaching importance; third, it has a tremendous psychological advantage in that investigators can exploit their intellectual curiosity and gain a feeling of accomplishment when they reach a milestone (even though there may be many milestones of many different sizes and shapes). Any investigator who makes a pointed effort to find a cancer cure is likely to develop after a decade or two of failure a feeling of futility and frustration.

There is nothing more fundamental in biochemistry than the amino acids, proteins, minerals, lipids, carbohydrates, vitamins, coenzymes, enzyme complexes, hormones, nucleic acids, viruses, genes and other fundamental units that enter into the machinery of living things. All of these are involved in the cancer problem in a highly significant way, and anyone who contributes to scientific knowledge about any one of these is making a potential contribution to the cancer problem as well as to the understanding of all diseases associated with the malfunctioning of cells. Parenthetically, I believe this includes all diseases.

There is nothing in our history that would imply that our Institute’s objectives must, in perpetuity or even for a stated period, be centered upon any specific disease or upon any particular approach. It is my hope and expectation that the direction which investigators will take 10 or 20 years from now will be determined by the investigators who from their respective vantage points will be free to use their own best judgments.

Before listing some of the contributions of this Institute, it is desirable to clarify further some fundamental attitudes which have prevailed.

We have consistently promoted independent thinking on the part of members of the Institute. It follows therefore that there can never be in this Institute such a thing as a settled orthodox credo or point of view on which all must agree. There is, in my opinion, no place for orthodoxy in science.

This conviction is based partly on past experience. I am inclined toward the view that whenever a committee of scientists, an editorial board, a review panel, or what not, attempts to settle a scientific question, they are not only liable to be wrong as to the settlement, but they are making a basic mistake. They overlook the truth in Orville Wright’s saying, "If we all worked on the assumption that what is accepted as true is really true, there would be little hope of advance."

I have personally witnessed in the field of biochemistry two far-reaching examples of "settled" points of view which have had to be shortly abandoned. Other such abandonments are in the offing.

As a beginner in research I became interested in the possible role of vitamins in the nutrition of yeast cells. After I had been investigating this area several years intermittently without signal success, I received a friendly letter from a very prominent investigator—an editor—advising me that to investigate vitamins one must work with the nutrition of animals, not with yeast. He urged me as a young man not to waste my efforts. This was the orthodox settled view at the time. In the light of subsequent developments involving now a generation when most of the findings about vitamins have been and are being made using microorganisms, such a view seems ridiculous.

Another abandonment of orthodoxy has taken place in the field of cancer. Based partly on findings in our laboratory and partly on the extensive investigations of Duran-Reynals, both Dr. Taylor and I became convinced in the early 1940’s that in all probability virus-like agents were involved in the production of substantially all cancers. In 1944 I took part in a symposium at Atlantic City where I expounded this view. Dr. Vincent du Vigneaud was the presiding officer and was kind enough to remind the audience that since I had been right in anticipating the vitamin status of pantothenic acid, I quite possibly might be right in my opinion that viruses were involved in the production of cancers. But this was an unorthodox view and was discredited by most cancer investigators for at least a decade. Now it is generally accepted. No one should quarrel with the need for conclusive evidence—this was not on hand at the time of the Atlantic City symposium—but one may quarrel quite justifiably with the thought tenaciously held for many years that the question of the virus origin of cancer had been settled in the negative.

What seems unorthodox at one time may be quite proper and respectable at a later date. This has happened repeatedly and will continue to happen. To appreciate all the major contributions of the Institute, it is essential that this unorthodox respectability process be recognized, because some of the more important contributions of the Institute have been in the realm of advanced ideas, and these do not always find a quick roosting place in scientists’ minds. It is of course possible that some of the contributions which I would regard as important may never gain respectability. It is the inalienable right of every investigator and thinker to be wrong part of the time. Even ideas which turn out to be erroneous, however, do have value if they provoke thought and stimulate investigation.

Some concept of the work carried on in the Clayton Foundation Biochemical Institute can be gained by perusing the appended titles of the approximately 700 scientific articles (and books) that have been published during its operation. The articles are in most instances technical in nature, and represent the efforts of nearly 300 investigators who are the authors and coauthors. To all of these much credit is due. These citations alone, however, do not fulfill the purpose of this record; to supplement them I have run the risk of selecting what I regard as the more outstanding and provocative contributions and commenting briefly on some of these.

Since it is expected that the material in this short history will be of interest to others than trained biochemists, I have discussed more fully the contributions that are of some general interest and have abbreviated or omitted discussions related to more highly technical contributions. The treatment of topics is thus necessarily uneven. Certainly the importance of a contribution should not be judged on the basis of the space given to its discussion.

It should be understood that if Dr. Reed or any of my other colleagues were to select for discussion the outstanding contributions of the Institute, the selections would be different from mine. The published papers speak for themselves to the many who have read or will read them. My selected contributions will be grouped according to their nature and considered without regard for strict chronology. The grouping must be imperfect since some contributions do not fit into any single pigeon hole.

 

II

Contributions Related Primarily to the B Vitamins and Closely Related Substances

1. Determination of structure and synthesis of pantothenic acid. The discovery of this vitamin took place before the Institute was founded, but its structure was announced jointly from the University of Texas and the Merck Laboratories in 1940 (Publ. 3), and it was synthesized with high yield in the laboratories of this Institute at that time.

2. Clearing up of the vexing "bios" problem (Publ. 17). This had presented an enigma for about 40 years.

3. Development and application of microbiological assay methods for riboflavin, pantothenic acid, biotin, nicotinic acid, pyridoxin, inositol, thiamin, folic acid (the vitamin needed to cure the typical nutritional macrocytic anemias) (Publs. 11, 24, 29, 30, 31, 32, 33, 34, 35, 36) and later the anti-pernicious anemia factor (vitamin B12) (Publs. 197, 220), and lipoic acid (Publs. 160, 161, 242).

The use of microbiological assays in the Institute laboratories has been of outstanding importance. Up to March 1952 at least 36 different microbiological assays had been developed and used in addition to those for most of the protein-derived amino acids. A few of these assays proved to be spurious, some were abandoned without complete investigation, but many of them turned out to be assays for new vitamin-like substances or for metabolites of unusual interest.

4. Establishment of the cause of (raw) "egg white injury" in experimental animals and the discovery, purification, and crystallization of avidin (Publs. 4, 15, 19, 20, 45).

5. Extensive studies on the distribution of B vitamins in tissues and foods. From these it was first deduced that B vitamins are to be found in all living cells, findings which contributed considerable strength to the concepts then developing and currently accepted concerning the "unity in biochemistry" of all living organisms. (Publs. 37, 60-70).

6. The finding that each type of mammalian tissue, whether from rats, mouse or human, tends to have a characteristic pattern with respect to its content of the various B vitamins (Publs. 62, 63).

7. Isolation of "folic acid" from spinach. We gave this vitamin its name because of its relative abundance in leaves (Latin—folium—leaf). Thirty tons of spinach were processed and samples of highly concentrated folic acid were furnished upon request to 150 or more laboratories throughout the world. This distribution was made possible by a specific Federal grant (Publs. 21, 91, 102).

8. Further contributions relating to pantothenic acid.

(a) In chick "dermatitis" (pantothenic acid deficiency) in which the readily observable symptoms are those where skin and feathers are conspicuously affected, we found general impairment of muscles, kidneys, liver, brain, etc. in spite of the absence of any conspicuous lesions in these tissues (Publ. 12).

(b) Human muscle (the most abundant tissue) was found to be over twice as rich in pantothenic acid as beef, swine or sheep muscle. The ratio of pantothenic acid content to thiamin content is about three times as high in human milk as in cows’ milk. Mouse milk (very rich in B vitamins) contains 60 times as much thiamin as human milk but only 15 times as much pantothenate (Publs. 63, 69, 70). The relative abundance of pantothenic acid in human muscle and in human milk suggests, on the assumption that all this pantothenic acid has an exogenous origin, that human pantothenic acid deficiency is, a priori, not improbable.

(c) Pantoyltaurine, the first pantothenic acid antagonist was synthesized (Publ. 25).

(d) When hens and pregnant rats and mice were fed additional pantothenate, the hatchability of the eggs increased and the litter sizes of the rats and mice increased (Publs. 27, 89).

(e) Extra pantothenate (added to a supposedly wholly adequate diet) increased the longevity of mice significantly by 19 per cent (Publ. 551).

(f) Pantothenyl alcohol was synthesized (Publ. 125).

(g) Our Institute collaborated with F. Lipmann to show for the first time the presence of pantothenic acid in coenzyme A (Publ. 176).

(h) Identification of the Lactobacillus bulgaricus factor as pantethine (Publ. 291).

9. The discovery of pyridoxal and pyridoxamine, the metabolically active forms of vitamin B6, and their mode of functioning in metabolism. This monumental and highly technical work merits especial emphasis because of the quality and quantity of the work involved (Publs. 115, 117, 121, 122, 123, 124, 128, et seq.).

10. The isolation of vitamin B12 (using assay methods developed in our Institute) from liver preparations used in treating pernicious anemia (Publs. 197, 220). Priority on this contribution cannot be claimed by our Institute because a commercial firm having many times our manpower resources produced the same compound five months earlier. They used an assay method developed at the University of Maryland.

11. Patented process for producing vitamin B12. This, like the pantothenic acid patents, brought into the Institute a substantial supplement to its other funds (U.S. Patent 2,628,186, 1953).

12. The isolation, determination of structure and synthesis of lipoic acid (acetate replacing factor, pyruvate oxidation factor, protogen) with the collaboration of Professor I. C. Gunsalus of the University of Illinois and Eli Lilly and Co. (Publs. 234, 244, 278, 317, 319). By that time (1951) this vitamin-like substance had been investigated intensively in our laboratory for about five years and its isolation was a culmination of this work.

 

III

Contributions Related Specifically to Cancer

13. Cancers from different species (rat, mouse, human) regardless of tissue of origin, and whether spontaneous or artificially induced, were found to have a resemblance to each other, so far as the content and distribution of B vitamins are concerned. (Publ. 64).

14. The finding that folic acid tends to be in relatively high concentration in cancer tissue (from rats, mice and human) whereas other B vitamins tend to be low. This finding was to have far-reaching effects in other laboratories where many folic acid analogs and presumed antagonists were explored with substantial success and found to be useful agents to combat some forms of cancer, notably leukemia. (Publs. 64, 150, 74-78).

15. The finding that the injection of various individual B vitamins into developing eggs may cause the embryos to develop into abnormally large chicks, or it may inhibit their growth, or it may cause the formation of deformed chicks. (Publ.27).

16. Technique of cultivating cancers in the yolk sac of chick embryos. (Publs.51,96, 114,200,328).

17. Lowered hemoglobin levels associated with cancer growth. (Publs.46,97,145).

18. Evidence for the virus etiology of mammalian cancers. (Publs.80, 118,137,139, 167,170,207).

The literature on this subject is voluminous. Dr. Taylor (Publ. 80) produced mammalian cancers by injecting cell-free material but could not obtain such results regularly and consistently, for reasons which are not wholly obscure in the light of present knowledge. The most conclusive evidence he obtained in support of the cancer-virus idea was the repeated production, by the use of one type of cancer-derived material, of many different types of cancers, entirely different histologically from the original cancer from which the cancer-inducing material was derived. This included intraocular cancers in rats produced by administering mouse material. It is difficult to explain these results, which were obtained dozens of times, on any basis other than the presence of virus-like infective agents.

 

IV

Contributions Related to the Composition, Structure and Functioning of Living Cells, Including Enzyme Studies

19. Protein structure is of paramount importance in biochemistry. The first microbiological determinations of amino acids derived from proteins (Publ. 110) were carried out in our laboratories and these were destined to be widely used in fundamental investigations.

20. Ascending paper chromatography was first used and developed in our laboratory (Publ. 182). This is a widely used tool for fundamental studies.

21. The development and application of competitive analog-metabolite techniques (inhibition analysis) for studying metabolic transformations and the mechanisms involved (Publs. 155, 156, 157, 158, 166, 179, 186, 191,220, et seq.). These pioneering studies have been progressively highly productive in many directions, including the elucidation of biological control mechanisms. Many of the contributions are highly technical and cannot well be discussed here.

22. The initial discovery that biotin functions by participating in processes involving carboxylations (Publ. 180).

23. Identification of 5(4)-amino-4(5)-imidazolecarboxamide as a metabolite and a precursor of purines. (Publ.178).

24. Discovery of formyl folic acid, a functional derivative of folic acid (Publ.189).

25. The isolation of thymidine from liver extracts used in the treatment of pernicious anemia, and the demonstration of its important relationships to vitamin B12 and nucleic acid metabolism (Publ.197).

26. Functional interrelationships between purines and vitamin B12 (Publ.199).

27. Erythein and apoerythein and their relationship to vitamin B12 and to the intrinsic and extrinsic factors which cure pernicious anemia. (Publ.212).

28. Discovery of folinic acids and their first chemical syntheses. (Publ. 211).

29. Widespread investigations (see above items 3, 21, 23, 24, 25, 26, 28) yielded many of the important clues as to how nucleic acids are built up in living organisms. This information is invaluable in the light of recent investigations in the area of biochemical genetics and for understanding normal and pathological growth and development.

30. Isolation and identification of a "cabbage juice factor" as the methylsulfonium derivative of methionine (Publ. 357).

31. Arginosuccinic acid was discovered and identified independently in the Institute laboratories (Publs. 273, 345) but this finding was anticipated in New York by Dr. Sarah Ratner.

32. Discovery of glutamine as an agent which reverses the toxicity of alcohol for microorganisms (Publ. 382), reduces the voluntary consumption of alcohol by rats (Publ. 403); and the finding that this compound appears to be for some human individuals highly effective in reducing their appetite for alcohol (Publs. 464, 686).

33. Contributions to biogeochemistry and to the problem of what chemical elements find usefulness in living matter. (Publ. 574).

34. The discovery of a group of unique enzymes belonging in the general group of oxygenases (Publs. 670, 678, 679). These are essential for the detoxification by the liver of certain harmful nitrogenous compounds which would otherwise accumulate, and for the inactivation of certain hormones and hormone-like substances which are produced by other tissues. This production of certain substances by one tissue and their inactivation by another is one of the delicate control mechanisms in highly organized types of life.

Other enzymes of this group are essential for the building and degradation of sterols and steroids (adrenal, ovarian and testicular hormones) including cholesterol. The building of cholesterol in the body is an essential process during growth. The continued synthesis of cholesterol in adults can be excessive and unless the mechanisms for degrading it to bile acids keep pace, blood vessel disorders may develop in one’s heart, brain, kidneys and elsewhere. Knowledge about these new enzymes is not only basic, it is of the utmost importance in the understanding of and designing of therapeutic controls for a number of metabolic disorders associated with "hardening of the arteries."

35. Possibly the most elegant work contributed by our Institute is that dealing with the multienzyme units—the pyruvate dehydrogenase complex and the a-ketoglutarate dehydrogenase complex. (Publs. 570, 571,572, 628, 666, 684, 688, 694). The make-up of these units (each is distinctive) may be illustrated by the case of the pyruvate dehydrogenase complex which has a molecular weight of about 4.8 million and has in it 42 molecules of enzymes of three different kinds. One type of enzyme has thiamin in it, another has lipoic acid, and another riboflavin.

These multienzyme units have both been obtained in a highly purified state and electron microscope pictures show that they are made up of many subunits clustered together according to a fixed closely fitting pattern. By suitable mild treatment the cluster can be partially or wholly dissociated, and electron microscope pictures of the "pieces" have confirmed that this takes place. Each individual enzyme, however, retains its own particular activity.

Most remarkable of all is the fact that when these individual enzymes are put together in the same solution in the proper proportions under suitable conditions they "fall together" naturally to produce the original multienzyme unit, which functions as originally and which, according to electron microscope pictures, has the same cluster structure as that originally observed before the complex was dissociated.

The implications of these findings which involve multienzyme units from bacterial cells and beef kidney cells, are far-reaching. As a result of these clear-cut demonstrations, it seems highly probable that living cells instead of being bags full of an assortment of enzymes, are highly organized in many particulars and that the enzymes are associated together in a particular way so as to make the machinery of the cell work.

These investigations are a follow-up of the isolation and synthesis of lipoic acid (item 12 above) and constitute an important contribution to our knowledge of how the biochemical machinery of cells operates. It will serve as a model for many later investigations.

 

V

The Problem of the Origin of Life

36. Evolution of Metabolism (Publ. 659). This paper, in which the author has outlined in considerable detail how the beginnings of metabolism probably antedated by millions of years the beginning of "life" on earth, has received, in terms of requests for reprints, far more attention than any other publication arising out of Institute studies during the 25 years of its existence. It is a publication of great originality and is thoroughly modern in its approach and incorporates keenest biochemical insight.

 

VI

The Problem of Differentiation

37. Before the mid 1950’s there were so many gaps in our knowledge about what goes on within each living cell that it was difficult or impossible to study biochemically what goes on between the cells. Our contributions related to vitamin B12, lipoic acid and the building of nucleic acids helped to fill in these gaps.

About 1955 one of our members seriously attacked the problem of differentiation. This problem is set forth by a consideration of the following facts: Single fertilized egg cells—these are the starting point for every human being and for every mammal—are similar in general make-up to that of a single-celled organism. However, they are also vastly different. When a single-celled organism is in a favorable environment it replicates or copies itself; that is, it produces successively more single-celled organisms just like the original. When, however, a mammalian fertilized egg cell produces "offspring," at first they resemble the parent cell, but the offspring eventually become vastly different in size, shape, composition and function. To illustrate extreme differences in size, some human cells are little pellets about 5 microns in diameter (a micron is 1/25,000of an inch) while some other cells (motor nerve) may be150,000 times this long (30 inches).

The process of becoming successively different after a number of cell generations is called differentiation and takes place in all many-celled organisms, plant and animal. The factors which control what types of cells are produced and how many of each are almost completely unknown. One striking fact is that the cells produced from a human fertilized egg cell are all human cells with the human quota of chromosomes and genes. How this can happen is as yet mysterious. One reason for wishing to understand it better is because when cancer cells develop, there is evidence that the normal control mechanisms have become impaired, and it would be of the greatest help in dealing with cancer if we knew about the basic mechanism and the kind of impairment that develops when the disease takes hold.

The kinds of organisms used by investigators in our laboratories for the study of differentiation include: (1) simple multicellular plants—molds and mosses—in which only a few different kinds of cells are produced; (2) primitive invertebrates, hydra and planarian worms (flat worms) which can in a short time regenerate new parts if these are cut away—embryonic (undifferentiated) cells remaining within these organisms are caused, as a result of the cutting, to differentiate and restore the missing parts; (3) tadpoles whose vital organs during their normal metamorphosis undergo a drastic revision of their biochemical, physiological, and morphological constitution (they change from a vegetarian-fishlike creature to a carnivorous-terrestrial animal); (4) chick embryos in which development can be studied and altered by the use of specific chemicals.

The findings so far may be briefly outlined: In molds and mosses, chemicals naturally produced by the organisms, as well as synthetic products which resemble them, can markedly affect development, and often their effects depend on their presence at precisely the right stage of development.

In hydra and planaria both the rate and the normalcy of regeneration of the several parts can be altered (and even monstrosities produced) by specific chemical agents. The actions of these compounds are probably fundamentally like those of carcinogens (cancer-producing substances).

In tadpoles at about the mid-point of metamorphosis the synthesis of new ribonucleic acids and deoxyribonucleic acid derivatives takes place first, at a time interval considerably before the enzymes are developed to change the nitrogenous excretion product of tadpoles (ammonia) into urea, the product excreted by adult frogs. During the last portion of the metamorphosis period, the carbohydrate-splitting enzyme—a-amylase—becomes relatively inactive. This is appropriate because of the organism’s change in diet. Agents which speed up metamorphosis (e.g. thyroxin) and those which slow it down (e.g. thiouracil) affect the enzyme changes just as they do the anatomical changes.

In developing chick embryos (where a large part of the differentiation occurs during the first five days) it was found first that the idea of Needham, the famous English embryologist, that ammonia excretion takes place first during embryonic development is in error even though it had been accepted for at least twenty years; secondly, that no dramatic changes, qualitative or quantitative, take place in the ribonucleic acid composition of neural tissues, paralleling the sudden appearance of electrical activity (electroencephalograms, brain waves) when the chick embryo brain becomes functional; and thirdly, four different and chemically unrelated compounds (oral carcinogens) affect the proliferation and morphology of liver cells in developing chick embryos and at the same time induce biochemical changes related to nucleic acid metabolism. These changes occur only during the last 5-10 days of the normal 21 day hatching period. The contributions dealing with the subject of development and differentiation include Publs. 422, 436, 461, 462,468, 469, 474, 475, 496, 497, 531, 532, 539, 553, 575,580, 584, 585, 615, 616, 617, 618, 619, 620, and 634.

The process of differentiation is of great interest for many reasons, including those suggested under items 41and 42 in this text. Two closely related animals (or human beings) which have about the same chromosomes and gene patterns may nevertheless have highly distinctive endocrine patterns because the unknown factors which control differentiation may allow in one case the development of a large and active thyroid gland(for instance) and in another a small one.

The subject of differentiation is like a new biochemical continent which is just beginning to be explored.

 

VII

Contributions Related Primarily to the Broad Applications of Biochemistry

38. We first attacked the problem of the etiology of alcoholism on the hypothesis that it was based upon the interplay between hereditary and environmental influences (Publ. 172). Ensuing investigations led to the publication of a book "Nutrition and Alcoholism" (Publ.239) which was superseded by "Alcoholism: The Nutritional Approach," (Publ. 533) (See also item 32).The ideas set forth in these books are based upon the broader concept of nutrition discussed under item 42, and upon the genetotrophic principle (item 39). In October 1964 the Institute co-sponsored with the Christopher D. Smithers Foundation a symposium in New York on Biochemical and Nutritional Aspects of Alcoholism. A 93-page report of this was published in1965. (Publs. 685-7).

39. The genetotrophic principle (viz., the nutrition of any organism depends upon its genetic background) and the concept of genetotrophic disease (Publs. 203, 213, 222, 225, 354, 406). This latter concept is that disease can result from the failure of any organism to obtain sufficient supply of the nutritional needs peculiar to that organism. Human individuals (who have different genetic backgrounds) must have at least slightly different nutritional needs (quantitatively considered). Nutritional deficiency and disease can therefore result in one individual but not in another even though they consume identical food. Though alcoholism is thought to be an example of a genetotrophic disease, the concept is much broader and its validity does not rest upon its applicability to any specific disease.

40. Exploration of individual metabolic patterns and their relationship to human diseases. (Publs. 246-267, 306, 405, 451).

41. Biochemical individuality. Contributions related to this topic have been (1) in the realm of ideas, (2) in investigations (see, for example, item 40 above) and (3) in collection of material and the publication of a book on the subject (Publ. 414). The basic idea which we have contributed is that since evidence indicates that every individual has his own inborn metabolic characteristics, every application of biochemistry to human beings must take these differences into account, particularly so since the differences between so-called normal individuals often turn out, unexpectedly, to be very large.

Since one of the important objectives of studying biochemistry is to gain the knowledge it may disclose concerning human health and disease, the phenomenon of biochemical individuality should become incorporated into all aspects of the discipline. It should be treated neither as an undesirable "fly in the ointment," nor as a trifling detail.

According to concepts arising directly out of this study, all diseases, including those such as cancer, arthritis, heart disease, alcoholism, schizophrenia and even to a lesser degree infectious diseases, have genetic roots and are related to biochemical individuality. The entire study of pathology is certain to change because of this concept. The knowledge about the genetic roots of disease does not by any means close the door to environmental treatment. Indeed a study of biochemical individuality opens the door to recognizing in advance the disease proneness of individuals (Publ. 591), and the possibility of preventing the diseases, whatever they may be, from taking hold.

42. A Broader concept of nutrition. This contribution in the realm of ideas is based upon many laboratory findings of diverse nature (see above items 5, 6, 8, 15, 21,29, 32, 37, 38, 39, 40, 41). It is particularly worthy of attention and emphasis in the writer’s opinion, because applied nutrition at the expert level has remarkable potential and has in general been badly neglected by medical science.

This broader view involves the recognition of the following facts: (1) Cells of all sorts (yeast, bacterial, protozoal, mammalian) are capable of being nourished at many levels of efficiency—the environmental medium may be so deficient as barely to maintain life; it may be of such high quality as to make for maximum well-being or it may be at any point between these two extremes. (2) Satisfactory mammalian nutrition is necessary for every cell and tissue, not merely for "the body as a whole" (The nutrition of human beings studied without cellular perspective is like anatomy studied without recognizing the existence of microscopic anatomy). (3) Different types of body cells have distinctive and different nutritional requirements as has been demonstrated by tissue culture experiments. (4) There are specific nutrients which are required by some somatic cells and not others and not by the body as a whole. Glutamine is one clear-cut example; inositol and lipoic acid may be others. As a consequence of this, the existence of intercellular nutritional symbiosis (the production of specific nutrients by some cells and the requirement of these same nutrients by other cells) must be recognized. This requires extensive exploration. (5) For genetic reasons the nutritional needs of individual human beings(for their bodies as a whole and for their individual cells and tissue) cannot be identical. Actually in many cases they appear to be highly diverse.

This view of nutrition gives quite a different outlook on the prevalence and character of nutritional deficiency. In the medical field nutritional deficiency has traditionally been associated with specific deficiency diseases: scurvy, beri-beri, rickets, pellagra and the like. Our experiments with pantothenic acid deficiency (8 above) showed clearly that impairment in many tissues can take place without overt lesions. In later studies (Publ. 407) we found that baby chicks show nutritional deficiency by decreased growth and lowered food efficiency, as early as 18 hours after they begin eating, if the diet lacks a needed nutrient. This is long before a deficiency disease, in the usual sense, has had time to develop.

We regard identification of human nutritional deficiency with the presence of the symptoms of a recognized deficiency disease as an extremely circumscribed view. We cannot dismiss human pantothenic acid deficiency, for example, as non-existent or unworthy of consideration.

According to the broader view of nutrition, the following are among the effects of nutritional deficiency: (1) decreased growth of young; (2) decreased reproductive ability (see item 8); (3) decreased length of life (item 8); (4) decreased stamina; (5) decreased vigor as evidenced by loss of physical activity and playfulness; (6) decreased food efficiency; (7) impaired appetite; (8) impaired "body wisdom" with respect to food choices (deficient animals consume by choice more sugar and more alcohol than well nourished animals); (9) loss of learning ability;(10) loss of memory, and probably many other losses. None of the above effects is associated with any easily recognized lesions in any specific tissue; yet every one may be highly important in the realm of human health and well-being. The incidence of such human nutritional impairments may be high.

The broader view of nutrition also encompasses the possibility that individuality in nutrition may be highly significant. Many observations of a miscellaneous nature have been made—many by me personally—which suggest this. For example, oral riboflavin intake in some cases dramatically abolishes extreme sensitivity to light; vitamin A in some cases greatly benefits respiratory difficulties, psoriasis and acne; oral pantothenic acid similarly may benefit allergies or constipation or partially restore the color of grey hair or restore failing memory; nutritional supplements, such as have been recommended in the treatment of alcoholism, have in individual cases relieved headaches, insomnia, high blood pressure, addiction to barbiturates, and surprisingly have rendered innocuous extremely malodorous feet; ascorbic acid in larger than usual doses may in some cases relieve serious difficulties with teeth and gums; oral thiamin has been known to restore in part the color of grey hair or to relieve eyestrain; niacin may relieve arthritic pain; individual amino acid deficiencies may in some individual cases induce personality deterioration, in others loss of mental acuity and in others serious impairment of and loss of teeth; oral glutamine, according to the work of Dr. Shive and his medical collaborators, hastens in some individuals the healing of peptic ulcers. In some of the above miscellaneous cases it seems clear that only certain individuals are affected.

While some of the above observations may be manifestations of the placebo effect (suggestion), many of the results were dramatic or entirely unexpected and in a number of cases well-qualified critical scientists or physicians were involved. The fact that such results as these are obtained inconsistently and have no statistical validity is in line with the possible importance of individuality in nutrition.

Another observation which points to the importance of individuality in nutrition is the well-known but little considered fact that some individuals (the late Winston Churchill is a notable example) can violate all general rules about eating and drinking and yet live magnificently to old age.

This broader concept of nutrition which has developed in our Institute is, I believe, far too little understood. Further information may be found in Publs. 410, 593, 626, 627, and 699.

43. Various attempts have been made in our laboratories to determine the biochemical peculiarities that reside in potential alcoholics and are associated with their vulnerability (Publs. 230, 508, 518, 592). The recent study of Siegel and co-workers (Publs. 672, 673) is probably the most meaningful of these, and strongly suggests that the goal is an attainable one provided the plasma amino acid (and other) patterns are carefully studied and subjected to discriminate analysis using highs peed computers.

 

VIII

Exploration in the Future

There is no disposition on my part to place the "dead hand of the past" on the Institute or to outline its future activities. That there is enormous room for developments may be appreciated by a consideration of such subjects as differentiation (item 37), the broader concept of nutrition (item 42), and also the following facts:

(a) We have merely begun to get detailed information about the structure and functioning of living cells.(b) Though striking advances have been made in the elucidation of the mechanisms of inheritance in single-celled organisms (where only replication is involved), biochemical genetics as it applies to mammals and other multicellular organisms (in which differentiation is crucial, indispensable and highly determinative), is still in a dense fog. (c) We are almost totally ignorant as yet as to how hormones work biochemically. (d) A bridge between biochemistry and psychology is, for the most part, yet to be built.

 

IX

Present Interests of Members of the Institute

David J. Cox. Dr. Cox’s interests lie in the field of the physical chemistry of macromolecules (particularly proteins) and the use of peptide models in the study of their structure. In the past decade it has become increasingly evident that proteins, as they occur in living systems, are not merely chains of amino acid residues but are organized so as to have definite spatial structures and interrelationships. Such studies are essential if we are to understand the workings of the machinery of living matter.

Robert E. Eakin. Dr. Eakin’s interest is indicated in the discussion of differentiation given under item 37. He is also concerned with the biochemistry associated with the origin and development of life on this planet.

Boyd A. Hardesty. Dr. Hardesty’s long term objective is to investigate the difficult but very basic problem of how protein synthesis is controlled in living organisms. Understanding these mechanisms would contribute immeasurably to our insight into the problems of differentiation and cancer with which protein synthesis is intimately associated. Already Dr. Hardesty and his co-workers using a sophisticated approach have made important steps toward the refinement and exploration of protein synthesizing cell-free systems. The results of some of this work will shortly be published.

Lester J. Reed. Dr. Reed’s present research interests are suggested by his leadership in the investigation of lipoic acid (item 12) and the multienzyme units (item 35).

William Shive. Dr. Shive’s research interests are suggested by the many important contributions made by him and his associates in the areas of intermediary metabolism, biological control systems, the relation between chemical structure and biological activity, and inhibition analysis. See particularly items 10, 11, 22, 23, 24, 25, 26, 28, 29, 30 and 32.

Roger J. Williams. My present interests lie largely along lines suggested by the discussion under item 42—a broader concept of nutrition. In addition we are interested in the fundamental problem of sleep—what is accomplished biochemically when we sleep. This involves pioneering exploratory work; it is much too early for a biochemical theory of sleep. One of the reasons for being interested in this field is because of the tremendous inter-individual variation in sleep patterns, which must be based on biochemical individuality. Sleep is a problem for many people and we need to understand the basic facts upon which the need for sleep rests.

Daniel M. Ziegler. Dr. Ziegler’s interests are in part revealed by the discussion under item 34. One of his longer range objectives is to contribute to our knowledge of how hormones function biochemically.

Publication List

(Arranged Chronologically by Year)

1. Snell, E. E., and R. J. Williams, Biotin as a Growth Factor for the Butyl Alcohol Producing Anaerobes, J. Am. Chem. Soc., 61, 3594 (1939).

2. Snell, E. E., R. E. Eakin, and R. J. Williams, A Quantitative Test for Biotin and Observations Regarding Its Occurrence and Properties, J. Am. Chem. Soc., 62, 175–8 (1940).

3. Williams, R. J., and R. T. Major, The Structure of Pantothenic Acid, Science, 91, 246 (1940).

4. Eakin, R. E., W. A. McKinley, and R. J. Williams, Egg-White Injury in Chicks and Its Relationship to a Deficiency of Vitamin H (Biotin), Science, 92, 224–5 (1940).

5. Mitchell, H. K., H. H. Weinstock, E. E. Snell, S. R. Stanbery, and R. J. Williams, Pantothenic Acid. V. Evidence for Structure of Non-beta-Alanine Portion, J. Am. Chem. Soc., 62, 1776–9 (1940).

6. Zschiesche, E., and H. K. Mitchell, Pantothenic and Hydroxypantothenic Acids in Animal Nutrition, Proc. Soc. Expt. Biol. Med., 45, 565 (1940).

7. Stanberry, S. R., E. E. Snell, and T. D. Spies. A Note on an Assay Method for Pantothenic Acid in Human Blood, J. Biol. Chem., 135, 353 (1940).

8. Williams, R. J., H. K. Mitchell, H. H. Weinstock, and E. E. Snell, Pantothenic Acid. VII. Partial and Total Synthesis Studies, J. Am. Chem. Soc., 62, 1784–5 (1940).

9. Mitchell, H. K., E. E. Snell, and R. J. Williams, Pantothenic Acid. IX. The Biological Activity of Hydroxypantothenic Acid, J. Am. Chem. Soc., 62, 1791–2 (1940).

10. Williams, R. J., Vitamin Study at The University of Texas, Science, 92, 579 (1940).

11. Pennington, D., E. E. Snell, and R. J. Williams, An Assay Method for Pantothenic Acid, J. Biol. Chem., 135, 213–22 (1940).

12. Snell, E. E., D. E. Pennington, and R. J. Williams, The Effect of Diet on the Pantothenic Acid Content of Chick Tissue, J. Biol. Chem., 133, 559–65 (1940).

13. Spies, T. D., S. R. Stanberry, R. J. Williams, T. H. Jukes, and S. H. Babcock, Pantothenic Acid in Human Nutrition, J. Am. Med. Assoc., 115, 523–4 (1940).

14. Williams, R. J., R. E. Eakin, E. E. Snell, The Relationship of Inositol, Thiamin, Biotin, Pantothenic Acid and Vitamin B6 to the Growth of Yeasts, J. Am. Chem. Soc., 62, 1204–7 (1940).

15. Eakin, R. E., E. E. Snell, and R. J. Williams, A Constituent of Raw Egg White Capable of Inactivating Biotin in Vitro, J. Biol. Chem., 136, 801–2 (1940).

16. Mitchell, H. K., and R. J. Williams, The Importance of Amino-Acids as Yeast Nutrients, Biochem. J., 34, 1532–5 (1940).

17. Williams, R. J., Growth-Promoting Nutrilites for Yeasts, Biol. Rev., 16, 49–80 (1941).

18. Williams, R. J., The Importance of Microorganisms in Vitamin Research, Science, 93, 412–4 (1941).

19. Eakin, R. E., E. E. Snell, and R. J. Williams, The Concentration and Assay of Avidin, The Injury-Producing Protein in Raw Egg White, J. Biol. Chem., 140, 535–43 (1941).

20. Gyorgy, P., C. S. Rose, R. E. Eakin, E. E. Snell, and R. J. Williams, Egg-White Injury as the Result of Nonabsorption or Inactivation of Biotin, Science, 93, 477–8 (1941).

21. Mitchell, H. K., E. E. Snell, and R. J. Williams, The Concentration of "Folic Acid", J. Am. Chem. Soc., 63, 2284 (1941).

22. Williams, R. J., Pantothenic Acid, Enzymologia, IX, 387–94 (1941).

23. Williams, R. J., Pantothen, Science, 94, 462–3 (1941).

24. Snell, E. E., and L. D. Wright, A Microbiological Method for the Determination of Nicotinic Acid, J. Biol. Chem., 139, 675 (1941).

25. Snell, E. E., Growth Inhibition by N-(a,g-Dihydroxy-b,b-dimethylbutyryl)taurine and Its Reversal by Pantothenic Acid, J. Biol. Chem., 141, 121 (1941).

26. Snell, E. E., and E. Quarles, The Effect of Incubation on the Vitamin Content of Hen Eggs, J. Nutr., 22, 483 (1941).

27. Taylor, A., J. Thacker, and D. E. Pennington, The Effect of Increased Pantothenic Acid in the Egg on the Development of the Chick Embryo, Science, 94, 542 (1941).

Biochemical Institute Studies I—Studies on the Vitamin Content of Tissues I, Univ. Texas Publ., 4137, (1941).

28. Williams, R. J., Introduction, 7–9.

29. Snell, E. E., and F. M. Strong, Assay Method for Riboflavin, 11–13.

30. Pennington, D. E., E. E. Snell, H. K. Mitchell, J. R. McMahan, and R. J. Williams, Assay Method for Pantothenic Acid, 14–17.

31. Snell, E. E., R. E. Eakin, and R. J. Williams, Assay Method for Biotin, 18–21.

32. Snell, E. E., and L. D. Wright, Assay Method for Nicotinic Acid, 22–23.

33. Williams, R. J., R. E. Eakin, and J. R. McMahan, Assay Method for Pyridoxin, 24–6.

34. William, R. J., A. K. Stout, H. K. Mitchell, and J. R. Mitchell, and J. R. McMahan, Assay Method for Inositol, 27–30.

35. Williams, R. J., J. R. McMahan, and R. E. Eakin, Assay Method for Thiamin, 31–5.

36. Mitchell, H. K., and E. E. Snell, Assay Method for "Folic Acid", 36–37.

37. Wright, L. D., J. R. McMahan, V. H. Cheldelin, A. Taylor, E. E. Snell, and R. J. Williams, The "B Vitamins" in Normal Tissues (Autolysates), 38–60.

38. Williams, R. J., A. Taylor, and V. H. Cheldelin, Changes in "B Vitamin" Content of Tissues During Development, 61–66.

39. Taylor, A., H. K. Mitchell, and M. A. Pollack, Modification of "B Vitamin" Content During Embryological Development, 67–80.

40. Thompson, R. C., R. E. Eakin, and R. J. Williams, The Extraction of Biotin from Tissues, Science, 94, 589–90 (1941).

41. Snell, E. E., and H. K. Mitchell, Purines and Pyrimidine Bases as Growth Substances for Lactic Acid Bacteria, Proc. Natl. Acad. Sci., 27, 1 (1941).

42. Snell, E. E., E. Aline, J. R. Couch, and P. B. Pearson, The Effect of Diet on the Pantothenic Acid Content of Eggs, J. Nutr., 21, 201 (1941).

43. Snell, E. E., A Specific Growth Inhibition Reversed by Pantothenic Acid, J. Biol. Chem., 139, 975 (1941).

44. Williams, R. J., An Introduction to Organic Chemistry, (Book) 1927, 2nd ed. 1931, 3rd ed. 1935, 4th ed. 1941, 5th ed. (with L. F. Hatch) 1948, D. Van Nostrand Co., Inc., New York.

45. Pennington, D. E., E. E. Snell, and R. E. Eakin, Crystalline Avidin, J. Am. Chem. Soc., 64, 469 (1942).

46. Taylor, A., and M. A. Pollack, Hemoglobin Level and Tumor Growth, Cancer Res., 2, 223 (1942).

47. Pollack, M. A., and M. Lindner, Glutamine and Glutamic Acid as Growth Factors for Lactic Acid Bacteria, J. Biol. Chem., 143, 272 (1942).

49. Eakin, R. E., and E. A. Eakin, A Biosynthesis of Biotin, Science, 96, 187 (1942).

50. Snell, E. E., and H. K. Mitchell, Some Sulfanilamide Antagonists as Growth Factors for Lactic Acid Bacteria, Arch. Biochem., 1, 93 (1942).

51. Taylor, A., J. Thacker, and D. E. Pennington, Growth of Cancer Tissue in the Yolk Sac of the Chick Embryo, Science, 96, 342 (1942).

52. Pollack, M. A., A. Taylor, and C. L. Sortomme, The Effect of Variations in Oxygen Pressure Upon Tumor Transplants, Cancer Res., 2, 828 (1942).

53. Snell, E. E., Effect of Heat Sterilization on Growth-Promoting Activity of Pyridoxine for Streptococcus lactis R., Proc. Soc. Exptl. Biol. Med., 51, 356 (1942).

54. Williams, R. J., Vitamins in the Future, Science, 95, 340–44 (1942).

55. Snell, E. E., B. M. Guirard, and R. J. Williams, Occurrence in National Products of a Physiologically Active Metabolite of Pyridoxine, J. Biol. Chem., 143, 519–30 (1942).

56. Williams, R. J., The Approximate Vitamin Requirements of Human Beings, J. Am. Med. Assoc., 119, 1–7 (1942).

57. Teague, P. C., and R. J. Williams, Pantothenic Acid and the Utilization of Glucose by Living and Cell-Free Systems, J. Gen. Physiol., 25, 777–83 (1942).

58. Cheldelin, V. H., and R. J. Williams, Adsorption of Organic Compounds. I. Adsorption of Ampholytes on an Activated Charcoal, J. Am. Chem. Soc., 64, 1513–6 (1942).

59. Williams, R. J., Pantothenic Acid and the Microbiological Approach to the Study of Vitamins, The Biological Action of the Vitamins (E. A. Evans, ed.), Univ. Chicago Press, 120–35 (1942).

Biochemical Institute Studies II—Studies on the Vitamin Content of Tissues II, Univ. Texas. Publ. 4237, (1942).

60. Williams, R. J., Introduction—Microbiological Assay Methods, 7–14.

61. Cheldelin, V. H., M. A. Eppright, E. E. Snell, and B. M. Guirard, Enzymatic Liberation of B Vitamins from Plant and Animal Tissues, 15–36.

62. Mitchell, H. K., and E. R. Isbell, B Vitamin Content of Normal Rat Tissues, 37–40.

63. Taylor, A., M. A. Pollack, and R. J. Williams, B Vitamins in Normal Human Tissues, 41–55.

64. Pollack, M. A., A. Taylor, and R. J. Williams, B Vitamins in Human, Rat and Mouse Neoplasms, 56–71.

65. Taylor, A., M. A. Pollack, and C. L. Sortomme, Effect of B Vitamins in the Diet on Tumor Transplants, 72–80.

66. Isbell, E. R., H. K. Mitchell, A. Taylor, and R. J. Williams, A Preliminary Study of B Vitamins in Cell Nuclei, 81–3.

67. Woods, A. M., J. Taylor, M. J. Hofer, G. A. Johnson, R. L. Lane, and J. R. McMahan, The B Vitamin Content of Organisms of Different Biological Phyla, 84–86.

68. Thompson, R. C., Synthesis of B Vitamins by Bacteria in Pure Culture, 87–96.

69. Williams, R. J., V. H. Cheldelin, and H. K. Mitchell, The B Vitamin Content of Milk from Animals of Different Species, 97–104.

70. Cheldelin, V. H., and R. J. Williams, The B Vitamin Content of Foods, 105–24.

71. Mitchell, H. K., and E. R. Isbell, Intestinal Bacterial Synthesis as a Source of B Vitamins for the Rat, 125–34.

72. Taylor, A., D. E. Pennington, and J. Thacker, The Vitamin Requirements of Cecectomized Rats, 135–44.

73. Mitchell, H. K., A Simple Microgrinder for Tissues, 145.

74. Pollack, M. A., A. Taylor, J. Taylor, and R. J. Williams, B Vitamins in Cancerous Tissues. I. Riboflavin, Cancer Res., 2, 739–43 (1942).

75. Taylor, A., M. A. Pollack, M. J. Hofer, and R. J. Williams, B Vitamins in Cancerous Tissues. II, Nicotinic Acid, Cancer Res., 2, 744–7 (1942).

76. Pollack, M. A., A. Taylor, A. Woods, R. C. Thompson, and R. J. Williams, B Vitamins in Cancerous Tissues. III. Biotin, Cancer Res., 2, 748–51 (1942).

77. Taylor, A., M. A. Pollack, M. J. Hofer, and R. J. Williams, B Vitamins in Cancerous Tissues. IV. Pantothenic Acid, Cancer Res., 2, 752 (1942).

78. Taylor, M. A. Pollack, and R. J. Williams, Uniformities in the Content of B Vitamins in Malignant Neoplasms, Science, 96, 322–3 (1942).

79. Williams, R. J., A Textbook of Biochemistry (Book) 1938, 2nd ed. 1942, D. Van Nostrand Co., Inc., New York.

80. Taylor, A., The Successful Production of a Mammalian Tumor with a Virus-Like Principle, Science, 97, 123 (1943).

81. Snell, E. E., L. Chan, S. Spiridanoff, E. L. Way, and C. D. Leake, Production of Pantothenic Acid Deficiency in Mice with Pantoyltaurine, Science, 97, 168 (1943).

82. Mitchell, H. K., E. R. Isbell, and R. C. Thompson, Microbiological Assays for p-Aminobenzoic Acid, J. Biol. Chem., 147, 485 (1943).

83. Snell, E. E., and B. M. Guirard, Some Interrelationships of Pyridoxine, Alanine and Glycine in Their Effect on Certain Lactic Acid Bacteria, Proc. Natl. Acad. Sci., 92, 66 (1943).

84. Williams, R. J., The Significance of the Vitamin Content of Tissues, Vitamins and Hormones, (R. S. Harris and K. Thimann, ed.), Academic Press, N. Y., 229–47 (1943).

85. Williams, R. J., Water-Soluble Vitamins, Annual Review of Biochemistry (J. M. Luck, ed.), Stanford Univ. Press, XII, 305–52 (1943).

86. Williams, R. J., The Chemistry and Biochemistry of Pantothenic Acid, Advances in Enzymology (F. F. Nord and C. H. Werkman, ed.), Interscience Publishers, N. Y., 253–87 (1943).

87. Williams, R. J., Isotel, Isotelic, Science, 98, 386 (1943).

88. Cheldelin, V. H., A. M. Woods, and R. J. Williams, Losses of B Vitamins Due to Cooking of Foods, J. Nutr., 26, 477–85 (1943).

89. Taylor, A., D. E. Pennington, and J. Thacker, The Effect of High Levels of Pantothenic Acid on Reproduction in the Rat and the Mouse, J. Nutr., 25, 389 (1943).

90. Pollack, M. A., The Absence of beta-Alanine in Proteins, J. Am. Chem. Soc., 65, 484 (1943).

91. Mitchell, H. K., Biological Specificity of Folic Acid, Science, 97, 442 (1943).

92. Thompson, R. C., E. R. Isbell, and H. K. Mitchell, A Microbiological Assay Method for p-Aminobenzoic Acid, J. Biol. Chem., 148, 281–7 (1943).

93. Pollack, M. A., Growth Effects of alpha-Methyl Homologs of Pantothenic Acid and beta-Alanine, J. Am. Chem. Soc., 65, 1335 (1943).

94. Thompson, R. C., The B Vitamin Requirements of the Propionibacteria, J. Bact., 46, (1943).

95. Taylor, A., The Problem of the Etiology of the Cancer Process, Southern Med. and Surgery, 104, 291 (1943).

96. Taylor, A., R. E. Hungate, and D. R. Taylor, Yolk Sac Cultivation of Tumors, Cancer Res., 3, 537 (1943).

97. Taylor, D. R., M. McAfee, and A. Taylor, The Effect of Yolk Sac-Cultivated Tumors on the Hemoglobin Level in the Embryonic Chick, Cancer Res., 3, 542 (1943).

98. Snell, E. E., Growth Promotion on Tryptophan-Deficient Media by o-Aminobenzoic Acid and Its Attempted Reversal with Orthanilamide, Arch. Biochem., 2, 389 (1943).

99. Cheldelin, V. H., and R. L. Lane, B Vitamins in Germinating Seeds, Proc. Soc. Exptl. Biol. Med., 54, 53 (1943).

100. Pollack, M. A., and M. Linder, A Growth Stimulant for Lactobacillus casei, J. Biol. Chem., 147, 183 (1943).

101. Lankford, C. E., and E. E. Snell, Glutamine as a Growth Factor for Certain Strains of Neisseria gonorrhoeae, J. Bact., 45, 410 (1943).

102. Mitchell, H. K., and R. J. Williams, Folic Acid. III. Chemical and Physiological Properties, J. Am. Chem. Soc., 66, 271–4 (1944).

104. Williams, R. J., F. Schlenk, and M. A. Eppright, The Assay of Purified Proteins, Enzymes, Etc., for "B Vitamins," J. Am. Chem. Soc., 66, 896–8 (1944).

105. Chu, E. J. H., and R. J. Williams, A Reported Growth Stimulant for Lactobacillus casei, J. Biol. Chem., 155, 9–11 (1944).

106. Eppright, M. A., and R. J. Williams, Thiamine Determination—Comparative Study of Yeast Growth, Yeast Fermentation and Thiochrome Methods, Ind. Eng. Chem., Anal. Ed., 16, 576–9 (1944).

107. Chu, E. J. H., and R. J. Williams, The Question of the Existence and Significance of Avidin-Uncombinable Biotin Isotels, J. Am. Chem. Soc., 66, 1678–80 (1944).

108. Williams, R. J., M. A. Eppright, E. Cunningham, and C. A. Mills, B Vitamins in the Tissues of Rats Maintained at High and Low Temperatures, Arch. Biochem., 5, 299–306 (1944).

109. Williams, R. J., B Vitamins and Cancer, Proc. Am. Assoc. Adv. Sci. Research Conf., 253–66 (1944).

110. McMahan, J. R., and E. E. Snell, The Microbiological Determination of Amino Acids, I. Valine and Arginine, J. Biol. Chem., 152, 83 (1944).

111. Snell, E. E., Effect of Alanine on Response of Lactobacillus casei to Pyridoxine and Folic Acid, Proc. Exptl. Biol. Med., 55, 36 (1944).

112. Snell, E. E., The Effect of Polyamines on Bacteriostasis by 4,4-Diamidinodiphenoxypropane, J. Biol. Chem., 152, 475 (1944).

113. Mitchell, H. K., Folic Acid, IV. Absorption Spectra, J. Am. Chem. Soc., 66, 274 (1944).

114. Hungate, R. E., A. Taylor, and R. C. Thompson, The Relations to Chick Tissues of Tumors Produced by the Yolk Injection Technic, Cancer Res., 4, 289 (1944).

115. Snell, E. E., The Vitamin Activities of "Pyridoxal" and "Pyridoxamine," J. Biol. Chem., 154, 313 (1944).

116. Thompson, M. L., E. Cunningham, and E. E. Snell, The Nutritive Value of Canned Foods. IV. Riboflavin and Pantothenic Acid, J. Nutrition, 28, 123 (1944).

117. Snell, E. E., The Vitamin B6 Group. I. Formation of Additional Members from Pyridoxine and Evidence Concerning their Structure, J. Am. Chem. Soc., 66, 2032 (1944).

118. Taylor, A., and A. Kynette, The Virus Production of Mammalian Tumors, Am. Assoc. Adv. Sci. Research Conf. on Cancer (1944).

119. Mitchell, H. K., E. E. Snell, and R. J. Williams, Folic Acid. I. Concentration from Spinach, J. Am. Chem. Soc., 66, 269–71 (1944).

120. Frieden, E. H., H. K. Mitchell, and R. J. Williams, Folic Acid. II. Studies on Adsorption, J. Am. Chem. Soc., 66, 269–71 (1944).

121. Snell, E. E., and A. N. Rannefeld, The Vitamin Be Group. III. The Vitamin Activity of Pyridoxal and Pyridoxamine for various Organisms, J. Biol. Chem., 157, 475–89 (1945).

122. Snell, E. E., The Vitamin B6 Group. IV. Evidence for the Occurrence of Pyridoxamine and Pyridoxal in Natural Products, J. Biol. Chem., 157, 491 (1945).

123. Schlenk, F., and E. E. Snell, Vitamin B6 and Transamination, J. Biol. Chem., 157, 425 (1945).

124. Snell, E. E., The Vitamin B6 Group. V. The Reversible Interconversion of Pyridoxal and Pyridoxamine by Transamination Reactions, J. Am. Chem. Soc., 67, 194 (1945).

125. Snell, E. E. and W. Shive, Growth Inhibition by Analogues of Pantothenic Acid. Pantothenyl Alcohol and Related Compounds, J. Biol. Chem., 158, 551 (1945).

126. Chu, E. J., Synthesis of Compounds of Related to Vitamin K. III. 4-(3-Methyl-4-hydroxynaphthylazo-benzenesulfonamide and Related Compounds, J. Am. Chem. Soc., 67, 811 (1945).

127. Hac, L. R., E. E. Snell, The Microbiological Determination of Amino Acids. III. Assay of Aspartic Acid with Leuconostoc mesenteroides, J. Biol. Chem., 159, 291 (1945).

128. Cunningham, E., and E. E. Snell, The Vitamin B6 Group. VI. The Comparative Stability of Pyridoxine, Pyridoxamine, and Pyridoxal, J. Biol. Chem., 158, 491 (1945).

129. Snell, E. E., The Vitamin B6 Group. VII. Replacement of Vitamin B6 for some Micro-organisms by d(–)-Alanine and an Unidentified Factor from Casein, J. Biol. Chem., 158, 497 (1945).

130. Shive, W., and E. E. Snell, Growth Inhibition by Analogues of Pantothenic Acid. II. a- and b-Substituted Pantothenic Acids and Related Compounds. Science, 102, 401 (1945).

131. Williams, R. J., "Starring" in American Men of Science in Relation to the Status of Chemistry, Science, 101, 222–3 (1945).

132. Williams, R. J., The Clinical Possibilities of Pantothenic Acid, Dietotherapy—Clinical Application of Modern Nutrition (M. G. Wohl, ed.), W. B. Saunders Co., Philadelphia, 263–90 (1945).

133. Chu, E. J. H., Nutritional Requirements of Drosophila Hydei., Texas Rpts. Biol. Med., 3, 4, 513–527 (1945).

134. Snell, E. E., The Nutritional Requirements of the Lactic Acid Bacteria and Their Application to Biochemical Research, J. Bact., 50, 373 (1945).

135. Williams, R. J., What to Do About Vitamins, (Book) 1945, University of Oklahoma Press, Norman.

Biochemical Institute Studies III—Cancer Studies, Univ. Texas Publ. 4507 (1945).

136. Williams, R. J., A Broad Approach to the Cancer Problem, 7–12.

137. Taylor, A., A. Kynette, and R. E. Hungate, Demonstration of a Virus-like Tumor Agent by Filtration and Desiccation of Materials from Eggs Bearing Mouse Mammary Carcinoma, 13–32.

138. Taylor, A., and A. Kynette, Evidence for a Cancer Virus Using Intraocular Implants of Mouse Tumor in Rats, 33–42.

139. Taylor, A., The Virus Concept in Cancer Res., 43–46.

140. Thompson, R. C., and B. B. Morgan, Factors Affecting the Propagation of Cancers in Incubating Eggs, 47–52.

141. Hungate, R. E., and H. Snider, The Nutritional Adequacy of the Embryonated Egg for Growth of a Mammalian Tumor, 53–64.

142. Kynette, A., A. Taylor, and R. C. Thompson, Effects of Egg Grown Heterologous Tumor Tissue on the Chick Embryo, 65–74.

143. Hungate, R. E., H. Snider, A. Taylor, and R. C. Thompson, Results of Injecting Mice with Fresh Materials from Tumor-bearing Eggs, 75–90.

144. Hungate, R. E., The Effectiveness of Moderate Centrifugation for Separating Tumor Cells from Yolk, 91–94.

145. Taylor A., Changes in Hemoglobin Concentration, Total Hemoglobin, and Blood Volume Associated with Tumor Growth, 95–102.

146. Hungate, R. E., Observations on Effects of Tumor Cells on Hemoglobin in Vitro, 103–104.

147. Hungate, R. E., and H. Snider, Experiments on the Transplantation of C3H and dba Mammary Carcinomas into the Donor and Non-donor Strains, 105–108.

148. Hungate, R. E., and H. Snider, Experiments on Factors Inhibiting the Growth of Mammalian Tumors in Eggs, 109–118.

149. Taylor, A., and R. J. Williams, Diet and Spontaneous Lung Tumors in Strain A Mice, 119–22.

150. Loo, Y. H., and R. J. Williams, A Study of Folic Acid Distribution with Respect to Its Possible Relationship to Cancer, 123–34.

151. Williams, R. J., Achieving Full Employment After the War, Science, 101, 537–8 (1945).

152. Hac, L. R., E. E. Snell, and R. J. Williams, The Microbiological Determination of Amino Acids. II. Assay and Utilization of Glutamic Acid and Glutamine by Lactobacillus arabinosus, J. Biol. Chem., 159, 273–89 (1945).

153. Shive, W., and E. E. Snell, Growth Inhibition by Analogues of Pantothenic Acid. III. N-Pantoylalkylamines and Related Compounds. J. Biol. Chem., 160, 287 (1945).

154. Roberts, E. C., and E. E. Snell, An Improved Medium for Microbiological Assays with Lactobacillus casei, J. Biol. Chem., 163, 2, 499–509 (1946).

155. Shive, W., and J. Macow, Biochemical Transformations as Determined by Competitive Analogue-Metabolite Growth Inhibitions. I. Some Transformations Involving Aspartic Acid, J. Biol. Chem., 162, 451–62 (1946).

156. Shive, W., and E. C. Roberts, Biochemical Transformations as Determined by Competitive Analogue-Metabolite Growth Inhibitions. II. Some Transformations Involving p-Aminobenzoic Acid, J. Biol. Chem., 162, 463–71 (1946).

157. Beerstecher, E., Jr., and W. Shive, Biochemical Transformations as Determined by Competitive Analogue-Metabolite Growth Inhibitions. III. A Transformation Involving Phenylalanine, J. Biol. Chem., 164, 53–61 (1946).

158. Ravel, J. M., and W. Shive, Biochemical Transformations as Determined by Competitive Analogue-Metabolite Growth Inhibitions. IV. Prevention of Pantothenic Acid Synthesis by Cysteic Acid, J. Biol. Chem., 166, 407–15 (1946).

159. Guirard, B. M., E. E. Snell, and R. J. Williams, The Microbiological Determination of Amino Acids. IV. Lysine, Histidine, Arginine and Valine, Proc. Soc. Expt. Biol. Med., 61, 158–61 (1946).

160. Guirard, B. M., E. E. Snell, and R. J. Williams, The Nutritional Role of Acetate for Lactic Acid Bacteria. I. The Response to Substances Related to Acetate, Arch. Biochem., 9, 361–79 (1946).

161. Guirard, B. M., E. E. Snell, and R. J. Williams, The Nutritional Role of Acetate for Lactic Acid Bacteria. II. Fractionation of Extracts of Natural Materials, Arch. Biochem., 9, 381–6 (1946).

162. Eppright, M. A., and R. J. Williams, Effects of Certain Limiting Conditions on the Synthesis of B Vitamins by Yeast, J. Gen. Physiol., 30, 61–72 (1946).

164. Williams, R. J., Fuel Foods That Lack Vitamins, Your Health, 8, 70 (1946).

165. Williams, R. J., The Human Frontier, (Book) 1946, Harcourt Brace, New York.

166. Beerstecher, E., Jr., and W. Shive, Biochemical Transformations as Determined by Competitive Analogue-Metabolite Growth Inhibitions. V. Prevention of Tyrosine Synthesis by b-2-Thienylalanine, J. Biol. Chem., 167, 49–52 (1947).

167. Taylor, A., and N. Carmichael, Stromal Malignancy in Mouse-Grown Transplants of Egg-Cultivated Mouse Mammary Carcinoma, Cancer Res., 7, 77–81 (1947).

168. Beerstecher, E., Jr., and W. Shive, Prevention of Phenylalanine Synthesis by Tyrosine, J. Biol. Chem., 167, 527–34 (1947).

169. Shive, W., W. W. Ackermann, J. M. Ravel, and J. E. Sutherland, Biosyntheses Involving Pantothenic Acid, J. Am. Chem. Soc., 69, 2567 (1947).

170. Taylor, A., A Further Report on Stromal Malignancy in Mouse-Grown Transplants of Egg-cultivated House Mammary Carcinoma. Fourth International Cancer Research Congress, September, 1947, St. Louis, Missouri. (Published in Acto Unio. Intern. contra. Cancrum).

171. Williams, R. J., Humanics: A Crucial Need, Scientific Monthly, 64, 174–80 (1947).

172. Williams, R. J., The Etiology of Alcoholism: A Working Hypothesis Involving the Interplay of Heredity and Environmental Factors, Quarterly J. Studies on Alcohol, 7, 567–87 (1947).

173. Williams, R. J., Will Science Meet a New Challenge?, Am. Scientist, 35, 282–6 (1947).

174. Williams, R. J., Biochemical Individuality and Its Implications, Chem. Eng. News, 25, 1112–3 (1947).

175. Eppright, M. A., and R. J. Williams, Factors Not Synthesized by Yeast in the Presence of Cyanide, Proc. Soc. Biol. Med., 64, 123–5 (1947).

176. Lipmann, F., N. O. Kaplan, G. D. Novelli, L. C. Tuttle, and B. M. Guirard, Coenzyme for Acetylation, a Pantothenic Acid Derivative, J. Biol. Chem., 167, 869–70 (1947).

177. Beerstecher, E., Jr., and W. Shive, Tryptophan as a Competitive Growth Inhibiting Analog of Phenylalanine, J. Am. Chem. Soc., 69, 461 (1947).

178. Shive, W., W. W. Ackermann, M. Gordon, M. E. Getzendaner, and R. E. Eakin, 5 (4)-Amino-4(5)-Imidazolecarboxamide, A Precursor of Purines. J. Am. Chem. Soc., 69, 725 (1947).

179. Rogers, L. L., and W. Shive, Biochemical Transformations as Determined by Competitive Analogue-Metabolite Growth Inhibitions. VI. Prevention of Biotin Synthesis by 2-Oxo-4-Imidazolidinecaproic Acid., J. Biol. Chem., 169, 57 (1947).

180. Shive, W., and L. L. Rogers, Involvement of Biotin in the Biosynthesis of Oxalacetic and a-Ketoglutaric Acids. J. Biol. Chem., 169, 453–4 (1947).

181. Taylor, A., N. Carmichael, and T. Norris. Temperature Level and the Growth of Embryo and Tumor of Tumor-Bearing Eggs, Proc. Soc. Exptl. Bio. Med., 66, 165 (1947).

182. Williams, R. J., and H. Kirby, Paper Chromatography Using Capillary Ascent, Science, 107, 481–3 (1948).

183. Williams, R. J., and R. C. Thompson, A Device for Obtaining a Continuous Record of Body Temperature from the External Auditory Canal, Science, 108, 90–1 (1948).

184. Lane, R. L., and R. J. Williams, Inositol, An Active Constituent of Pancreatic (alpha) Amylase, Arch. Biochem., 19, 329–35 (1948).

185. Ravel, J. M., R. E. Eakin, and W. Shive. Glycine, A Precursor of 5(4)-Amino-4(5)Imidazolecarboxamide. J. Biol. Chem., 172, 67 (1948).

186. Rogers, L. L., and W. Shive. Biochemical Transformations as Determined by Competitive Analogue-Metabolite Growth Inhibitions. VII. Relationship of Purines and Thymine to Folic Acid., J. Biol. Chem., 172, 751 (1948).

187. Taylor, A., and N. Carmichael, Yolk Sac Cultivated Tumor Tissue and Experiments in Tumor Chemotherapy. I. Riboflavin. Texas Rpts. Biol. Med., 6, 504–12 (1948).

188. Williams, R. J., Alcoholics and Metabolism, Scientific Am., 179, 50–53 (1948).

189. Gordon, M., J. M. Ravel, R. E. Eakin, and W. Shive. Formylfolic Acid, A Functional Derivative of Folic Acid, J. Am. Chem. Soc., 70, 878 (1948).

190. Ackermann, W. W., and A. Taylor, Application of a Metabolic Inhibitor to the Developing Chick Embryo. Proc. Soc. Exptl. Biol. Med., 67, 449–452 (1948).

191. Harding, W. M., and W. Shive, Biochemical Transformations as Determined by Competitive Analogue-Metabolite Growth Inhibitions. VIII. An Interrelationship of Methionine and Leucine, J. Biol. Chem., 174, 743–56 (1948).

192. Brewster, R. Q., and R. J. Williams, A Laboratory Manual of Organic Chemistry (Book) 1928, 2nd ed. 1934, 3rd ed. 1939, 4th ed. 1948, D. Van Nostrand Co., Inc., New York.

193. Thompson, R. C., and H. M. Kirby. The Microbiological Assay of Extracts Containing Toxic Materials. Arch. Biochem., 18, 127–30 (1948).

194. Ackerman, W. W., and H. M. Kirby. Evidence for the Natural Occurrence of a-Amino-b,b-Dimethyl-g-Hydroxybutyric Acid (Pantonine). J. Biol. Chem., 175, 483–4 (1948).

195. Shive, W., R. E. Eakin, W. M. Harding, J. M. Ravel, and J. E. Sutherland, A Crystalline Factor Functionally Related to Folic Acid. J. Am. Chem. Soc., 70, 2299 (1948).

196. Ackermann, W. W., and W. Shive, a-Amino-b, b-Dimethyl-g-Hydroxybutyric Acid; A Precursor of Pantoic Acid., J. Biol. Chem., 175, 867–70 (1948).

197. Shive, W., J. M. Ravel, and R. E. Eakin, An Interrelationship of Thymidine and Vitamin B12. J. Am. Chem. Soc., 70, 2614 (1948).

198. Wagner, R. P., and B. M. Guirard. A Gene-Controlled Reaction in Neurospora Involving the Synthesis of Pantothenic Acid. Proc. Natl. Acad. Sci., 34, 398 (1948).

199. Shive, W., J. M. Ravel, and W. M. Harding. An Interrelationship of Purines and Vitamin B12. J. Biol. Chem., 176, 991 (1948).

200. Taylor, A., N. Carmichael, and T. Norris. A Further Report on Yolk Sac Cultivation of Tumor Tissue. Cancer Res., 8, 264–9 (1948).

201. Blumel, J., and H. M. Kirby. Amino Acid Constituents of Tissues and Isolated Chromosomes of Drosophila. Proc. Natl. Acad. Sci., 34, 561–6 (1948).

202. Williams, R. J., and E. Beerstecher, Jr., An Introduction to Biochemistry, (Book) 2nd edit., 1948, D. Van Nostrand Co., Inc., New York.

203. Williams, R. J., L. J. Berry, and E. Beerstecher, Jr., Individual Metabolic Patterns, Alcoholism, Genetotrophic Diseases, Proc. Natl. Acad. Sci., 35, 265–71 (1949).

204. Williams, R. J., Shall We Pioneer Too? Proc. Philosophical Soc. of Texas, 5–26 (1949).

205. Berry, H. B., and L. Cain. Biochemical Individuality. IV. A Paper Chromatographic Technique for Determining Excretion of Amino Acids in the Presence of Interfering Substances. Arch. Biochem., 24, 179–89 (1949).

206. Thompson, R. C., and H. M. Kirby. Biochemical Individuality. II. Variation in the Urinary Excretion of Lysine, Threonine, Leucine, and Arginine. Arch. Biochem., 21, 210–6 (1949).

207. Taylor, A., and N. Carmichael. The Effect on the Embryo of Continued Serial Tumor Transplantation in the Yolk Sac. Cancer Res., 9, 498–503 (1949).

208. Taylor, A., and N. Carmichael. Male Mice Tolerate Dosages of Pteroylglutamic Acid Lethal to Females. Proc. Soc. Exptl. Biol. Med., 71, 544 (1949).

209. Beerstecher, E., Jr., Contributions of Natural Science to the Program of Home Life Education in the Junior College. Report of the 8th Annual Junior College Conference-Laboratory, Univ. Texas, June, (1949).

210. Bardos, T. J., T. J. Bond, J. Humphreys, and W. Shive. Relationship of the Folinic Acid Group and the Leuconostoc citrovorum Factors. J. Am. Chem. Soc., 71, 3852 (1949).

211. Bond, T. J., T. J. Bardos, M. Sibley, and W. Shive. The Folinic Acid Group, a Series of New Vitamins Related to Folic Acid. J. Am. Chem. Soc., 71, 3852 (1949).

212. Ternberg, J. L., and R. E. Eakin. Erythein and Apoerythein and their Relation to the Antipernicious Anemia Principle. J. Am. Chem. Soc., 71, 3858 (1949).

213. Williams, R. J., L. J. Berry, and E. Beerstecher, Jr., Biochemical Individuality. III. Genetotrophic Factors in the Etiology of Alcoholism. Arch. Biochem., 23, 275–90 (1949).

214. Taylor, A., and I. Galinsky, Yolk Sac Cultivated Tumor Tissue and Experiments in Tumor Chemotherapy. II. Neutral, Red. Ethyl Violet and Janus Green. Cancer Res., 9, 622 (1949).

215. Beerstecher, E., Jr., Bacterial Inhibition by a Penicillin Moiety. Proc. Soc. Exptl. Biol. Med., 73, 200–201 (1950).

216. Beerstecher, E. Jr., The Comparative Biochemistry of Vitamin Function. Science, 111, 300–302 (1950).

217. Reed, L. J., The Occurrence of g-Aminobutyric Acid in Yeast Extract: Its Isolation and Identification. J. Biol. Chem., 183, 451–58 (1950).

218. Beerstecher, E. Jr., The Effects of Tropical Acclimatization Upon the Female Menstrual Cycle. Am. J. Trop. Med., 30, 469–71 (1950).

219. Beerstecher, E. Jr., A Simple Procedure for the Determination of Microgram Amounts of Cyanide. The Analyst, 75, 280–281 (1950).

220. Shive, W., The Utilization of Antimetabolites in the Study of Biochemical Processes in Living Organisms, Annals New York Acad. Sci., 52, 1212–34 (1950).

221. Taylor, A., The Use of Yolk Sac Cultivated Tumors in Cancer Chemotherapy Studies. Texas Rpts. Biol. Med., 8, 227–237 (1950).

222. Williams, R. J., E. Beerstecher, Jr., L. J. Berry, The Concept of Genetotrophic Disease, The Lancet, 287–9 (Feb. 18, 1950).

223. Williams, R. J. L. J. Berry, and E. Beerstecher, Jr., Genetotrophic Diseases: Alcoholism, Texas Rpts. Biol. Med., 8, 238 (1950).

224. Williams, R. J., R. E. Eakin, E. Beerstecher, Jr., and W. Shive, The Biochemistry of B Vitamins, Am. Chem. Soc. Monograph No. 110, Reinhold Publishing Corp., N.Y. (1950).

225. Williams, R. J., Concept of Genetotrophic Disease, Nutrition Rev., 8, 9, 257–260 (Sept. 1950).

226. Williams, R. J., Men and Marbles (address), Am. Chem. Soc. Regional Award Address, Southwest Report, 16–18 (January, 1951).

227. Shive, W., T. J. Bardos, T. J. Bond, and L. L. Rogers. Synthetic Members of the Folinic Acid Group. J. Am. Chem. Soc., 72, 2817 (1950).

228. Thompson, R. C., and M. Abdulnabi. A Study of the Urinary Excretion of a-Amino Nitrogen and Lysine by Humans. J. Biol. Chem., 185, No. 2, 625–8 (1950).

229. Beerstecher, E. Jr., Micromethod for Estimation of Potassium by Paper Chromatography. Anal. Chem., 22, 1200 (1950).

230. Beerstecher, E., Jr., H. E. Sutton, H. K. Berry, W. D. Brown, J. Reed, G. B. Rich, L. J. Berry, and R. J. Williams. Biochemical Individuality V. Explorations with Respect to the Metabolic Patterns of Compulsive Drinkers. Arch. Biochem., 29, 27–40 (1950).

231. Beerstecher, E. Jr., and H. E. Sutton. Urography: A New Technique in the Study of Individual Metabolic Spectra. Texas Rpts. Biol. Med., 9, 8–12 (1951).

232. Shive, W., M. E. Sibley, and L. L. Rogers. Replacement of Vitamin B12 by Desoxynucleotides in Promoting Growth of Certain Lactobacilli. J. Am. Chem. Soc., 73, 867 (1951).

233. Flynn, E. H., T. J. Bond, T. J. Bardos, and W. Shive. A Synthetic Compound with Folinic Acid Activity. J. Am. Chem. Soc., 73, 1979 (1951).

234. Reed, L. J., B. G. DeBusk, I. C. Gunsalus, and C. S. Hornberger, Jr., Crystalline a-Lipoic Acid: A Catalytic Agent Associated with Pyruvate Dehydrogenase, Science, 114, 93–94 (1951).

235. May, M., T. J. Bardos, F. L. Barger, M. Lamford, J. M. Ravel, G. L. Sutherland, and William Shive. Synthetic and Degrative Investigations of the Structure of Folinic Acid-SF. J. Am. Chem. Soc., 73, 3067 (1951).

236. Taylor, A., and N. Carmichael. Folic Acid Analogs and the Growth of Embryo and Tumor Tissue. Cancer Res., 11, 519–522 (1951).

237. Cheldelin, V. H., A. P. Nygaard, H. A. Kornberg, and R. J. Williams. Vitamin B6 Phosphates, Growth Factors for Leuconostoc mesenteroides. J. Bact., 62, 134–135 (1951).

238. Pohland, A., E. H. Flynn, R. G. Jones, and W. Shive. A Proposed Structure for Folinic Acid-SF, A Growth Factor Derived from Pteroylglutamic Acid. J. Am. Chem. Soc., 73, 3247 (1951).

239. Williams, R. J., Nutrition and Alcoholism, (Book) The Univ. of Oklahoma Press, Norman (1951).

241. Williams, R. J., The Unexplored Field of Genetotrophic Disease, MD, 6, 123–4, 136 (1951).

242. Reed, L. J., B. G. DeBusk, P. M. Johnston, and M. E. Getzendaner. Acetate-Replacing Factors for Lactic Acid Bacteria. I. Nature, Extraction and Distribution. J. Biol. Chem., 192, 851–58 (1951).

243. Reed, L. J., M. E. Getzendaner, B. G. DeBusk, and P. M. Johnston. Acetate-Replacing Factors for Lactic Acid Bacteria. II. Purification and Properties. J. Biol. Chem., 192, 859–65 (1951).

244. Reed, L. J., B. G. DeBusk, I. C. Gunsalus and G. H. F. Sehnakenberg. Chemical Nature of alpha-Lipoic Acid. J. Am. Chem. Soc., 73, 5920 (1951).

245. Reed, L. J., and M. J. Cormier. Acetate-Replacing Factors for Lactic Acid Bacteria: Intracellular Distribution in Rat Liver. Soc. Exptl. Biol. Med., 77, 724–5 (1951).

Biochemical Institute Studies IV—Individual Metabolic Patterns and Human Disease: An Exploratory Study Utilizing Predominantly Paper Chromatographic Methods, Univ. Texas Publ. 5109 (1951).

246. R. J. Williams, Introduction, General Discussion and Tentative Conclusions, 7–22.

247. Berry, H. K., H. E. Sutton, L. Cain, and J. S. Berry. Development of Paper Chromatography for Use in the Study of Metabolic Patterns, 22–55.

248. Jirgensons, B. The Influence of Solvent Composition, Temperature and Some Other Factors on the Rf Values of Amino Acids in Paper Chromatography, 56–70.

249. Berry, H. K., and L. Cain. Quantitative Study of Urinary and Salivary Amino Acids Using Paper Chromatography, 71–76.

250. Cain, L., and H. K. Berry. The Quantitative Determination of Histidine Using Paper Chromatography, 77–79.

251. Berry, H. K., and L. Cain. The Quantitative Determination of Creatinine in Urine Using Paper Chromatography, 80–81.

252. Cain, L. The Quantitative Determination of Creatine in Urine by Paper Chromatography, 82–83.

253. Berry, H. K. The Quantitative Estimation of Uric Acid by Paper Chromatographic Methods, with Applications to Human Urine and Saliva, 84–87.

254. Berry, H. K. The Quantitative Estimation of Urea by Paper Chromatographic Methods with Applications to Human Urine, 88–92.

255. Sutton, H. E. A Micro Determination of Sodium Using Paper Chromatography, 93–96.

256. Bloch, E., E. Beerstecher, Jr., and R. C. Thompson. Quantitative Study of Ketosteroids by Paper Chromatographic Methods with Applications to Human Urine, 97–108.

257. Sutton, H. E., and E. Beerstecher, Jr. The Determination of Ferric Chloride Chromogens in Human Urine by Paper Chromatographic Methods, 109–114.

258. Beerstecher, E., Jr., J. G. Reed, W. D. Brown, and L. J. Berry. The Effects of Single Vitamin Deficiencies on the Consumption of Alcohol by White Rats, 115–138.

259. Reed, J. G. Individual Excretion Patterns in Laboratory Rats, 139–143.

260. Reed, J. G. A Study of the Alcoholic Consumption and Amino Acid Excretion Patterns of Rats of Different Inbred Strains, 144–149.

261. Berry, H. K., L. Cain, and L. L. Rogers. A Study of the Urinary Excretion Patterns of Six Human Individuals, 150–156.

262. Berry, H. K. Further Studies on Individual Urinary and Salivary Amino Acid Patterns, 157–164.

263. Berry, H. K., and L. Cain. Individual Urinary Excretion Patterns of Young Children, 165–172.

264. Sutton, H. E. A Further Study of Urinary Excretion Patterns in Relation to Diet, 173–180.

265. Brown, J. D. and E. Beerstecher, Jr. Metabolic Patterns of Underweight and Over-weight Individuals, 181–188.

266. Young, M. K., Jr., H. K. Berry, E. Beerstecher, Jr., and J. S. Berry. Metabolic Patterns of Schizophrenic and Control Groups, 189–197.

267. Cain, L. Exploration of Metabolic Patterns in Mentally Deficient Children, 198–205.

268. Taylor, A., N. Carmichael, G. F. McKenna, and N. M. Burlage. Inhibition of the Growth of Egg Cultivated Tissue by Extracts of Cooperia pedunculata Herb. Proc. Soc. Exptl. Biol. Med., 77, 841–843 (1951).

269. Klatt, O. A., and A. Taylor. The Effect of Tumor Growth on Liver Catalase Concentration. Cancer Res., 11, 764–767 (1951).

270. Shive, W. B-Vitamins and the Biosyntheses of Purines and Pyrimidines. J. Cell. and Comp. Physiol., 38, supplement 1, 203 (1951).

271. Shive, W. The Functions of B-Vitamins in the Biosynthesis of Purines and Pyrimidines. Vitamins and Hormones, IX, 75–130 (1951).

272. Radin, N. S. a-Lipoic Acid in Oxidative Reactions of a Corynebacterium. Proc. Soc. Exptl. Biol. Med., 79, 723–726 (1952).

273. Walker, J. B. Arginosuccinic Acid from Chlorella. Proc. Natl. Acad. Sci., 38, 561–566 (1952).

274. Radin, N. S. Apparatus for Distillation and Stirring. Anal. Chem., 24, no. 10, 1686 (Oct. 1952).

275. Williams, R. J. Nutritional Vulnerability and Alcoholism, Research Reviews, 4–8 (1952).

276. Williams, R. J. Alcoholism as a Nutritional Problem, J. Clin. Nutr., 32 (Sept.–Oct. 1952).

277. Hornberger, C. S., Jr., R. F. Heitmiller, I. C. Gunsalus, O. H. F. Schnakenberg, and L. J. Reed. Synthetic Preparation of Lipoic Acid. J. Am. Chem. Soc., 74, 2382 (1952).

278. Reed, L. J., Q. F. Soper, G. H. F. Schnakenberg, S. F. Kern, H. Boaz, I. C. Gunsalus. Identification of the Carbon Skeleton of a-Lipoic Acid. J. Am. Chem. Soc., 74, 2383 (1952).

279. Reed, L. J., and B. G. DeBusk, Lipothiamide and its Relation to a Thiamin Coenzyme Required for Oxidative Decarboxylation of a-Keto Acids. J. Am. Chem. Soc., 74, 3457 (1952).

280. Reed, L. J., and B. G. DeBusk. Lipothiamide Pyrophosphate: Coenzyme for Oxidative Decarboxylation of a-Keto Acids. J. Am. Chem. Soc., 74, 3964 (1952).

281. Reed, L. J., and B. G. DeBusk. Lipoic Acid Conjugase. J. Am. Chem. Soc., 74, 4727 (1952).

282. Reed, L. J., and B. G. DeBusk. A Conjugate of a-Lipoic Acid Required for Oxidation of Pyruvate and a-Ketoglutarate by an Escherichia coli Mutant. J. Biol. Chem., 199, 873 (1952).

283. Reed, L. J., and B. G. DeBusk. Chemical Nature of an a-Lipoic Acid Conjugate Required for Oxidation of Pyruvate and a-Ketoglutarate by an Escherichia coli mutant. J. Biol. Chem., 199, 881 (1952).

284. Snell, E. E. Correlation of Chemical Enzymatic and Growth-Promoting Properties of Vitamin B6. Symposium sur le Metabolism Microbien, II. Congres International de Biochimie. Paris, July 21–27, pp. 47–63 (1952).

285. Kihara, H., W. G. McCullough, and E. E. Snell. Peptides and Bacterial Growth. I. Purification of a Peptide Factor required for Growth of Lactobacillus casei. J. Biol. Chem., 197, 783–789 (1952).

286. Kihara, H., and E. E. Snell. Peptides and Bacterial Growth, II. L-Alanine Peptides and Growth of Lactobacillus casei J. Biol. Chem., 197, 791–800 (1952).

287. Kihara, H., O. A. Klatt, and E. E. Snell. Peptides and Bacterial Growth. III. Utilization of Tyrosine and Tyrosine Peptides by Streptococcus faecalis J. Biol. Chem., 197, 801–807 (1952).

288. Lansford, E. M., Jr., and W. Shive. The Microbiological Activity of N-(DL-Pantonyl) b-Alanine. J. Biol. Chem., 194, 329–336 (1952).

289. Metzler, D. E., and E. E. Snell. Deamination of serine I. Catalytic deamination of serine and cysteine by pyridoxal and metal salts. J. Biol. Chem., 198, 353–361 (1952).

290. Metzler, D. E., and E. E. Snell. Deamination of serine II. D-Serine Dehydrase, a Vitamin B6 Enzyme from Escherichia coli. J. Biol. Chem., 198, 363–373 (1952).

291. Brown, G. M., and E. E. Snell. The relationship of Pantethine to naturally Occurring Forms of the Lactobacillus bulgaricus factor. J. Biol. Chem., 198, 375–383 (1952).

292. Naher, E. C., E. E. Snell, and W. W. Cravens. Effects of nucleic Acid Derivatives in the Reversal of Aminopterin Inhibition in the Chick Embryo, Proc. Soc. Exptl. Biol. Med., 81, 20–23 (1952).

293. Olivard, J. D. E. Metzler, and E. E. Snell. Catalytic Racemization of Amino Acids by Pyridoxal and Metal Salts. J. Biol. Chem., 199, 669–674 (1952).

294. Tittsler, R. P., C. S. Pederson, E. E. Snell, D. Hendlin, and C. F. Niven, Jr. Symposium on the Lactic Acid Bacteria. Bacteriol. Reviews, 16, 227–260 (1952).

295. Lamford, E. M., Jr., and W. Shive. Growth Inhibition by some b-Arylalanines, Arch. Biochem. and Biophys., 38, 347–351 (1952).

296. Lansford, E. M., Jr., and W. Shive. Microbiological Activity of a-Keto-b,b-dimethyl-7-butyrolactone. Arch. Biochem. and Biophys., 38, 353–355 (1952).

297. Shive, W. Inhibition Analysis as a Method of Vitamin Research. International Review of Vitamin Research, 23, 3, 392–404 (1952).

298. Shive, W. Biological Activities of Metabolite Analogues. Annual Review of Microbiology, 6, 437–466 (1952).

299. Williams, R. J., and W. Wenner. Pantothenic Acid, Encyclopedia of Chemical Technology, 9, The Interscience Encyclopedia, Inc., 805–811 (1952).

300. Taylor, A., G. D. McKenna, and H. M. Burlage. Cancer Chemotherapy Experiments with Plant Extracts. Texas Rpts. Biol. Med., 10, No. 4, 1062–74 (1952).

301. Knox, J. C., Jr., H. F. Rosene, and A. Taylor. The Effect of Various Tumor Growths on the Water Content of the Liver in Mice and Chick Embryos. Texas Rpts. Biol. Med., 10, No. 4, 830–844 (1952).

302. Burlage, H. M., M. E. Jones, G. F. McKenna, and A. Taylor. Studies on Toxic Plants for Antibacterial Effects. Texas Rpts. Biol. Med., 10, No. 4, 803–815 (1952) Winter.

303. Li, Si-Oh. Synthesis of N-Phosphoryl Amino Esters, J. Am. Chem. Soc., 74, 5959 (1952).

304. Snell, E. E., and J. C. Rabinowitz. Vitamin Bo Antagonists and Growth of Microorganisms. I. 4-Desoxypyridoxine. Arch. of Biochem. and Biophys., 43, No. 2, 399–407 (1952).

305. Snell, E. E., and J. C. Rabinowitz. Vitamin B6 Antagonists and Growth of Microorganisms. II. 5-Desoxypyridoxal and Related Compounds, Arch. Biochem. and Biophysics., 43, No. 2, (1952).

306. Williams, R. J. Muscular Dystrophy and Individual Metabolic Patterns: The Possibilities of a Nutritional Therapeutic Approach, Proc. of the First and Second Medical Conferences of the Muscular Dystrophy Assoc. of America, Inc., 118–122, (1953).

307. Williams, R. J. Free and Unequal, (Book) Univ. of Texas Press, Austin (1953).

308. Williams, R. J., and L. L. Rogers. The Formulation of a Genetotrophic Supplement for the Experimental Treatment of Diseases of Obscure Etiology, Texas Rpts. Biol. Med. 11, 573–581 (1953).

309. Williams, R. J. Biochemistry Moves Toward Human Understanding (An Abstract) Symposium of B Vitamins, Biochem. Institute, Univ. of Texas (1953).

310. Taylor, A., and G. F. McKenna. The Use of Yolk Sac Cultivated Bacteria in Bacterial Studies, Texas Rpts. Biol. Med., 11, No. 2, 283–286 (1953).

311. Shive, W. B-Vitamins Involved in Single Carbon Unit Metabolism, Fed. Proc., 12, No. 2, 639–646 (1953).

312. Snell, E. E., and G. M. Brown. Pantethine and Related Forms of the Lactobacillus Bulgaricus Factor (LBF). Advances in Enzymology, Interscience Publishers, Inc., XIV. 49–71 (1953).

313. Snell, E. E., and J. C. Rabinowitz. The Microbiological Activity of Pyridoxylamines, J. Am. Chem. Soc., 75, 998 (1953).

314. Snell, E. E., E. L. Whittle, J. A. Moore, R. W. Stipek, F. E. Peterson, V. M. McGlohon, O. D. Bird, G. M. Brown. The Synthesis of Pantetheine-Pantethine, J. Am. Chem. Soc., 75, 1694–1700 (1953).

315. Snell, E. E., and G. M. Brown. The Chemical Nature of the Lactobacillus Bulgaricus Factor, J. Am. Chem. Soc., 75, 1691–1693 (1953).

316. Snell, E. E., V. J. Peters, G. M. Brown, and W. L. Williams. Isolation of the Lactobacillus Bulgaricus Factor from Natural Sources, J. Am. Chem. Soc., 75, 1688–1691 (1953).

317. Reed, L. J., I. C. Gunsalus, G. H. F. Schnakenberg, Q. F. Soper, H. E. Boaz, S. F. Kern, and T. V. Parke. Isolation, Characterization and Structure of alpha-Lipoic Acid. J. Am. Chem. Soc., 75, 1267–1270 (1953).

318. Reed, L. J., B. G. DeBusk, C. S. Hornberger, Jr., and I. C. Gunsalus. Interrelationships of Lipoic Acids. J. Am. Chem. Soc., 75, 1271–1273 (1953).

319. Hornberger, C. S. Jr., R. F. Heitmiller, I. C. Gunsalus, G. H. F. Schakenberg, and L. J. Reed. Synthesis of DL-alpha-Lipoic Acid, J. Am. Chem. Soc., 75, 1273–1277 (1953).

320. Reed, L. J., and B. G. DeBusk. Mechanism of Enzymatic Oxidative Decarboxylation of Pyruvate, J. Am. Chem. Soc., 75, 1261 (1953).

321. Snell, E. E., O. A. Klatt, H. W. Bruins, and W. W. Cravens. Growth-Promotion by Lyxoflavin. II. Relationship to Riboflavin in Bacteria and Chicks. Soc. Exptl. Biol. Med., 82, 583–590 (1953).

322. Peters, V. J., J. M. Prescott, and E. E. Snell. Peptides and Bacterial Growth. IV. Histidine Peptides as Growth Factors for Lactobacillus delbrneckii 9649. J. Biol. Chem., 202, No. 2, 521–532 (1953).

323. Prescott, J. M., V. J. Peters, and E. E. Snell. Peptides and Bacterial Growth. V., Serine Peptides and Growth of Lactobacillus delbrueckii 9649. J. Biol. Chem., 202, No. 2, 533–540 (1953).

324. Brown, G. M., and E. E. Snell. N-Pantothenylcysteine as a Precursor for Pantetheine and Coenzyme A., J. Am. Chem. Soc., 75, 2872 (1953).

325. Metzler, D. E., J. B. Longenecker, and E. E. Snell. Reversible Catalytic Cleavage of Hydroxyamino Acids by Pyridoxal and Metal Salts, J. Am. Chem. Soc., 75, 2786 (1953).

326. Walker, J. B., and J. Myers. The Formation of Argniosuccinic Acid from Arginine and Fumarate, J. Biol. Chem., 203, 1,143–153 (1953).

Biochemical Institute Studies V—Cancer Studies II, Univ. of Texas Publ. 5314 (1953).

327. Taylor, A. Cancer Etiology, 1–12.

328. Taylor, A. The Yolk Sac Method of Cultivating Tumor Tissue in Eggs, 13–26.

329. Taylor, A. The Use of Embryonated Eggs in Cancer Therapy Experiments, 27–35.

330. Taylor, A., and N. Carmichael. The Effect of Metallic Chlorides on the Growth of Tumor and Non-Tumor Tissue, 36–79.

331. Young, M. K., and A. Taylor. Factors Influencing the Utilization of Glucose by Suspensions of Living Tumor and Embryonic Cells, 80–88.

332. Reed, L. J., and B. G. DeBusk. Enzymes and Cofactors Functioning in Oxidative Decarboxylation of a-Keto Acids, (An Abstract), Symposium on B Vitamins, Biochemical Institute, University of Texas (1953).

333. Walker, J. B., Inorganic Micronutrient Requirements of Chlorella. I. Requirements for Calcium (or Strontium), Copper and Molybdenum. Arch. Biochem. Biophysics, 46, 1, 1–11 (1953).

334. Walker, James B., An Enzymatic Reaction Between Canavine and Fumarate, J. Biol. Chem., 204, 1, 103–146 (1953).

335. Broquist, H. P., and E. E. Snell. Biotin and Bacterial Growth. II. Avidin and the Response of Lactobacillus arabinosus to Oleic Acid, Archives of Biochemistry and Biophysics, 46, 2, 432–442 (1953).

336. Reed, L. J. Metabolic Functions of Thiamine and Lipoic Acid, Physiological Reviews, 33, 544–559 (1953).

337. Berry, H. K. Variations in Urinary Excretion Patterns in a Texas Population. Am. J. Phys. Anthrop., n.s. 11, 4, 559–575 (1953).

338. Snell, E. E. Summary of Known Metabolic Functions of Nicotinic Acid, Riboflavin and Vitamin B6, Physiological Reviews, 33, 4, 509–524 (1953).

339. Weaver, J. M., and W. Shive. Involvement of Thymidine in the Utilization of 5-Amino-4-imidazolecarboxamide, J. Am. Chem. Soc., 75, 4628 (1953).

340. Taylor, A., and N. Carmichael, Egg Cultivated Tumor Protects Embryo Against Vaccinia Virus, Proc. Soc. Exptl. Biol. Med., 83, 676–678 (1953).

341. Metzler, D. E., M. Ikawa, and E. E. Snell. Reactions of Pyridoxal With Amino Acids, An Abstract, Symposium on B Vitamins, Biochemical Institute, University of Texas, (1953).

342. Eakin, R. E. In Vitro Studies of B12-Binding Proteins, An Abstract, Symposium on B Vitamins, Biochemical Institute, University of Texas, (1953).

343. Lansford, E. M., J. M. Weaver, R. M. Trubey, and W. Shive. Studies on Thymidine Function and Distribution in Tissues, An Abstract, Symposium on B Vitamins, Biochemical Institute, University of Texas, (1953).

344. Brown, G. M., and E. E. Snell. Microbiological Activity and Biosynthesis of Pantethine and Related Compounds, An Abstract, Symposium on B Vitamins, Biochemical Institute, University of Texas, (1953).

345. Walker, J. B. Metabolism of Arginosuccinic and Canavanosuccinic Acids, An Abstract, Symposium on B Vitamins, Biochemical Institute, University of Texas, (1953).

346. Dien, L. T. H., J. M. Ravel, and W. Shive. Some Inhibitory Interrelationships among Leucine, Isoleucine and Valine, Archives of Biochem. Biophysics, 49, 2, 283–292 (1954).

347. Brown, G. M., and E. E. Snell. Pantothenic Acid Conjugates and Growth of Acetobacter Suboxydans, J. Bacteriology, 67, 4, 465–471 (1954).

348. Metzler, D. E., M. Ikawa, and E. E. Snell. A General Mechanism for Vitamin B6-catalyzed Reactions. J. Am. Chem. Soc., 76, 648–652 (1952).

349. Metzler, D. E., J. B. Longenecker, and E. E. Snell. The Reversible Catalytic Cleavage of Hydroxyamino Acids by Pyridoxal and Metal Salts, J. Am. Chem. Soc., 76, 639–644 (1954).

350. Ikawa, M., and E. E. Snell. Benzene Analogs of Pyridoxal. The Reactions of 4-Nitro- salicylaldehyde with Amino Acids, J. Am. Chem. Soc., 76, 653 (1954).

351. Ikawa, M., and E. E. Snell Synthesis and Biological Activity of Homologs of Pyridoxal and Pyridoxamine, J. Am. Chem. Soc., 76, 637 (1954).

352. Metzler, D. E., J. Olivard, and E. E. Snell. Transamination of Pyridoxamine and Amino Acids with Glyoxylic Acid, J. Am. Chem. Soc., 76, 644–648 (1954).

353. Walker, J. B. Inorganic Micronutrient Requirements of Chlorella. II. Quantitative Requirements for Iron, Manganese, and Zinc, Arch. Biochem. and Biophysics, 53, 1, 1–8 (1954).

354. Williams, R. J. The Genetotrophic Concept, Nutritional Deficiencies and Alcoholism, Annals of N. Y. Acad. Sciences, 57, 794–809 (1954).

355. Williams, R. J. Early Experiences with Pantothenic Acid, A retrospect, Nutrition Reviews, 12, 3, 65–68 (1954).

356. Peters, V. J., and E. E. Snell. Peptides and Bacterial Growth. VI. The Nutritional Requirements of Lactobacillus delbrueckii, J. Bact., 67, 1, 69–76 (1954).

357. McRorie, R. A., G. L. Sutherland, M. S. Lewis, A. D. Barton, M. R. Glazeher, and W. Shive. Isolation and Identification of a Naturally Occurring Analog of Methionine, J. Am. Chem. Soc., 76, 115–118 (1954).

358. Harding, W. M., and W. Shive. Cyclopentaneglycine, An Inhibitory Analogue of Isoleucine, J. Biol. Chem., 206, 401–410 (1954).

359. Ravel, J. M., L. Woods, B. Felsing, and W. Shive. Some Interrelationships of Aspartic Acid, Threonine and Lysine, J. Biol. Chem., 206, 391–400 (1954).

360. Ravel, J. M., B. Felsing, and W. Shive. Glutamic Acid Inhibition of Aspartic Acid Utilization in Threonine Biosynthesis, J. Biol. Chem., 206, 2, 791–796 (1954).

361. McKenna, G. F., A. Taylor, and H. M. Burlage. Chemotherapy Experiments with Plant Extracts and Transplantable Tumors, Texas Rpts. Biol. Med., 12, 3, 500–508 (1954).

362. Burlage, H. M., S. M. Gibson, G. IV. McKenna, and A. Taylor. Studies on Toxic Plants for Antibacterial Effects II. Texas Rpts. Biol. Med., 12, 2, 229–235 (1954).

363. Taylor, A., G. IV. McKenna, H. M. Burlage, and Stokes, D. M. Plant Extracts Tested Against Egg Cultivated Viruses, Texas Rpts. Biol. Med., 12, 3, 551–557 (1954).

364. McRorie, R. A., M. R. Glazener, C. G. Skinner, and W. Shive. Microbiological Activity of the Methylsulfonium Derivative of Methionine, J. Biol. Chem., 211, 489–497 (1954).

365. Wahba, A. J., and W. Shive. A Role of Aspartic Acid in Purine Biosynthesis, J. Biol. Chem., 211, 155–161 (1954).

366. Woods, L., J. M. Ravel, and W. Shive. Relationship of Aspartic Acid to Pyrimidine Biosynthesis, J. Biol. Chem., 209, 559–567 (1954).

367. Wahba, A. J., J. M. Ravel, and W. Shive. Involvement of Aspartic Acid in Purine Biosynthesis, Biochem. et Biophy. Acta, 14, 569 (1954).

368. Reed, L. J., and B. G. DeBusk. Enzymatic Synthesis of a Lipoic Acid Coenzyme, Federation Proceedings, 13, 723–731 (1954).

369. Reed, L. J. Availability of Crystalline DL-a-Lipoic Acid, Science, 120, 854 (1954).

370. Ikawa, M., and E. E. Snell. Oxidative Deamination of Amino Acids by Pyridoxal and Metal Salts, J. Am. Chem. Soc., 76, 4900 (1954).

371. Guirard, B. M., and E. E. Snell. Pyridoxal Phosphate and Metal Ions as Cofactors of Histidine Decarboxylase, J. Am. Chem. Soc., 76, 4745 (1954).

372. Walker, J. B. Canavanine and Homoarginine as Antimetabolites of Arginine and Lysine in Yeast and Algae, J. Biol. Chem., 212, 207–215, (1955).

373. Brown, Gene M., M. Ikawa, and E. E. Snell. Synthesis and Microbiological Activity of Some Pantothenic Acid Conjugates, J. Biol. Chem., 213, 855–867 (1955).

374. Ward, G. B., G. M. Brown, and E. E. Snell. Phosphorylation of Pantothenic Acid and Pantethine by an Enzyme from Proteus morganii, J. Biol. Chem., 213, 869–876 (1955).

375. Walker, J. B. Homoarginine Inhibition of Escherichia coli B, J. Biol. Chem., 212, 617–621 (1955).

376. Olivard, J., and E. E. Snell. Growth and Enzymatic Activities of Vitamin B6 Analogues. I. D-Alanine Synthesis, J. Biol. Chem., 213, 203–213 (1955).

377. Kihara, H., and E. E. Snell. Peptides and Bacterial Growth. VII. Relation to Inhibitions by Thienylalanine, Ethionine and Canavanine, J. Biol. Chem., 212, 83–94 (1955).

378. Olivard, J., and E. E. Snell. Growth and Enzymatic Activities of Vitamin B6 Analogues. II. Synthesis of Miscellaneous Amino Acids, J. Biol. Chem., 213, 215–228 (1955).

379. Longenecker, J. B., and E. E. Snell. A Possible Mechanism for Kynureninase Action, J. Biol. Chem., 213, 229–235 (1955).

380. Ravel, J. M., B. Felsing, and W. Shive. Comparative Inhibitory Effects of Glutamic and Cysteic Acids on Aspartic Acid Utilization, Arch. Biochem. and Biophysics, 54, 541–548 (1955).

381. Ravel, J. M., and W. Shive. A Study of Biotin Sulfone Inhibition of Lactobacillus arabinosus, Arch. Biochem. and Biophys., 54, 341–348 (1955).

382. Ravel, J. M., B. Felsing, E. M. Lansford, Jr., R. H. Trubey, and W. Shive. Reversal of Alcohol Toxicity by Glutamine, J. Biol. Chem., 214, 497–501 (1955).

383. Lansford, E. M., Jr., and W. Shive. Antimetabolites in Study of Biochemistry of Purines and Pyrimidines. Reprinted from Antimetabolites and Cancer, Am. Assoc. for the Advancement of Science (1955).

384. Reed, L. J., and C. Niu. Syntheses of DL-alpha-Lipoic Acid, J. Am. Chem. Soc., 77, 416 (1955).

385. Li, Si-Oh, and R. E. Eakin. Synthesis of N-Phosphorylated Derivatives of Amino Acids, J. Am. Chem. Soc., 77, 1866 (1955).

386. Dennis, R. L., W. J. Plant, C. G. Skinner, G. L. Sutherland, and W. Shive. Synthesis of 2-Cyclopentene-l-glycine, an Inhibitory Amino Acid Analog, J. Am. Chem. Soc., 77, 2362 (1955).

387. Li, Si-Oh, and R. E. Eakin. Infrared Spectra of N-Phosphorylated Derivatives of Amino Acids, J. Am. Chem. Soc., 77, 3519 (1955).

388. Leach, F. R., K. Yasunobu, and L. J. Reed. Lipoic acid activation of the a-ketobutyrate oxidation system in cell-free extracts of Streptococcus faecalis. Biochim. et Bioph. Acta, 18, 297–298 (1955).

389. Thomas, R. C., and L. J. Reed. Synthesis and Properties of High Specific Activity DL-alpha-Lipoic Acid-S235. J. Am. Chem. Soc., 77, 5446–47 (1955).

390. Walker, J. B. Biosynthesis of Canavaninosuccinic Acid from Canavanine and Fumarate in Kidney. Arch. Biochem. Biophys., 59, 233–245 (1955).

391. Skinner, C. G., and W. Shive. Synthesis of Some 6-(Substituted)-Aminopurines. J. Am. Chem. Soc., 77, 6692–6693 (1955).

392. Singer, H., and W. Shive. Synthesis of 7-Indolecarboxylic Acid. J. Am. Chem. Soc., 77, 5700–5702 (1955).

393. Singer, H., and W. Shive. Synthesis of Indole Derivatives. 5-Indolecarboxylic Acid. J. Org. Chem., 20, 1458–1460 (1955).

394. Ravel, J. M., J. L. Reger, and W. Shive. Aspartic Acid Inhibition of Glutamic Acid Utilization for Proline, Citrulline and Glutamine Biosynthesis. Arch. Biochem. Biophys., 57, 312–322 (1955).

395. Ravel, J. M., and W. Shive. Arginine Inhibition of Glutamate Utilization. Biochimica et Biophysica Acta, 18, 535–539 (1955).

396. Sandman, R., and E. E. Snell. Some Effects of w-Methyl Analogues of Vitamin B6 in Rats. Proc. Soc. Exptl. Biol. Med., 90, 63–67 (1955).

397. Mitoma, C., and E. E. Snell. The Role of Purine Bases as Histidine Precursors in Lactobacillus casei Proc. Natl. Acad. Sci., 41, 891–894 (1955).

398. Snell, E. E., N. S. Radin, and M. Ikawa. The Nature of D-Alanine in Lactic Acid Bacteria. J. Biol. Chem., 217, 803–818 (1955).

399. Kihara, H., J. M. Prescott, and E. E. Snell. The Bacterial Cleavage of Canavanine to Homoserine and Guanidine. J. Biol. Chem., 217, 497–503 (1955).

400. Hurley, K. E., and R. J. Williams. Urinary Amino Acids, Creatinine, and Phosphate in Muscular Dystrophy, Arch. Biochem. Biophy., 54, 384–391 (1955).

401. DeBusk, B. G., and R. J. Williams. Effect of Lipoic Acid on the Growth Rate of Young Chicks and Rats, Arch. Biochem. Biophy., 55, 587–588 (1955).

402. Williams, R. J., Implications of Humanics for Law and Science, J. Public Law, Emory Univ. Law School, 3, 328–344 (1955).

403. Rogers, L. L., R. B. Pelton, and R. J. Williams. Voluntary Alcohol Consumption by Rats Following Administration of Glutamine, J. Biol. Chem., 214, 503–506 (1955). 404. Williams, R. J., R. B. Pelton, and L. L. Rogers. Dietary Deficiencies in Animals in Relation to Voluntary Alcohol and Sugar Consumption, Quar. J. Studies on Alcohol, 16, 234–244 (June, 1955).

405. Williams, R. J., W. D. Brown, and R. W. Shideler. Metabolic Peculiarities in Normal Young Men as Revealed by Repeated Blood Analyses, Proc. Natl. Acad. Sci.,, 41, 615–620 (1955).

406. Williams, R. J. The Genetotrophic Approach to Alcoholism, Origins of Resistance to Toxic Agents, Proc. of Symposium held in Wash., D. C., March 25–27, 1954. Academic Press, N. Y. (1955).

407. Williams, R. J., and G. B. DeBusk. Overnight Nutritional Responses of Chicks, Proc. Natl. Acad. Sci., 41, 894–899 (1955).

408. Williams, R. J., Biochemical Approach to the Study of Personality. Psychiatric Research Rpts., 2, 31–37 (1955).

409. Taylor, A., and R. J. Williams. The Control of A Cancer Growth In Embryonated Eggs. Proc. Natl. Acad. Sci., 42, 54–60 (1956).

410. Williams, R. J. Human Nutrition and Individual Variability. Borden’s Review of Nutrition Research, 17, 11–26 (1956).

411. Rogers, L. L., R. B. Pelton, and R. J. Williams. Amino Acid Supplementation and Voluntary Alcohol Consumption by Rats, J. Biol. Chem., 220, 321–323 (1956).

412. Williams, R. J. What Is Behavioral Science? Science, 124, 276–277 (1956).

413. Williams, R. J. Biochemical Individuality—An Inescapable Basic Factor in the Alcoholism Problem (Paper presented at Istanbul, September, 1956, published by International Bureau Against Alcoholism, Lausanne, Switzerland.).

414. Williams, R. J. Biochemical Individuality (Book) John Wiley & Sons, New York, (1956). (Translated into Russian, Italian and Polish.)

415. Steber, M., O. F. McKenna, H. M. Burlage, A. Taylor, and D. M. Smith. Studies on Toxic Plants for Antibacterial Effects III. Texas J. Sci., 8, 227–234 (1956).

416. Dunn, F. W., J. M. Ravel, and W. Shive. Inhibition Studies with Peptides of Thienylalanine and Phenylalanine. J. Biological Chem., 219, 809–822 (1956).

417. Snell, E. E., and D. E. Metzler. Water-Soluble Vitamins, Part II. Annual Rev. Biochem., 25, 435–462 (1956).

418. Ikawa, M., and E. E. Snell. D-Glutamic Acid and Amino Sugars as Cell Wall Constituents in Lactic Acid Bacteria Biochem. Biophys. Acta, 19, 576–578 (1956).

419. Longenecker, J. B., and E. E. Snell. On the Mechanism and Optical Specificity of Transamination Reactions. Proc. Natl. Acad. Sci., 42, 221–227 (1956).

420. Ham, R. G., and R. E. Eakin. Inhibition of Glyceraldehyde Phosphate Dehydrogenase by Salts other than Lithium Chloride. J. Embryol. Exptl. Morph., 4, 93–95 (1956).

421. Skinner, C. G., T. J. McCord, J. M. Ravel, and W. Shive. O-Carbamyl-L-serine, an Inhibitory Analog of L-Glutamine. J. Am. Chem. Soc., 78, 2412 (1956).

422. Ham, R. G., R. E. Eakin, C. G. Skinner, and W. Shive. Inhibition of Regeneration in Hydra by Certain New 6-(Phenylalkyl)-Aminopurines. J. Am. Chem. Soc., 78, 264 (1956).

423. Skinner, C. O. Inexpensive Micro Vacuum Desiccator. Analytical Chem., 28, 924 (1956).

424. Thomas, R. C., and L. J. Reed. Synthesis of DL-1, 2-Dithiolane-3-caproic Acid and DL-1, 2-Dithiolane-3-butyric Acid, Homologs of alpha-Lipoic Acid. J. Am. Chem. Soc., 78, 6151–6153 (1956).

425. Thomas, R. C., and L. J. Reed. Synthesis of DL-1, 2-Dithiolane-3-butanesulfonamide, an Analog of alpha-Lipoic Acid. J. Am. Chem. Soc., 78, 6150–6151 (1956).

426. Thomas, R. C., and L. J. Reed. Disulfide Polymers of DL-alpha-Lipoic Acid. J. Am. Chem. Soc., 78, 6148–6149 (1956).

427. Williams, R. J. Biochemical Individuality, 1963 (paperback edition), John Wiley & Sons, New York. (Translated into Russian, Italian and Polish.)

428. Estes, J. M., J. M. Ravel, and W. Shive. A Role of Biotin in the Interaction of Ornithine and Carbamyl Phosphate. J. Am. Chem. Soc., 78, 6410 (1956).

429. Pal, P. R., C. G. Skinner, R. L. Dennis, and W. Shive. Cyclopentanealanine and 1-Cyclopentene-l-alanine, Inhibitory Analogs of Leucine and Phenylalanine. J. Am. Chem. Soc., 78, 5116–5118 (1956).

430. Skinner, C. G., W. Shive, R. G. Ham, D. C. Fitzgerald, Jr., and R. E. Eakin. Effects of Some 6-(Substituted)-purines on Regeneration of Hydra. J. Am. Chem. Soc., 78, 5097–5100 (1956).

431. Taylor, A., G. F. McKenna, and H. M. Burlage. Anticancer Activity of Plant Extracts. Texas Rpts. Biol. Med., 14, 538–556 (Winter, 1956).

432. Skinner, C. G., R. G. Ham, D. C. Fitzgerald, Jr., R. E. Eakin, and W. Shive. Synthesis and Biological Activity of Some 6-(Substituted)thiopurines. J. Org. Chem., 21, 1330–1331 (1956).

433. Ifland, P. W., and W. Shive. The Inhibition of Aspartic Acid Utilization in the Synthesis of the Adaptive "Malic Enzyme" in Lactobacillus arabinosus. J. Biol. Chem., 223, 949957 (1957).

434. Skinner, Charles G., J. R. Claybrook, F. D. Talbert, and W. Shive. Stimulation of Seed Germination by 6-(Substituted)thiopurines. Arch. Biochem. Biophys., 65, 567569 (1956).

435. Dunn, F. W., J. M. Ravel, B. F. Mollenhauer, and W. Shive. A Study of Growth Inhibitions by Thienylpyruvic Acid and Related Compounds. J. Biol. Chem., 223, 959–967 (1956).

436. Ham, R. G., D. C. Fitzgerald, Jr., and R. E. Eakin. Effects of lithium ion on regeneration of hydra in a chemically defined environment. J. Exptl. Zool., 133, 559–572 (1956).

437. Huennekens, E. M., S. P. Felton, and E. E. Snell. Lyxoflavin Nucleotides. J. Am. Chem. Soc., 79, 2258–2261 (1957).

438. Longenecker, J. B., and E. E. Snell. Pyridoxal and Metal Ion Catalysis of a b Elimination Reactions of Serine-3-Phosphate and Related Compounds. J. Biol. Chem., 225, 409–417 (1957).

439. Longenecker, J. B., and E. E. Snell. The Comparative Activities of Metal Ions in Promoting Pyridoxal-catalyzed Reactions of Amino Acids. J. Am. Chem. Soc., 79, 142–145 (1957).

440. Skinner, C. G., J. R. Claybrook, F. Talbert, and W. Shive. Effect of 6-(Substituted) Thio- and Amino-Purines on Germination of Lettuce Seed. Plant Physiology, 32, 117–120 (1957).

441. Shaw, W. H. R., and B. Grushkin. The Toxicity of Metal Ions to Aquatic Organisms. Arch. Biochem. Biophys., 67, 447–452 (1957).

442. Ikawa, M., and J. S. O’Barr. Synthesis of Pantoic Acid and Its Congenera by Neurospora. Soc. Exptl. Biol. Med., 94, 334–337 (1957).

443. Kihara, K., and E. E. Snell. The Enzymatic Cleavage of Canavanine to O-Ureidohomo-serine and Ammonia. J. Biol. Chem., 226, 485–495 (1957).

444. Longenecker, J. B., and E. E. Snell. The Comparative Activities of Metal Ions in Promoting Pyridoxal-catalyzed Reactions of Amino Acids, J. Am. Chem. Soc., 79, 142-145 (1957).

445. Rogers, L. L., and R. B. Pelton. Effect of Glutamine on IQ Scores of Mentally Deficient Children. Texas Rpts. Biol. Med., 15, 84–90 (1957).

446. Reed, L. J. The Chemistry and Function of Lipoic Acid. Advances in Enzymology, 18, 319–347 (1957).

447. Skinner, C. G., P. D. Gardner, and W. Shive. Synthesis and Biological Activity of Some 6-(Substituted)-aminopurines. J. Am. Chem. Soc., 79, 2843–2846 (1957).

448. Singer, H., and W. Shive. Synthesis of 7-Nitroindole. J. Org. Chem., 22, 84–85 (1957).

449. Gorton, B. S., and W. Shive. Synthesis of 1-Deazaguanine. J. Am. Chem. Soc., 79, 670–672 (1957).

450. Williams, R. J. Biochemical Genetics and Its Human Implications, Acta genet., 7, 163–175 (1957).

451. Williams, R. J. Normal Young Men, Persp. Biol. Med., l, 97–104 (1957).

452. Williams, R. J. Standard Human Beings versus Standard Values. Science, 126, 453–4 (1957).

453. Williams, R. J. Individuality and Education. Educational Leadership (December, 1957).

454. Williams, R. J. Weight Control as a Biological Process. Nutrition News, 20, (December, 1957).

455. Williams, R. J. Improved Teaching of Chemistry Held Responsibility of All. New York J. Commerce (September 10, 1957).

456. Williams, R. J. Fiddlers’ Dreams, Chem. & Engr. News, 49, 116–120 (1957).

457. Williams, R. J. Forty Ways to be Dumb. J. Chem. Ed., 34, 261 1957).

458. Williams, R. J. The Importance of Foundation Supported Research in Texas. Conference of Southwest Foundation Newsletter, 1, 1 (1957).

459. Skinner, C. G., and W. Shive. Effect of Some Isomeric Purine Analogues on Germination of Lettuce Seed. Plant Physiology, 32, 500–501 (1957).

460. Rogers, L. L., and R. B. Pelton. Effect of Some Glutamine Antagonists on Alcohol Consumption by Rats. (Presented to Fed. of Am. Societies for Exptl. Biology, April,1957, Chicago, Ill.) Fed. Proc., 16, 238–239 (1957). (ABSTRACT)

461. Ham, R. G., and R. E. Eakin. Use of Hydra for Biochemical Studies on Regeneration. (Presented to Fed. of Am. Societies for Exptl. Biology, April, 1957, Chicago, Ill.) Fed. Proc., 16, 191 (1957). (ABSTRACT)

462. Gorton, B. S., C. G. Skinner, and R. E. Eakin. Activity of Some 6-(Substituted) Purines on the Development of the Moss Tortella caespitosa. Arch. Biochem. Biophys., 66, 493–496 (1957).

463. Reed, L. J. Metabolism and Function of Lipoic Acid. Proc. Int. Symposium on Enzyme Chem.—Tokyo and Kyoto, 71–77 (1957).

464. Rogers, L. L., and R. B. Pelton. Glutamine in the Treatment of Alcoholism. A Preliminary Report. Quarterly J. Studies on Alcohol, 18, 581–587 (1957).

465. Dunri, F. W., J. Humphreys, and W. Shive. Utilization of Tripeptides Arch. Biochem. Biophys., 71, 475–476 (1957).

466. Ravel, J. M., J. M. Estes, B. F. Mollenhauer, and W. Shive. Some Inhibitory Properties of Carbamyl Phosphate J. Biol. Chem., 229, 93–99 (1957).

467. Longenecker, J. B., M. Ikawa, and E. E. Snell. The Cleavage of a-Methylserine and a-Methylolserine by Pyridoxal and Metal Ions. J. Biol. Chem., 226, 663–666 (1957).

468. Fisher, J. R., and R. E. Eakin. Nitrogen Excretion in Developing Chick Embryos. J. Embryol. Exptl. Morph., 5, 215–224 (1957).

469. Gorton, B. S., and R. E. Eakin. Development of the Gametophyte in the Moss Tortella caespitosa. Botanical Gazette, 119, 31–38 (1957).

470. Shive, W., R. N. Snider, B. DuBilier, J. C. Rude, G. E. Clark, Jr., and J. O. Ravel. Glutamine in Treatment of Peptic Ulcer, Texas State J. Med., 53, 840–843 (1957).

471. McCord, T. J., J. M. Ravel, G. G. Skinner, and W. Shive. DL-4-Oxalysine, an Inhibitory Analog of Lysine. J. Am. Chem. Soc., 79, 5693–5696 (1957).

472. Edelson, J., P. R. Pal, G. G. Skinner, and W. Shive. Synthesis of 2-Cyclohexene-1-glycine and 1-Gyclohexene-l-alanine, Inhibitory Amino Acid Analogs. J. Am. Chem. Soc., 79, 5209–5212 (1957).

473. Gawienowski, A. M. The Detection of Iodine-Containing Compounds on Paper Chromatograms. The Analyst, 82, 452–453 (1957).

474. Behal, F. J., and R. E. Eakin. Biochemical Studies of Differentiation in Aspergillus niger. Fed. Proc., 17, 188 (1958).

475. Ham, R. G. Chemically-Induced Loss of Regenerative Capacity in Hydra. Fed. Proc., 17, 236 (1958). (ABSTRACT)

476. Lamford, E. M., Jr., W. M. Harding, and W. Shive. Thymidine Determination by Some Microbiological Assay Methods, Arch. Biochem. Biophys., 73, 180–190 (1958).

477. Lamford, E. M. Jr., G. G. Skinner, and W. Shive. Augmented Inhibition by Kinetin and Related Compounds of Growth of Pteridine-Inhibited Lactobacillus arabinosus, Archives Biochem. Biophys., 73, 191–197 (1958).

478. Skinner, C. G., F. D. Talbert., and W. Shive. Effect of 6-(Substituted) Purines and Gibberellin on the Rate of Seed Germination. Plant Physiology, 33, 190–194 (1958).

479. Ravel, J. M., T. J. McCord, C. O. Skinner, and W. Shive. S-Carbamyl-L-Cysteine, An Inhibitory Amino Acid Analogue. J. Biol. Chem., 232, 159–168 (1958).

480. Edelson, J., J. D. Fissekis, C. G. Skinner, and W. Shive. 3-Cyclohexene-l-glycine, an Isoleucine Antagonist, J. Am. Chem. Soc., 80, 2698–2700 (1958).

481. Ravel, J. M., M. L. Grona, J. S. Humphreys, and W. Shive. Role of Biotin in Carbamylation Reactions. J. Am. Chem. Soc., 80, 2344 (1958).

482. Mefferd, R. B., Jr., W. W. Webster, and M. A. Nyman. Lipid Metabolism in X-Irradiated Mice and Rats. Radiation Res., 8, 461–465 (1958).

483. Mefferd, R. B., Jr., and H. B. Hale. Effects of Thermal Conditioning on Metabolic Responses of Rats to Altitude. Am. J. Physiology, 195, 735–738 (1958).

484. Mefferd, R. B., Jr., M. A. Nyman, and W. W. Webster. Whole Body Lipid Metabolism of Rats After Chronic Exposure to Adverse Environments. Am. J. Physiology, 195, 744–746 (1958).

485. Mefferd, R. B., Jr., and H. B. Hale. Effects of Abrupt Temperature Changes on Excretion Characteristics of Rats Acclimated to Cold, Neutral or Hot Environments. Am. J. Physiology, 195, 726–734 (1958).

486. Hale, H. B., and R. B. Mefferd, Jr. Metabolic Responses to Thermal Stressors of Altitude-Acclimated Rats. Am. J. Physiology, 195, 739–743 (1958).

487. Dalal, U. C., A. Taylor, and G. F. McKenna. The Effect of Plant Extracts on Egg Cultivated Tumor Tissue. Texas Rpts. Biol. Med., 16, 439–442 (1958).

488. Shive, W., and C. G. Skinner. Metabolic Antagonists. Annual Rev. Biochem., 27, 643–678 (1958).

489. Skinner, C. G., J. R. Claybrook, D. L. Ross, and W. Shive. Synthesis of Some alpha- and beta-(6-Purinylthio) carboxylic Acids. 1. Org. Chem., 23, 1223–1224 (1958).

490. Skinner, C. G., G. F. McKenna, T. J. McCord, and W. Shive. Antitumor Activity of Some Amino Acid Analogues. Texas Rpts. Biol. Med., 16, 493–499 (1958).

491. McCord, T. J., J. M. Ravel, C. G. Skinner, and W. Shive. O-Carbazyl-DL-serine, an Inhibitory Analog of Glutamine. J. Am. Chem. Soc., 80, 3762–3764 (1958).

492. Davis, A. L., J. M. Ravel, C. G. Skinner, and W. Shive. The Synthesis and Biological Activity of Some Diamino Acid Analogs. Arch. Biochem. Biophys., 76, 139–147 (1958).

493. Hale, H. B., and R. B. Mefferd, Jr. Factorial Study of Environmentally-Induced Metabolic Changes in Rats. Am. J. Physiology, 194, 469–475 (1958).

494. Mefferd, R. B., Jr., H. B. Hale, and H. H. Martens. Nitrogen and Electrolyte Excretion of Rats Chronically Exposed to Adverse Environments. Am. J. Physiology, 192, 209–218 (1958).

495. Criscuolo, D., H. B. Hale, and R. B. Mefferd, Jr. Oxygen Transport, Utilization and Storage in Rats Acclimated to Altitude at Different Temperatures, 13, 353–356 (1958).

496. Ham, R. G., and R. E. Eakin. Time Sequence of Certain Physiological Events During Regeneration in Hydra. J. Exptl. Zool., 139, 33–54 (1958).

497. Ham, R. G., and R. E. Eakin. Loss of Regenerative Capacity in Hydra Treated with Lipoic Acid. J. Exptl. Zool., 139, 55–68 (1958).

498. McCord, T. J., C. G. Skinner, and W. Shive. Some O-(Substituted Carbamyl) Serines. J. Org. Chem., 23, 1963–1965 (1958).

499. Sund, R. F., J. M. Ravel, and W. Shive. Ornithine-Citrulline Enzyme Synthesis in Biotin-Deficient Cells of Streptococcus Lactis. J. Biol. Chem., 231, 807–811 (1958).

500. Gorton, B. S., J. M. Ravel, and W. Shive. Deazapteridines and Deazapurines Inhibitory Analogues of Folic Acid and Guanine. J. Biol. Chem., 231, 331–338 (1958).

501. Ball, E., J. Humphreys, and W. Shive. Some Antagonisms between Naturally Occurring Amino Acids, Peptides and Keto Acids in Adaptive Enzyme Synthesis and Growth. Arch. Biochem. Biophys., 73, 410–419 (1958).

502. Ifland, P. W., E. Ball, F. W. Dunn, and W. Shive. Peptide and Keto Acid Utilization in Replacing Phenylalanine in Adaptive Enzyme Synthesis. J. Biol. Chem., 230, 897–904 (1958).

503. Skinner, C. G., and W. Shive. Synergistic Effect of Gibberellin and 6-(Substituted)purines on Germination of Lettuce Seed. Arch. Biochem. Biophysics, 74, 283–285 (1958).

504. Williams, R. J. Clinical Implications of Biochemical Differences Between Individuals. Modern Medicine, 26, 134–159 (1958).

505. Williams, R. J. The Improper Study of Mankind. The Texas Quarterly, 1, 16–32 (1958).

506. Williams, R. J. Individuality and Its Significance in Human Life (CHAPTER) In Essays on Individuality, Felix Morley (ed.) Univ. Penn. Press, Philadelphia, 125–145 (1958).

507. Williams, R. J. Chemical Anthropology—An Open Door. Am. Scientist, 46, 1–23 (1958).

508. Williams, R. J., R. B. Pelton, H-M. Hakkinen, and L. L. Rogers. Identification of Blood Characteristics Common to Alcoholic Males. Proc. Natl. Acad. Sci., 44, 216–222 (1958).

509. Mefferd, R. B., Jr., E. H. LaBrosse, A. M. Gawienowski, and R. J. Williams. Influence of Chlorpromazine on Certain Biochemical Variables of Chronic Male Schizophrenics. J. Nervous & Mental Disease, 127, 167–179 (1958).

510. Williams, R. J. Identifying and Treating Potential Alcoholics. J. Criminal Law, Criminology and Police Science, 49, 218–221 (1958).

511. Pelton, R. B., and R. J. Williams. Effect of Panthothenic Acid on Longevity of Mice. Soc. Exptl. Biol. Med., 99, 632–633 (1958).

512. Reed, L. J., M. Koike, M. E. Levitch, and F. R. Leach. Studies on the Nature and Reactions of Protein-Bound Lipoic Acid. J. Biol. Chem., 232, 143–158 (1958).

513. Reed, L. J., F. R. Leach, and M. Koike. Studies on a Lipoic Acid-Activating System. J. Biol. Chem., 232, 123–142 (1958).

514. McKenna, G. F., A. Taylor, and N. Carmichael. Cancer Chemotherapy with Plant Extracts. Texas Rpts. Biol. Med., 16, 203–214 (1958).

515. Rogers, L., and R. B. Pelton. Effect of Behavior-Altering Drugs on Alcohol Consumption by Rats. Texas Rpts. Biol. Med., 16, 133–136 (1958).

516. Shaw, W. H. R. Kinetics of Enzyme Catalyzed Reactions in the Presence of Inhibitors. Chemical Warfare Laboratories Special Publication 3—Report of Symposium LX, (June, 1958).

517. Williams, R. J. Nutritional Insurance With Vitamins: Available But Not Simple. Chem. & Engineering News, 37, 86–89 (1959).

518. Pelton, R. B., R. J. Williams, and L. L. Rogers. Metabolic Characteristics of Alcoholics. I. Response to Glucose Stress Quarterly J. Studies on Alcohol, 20, 28–32 (1959).

519. Skinner, C. G., and W. Shive. Stimulation of Lettuce Seed Germination by 6-(Substituted) Purines. Plant Physiology, 34, 1–3 (1959).

520. Rogers, L. L., and A. M. Gawienowski. Metabolic Characteristics of Alcoholics. II. Serum Copper Concentrations in Alcoholics. Quarterly J. Studies on Alcohol, 20, 33–37 (1959).

521. Koike, M., and L. J. Reed. On the Mechanism of Oxidative Decarboxylation of Pyruvate. J. Am. Chem. Soc., 81, 505 (1959).

522. Reed, L. J., A. C. Schram, and L. E. Loveless. Inhibition of Saccharomyces cerevisiae by p-Aminobenzoic Acid and Its Reversal by the Aromatic Amino Acids. J. Biol. Chem., 234, 904–908 (1959).

523. Nawa, H., W. T. Brady, M. Koike, and L. J. Reed. On the Nature of Protein-Bound Lipoic Acid. J. Am. Chem. Soc., 81, 2908 (1959).

524. Fissekis, J. D., C. G. Skinner, and W. Shive. Synthesis and Biological Activity of Some Cycloalkaneglyoxylic Acids. J. Am. Chem. Soc., 81, 2715–2718 (1959).

525. Ravel, J. M., M. L. Grona, J. S. Humphreys, and W. Shive. Properties and Biotin Content of Purified Preparations of the Ornithine-Citrulline Enzyme of Streptococcus lactis. J. Biol. Chem., 234, 1452–1455 (1959).

526. Leonard, E. O., C. G. Skinner, E. M. Lansford, Jr., and W. Shive. Synthesis and Biological Activity of Some 2-Amino-6-(substituted)-purines. J. Am. Chem. Soc., 81, 907–909 (1959).

527. Edelson, J., C. G. Skinner, and W. Shive. Synthesis and Biological Activity of Some N (Substituted) Glutamines. J. Medicinal and Pharmaceutical Chem., 1, 165–170 (1959).

528. Edelson, J., C. G., Skinner, J. M. Ravel, and W. Shive. 3-Cyclohexene-l-DL-alanine, an Analog of Leucine. Arch. Biochem. Biophys., 80, 416–420 (1959).

529. McKenna, G. F., A. Taylor, and B. S. Gibson. Further Studies of Plant Extracts in Cancer Chemotherapy. Texas Rpts. Biol. Med., 17, 123–133 (1959).

530. Ravel, J., F. Hunter, and W. Shive. The Effect of Proline on Pyrimidine Inhibition of Aspartate Carbamyl Transferase Synthesis. Fed. Proc., 18, 1217 (1959). ABSTRACT.

531. Behal, F. J., and R. E. Eakin. Inhibition of Mold Development by Purine and Pyrimidine Analogs. Arch. Biochem. and Biophys., 82, 439–447 (1959).

532. Behal, F. J., and R. E. Eakin. Metabolic Changes Accompanying the Inhibition of Spore Formation in Aspergillus niger. Arch. Biochem. Biophys., 82, 448–454 (1959).

533. Williams, R. J. Alcoholism: The Nutritional Approach (Book) The University of Texas Press, Austin (1959).

534. Williams, R. J. Individuality of Amino Acid Needs (CHAPTER) in Protein and Amino Acid Nutrition, Anthony A. Albanese (ed.) Academic Press, New York and London, 45–56 (1959).

535. Williams, R. J. Biochemical Individuality and Cellular Nutrition: Prime Factors in Alcoholism. Quarterly J. Studies on Alcohol, 20, 452–463 (1959).

536. Williams, R. J. A Nutritional Approach to Alcoholism. First International Conference on the Alcoholic Beverages Research, June 2–4, 1958, C. Radouco-Thomas (ed.), Pool Finsec S.A., Lausanne, 29–34 (1959).

537. Williams, R. J. The Functioning of Vitamins and Hormones. J. Chem. Ed., 36, 538–539 (1959).

538. Siegel, F. L., and R. J. Williams. The Use of Baby Chicks in Studying Inherent Individuality and its Relationship to Alcoholism. First International Conference on the Alcoholic Beverages Research, June 2–4, 1958, C. Radouco-Thomas (ed.), Pool Finsec S.A., Lausanne, 35–37 (1959).

539. Henderson, R. F., and R. E. Eakin. Alteration of Regeneration in Planaria Treated with Lipoic Acid. J. Exptl. Zool., 141, 175–190 (1959).

540. Ross, D. L., C. G. Skinner, and W. Shive. O-(Substituted)-alpha-amino-beta-hydroxybutyric Acids. J. Org. Chem., 24, 1440–1442 (1959).

541. Fissekis, J. D., C. G. Skinner, and W. Shive. Synthesis of Some Heterocyclic Derivatives of alpha-Keto Acids. J. Org. Chem., 24, 1722–1725 (1959).

542. Ross, D. L., C. G. Skinner, and W. Shive. 2-Amino-2-carboxyethanesulfonamide. J. Org. Chem., 24, 1372–1373 (1959).

543. Ravel, J. M., R. F. Sund, and W. Shive. Protection and Reactivation of Carbamyl Phosphate Synthetase with Sulfate. Biochem. Biophys. Res. Comm., 1, 186–190 (1959).

544. Lansford, E. M., Jr., W. Shive. A Study of the Interactions of Folio Acid Analogues and 6-(Substituted) purines as Growth Inhibitors. J. Medicinal and Pharmaceutical Chem., 1, 245–262 (1959).

545. Edelson, J., C. G. Skinner, J. M. Ravel, and W. Shive. Structural Specificity of Some Amino Acid Antagonists. J. Am. Chem. Soc., 81, 5150–5153 (1959).

546. Ravel, J. M., F. Hunter, and W. Shive. The Effect of Glycine on the Uracil Inhibition of Aspartate Transcarbamylase Synthesis in Escherichia coli W. Biochem. Biophys. Res. Comm., 1, 115–117 (1959).

547. Gilbert, J. B., and Y. Ku. Urinary Excretion of a Ninhydrin-Positive Compound, Probably a Peptide, after Administration of b-Aminoisobutyric Acid to the Mouse. Nature, 186, 160–161 (1960).

548. Fissekis, J. D., C. G. Skinner, and W. Shive. Cycloalkyl Analogs of Pantothenic Acid. J. Am. Chem. Soc., 82, 1654 (1960).

549. Fissekis, J. D., C. G. Skinner, and W. Shive. N-Pantoyl-(Substituted)Amines, Pantothenic Acid Analogues. J. Medicinal and Pharmaceutical Chem., 2, 47–56 (1960).

550. Davis, A. L., C. G. Skinner, and W. Shive. 3-Aminomethylcyclohexaneglycine, a Lysine Analog. Arch. Biochem. Biophys., 87, 88–92 (1960).

551. Nawa, H., W. T. Brady, M. Koike, and L. J. Reed, Studies on the Nature of Protein-bound Lipoic Acid. J. Am. Chem. Soc., 82, 896–903 (1960).

552. Henderson, T. R. Inhibition of Xanthine Oxidase by Kinetin and Kinetin Analogues. Fed. Proc., 19, 314 (March, 1960). ABSTRACT

553. Claybrook, D. L., and R. E. Eakin. A Heat-Inactivated Factor Required for Asexual Growth of Hydra. Fed. Proc., 19, 325 (March, 1960). ABSTRACT

554. Siegel, F. L., and R. J. Williams. Response Patterns to Alcohol in Baby Chicks (ABSTRACT). Fed. Proc., 19, 40 (1960).

555. Reed, L. J. Lipoic Acid (CHAPTER) in The Enzymes, (P. D. Boyer, H. Lardy, and K. Myrback, eds.) 3, Academic Press, New York, 195–223 (1960).

556. Edelson, J., J. Humphreys, and W. Shive. Utilization of Amino Acid Esters by Intact Cells. Texas Rpts. Biol. Med., 18, 596–601 (1960).

557. Fissekis, J. D., C. G. Skinner, and W. Shive. Cycloalkyl Analogs of Pantothenic Acid. J. Am. Chem. Soc., 82, 1654–1656 (1960).

558. Skinner, C. G., and W. Shive. N-Substituted N-Phenylureas. J. Org. Chem., 25, 2046–2047 (1960).

559. Lansford, E. M., Jr., I. D. Hill, and W. Shive. Reversal by Ribonucleosides of Bacterial Growth Inhibition Caused by Alcohol. J. Biological Chem., 235, 3551–3555 (1960).

560. McDuffie, N. G., Jr., B. S. Gibson, and A. Taylor. Study of Toxic Factors Associated with Mouse Mammary Carcinomas in Egg Cultures. Cancer Res., 20, 1631–1635 (1960).

561. Taylor, A., and N. Carmichael. Toxic Factor Associated with Egg-Cultivated Tumors. Cancer Res., 20, 1636–1639 (1960).

562. Williams, R. J. Why Human Genetics? J. Heredity, 51, 91–98 (1960).

563. Williams, R. J. The Biological Approach to the Study of Personality (Presented to Berkeley Conf. on Personality Development in Childhood, Univ. of Calif., May 5, 1960.)

564. McKenna, G. F., A. Taylor, and B. S. Gibson. Extracts of Plants and Cancer Chemotherapy. Texas Rpts. Biol. Med., 18, 233–246 (1960).

565. Rogers, L. L., and A. W. Newton. Serum Electrolytes in Mentally Retarded Children Fed L-Glutamine. Fed. Proc., 19, 20 (March, 1960) ABSTRACT.

566. Crane, F. L. Quinones in Electron Transport. I. Coenzymatic Activity of Plastoquinone, Coenzyme Q, and Related Natural Quinones. Arch. Biochem. Biophys., 87, 198–202 (1960).

567. Jacobs, E. E., and F. L. Crane. Phosphorylation Coupled to Electron Transport Mediated by Short Chain Derivatives of Coenzyme Q. Biochem. Biophys. Res. Comm., 2, 218–221 (1960).

568. Crane, F. L., and B. Ehrlich. Quinones in Electron Transport. II. Influence of Accessory Lipid Factors on the Activity of Coenzyme Q Analogs. Arch. Biochem. Biophys., 89, 134–138 (1960).

569. Crane, F. L., B. Ehrlich, and L. P. Kegel. Plastoquinone Reduction in Illuminated Chloroplasts. Biochem. Biophys. Res. Comm., 3, 37–40 (1960).

570. Koike, M., L. J. Reed, and W. R. Carroll. a-Keto Acid Dehydrogenation Complexes I. Purification and Properties of Pyruvate and a-Ketoglutarate Dehydrogenation Complexes of Escherichia coli. J. Biol. Chem., 235, 1924–1930 (1960).

571. Koike, M., and L. J. Reed, a-Keto Acid Dehydrogenation Complexes II. The Role of Protein-Bound Lipoic Acid and Flavin Adenine Dinucleotide. J. Biol. Chem., 235, 1931–1938 (1960).

572. Koike, M., P. C. Shah, and L. J. Reed. a-Keto Acid Dehydrogenation Complexes III. Purification and Properties of Dihydrolipoic Dehydrogenase of Escherichia coil, J. Biol. Chem., 235, 1939–1943 (1960).

573. Jacobs, E. E., and F. L. Crane. Uncoupling and Inhibition of Succinate Oxidation by Short Chain Derivatives of Coenzyme Q. Biochem. Biophys. Res. Comm., 3, 333–336 (1960).

574. Shaw, W. H. R. Studies in Biogeochemistry I and II. Geochimica et Cosmochimica Acta, 19, 196–207 (1960).

575. Spangenberg, D. B., and R. G. Ham. The Epidermal Nerve Net of Hydra. J. Exptl. Zool., 143, 195–202 (1960).

576. Henderson, R. F., and R. E. Eakin. Inhibition of Malic Dehydrogenase by Cyclic Disulfides. Biochem. Biophys. Res. Comm., 3, 169–172 (1960).

577. Williams, R. J. Vitamins as Medicinal Agents. J. Chem. Ed., 37, 177 (1960).

578. Gilbert, J. B., Y. Ku, L. L. Rogers, and R. J. Williams. The Increase in Urinary Taurine after Intraperitoneal Administration of Amino Acids to the Mouse. J. Biological Chem., 235, 1055–1060 (1960).

579. Williams, R. J. Etiological Research in the Light of the Facts of Individuality. Texas Rpts. Biol. Med., 18, 168–185 (1960).

580. Claybrook, D. L., and R. E. Eakin. A Nutritional Requirement for Asexual Reproduction of Hydra. J. Exptl. Zool., 145, 179–190 (1960).

581. Das, M. L., M. Koike, and L. J. Reed. On the Role of Thiamine Pyrophosphate in Oxidative Decarboxylation of a-Keto Acids. Proc. Natl. Acad. Sci., 47, 753–759 (1961).

582. Koike, M., and L. J. Reed. Resolution and Reconstitution of the Escherichia coli Pyruvate Dehydrogenation Complex. J. Biol. Chem., 236, PC33–PC34 (1961).

583. McKenna, G. F., A. Taylor, and C. C. Albers. Essential Oils, Plant Extracts and Chemicals from Plants in Cancer Chemotherapy. Texas Rpts. Biol. Med., 19, 321–326 (1961).

584. Claybrook, J. R., and R. E. Eakin. Effects of Thyroxine on Amphibian Pancreas: Digestive Enzyme Levels and Subcellular Structure in Metamorphosis. Fed. Proc., 20, 206 (1961). ABSTRACT

585. Spangenberg, D. B., and D. L. Claybrook. Infection of Hydra by Microsporidia, J. Protozoology, 8, 151–152 (1961).

586. Hayashi, K., C. G. Skinner, W. Shive. Thioester Analogs as Non-Competitive Metabolic Antagonists. Texas Rpts. Biol. Med., 19, 277–282 (1961).

587. Shive. W. Some Effects of Spermine Related to Deoxyribonucleic Acid. Proceedings of the Robert A. Welch Foundation Conferences on Chemical Research V. Molecular Structure and Biochemical Reactions, Houston, Texas, 221–226, December 4–6 (1961).

588. Williams, R. J. Biochemical Individuality (ARTICLE) in Encyclopedia of Biological Sciences, Peter Gray (ed.) Reinhold Publishing Corp., New York, (1961).

589. Williams, R. J. On Individuality. The Graduate Journal, IV (1), 134–141 (1961).

590. Williams, R. J., and F. L. Siegel. The Physiological Effects of Alcohol in Relation to the Problem of Alcoholism. Advances in Alcohol and Alcoholic Beverages Research, Gl. Nosal (ed.), Pool Finsec, Geneva, Switzerland, 2, 10–17 (May, 1961).

591. Williams, R. J., and F. L. Siegel. "Propetology," A New Branch of Medical Science? Am. J. Med., XXXI (3), 325–327 (1961).

592. Williams, R. J. Investigation of Disease Resistance and the Mathematical Problem of Patterns. Proc. Natl. Acad. Sci., 47, 221–224 (1961).

593. Williams, R. J. The Expanding Horizon in Nutrition. Texas Rpts. Biol. Med., 19, 245–258 (1961).

594. Leonard, E. O., C. G. Skinner, and W. Shive. Synthesis of 2-Fluoro-6-benzylaminopurine and Other Purine Derivatives. Arch. Biochem. Biophys., 92, 33–37 (1961).

595. Reed, L. J. Biochemistry of a-Keto Acid Dehydrogenation Complexes. Proceedings of the Robert A. Welch Foundation Conferences on Chemical Research. V. Molecular Structure and Biochemical Reactions, Houston, Texas, 117–127. December 4–6 (1961).

596. Ravel, J. M., J. S. Humphreys, and W. Shive. A Study of Carbamyl Phosphate Synthesis in Streptococcus lactis. Arch. Biochem. Biophys., 92, 525–531 (1961).

597. Skinner, C. G., J. Edelson, and W. Shive. A Conformation of Methionine Essential for its Biological Utilization. J. Am. Chem. Soc., 83, 2281–2285 (1961).

598. Davis, A. L., C. G. Skinner, and W. Shive. The Conformation of Lysine on its Site of Biological Utilization. J. Am. Chem. Soc., 83, 2279–2281 (1961).

599. Ross, D. L., C. G. Skinner, and W. Shive. S-(Alkyl- and Arylcarbamoyl)-L-Cysteines. J. Medicinal & Pharmaceutical Chem., 3, 519–524 (1961).

600. Hayashi, K., C. G. Skinner, and W. Shive. Synthesis and Biological Properties of 4Amino-5-isopropyl-3-isoxazolidone, a Substituted Cycloserine. J. Org. Chem., 26, 1167–1170 (1961).

601. Norton, S. 3, C. G. Skinner, and W. Shive. DL-5-Hydroxy-2-pyridinealanine, a Tyrosine Analog. J. Org. Chem., 26, 1495–1498 (1961).

602. Fradejas, R. G., J. M. Ravel, and W. Shive. The Control of Shikimic Acid Synthesis by Tyrosine and Phenylalanine. Biochem. Biophys. Res. Comm., 5, 320–323 (1961).

603. Shaw, W. H. R., and D. N. Raval. The Inhibition of Urease by Metal Ions at pH 8.9. J. Am. Chem. Soc., 83, 3184–3187 (1961).

604. Siegel, F. L., and M. K. Roach. b-2-Thienyl-DL-alanine, Internal Standard for Automatic Determination of Amino Acids. Analytical Chem., 33, 1628 (1961).

605. Reed, L. J. Lipoic Acid (CHAPTER 36) in Organic Sulfur Compounds, Pergamon Press, London and New York, 443–452, (1961).

606. Taylor, A., and G. F. McKenna. A New Mouse Strain Susceptible to Mammary Cancer. Texas Rpts. Biol. Med., 19, 706–708 (1961).

607. Skinner, C. G., C. Hedgcoth, and D. Wagner. Synergistic Effects on Germination of Mixtures of 6-Benzyl-aminopurine and various Gibberellins. Phyton, 17(2), 141–145, XII-(1961).

608. Skinner, C. G., G. F. McKenna, D. L. Ross, and W. Shive. Antitumor Activity of Amino Acid Analogs. II. S-Methylcarbamoyl-L-Cysteine. Texas Rpts. Biol. Med., 19, 860–865 (1961).

609. Ravel, J. M., B. F. Mollenhauer, and W. Shive. The Indirect Role of Biotin in the Synthesis of Ornithine Transcarbamylase. J. Biol. Chem., 236, 2268–2270 (1961).

610. Maung, M. C., C. G. Skinner, and W. Shive. Biological Activities of Some Homologs of Isoleucine and Valine. Texas Rpts. Biol. Med., 19, 801–810 (1961).

611. Smith, L. C., C. G. Skinner, and W. Shive. Structural Requirements for Phenylalanine Antagonism. Arch. Biochem. Biophys.,, 94, 443–448 (1961).

612. Ross, D. L., C. G. Skinner, and W. Shive. 9-Ribityl Derivatives of Guanine and 8-Aza-guanine. J. Org. Chem., 26, 3582–3583 (1961).

613. Ables, P. G., J. M. Ravel, and W. Shive. The Indirect Role of Biotin in the Synthesis of the Malic Enzyme. J. Biol. Chem., 236, 3263–3266 (1961).

614. Parker, E. D., C. G. Skinner, and W. Shive. Biological Specificities of 4,5-Dehydro Analogues of Isoleucine and Alloisoleucine. J. Biol. Chem., 236, 3267–3271 (1961).

615. Spangenberg, D. B. A Study of Normal and Abnormal Regeneration of Hydra. The Biology of Hydra (Symposium), University of Miami Press, Coral Gables, Fla., 413–423 (1961).

616. Eakin, R. E. Studies on Chemical Inhibition of Regeneration in Hydra. The Biology of Hydra (Symposium), University of Miami Press, Coral Gables, Fla., 399–412 (1961).

617. Henderson, T. R., and R. E. Eakin. Irreversible Alteration of Differentiated Tissues in Planaria by Purine Analogues. J. Exptl. Zool., 146, 253–264 (1961).

618. Spangenberg, D. B., and R. E. Eakin. The Effect of Lipoic Acid on Regeneration of Chlorohydra viridissima. J. Exptl. Zool., 147, 211–218 (1961).

619. Spangenberg, D. B., and R. E. Eakin. A Study of Variation in the Regeneration Capacity of Hydra. J. Exptl. Zool., 147, 259–270 (1961).

620. Henderson, T. R., C. G. Skinner, and R. E. Eakin. Kinetin & Kinetin Analogues as Substrates and Inhibitors of Xanthine Oxidase. Plant Physiology, 37, 552–555 (1962).

621. Koike, M., L. J. Reed, and W. R. Carroll. Molecular Weight and FAD Content of Dihydrolipoic Dehydrogenase from Escherichia coli., 7, 16–17 (1962).

622. Daigo, K., and L. J. Reed. Synthesis and Properties of 2.Acetyl-3,4-dimethylthiazolium Iodide. J. Am. Chem. Soc., 84, 659–662 (1962).

623. Daigo, K., W. T. Brady, and L. J. Reed. Synthesis of Some N-Lipoyl Amino Acids and Peptides. J. Am. Chem. Soc., 84, 662–665 (1962).

624. Reed, L. J. Biochemistry of Lipoic Acid. (Chapter) in Vitamins and Hormones, Vol. 20, Academic Press Inc., New York and London, 1–38 (1962).

625. Gonzalez, E. E., G. F. McKenna, and J. N. Delgado. Anticancer Evaluation of Amphipterygium adstringens. J. Pharmaceutical Sciences, 51, 901–903 (1962).

626. Williams, R. J., Nutrition In A Nutshell, (book) 1962 (paperback); 1963 (hardbound), Doubleday, New York.

627. Williams, R. J., R. B. Pelton, and F. L. Siegel. Individuality as Exhibited by Inbred Animals; Its Implications for Human Behavior. Proc. Natl. Acad. Sci., 48, 1461–1466 (1962).

628. Daigo, K., and L. J. Reed. The Amino Acid Sequence Around the e-N-Lipoyllysine Residue in a-Keto Acid Dehydrogenation Complexes. J. Am. Chem. Soc., 84, 666–671 (1962).

629. Norton, S. J., J. M. Ravel, and W. Shive. Effect of Deoxyribonucleosides on Deoxyribonucleic acid synthesis in Vitamin B-deficient Lactobacillus leichmanni. Biochim. Biophys. Acta, 55, 222–224 (1962).

630. Norton, S. J., M. C. Maung, C. G. Skinner, and W. Shive. Structural Requirements for Phenylalanine Antagonism III. Some Unsaturated Straight-Chain Amino Acids. Arch. Biochem. Biophys., 96, 287–292 (1962).

631. Segal, H., and C. O. Skinner. Nitrogen Mustard Analog of Thiocytosine J. Org. Chem., 27, 199–201 (1962).

632. McKenna, G. F., and A. Taylor. The Effect of Feeding Chelidonium majus L. on the Incidence of Mammary Tumors in Mice. Texas Rpts. Biol. Med., 20, 64–69 (1962).

633. McKenna, O. F., and A. Taylor. Screening Plant Extracts for Anticancer Activity. Texas Rpts. Biol. Med., 20, 214–220 (1962).

634. Spangenberg, D. B., and R. E. Eakin. Histological Studies of Mechanisms Involved in Hydra Regeneration. J. Exptl. Zool., 151, 85–94 (1962).

635. Conway, T. W., E. M. Lamford, Jr., and W. Shive. A Modified Technique Utilizing Membrane Filtration for the Isolation of Nutritionally-Deficient Bacterial Mutants. Texas Rpts. Biol. Med., 20, 362–365 (1962).

636. Smith, L. G., J. M., Ravel, S. R. Lax, and W. Shive. The Control of 3-Deoxy-D-arabinoheptulosonic Acid 7-Phosphate Synthesis by Phenylalanine and Tyrosine. J. Biol. Chem., 237, 3566–3570 (1962).

637. Ravel, J. M., S. J. Norton, J. S. Humphreys, and W. Shive. Asparagine Biosynthesis in Lactobacillus arabinosus and Its Control by Asparagine through Enzyme Inhibition and Repression. J. Biol. Chem., 237, 2845–2849 (1962).

638. Conway, T. W., E. M. Lamford, Jr., and W. Shive. Purification and Substrate Specificity of a Phenylalanine-activating Enzyme from Escherichia coli 9723. J. Biol. Chem., 237, 2850–2854 (1962).

639. Lamford, E. M., Jr., I. D. Hill, and W. Shive. Effects of Asparagine and Other Related Nutritional Supplements upon Alcohol-Induced Rat Liver Triglyceride Elevation. J. Nutrition, 78, 219–222 (1962).

640. Smith, L. C., J. M. Ravel, C. G. Skinner, and W. Shive. 3,4 Dehydroproline, A Proline Antagonist. Arch. Biochem. Biophys., 99, 60–64 (1962).

641. Leonard, E. O., W. H. Orme-Johnson, T. R. McMurtray, C. G. Skinner, and W. Shive. 2-Hydroxy Derivatives of Some Biologically Active 6-(Substituted) purines. Arch. Biochem. Biophys., 99, 16–24 (1962).

642. Segal, H., C. Hedgcoth, and C. G. Skinner. Synthesis and Biological Activity of Some 4-(Substituted amino) pyrimidines. J. Med. and Pharmaceutical Chem., 5, 871–876 (1962).

643. McDuffie, N. G., Jr. Comparison of Mouse Mammary Tumors Fixed with KMnO4 and with Os04. Virology, 18, 501–503 (1962).

644. Parker, E. D., T. J. Cogdell, J. S. Humphreys, C. G. Skinner, and W. Shive. N-Pantoyl(substituted-phenyl) alkylamines, Inhibitory Analogs of Pantothenic Acid. J. Med. Chem., 6, 73–76 (1963).

645. Shive, W., and C. G. Skinner. Amino Acid Analogues (CHAPTER) in Metabolic Inhibitors, 1 (J. H. Quastel and R. M. Houchster, eds.), Academic Press, Inc., New York, N.Y., 1–73. (1963).

646. Smith, L. C., J. S. Humphreys, C. G. Skinner, and W. Shive, Biological Activities of Some Amino Acid Analogs. III. S-(Substituted-Thiocarbamoyl)-L-Cysteines. Texas Rpts. Biol. Med., 21, 296–301 (1963).

647. Ball, Sister M. I., C. G. Skinner, and W. Shive. Synthesis of Some Carbomoylated Amino Acid Analogs. Texas Rpts. Biol. Med., 21, 168–175 (1963).

648. Norton, S. J., J. M. Ravel, C. Lee, and W. Shive. Purification and Properties of the Aspartyl Ribonucleic Acid Synthetase of Lactobacillus arabinosus. J. Biol. Chem., 238, 269–274 (1963).

649. Gipson, R. M., F. H. Pettit, C. G. Skinner, and W. Shive. Catalytic Hydrogenolysis of Hydroxamic Acids to Amides. J. Org. Chem., 28, 1425– (1963).

650. Ross, D. L., C. G. Skinner, and W. Shive. N-(g-L-Glutamyl) aminobenzoic Acids. J. Medicinal Chem., 6, 208–209 (1963).

651. Turner, R. B., E. M. Lansford, Jr., J. M. Ravel, and W. Shive. A Metabolic Relationship of Spermine to Folinic Acid and Thymidine. Biochemistry, 2, 163–167 (1963).

652. Smith, L. C., K. Hayashi, J. M. Ravel, C. G. Skinner, and W. Shive. Spermine Reversal of Microbial Growth Inhibition by Thioesters of p-Aminosalicylic Acid. Biochemistry, 2, 159–163 (1963).

653. Conway, T. W., E. M. Lamford, Jr., and W. Shive. Influence of Phenylalanine Analogues Upon Bacterial Accumulation and Incorporation of Phenylalanine. J. Bacteriology, 85, 141–149 (1963).

654. Williams, R. J. Are We Prone to Certain Diseases? Alcalde (February, 1963).

655. Williams, R. J. Key to Health: Your Heredity. Science Digest, 31–39 (April, 1963).

656. Williams, R. J. Pantothenic Acid (CHAPTER) in Comprehensive Biochemistry, M. Florkin and E. H. Stotz (eds.) Elsevier Publishing Co., Amsterdam, 59–65, (1963).

657. Taylor, A., and N. C. Taylor. Protective Effect of Symphytum officiale on Mice Bearing Spontaneous and Transplant Tumors. Soc. Exptl. Biol. Med., 114, 772–774 (1963).

658. McDuffie, N. G., Jr. Small Particles Associated with Pox Viruses. J. Bacteriology, 85, 713–715 (1963).

659. Eakin, R. E. An Approach to the Evolution of Metabolism. Proc. Natl. Acad. Sci., 49, 360–366 (1963).

660. Suzuki, K., and L. J. Reed. Lipoamidase. J. Biol. Chem., 238, 40214025 (1963).

661. Orme-Johnson, W. H., and C. G. Skinner. Paper Chromatography Using Liquid Ion Exchangers. J. Chromatography, 11, 549–551 (1963).

662. Hedgcoth, C., J. Ravel, and W. Shive. The Separation of the Aspartyl- and Asparaginyl-RNA Synthetases of Lactobacillus arabinosus. Biochem. Biophys. Res. Comm., 13, 495–499 (1963).

663. Govardham, L. K., and C. G. Skinner. Cyclopentaneglycine (SECTION) in Biochemical Preparations, 10, John Wiley and Sons, Inc., New York, 40–42 (1963).

664. Hedgcoth, C., and C. G. Skinner. b-Hydroxy-DL-Aspartic Acid (SECTION) in Biochemical Preparations, 10, John Wiley and Sons, Inc., New York, 67–72 (1963).

665. McCord, T. J., and C. G. Skinner. O-Carbamoyl-DL-Serine and S-Carbamoyl-L-Cysteine (SECTION) in Biochemical Preparations, 10, John Wiley and Sons, Inc., New York, 18–23 (1963).

666. Koike, M., L. J. Reed, and W. R. Carroll. a-Keto Acid Dehydrogenation Complexes IV. Resolution and Reconstitution of the Escherichia coli Pyruvate Dehydrogenation Complex. J. Biol. Chem., 238, 30–39 (1963).

667. Matthews, J., and L. J. Reed. Purification and Properties of a Dihydrolipoic Dehydrogenase from Spinacia oleracea. J. Biol. Chem., 238, 1869–1876 (1963).

668. Siegel, F. L., and G. Gjerstad. Intermediary Metabolism of Ergot IV. Comparative Amino Acid Metabolism. Planta Medica, 1, 113–118 (1963).

669. Siegel, F. L., M. K. Roach, and W. B. DeVille. Plasma Amino Acid Patterns In Alcoholics: Ethanol Induced Modification. Fed. Proc., 22, 680 (March–April 1963). ABSTRACT.

670. Pettit, F. H., and D. M. Ziegler. The Catalytic Demethylation of N,N-Dimethylaniline-N-Oxide by Liver Microsomes. Biochem. Biophys. Res. Comm., 13, 193–197 (1963).

671. Rogers, L. L., and N. G. Maloney. Uric Acid Excretion in Glutamine-fed Mentally Retarded Children. Proceedings 6th International Congress of Nutrition, Edinburgh, Scotland, (August 9–15, 1963). (ABSTRACT)

672. Siegel, F. L., M. K. Roach, and L. R. Pomeroy. Plasma Amino Acid Patterns in Alcoholism: The Effects of Ethanol Loading. Proc. Natl. Acad. Sci., 51, 606–611 (1964).

673. Siegel, F. L., L. R. Pomeroy, and M. K. Roach. Multiple Discriminant Analysis of Plasma Amino Acid Patterns. Proc. Natl. Acad. Sci., 51, 866–871 (1964).

674. Shive, W. Metabolic Antagonists (CHAPTER) in Symposium on Foods: Proteins and Their Reactions, W. H. Schultz (ed.) The Avi Publishing Company, Inc., Westport, Conn., 389–408 (1964).

675. Orme-Johnson, W. H., J. D. Glass, C. G. Skinner, and W. Shive. Microbial Utilization of Phenylalanyl Peptides. Texas Rpts. Biol. Med., 22, 697–706 (1964).

676. Conway, T. W., E. M. Lansford, Jr., and W. Shive. Inhibition of Bacterial Phenylalanine Utilization and Activation. Arch. Biochem. Biophys., 107, 120–125 (1964).

677. Taylor, A., and N. C. Taylor. The Effect of Sodium Bromide on Tumor Growth. Cancer Res., 24, 751–753 (1964).

678. Ziegler, D. M. and F. H. Pettit. Formation of an Intermediate N-Oxide in the Oxidative Demethylation of N,N-Dimethylaniline Catalyzed by Liver Microsomes. Biochem. Biophys. Res. Comm., 15, 188–193 (1964).

679. Pettit, F. It., W. Orme-Johnson, and D. M. Ziegler. The Requirement for Flavin Adenine Dinucleotide by a Liver Microsomal Oxygenase Catalyzing the Oxidation of Alkylaryl Amines. Biochem. Biophys. Res. Comm., 16, 444–448 (1964).

680. Smith, L. C., J. M. Ravel, S. R. Lax, and W. Shive. The Effects of Phenylalanine and Tyrosine Analogs on the Synthesis and Activity of 3-Deoxy-D-arabino-Heptulosonic Acid 7-Phosphate Synthetases. Arch. Biochem. Biophys., 105, 424–430 (1964).

681. Ravel, J., S-F. Wang, and W. Shive. Separation and Properties of the Glutamyl- and Glutaminyl-tRNA Synthetases of E. coli W. Fed. Proc., 23, 381 (March–April 1964). ABSTRACT

682. Lansford, E. M., Jr., R. B. Turner, C. J. Weathersbee, and W. Shive. Stimulation by Spermine of Tetrahydrofolate Formylase Activity. J. Biol. Chem., 239, 497–501 (7964).

683. Shive, W. Types of Product Regulation of Biological Processes. Sixth International Congress of Biochemistry, New York City, N.Y., (July 26–August 1, 1964). ABSTRACT

684. Fernandez-Moran, H., L. J. Reed, M. Koike, and C. R. Williams. Electron Microscopic and Biochemical Studies of Pyruvate Dehydrogenase Complex of Escherichia coli. Science, 145, 930–932 (1964).

Symposium: Biochemical and Nutritional Aspects of Alcoholism Held in New York, Oct. 2, 1964, under the joint auspices of the Christopher D. Smithers Foundation and the Clayton Foundation Biochemical Institute. Published 93 pages (1965).

685. Williams, R. J. Fundamental Consideration Relating Alcoholism to Biochemistry and Nutrition, 6–16.

686. Shive, W. Glutamine as a General Metabolic Agent Protecting Against Alcohol Poisoning, 17–25.

Fincle, L. P., M.D., Staff Physician, Continued Treatment Service, Veterans Administration Hospital, Bedford, Mass., Experiments in Treating Alcoholics with Glutamic Acid and Glutamine, 26–37.

687. Siegel, F. L., Joseph P. Kennedy, Jr., Laboratory, Department of Pediatrics, University of Wisconsin Medical School, Madison, Wis., Plasma Amino Acid Patterns in Alcoholism. (Based on work done at the Clayton Foundation Biochemical Institute. Publ. 672, 673.), 38–58.

Parry, A. A., M.D., Chief of Alcoholic Service, Morristown Memorial Hospital, Morristown, New Jersey, Nutrition in the Practical Management of Alcoholics, 59–67. Quastel, J. H., Department of Biochemistry, McGill University, and Director, McGill-Montreal General Hospital Research Institute, Montreal, P.Q., Canada, Effects of Alcohols on Brain Metabolism, 68–81.

Vallee, B. L., M.D., Department of Medicine, Harvard Medical School, Boston, Mass., Enzymatic Aspects of Alcoholism, 82–93.

Mendelson, J. H., M.D., Department of Psychiatry, Massachusetts General Hospital, Boston, Mass., Discussant.

Kety, S., M.D., Chief, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Md., Discussant.

688. Mukherjee, B. B., J. Matthews, D. L. Homey, and L. J. Reed. Resolution and Reconstruction of the Escherichia coli a-Ketoglutarate Dehydrogenase Complex. J. Biol. Chem., 240, PC2268–69 (1965).

689. Ravel, J. M., M. N. White, and W. Shive. Activation of Tyrosine Analogs in Relation to Enzyme Repression. Biochem. Biophys. Res. Comm., 20, 352–359 (1965).

690. Ravel, J. M., S-F. Wang, C. Heinemeyer, and W. Shive. Glutamyl and Glutaminyl Ribonucleic Acid Synthetases of Escherichia coli W., J. Biol. Chem., 240, 432–438 (1965).

691. Lloyd, R. F., C. O. Skinner, W. Shive, and R. J. Stedman. a- and g-Glutamyl Derivatives of Aminobenzoic Acids. J. Medicinal Chem., 8, 398–400 (1965).

692. Taylor, A., and N. C. Taylor. Effects of Sodium Fluoride on Tumor Growth. Soc. Exptl. Biol. Med., 119, 252–255 (1965).

693. Shive, W. Some Effects of Spermine Related to Deoxyribonucleic Acid. Proceedings of The Robert A. Welch Foundation Conferences on Chemical Research, V. Molecular Structure and Biochemical Reactions, December 4–6, 1961, Houston, Texas. (printed in 1965).

694. Gipson, R. M., C. G. Skinner, and W. Shive. Relationship of Structure to Biological Activity of Some Unsaturated Derivatives of Cyclopentaneglycine. Arch. Biochem. Biophys., 111, 2 (1965).

695. Ravel, J. M., J. S. Humphreys, and W. Shive. Control of Glutamine Synthesis in Lactobacillus arabinosus. Arch. Biochem. Biophys., 111, 720–726 (1965).

696. Cox, D. J. Computer Simulation of Sedimentation in the Ultracentrifuge I. Diffusion. Arch. Biochem. Biophysics., 112, 249–258 (1965).

697. Cox, D. J. Computer Simulation of Sedimentation in the Ultracentrifuge II. Concentration-Independent Sedimentation. Arch. Biochem. Biophys., 112, 259–266 (1965).

698. Cox, D. J. and J. Hill. Studies of the Sedimentation Velocity of Ovalbumin in Concentrated Salt Solutions. J. Physical Chem., 69, 3032–3043 (1965).

699. Williams, R. J., and R. B. Pelton. Individuality in Nutrition: Effects of Vitamin A-Deficient and Other Deficient Diets on Experimental Animals. Proc. Natl. Acad. Sci., 55, 126–134 (1966).

700. Reed, L. J., and D. J. Cox. Macromolecular Organization of Enzyme Systems. Ann. Rev. Biochem. (in press) (1966).

Scanned references edited and corrected by Donald R. Davis and Marvin L. Hackert, April 2001