edited by
profile/ in chemi/try Helen M. Dyer. A Pioneer in Cancer Research Nina M. Roscher and Chlnh K. Nguyen The American University Washington, DC 20016 "In those days, there was no specialization and the word 'biochemistry' meant the chemistry of proteins, carbohydrates and minerals, enzymes and hormones, vitamins . . . and on and on. Of course, we did not have all the vast information we have now in any of the branches and we were iust startine to learn about them." stated Helen Dver. . .a pioneer in the field of cancer-related biochemistry, during an interview (I).As one of the early women chemists, Helen Marie Dyer applied her scientific know-how to biochemistry and to nutrition. She was inspired by her teachers and colleagues and, in turn, inspired her students. Her life and career were spent methodically, lecturing in university classrooms and performing research in various laboratories. Having written and cowritten more than 60 articles and being the first to have compiled an index on tumor chemotherapy, Dyer is still quite modest ahout the personal and professional accomplishments in her life, the story of which began on an early summer day near the turn of the century. As the second woman to hold office in 1959 in the Washington Chemical Society's history (2),Helen Marie Dyer was born on May 26, 1895, in Georgetown in Washington, DC. Helen's father, Joseph Edwin Dyer, was a local businessman and her mother, Florence Robertson Dyer, was once a public school teacher. They were both Roman Catholics. Unlike her older sister and two older brothers, Helen Dyer was sent to public school. She was enrolled in the old Curtis School in
ROGERR. FESTA Northeast Missouri State University Kirksville. Mo. 63501
Georgetown until she was in sixth grade, when her father, deciding that Georgetown was deteriorating, sold the house, moved the familv to a countrv home in Virginia for a while, and returned latkr to the cityto a house in ~ o u nPleasant. t She then continued her primary education at Morgan Elementary School and went on with her secondary education a t Western High School. At Western, she took four vears of Latin and four years of German; she was not particularly interested in science then but did take courses in biology, physics, and mathematics. She was an excellent and popular student, playing on the basketball team and participating in other extracurricular activities as well. Helen Dyer's high school teachers, Roberta Wallace in physics and Alice Wood in English, encouraged Helen to apply to Goucher College, located in Baltimore, Maryland (3). Dver was accented at Goucher and offered ascholarshi~ to attend school there. Her undergraduate years werr spent on a mawr in h l o r v under William Kellirutt. a iamous biolugist and excelleni professor. She also undertook a minor in physiology because she was inspired hy Lillian Welch, an outstanding medical scientist a t Johns Hopkins University who was then teaching at Goucher College. Dyer was also enrolled in courses in history, mathematics, and chemistry. She recrived hrr lxichelor's degree imtn Courher Collrgr in 1917 (3). When the First World War broke out in Europe, Helen Dver drooned her nlan to eo to China to teach bioloev in a cdllege o; which thk dean was Elizabeth Goucher. Instead, she returned to Washineton and oerformed war work initially for the Red Cross a i d thereafter for the Civil Service Commission. In 1919, she accepted an offer from Mt. Hol-
Volume 63 Number 3 March 1986
253
yoke to teach physiology under Abby Turner, who was the head of that department. While teaching there. Dver took extra chemistrycourses. Though she wasaskcd rosiny on at MI. Holw~kethe year after, she declined the offer, realizinr that she-would need to attend graduate school if she were to pursue a teaching career (3). Helen Dyer returned to Washington in 1920 and came to work for Carl Voegtlin, a renowned pharmacologist, in the Chemotherapy Laboratory a t the Hygienics Laboratory. At the time, Voegtlin was interested in arsenic products in the treatment of syphilis and especially in learnine the mechaDyer nism of the action of variou~chem~~~therapeuti~drugs. was to work out not only the toxirity of these drugs in rats and other animals but d s o the activity of these drGgs on an organism. These two hard working scientists conducted many experiments and published several papers on this subject. All of their work led them to conclude that the arsenicals, and later other metals, reacted in the body with the sulfiydryl compounds and thus became toxic to both the host tissue and the organism (3). In 1925, Voegtlin and Dyer began their study on some experimental rat tumors. They learned how these tumors grew and how fast their rate of growth was. Then they began to look for treatment of these tumors with various lead products. Since only negative results were collected from this study, nothing was published on that work except the mechanism involved. Dyer left the Chemotherapy Laboratory in 1927 to do graduate work a t Georee Washington Universitv- (GWU). . She took some organic and b i o ~ h e n k t r ~ c o u r aand e s wrote; thesis entitled "The Eftrvt of Growth of Rous Sarcoma on the Chemistry of Blood of Young Chicks," from which she earned her master's degree a t GWU in 1929. At that time, Dyer planned t o continue her graduate study under Mendel at Yale University. Unfortunately, Mendel turned ill and. therefore, she decided to stay on a t GWU, teaching gaduate courses in biochemistry while working on her doctoral degree under Vincent du Vigneaud, a future Nobel Laureate in 1955. During her time as a doctoral candidate, she held a teaching fellowship and worked with du Vigneaud on sulfur compounds. After receiving her PhD in 1935. Dver continued to teach graduate courses in biochemistry'add in the chemistry of nutrition a t George Washington University for the next seven years. Her students admired her for her thorough knowledge of practically every branch in biochemistrv. Throuahout her teaching iareer.8he served as an inspiration to many students a t the university. In 1938, Dver synthesized the ethyl analog of m ~ t h i o n i ~ase a poisihk substitute for methionine itself. She, huwever. later discovered that this analor was toxic and that it failed to r e ~ l a c emethionine. ~ ~This ----~ f&nding had an impact in the field of medicine, especially on sulfa drugs (4). In 1942, Dyer left her teaching position to return to work for Voeetlin, then head of the National Cancer Institute (NCI) of the National Institutes of Health in Bethesda, Maryland. Since the Civil Service Commission had placed a limit of 100 on the number of personnel (5)a t NCI, Dyer and another colleague, Thelma Dunn, came in as Fellows. There, Dyer was to continue the experimentation on dogs to study gastric cancer. This work lasted for several years as Voeetlin and Dyer decided to use the dogs in other experiments, involving the use of alcohol and hot water, as well. Dyer also participated in a group research, investigating the immunological effects in cancer. Her job in this project was to fractionate the lvm~hosarcomas.obtained fr&the rats, into various 'fractions. his work led her to develop certain techniques for isolating proteins and to conduct research, with her former student Margaret Kelly, on the effect of protein from an animal's own tumor. After critical and methodical reviews of the available ~
254
~~
Journal of Chemical Education
~~
chemical literature in biochemistry, Dyer compiled the first comprehensive index of tumor chemotherapy in 1949 (4). In this work, she discussed the earliest chemical treatments, the evolution and the recent developments in tumor chemotherapy. In selecting the material for the index, Dyer described the type of tumors and tumor hosts, the methods of testing and the type of test agents that are essential to chemotherapeutic investigations. The index recorded 5031 therapeutic tests, and the test agents are arranged alphabetically within the different groups. Literatures cited to the same test agent by various investigators were arranged chronologically, and then alphabetically, according to the publication year and the author's name. Dr. Dyer also remarked that the data for the same agent from different investigations were conflicting and thus unsuitable for further scientific conclusions. She, however, noted that the researches in tumor chemotherapy had recently been receiving more support and hoped that major discoveries in the field of cancer research would soon take place (6). Dyer's index served as one of the most essential aids to the National Cancer Institute in the development of its cancer chemotherapy program (4).
During her stay a t NCI, Dyer was transferred to a section called "Nutrition and Chemical Carcinogenesis" under Harold Morris. Together, they worked on following the metabolism of the chemical compounds that Morris used t o induce cancer in rats. These studies on tumors and enzymes of liver cancers required years of hard work and various papers were published on these projects (3). Toward the end of her research with Morris, Dyer had made significant contributions in the study of cancer. .'She has shown that the serum glutamic-oxalareric transaminase (GOT)of rats hcarinc Morris transplanted hepatoma No. 5123 was directly related to tumor size and could be returned t o normal by removal of the tumor" (4). In the late 1950's, Dyer and Morris began a new project that involved the role of Vitamin BEin N-2 fluorenvlacetamide carcinogenesis (4, 7). Dyer observed the effect of N-2 fluorenylacetamide (2-FAA), a potent liver carcinogen, on the metabolism of L-tryptophan. She found that the inclusion of 2-FAA in the diet of rats resulted in the rats' increased urinary output of free andlor conjugated xanthurenic acid, kynurenic acid, and hydroxvlated metabolites of kynurenine after administration~ofa challenging dose of Ltryptophan (7). The magnitude of this effect is relative to the amount of 2-FAA employed in the diets, the pyridoxine or Vitamin B6 content, and perhaps, other unidentified factors in the diets. 2-FAA was incorporated in the diets a t different concentrations for different groups of rats; Vitamin Be (pvridoxine hvdrochloride) was introduced via dextrin pl;lli ~it various ~ ~ amounts; - challenging ~ ~ doses of tryptophan were inserted with dextrin pills and later, with greater accuracy, by stomach tube. The tryptophan was solubilized by grinding with an equal amount of dextrin and emulsified in water (7). Dyer analyzed the rats' urine sample for the total nitrogen content and determined the tryptophan metabolites colorimetrically. Paper chromatography was used to confirm the spectrophotometric analyses and identifications of some of the metabolites. Dyer's findings suggested that more than the ordinary requirement of Vitamin B6 may he needed by rats ingesting aromatic amino carcinogens and that 2-FAA interfered with the normal metabolism of a load dose of tryptophan (7). Throughout her life and career, Dyer received many awards and recognitions, an Honorarv Decree of Doctor of Science from Goicher College in 1961 and The Garvan Medal of the ACS in 1962, t o name a few. As one of the United States delegates to the International Cancer Congress, she joined her NCI colleagues, Thelma Dunn and Sarah Stewart, in visiting Russia in late July, 1962, to participate in a conference on cancer. During her short stay in Moscow, Dyer
presented a paper on the role of monkeys in cancer research and came into contact with the Russian way of life. She discovered that the Russians laid a great stress on culture: ballets and tickets to various shows were inexpensive and good folk-dance demonstrations were performed in the Darks in the eveninas. Her colleaaues and she aareed that Itussian writings in med~rinehad hecome more factual and less . v r o.~ a-r a n d i s ~and i c uolitical and that most Russian scientists could speak ~ n ~ i i (8). s h In the following year, Dyer gave a talk on the trends in cancer research a t the Susan B. Anthony luncheon of the Interclub Council of Western New I'ork. Shespoke of earliest rfforts and modern techniques in cancer reiearchand stated that scientiits. hv the 1930's. first synthesized and isolated substances that induced cancer in rodents. Dyer noted that some of these substances were found in the soot that Percival Potts, a British surgeon hack in 1755. believed to have caused cancer in chimnev sweevs and that it took almost 150 years later for chemists-to prove that Potts'theorv was correct. She alsodiscussed the present work in viruses a n d the theory of viruses' involvement in cancer a t this meeting (9). Dyer continued to work actively in the field of cancer causation after her retirement in 1965. She acted as a consultant to a Washington company, compiling data for the Environmental Protection Agency. Besides her scientific work, she had often found time to oartici~atein manv social oraanizations and church activities. She acted as head of Goucher Alumnae Club of Washington in 1951, received the Goucher College Achievement and Service Award for Teaching and Researching in 1954, earned The Alumni Achievement Award from GWU in 1958, and became the 13th national honorary member of Iota Sigma Pi in 1972 (3).Dyer has been a ~ e f i o wof the ~ m e r i c a n ~ s s o c i a t i ofor n the Ad-
vancement of Sciences and a member of scientific societies such as ACS, Sigma Xi, The Polonium Chapter of Iota Sigma Pi, The American Association of Biological Chemistry, Institute of Nutrition, Society of Experimental Biology and Medicine, The American Association for Cancer Research, Sigma Delta Epsilon and several other organizations. In a speech awarding the Honorary Degree of Doctor of Science to Helen Marie Dyer on June 13, 1965, a t Goucher College, the ceremony's speaker, Moment, declared that "in her life and work [Dyer] has exemplified in high degree in three traits . . . [that are] . . . responsible for the staggering achievements of modern science: intellectual courage and imagination, practical ingenuity and skill and, finally, undiscourageable persistence and devotion" (10). Acknowledgment The authors would like to thank John G. Watts for his assistance in proofreading and providing criticism on this paper. Appreciation is also expressed to Helen M. Dyer for sending us her personal papers. Llterature Cited I
D . U r Helen M 1 l y p r . A Plonccr H # x l u m d " . 176th N n l ~ t m a lhlcnLna ~ ~ . ~ . . ~ ~ ~ r ' hU'..hmp. ~ ~ ~ ~n. al)Ca ilr p5t 19:'1:Amer8ranTI~rm. He.hlnn 1 n . D < ' . . l b 9 . H 1 S I I * wssueascr wnl ~ .I ,~ . ~~,t t . 2~ .;.I ~. , ..v . s ~ ' , ~ ~ : ~ l r , u'm,mrhm;,ts ~~~~;~we~n . ... . ~ ~ '
.I.N
I
.,,he
.nlSwicl)
,9
~~~
~
~
(31 Helen M. Dyer's private pawrs. (41 C h m Enp. NPWB, 1962,40 (121. ( 5 ) Roschos Nina M. The Capitol ChsmiL, May 1984.23. M."An Index of Tumor Chemotherapy": Gwemment Printing Office: (6) DV*,. Washington. DC, 1950, pp 1-8. (7) D ~ den ~ M. ~ : Morris. . H. P. J. Not. Cancer ImRsfilule1961.16.315. (81 R ~ ~U ~ ~ hJr. "SomeThinzs ~ ~ ~WereGwd,Others.Not ~ d . SoGoad," TkEvening
".",, .....e-..,-u.. "--"..-" -,-- -. 191 "Trends in Cancer Research Through the Yeam Analyzed," Buffalo Ewning N e w : Buffslo. 16 February 1963. (10) "The Award of the Deg~oeof Doetor of Science to Helen Marie Dyer," Goucher College, 13 June 1965
Volume 63 Number 3 March 1986
255
