KING, HELEN DEAN

(b. Owego, New York, 27 September 1869; d. Philadelphia, Pennsylvania, 7 March 1955)

genetics.

King was the daughter of William A. and Lenora Dean King. Her father was a prosperous businessman, president of the King Harness Company. She attended Owego Free Academy, and at the age of eighteen. She entered Vassar College, where she received the A.B. degree in 1892. In 1894 King returned to Vassar as a graduate student biology and assistant demonstrator in the biology laboratory. She began graduate studies at Bryn Mawr College in 1895 and received a Ph.D. in 1899 under Thomas Hunt Morgan. She continued postdoctoral work under Morgan and assisted in the Bryn Mawr biology laboratory from 1899 to 1904. At the same time she taught science at Miss Florence Baldwin’s School from 1899 to 1907.

Following two years (1906–1908) as a university fellow for research in zoology at the University of Pennsylvania, King joined the research staff of the Wistar Institute of Anatomy and Biology in Philadelphia. She remained there until her retirement in 1950. King became a full professor of embryology in 1927 and a member of Wistar’s. advisory board in 1928. She never married.

King had the best education a woman could receive in the 1890’s Vassar led all other women’s colleges in its expenditures on scientific apparatus in 1887, the year before King entered. At Bryn Mawr her major subject was morphology, which she studied under Morgan, and she was exposed to Darwinian theory in the paleontology classes of Florence Bascom. Bryn Mawr was an ideal spot for an aspiring woman biologist, for its biology department had been established by Edmund B. Wilson in 1885 and had been taken over by Morgan in 1891. Morgan’s brilliant researches in embryology and Wilson’s continued ties with Morgan guaranteed that the women were exposed to the latest research in embryology, cytology, and the newly emerging field of genetics.

Morgan suggested the topic of King’s dissertation: “The Maturation and Fertilization of the Egg of Bufo lentiginosus” (the common toad). After King published her dissertation in 1901, Morgan continued as her mentor, suggesting new problems until 1909, when she changed the subject of her research from amphibians to rats and Morgan abandoned embryology to work exclusively on the genetics of Drosophila.

King’s interest in sexual fertilization, the maturation of the egg, and the determination of sex reflect the influence of Morgan and the Entwinklungsmechanik school. She believed that embryological questions could be solved only through rigorous experimentation and a mechanistic interpretation.

In her work on sex determination, King emphasized the influence of environmental factors on altering the sex ratio. She was inclined to accept the view advanced by Nettie M. Stevens, Wilson, and Clarence E. McClung that there are two kinds of spermatozoa, those carrying the accessory element (the Y chromosome) and those from which it is absent. However, King opposed the prevailing theory advanced by Wilson in 1910 that any egg is capable of fertilization by any spermatozoon that happens to come in contact with it. She persisted in her hypothesis that ova exercise a kind of selection, accepting one kind of sperm and rejecting the other kind, on the basis of different environmental conditions.

In “Studies on Sex Determination in Amphibians” (1909–1912), King worked on toads’ eggs and increased the proportion of females by slightly drying the eggs or by withdrawing water from them by placing them in solutions of salts, acids, or sugars. Edwin G. Conklin singled out her work as important evidence for environmental influence on the alteration of the sex ratio. In other studies King found that hybridizing altered the sex ratio, as did the age of the female, and she suggested that the germ plasm undergoes changes due to age.

During her first ten years of inbreeding albino rats (1909–1919), King found that she could select for the tendency to produce an excess of males or an excess of females. She concluded that in the rat the sex ratio is, to a certain extent, amenable to selection and that the female has more influence in determining sex than does the male. King suggested that factors such as heredity, environment, and nutrition act on ova in such a way as to render them more easily fertilized by one kind of sperm than by the other. Her conclusion contained unmistakable feminist overtones. She wrote in 1919; “In the female element, as in the female organism, resides the power to select that which is for the best interests of the species,” In order to explain seasonal changes in the sex ratio of the rat, King suggested in 1927 that ova select some sperm and reject others because they have a greater chemical attraction or repulsion for one kind of sperm than for the other, depending upon seasonal changes in body metabolism.

King’s major research focused on the effects of inbreeding on albino rats and the effects of captivity on wild gray Norway rats. Before joining the Wistar Institute, she had devoted herself to cytological studies, performing painstaking operations on amphibian eggs. In 1909, however, she abandoned cytology and embarked on a lifelong project of animal breeding when she mated two males and two females from a single litter of albino rats. King would continue this dynasty for more than 130 nine generations, to develop what would later be called the King colony, a part of the famous Wistar Institute stock of white rats that figured in innumerable research projects throughout the world.

In 1919 King published the results of fifteen generations of mating brother and sister albino rats. Her study soundly refuted Darwin’s assertion that inbreeding invevtably leads to degeneration in animals. King concluded that the closest form of inbreeding in mammals is not necessarily inimical to body growth, fertility, or constitutional vigor, provided that one selects the best animals from a large population to breed. (After fifty generations of brother-sister matings King noted their superiority over stock controls in terms of fertility, growth size, and longevity.) Her results supported the contention of Edward M. East and H.K. Hayes (1912) that a completely homozygous strain can stand up forever if it has a good gametic constitution and a natural inherent vigor. King found that adverse environmental conditions, such as malnutrition, set back the rats only temporarily and did not alter their genetic constitution.

King suggested that some factors tended to be inherited together: for instance, large body size. early sexual maturity, high fecundity, superior vigor, and longevity. But she did not think these factors were linked, as were many of the genes in Drosophila, according to work being done by Morgan and his researches at Columbia.

King’s work followed the inbreeding experiments of William E. Castle, who found no decrease in fertility in Drosophilas or, in his later work, in rats. Her data supported Castle’s conclusion that selection from the productive pairs more than offsets the effects of inbreeding. King’s results differed sharply from those of Sewall Wright however, who noted a deterioration in vigor among guinea pigs inbred for more than twenty generations. Wright had not bred selectively, whereas King had allowed only the most vigorous individuals to reproduce. Much of King’s work on inbreeding pointed to the difficulty of establishing complete homozygosity in an animal stock and contributed in the 1920’sad and 1930’s that there is a tremendous genetic diversity even within a local population of a single species.

In 1927 King and Leo Loeb of the Washington University Medical School began some of the first tissue transplants to determine the extent of genetic similarity in two populations of inbred animals: King’s albino rats and Wright’s guinea pigs. Although King’s rats had been inbred for thirty-seven to thirty generations, and Wright’s guinea pigs for only fifteen to twenty-three generations, the researchers found the host’s reaction to donor tissue much more severe between inbred rats than between guinea pigs. A transplant from one inbred rat to another led to just as severe a reaction as a transplant between noninbred rats In order to explain the unexpected results, Loeb and King suggested that selection of the strongest individuals during many generations of inbreeding had caused heterozygosity to persist They cited the greater number of spontaneous mutations in the rat than in the guinea pig as another possible explanation. However, when Loeb, King, and Blumenthal (1943) did tissue transplants between individual rats that had been inbred for 102 to 106 generations, they noted that homozygosity in the strain had gradually increased since the earlier tissue transplants. Still, a completely homozygous condition had not been attained even after more than one hundred generations of brother-sister matins.

In another lengthy breeding experiment to determine the effects of captivity on wild animals, King bred twenty-five generations of gray Norway rats originating from six pairs of wild rats trapped in the Philadelphia streets. Reporting on changes from the eleventh to the twenty-fifth generation, King found that the rats grew more rapidly and attained a much larger size than their wild prototypes. This result agreed with earlier studies on the domestication of wild animals. At the same time Calvin Birdges King’s work followed the inbreeding experiments was breeding special stocks of Drosophila mutants at Columbia, King was discovering a number of mutations in her wild rats affecting coat color, structure of the fur, and eye color. With controlled mating she determined whether the mutations were autosomal or sex-linked, dominant or recessive, the result of a single gene mutation or of selection that affected modifying genes.

King inbred mutants to distinguish between homozygotes and heterozygotes. The inbreeding of rat mutants produced more mutants: cinnamon rats, waltzing rats, and stub rats a(runts with shortened tails). King rejected the hypothesis that the genes for all the mutations were present in the original six pairs of wild rats and remained latent until chance matings resulted in their phenotypic expression. She speculated that mutations appeared after several years of capacity because the very young and the very old females were allowed to reproduce, protected from the competition of natural selection. Thus, variability of the germ plasm due to age led to an increase in mutant individuals. King concluded.

In 1932 King presented a paper before the Sixth International Congress of Genetics summarizing the kinds of mutations that had occurred in twenty-eight generations, of captive Norway rats, comprising over forty-five thousand individuals. She suggested that captivity with its altered conditions of environment and nutrition, tends to produce diversity in a wild race, not to render it more homogeneous.

In the 1930’s King collaborated with Castle on four linkage studies of the Norway rat in which they mapped the genes for several newly discovered mutations. King did the matings, while Castle Provided the genetic analysis of the experimental data.

In her seventies, King performed a series of experiments with Margaret Reed Lewis, a Bryn Mawr classmate and Wistar colleague, on tumor transplants in rats. They were successful in extracting a fatsoluble, tumor-produced substance from rat sarcomas and inducing tumors by injecting the substance into rats of the same inbred strain. In a later experiment King and Lewis were able to inhibit the growth of tumors and make rats immune to the further growth of grafts of the same tumor by injecting a substance directly into the tumor. The substance was made by grinding tumors, both primary and induced, to a pulp, extracting them in 95 percent alcohol, and distilling the extract.

Like many early geneticists, King favored the use of eugenics to improve the human race. Although she found nothing wrong with consanguineous marriages if the original stock was good, she thought laws forbidding such marriages were necessary because one out of every fourteen persons carries some hidden defect in the germ plasm. King foresaw a time when marriage would be based on the physical fitness of the individuals and on their recorded pedigree for several generations. In the future, people would realize the great value of favorable genetic combinations that produce unusual ability, King predicted in 1935.

In 1932 King shared the Ellen Richards Prize with the astronomer Annie Jump Cannon. The prize had been awarded by the Association to Aid Women in Science since 1901 for the best piece of experimental work submitted by a woman in science.

King served as associate editor of the Journal of Morphology and Physiology from 1924 to 1927, and as vice president of the Society of Zoologists in 1937. She was a fellow of the American Association for the Advancement of Science and a member of the Society of Experimental Biology and Medicine, the Eugenics Research Association, the American Association of Anatomists, the American Society of Naturalists, and the American Genetics Association. She also was a member of Phi Beta Kappa and Sigma Xi.

BIBLIOGRAPHY

1.Original Works. Scientific articles published during King’s years at Bryn Mawr are in the bound reprint series of Bryn Mawr College Monographs, 1. no, l (1901), 1 , no. 3 (1904), and 6 (1906). Other works include “The Maturation and Fertilization of the Egg of Bufo lentiginosus, ; in”Journal of Morphology, 17 , no. 2 (1901), 293– 350; “Notes on Regeneration in Tubularia crocea,” in Biological Bulletin, 4 (1903), 287ff.; “The Effects of Heat on the Development of the Toad’s Egg,” ibid., 5 (1908). 218ff.; “Studies on Sex Determination in Amphibians, II,” ibid., 16 (1909), 27ff.; “The Effects of Various Fixatives on the Brain of the Albino Rat, with an Account of a Method of Preparing This Material for a Study of the Cells of the Cortex.” in Anatomical Record, 4 (1910), 213–244; “The Effects of Pneumonia and of Postmortem Changes on the Percentage of Water in the Brain of the Albino Rat,” in Journal of Comparative Neurology, 21 , no. 2 (1911), 147–154.

“The Effects of External Factors, Acting Before or During the Time of Fertilization, on the Sex Ratio of Bufo lentiginosus,” in Biological Bulletin, 20 (1911), 205ff.; “The Sex Ratio in Hybrid Rats,” ibid, 21 (1911) 104ff.; “The Effects of Some Amido-Acids on the Development of the Eggs of Arbacia and of Chaetopterus,” ibid., 22 (1912), 273ff.; Dimorphism in the Spermatozoa of Necturus maculosus (Baltimore, 1912):’ Some Anomalies in the Gestation of the Albino Rat (Mus norvegicus albinus), ’ in Biological Bulletin, 24 (1913), 377–391;’ The Effects of Formaldehyde on the Brain of the Albino Rat, ’ in Journal of Comparative Neurology, 23 (1913), 283–314; “On the Weight of the Albino Rat at Birth and the Factors That Influence It.” in Anatomical Record, 9 (1915), 213– 231; “On the Normal Sex Ratio and the Size of the Litter in the Albino Rat,” ibid., 9 (1915), 403–420, written with J. M. Stotsenburg; “The Growth and Variability in the Body Weight of the Albino Rat,” ibid., 9 (1915). 751– 776.

“On the Postnatal Growth of the Body and of the Central Nervous System in Albino Rats That Are Undersized at Birth,” ibid., 11 (1916), 41–52; “The Relation of Age to Fertility in the Rat,” ibid., 11 (1916), 269–287; “Studies in Inbreeding,” in Journal of Experimental Zoology, 26 , nos. 1 and 2 (1918), 27 , no, 1 (1918), and 29 , no. 1 (1919); Studies on Inbreeding (Philadelphia. 1919); “Linkage Studies of the Rat,” pls. 1–4, 9–10, in Proceedings of the National Academy of Sciences, 21 (1935), 390–399, 23 (1937), 56–60, 26 (1940), 578–580, written with W. E. Castle; ibid., 27 (1941), 250–254, written with Castle and Army L. Daniels; ibid., 27 (1941), 394–398, 30 (1944), 79ff., 34 (1948), 135ff., 35 (1949), 545–546, written with Castle; and in journal of Heredity, 38 (1947), 341– 344, written with Castle; and Life Processes in Gray Norway Rats During Fourteen Years in Captivity (Philadelphia, 1939).

Five volumes of King’s scientific papers are in the archives of the Wistar Institute of Anatomy and Biology, Philadelphia. The institute’s annual reports from 1924 to 1956 contain correspondence between King and the director regarding her research. A file on King’s graduate work under Morgan is in the Bryn Mawr College archives. For a discussion on the deliberations over the Ellen Richards Prize by the Association to Aid Women in Science, see the Mary Thaw Thompson papers at Vassar College, the Florence Sabin papers at the American Philosophical Society, and the Ida Hyde papers at the American Association of University Women headquarters in Washington, D. C.

II. Secondary Literature. References to King are in Jane M. Oppenheimer, “Thomas Hunt Morgan as an Embryologist: The View from Bryn Mawr.” in American Zoologist. 23 (1983). 845–854; and Margaret Rossiter. American Women in Science (Baltimore. 1982).

Mary Bogin