Ellsworth C Dougherty

AB degree in Zoology in 1940 at age 18, PhD in 1944 at age 22, and MD in 1946 at age 25.

1952-1961: Practicing physician (internal medicine) with Permanente Medical Group.

1957: Established the Laboratory of Comparative Biology, which was the founding unit of the Kaiser Foundation Research Institute.

Early work with animal parasites - Strongyloides and filarial nematodes. Later focus: nutritional requirements and axenic culture of nematodes and other micro-metazoa. Last work was on Rotifera.

From Transactions of the American Microscopical Society (1966):

Dougherty's Involvement and Contribution to Advances in Developmental Biology:

For a detailed treatise on Dougherty and his contributions, see Ferris, H., Hieb, W.F. 2015. Ellsworth C. Dougherty: A Pioneer in the Selection of Caenorhabditis elegans as a Model Organism. Genetics 200:991-1002.

Why Caenorhabditis elegans? Why has it been so important in biology? Interestingly, Sydney Brenner was turned on to this nematode as a model system by Dr. Ellsworth C. Dougherty, then in the Department of Nutritional Sciences at the University of California at Berkeley.

Actually, Dougherty first recognized the potential of C. briggsae, which had been found by Margaret Briggs on the campus of Stanford University in Palo Alto, California, in 1944 and used in her MS studies (Briggs, 1946). Briggs studied the lifecycle of what she identified as Rhabditis sp. in association with bacteria and in various culture media devoid of other organisms. She showed that the population could not be sustained in the absence of bacteria or even on dead bacterial cells, living bacteria were a necessary food source. However, survival of individuals was greater on some bacteria-free media than others.

Later (1949), Dougherty and Victor Nigon of France described the nematode used by Briggs as Rhabditis briggsae (Dougherty and Nigon, 1949) and later as Caenorhabditis briggsae. Dougherty wanted to culture nematodes in defined media, and was almost successful except for the necessary inclusion of a liver extract. The liver extract probably provided cholesterol which was later found to be necessary.

Dougherty was a medical doctor with the Permanente Medical Group who began to work on nematode nutrition in 1947, initially with the sexually-reproducing Rhabditis pellio. When he became aware that the nematode studied by Margaret Briggs was a self-fertilizing hermaphrodite, he realized that the impact of genetic variability could be reduced; he switched to that nematode. Briggs had attempted to culture the nematode on 12 gram -ve bacteria and 10 that were gram +ve. Six of the gram -ve bacteria, but only one of the gram +ve, supported the nematode monoxenically. Dougherty wondered what the differences among these bacteria were. Margaret Briggs later married and became Margaret Briggs Gochnauer. She published (Gochnauer and McCoy, 1954) on responses of R. briggsae to antibiotics.

The potential value of Rhabditis species for genetic research was pointed out by Dougherty and Calhoun (1948). Caenorhabditis elegans was initially described and named Rhabditis elegans by Maupas (1900); it was subsequently placed in the subgenus Caenorhabditis by Osche (1952) and then raised to generic status by Dougherty (1955). The name is a blend of Greek and Latin (Caeno, recent; rhabditis, rod; elegans, elegant).

Two strains of C. elegans have historical importance. One strain, Bergerac, was collected from the soil near Bergerac, France, by Victor Nigon of the Universite de Lyon (Nigon 1949), and the other strain, Bristol, was isolated by L.N. Staniland (National Agricultural Advisory Service, London) from mushroom compost near Bristol, England (Nicholas et al. 1959). Staniland was an applied nematologist; he published extensively on the nature and control of a variety of nematode problems between 1926 and 1967, including rhabditid swarming in mushroom beds

The Bristol isolate was sent to Gunther Osche of Friederich Alexanders Universitat, Erlangen, Germany. I'm not sure about the date, I assume 1947 or 48 because Nigon certainly had it prior to 1949. Osche confirmed that it was a Rhabditis. It was later sent to Nigon who identified the species as R. elegans, conforming with the original description by Maupas (1900). Osche (1952) placed R. elegans and R. briggsae (and maybe others) in subgenus Caenorhabditis; Dougherty (1955) elevated the subgenus to a genus. (see Andrássy, 1983).

Nigon and Dougherty (1949) were unsuccessful in crossing C. briggsae and C. elegans. Among other things, they found that the nematodes produced more male offspring at higher temperatures but that the males produced at those temperatures were sterile. Building on 70 years of earlier work with rhabditid nematodes, amplified by their own studies, they recognized that these were prime candidates for genetic studies (Nigon, 1949, Dougherty and Calhoun, 1948, etc), and described the first morphological mutant of C. briggsae (Nigon and Dougherty, 1950).

The Bergerac strain of C. elegans could not be cultured at temperatures above 18C; at that temperature it became infertile. The Bristol strain can be cultured at temperatures up to 25C, though males will not copulate below 20C (Fatt and Dougherty, 1963; Nicholas, 1975). In several reported cases, rhabditid nematodes seem to be adversely affected by higher temperatures. For example, embryogenesis fails at temperatures of 25C and higher in Rhabditis cucumeris isolated from soil in the Central Valley of California (Venette and Ferris, 1997).

Through his work with Nigon, Dougherty obtained a culture of the Bristol strain of C. elegans. Dougherty who was then at the Kaiser Foundation Research Institute in Richmond, California. Warwick Nicholas was Lecturer in the Department of Zoology, University of Liverpool from 1955 until 1960. After that he went to Australian National University. In 1956, Nicholas established the first axenic cultures of both Bristol and Bergerac strains of C. elegans (Fatt, 1961; Nicholas and McEntegard, 1957). In 1957 and 1958 he was on leave from University of Liverpool and was a Traveling Fellow of the British Medical Research Council (MRC) funded by a Rockefeller grant. During the tenure of the fellowship, he worked with Dougherty and Dr. Eder Hansen in the Lab of Comparative Biology at the Kaiser Foundation Research Inst. in Richmond CA. Among other things, they were trying to determine the nature of undefined components Rb and Cb needed for axenic culture of C. briggsae. Those components were provided by bovine liver extract and other sources and Rb and Cb are the initial letters of R. and later C. briggsae (Dougherty et al, 1959; Nicholas et al, 1959).

Consider the importance of the Nicholas MRC connection. Sydney Brenner was the mover and shaker at MRC and was debating the next steps in translating the successes of Watson and Crick into a greater understanding of "life". See his proposal and letter to Max Perutz. Some ideas must have been transferred to Brenner through Nicholas. When Brenner visited our department (Nematology, UC Davis) in about 1987, he talked about visiting Dougherty (then at UC Berkeley) and discussing C. elegans as the candidate worm. Before that he had been thinking about C. briggsae, based on the work of Dougherty, Nigon and others, as he began to learn about nematodes. He obtained his culture of the Bristol strain of C. elegans from Dougherty (Brenner, 1974).

In 1961, Dougherty moved to the Department of Nutritional Sciences at the UC Berkeley and continued to study the nutritional requirements and axenic cultivation of Caenorhabditis species, particularly C. briggsae, until his death in 1965. Although permanent cultures were maintained on nutrient agar slants inoculated with E. coli, an axenic medium with chemically undefined supplements was developed in 1954 (Dougherty et al. 1959).

In his studies, Dougherty recognized the potential for using C. briggsae in studies of genetics and developmental biology (Dougherty and Calhoun,1948) because of ease of culture and maintenance, different reproductive patterns (hermaphroditism and sexual), few chromosomes, less than 1000 cells, etc. and suggested C. elegans to Brenner as the model system. Nigon's original C. elegans isolate from France (Bergerac) strain is infertile above 18C, so the Bristol strain has been very important. Virtually all C. elegans genetics has been done with the Bristol strain, more specifically with the N2 line that Sydney Brenner derived from the Bristol culture he obtained from Ellsworth Dougherty. The Bristol culture had originally been extracted from mushroom compost in England by Staniland and taken to Dougherty's lab by Warwick Nicholas.

Back in Cambridge, after his visit with Dougherty, Brenner extracted nematodes from his own garden and liked what he saw. The worms on which were used in the genetics and development studies were the N2 strain from Dougherty. Dougherty and colleagues had found an autosomal dominant gene for heat tolerance that would be useful in work with C. elegans by Brenner and others (Fatt and Dougherty, 1963; Brown, 2003).

Interestingly, until the mid 1970s, people working in developmental biology frequently confused C. briggsae and C. elegans and many of the cultures being used were mis-identified. In the mid 1970s, graduate student Paul Friedman working with Ed Platzer at UC Riverside developed the diagnostic criteria for separating the two species and resolved the confusion (Friedman et al, 1977). Friedman and Platzer were testing antibiotics on C. briggsae and C. elegans cultures and getting inconsistent results. They decided that their cultures were genetically different. The two species are distinguished by the pattern of rays in the male bursa; a difficult feature when males are rare. Friedman and Platzer used SDS electrophoresis and also separated isozymes of malate dehydrogenase. Their results were consistent with those of morphological characters and mating tests.

References

Andrássy, I. 1983. A taxonomic review of the suborder Rhabditina (Nematoda: Secernentia). ORSTOM, Paris.

Ankeney, R.A. 2001. The natural history of C. elegans research. Nature Reviews Genetics 2: 474-478.

Brenner, S. 1974. The genetics of Caenorhabditis elegans. Genetics 77:71-94.

Briggs, M.P. 1946. Culture methods for a free-living soil nematode. MA Thesis, Stanford University, 63p.

Brown, A. 2003. In the Beginning Was the Worm. Simon & Schuster, London. 244p.
Dougherty, E.C. 1960. Cultivation of aschelminthes, especially rhabditid nematodes. Pp 297-318 in Sasser and Jenkins (eds) Nematology: fundamentals and recent advances. UNC Press, Chapel Hill.

Dougherty, E.C. and H.G. Calhoun. 1948. Possible significance of free-living nematodes in genetic research. Nature 161:29.

Dougherty, E.C. and V. Nigon. 1949. A new species of the free-living nematode genus Rhabditis of interest in comparative physiology and genetics. J. Parasitol. 35: 11.
Dougherty, E.C., E.L. Hansen, W.L. Nicholas, J.A. Mollett, and E.A. Yarwood. 1959. Axenic cultivation of Caenorhabditis briggsae (Nematoda: Rhabditidae) with unsupplemented and supplemented chemically defined media. Ann. N.Y. Acad. Sci. 77: 176-217.
Fatt, H.V. 1961. Genetic control of maturation and reproduction in the nematode Caenorhabditis elegans. MA Thesis, University of California, Berkeley. 49p.

Fatt, H.V. and E.C. Dougherty. 1963. Genetic control of differential heat tolerance in two strains of the nematode, Caenorhabditis elegans. Science 141:266-267.

Ferris, H., Hieb, W.F. 2015. Ellsworth C. Dougherty: A Pioneer in the Selection of Caenorhabditis elegans as a Model Organism. Genetics 200:991-1002.

Friedman, P.A., E.G. Platzer, and J.E. Eby. 1977. Species differentiation in C. briggsae and C. elegans. J. Nematol. 9: 197-203.
Gochnauer, M.B. and E. McCoy. 1954. Responses of a soil nematode, R. briggsae, to antibiotics. J. Exp. Zool. 125:377-406.

Hansen, E.L. 1966. Obituary: Ellsworth Charles Dougherty. Nematologica 12:470.

Maupas, E. 1900. Modes et formes de reproduction des Nématodes. Arch, Zool. Exp, et Gén., (3e série), 8:463-624.

Nicholas, W.L. and M.G. McEntegart 1957. A technique for obtaining axenic cultures of rhabditid nematodes. J. Helminthology 31:135-144.

Nicholas, W.L., E.C. Dougherty, and E.L. Hansen. 1959. Axenic cultivation of C. briggsae (Nematoda: Rhabditidae) with chemically undefined supplements; comparative studies with related nematodes. Ann. N.Y. Acad. Sci. 77: 218-236.
Nigon, V. 1949. Les modalités de la reproduction et le déterminisme du sexe chez quelques nematodes libres. Ann. Sci. Nat. Zool. Biol. Anim. 11: 1-132.

Nigon, V. and E.C. Dougherty. 1949. Reproductive patterns and attempts at reciprocal crossing of Rhabditis elegans Maupas, 1900 and Rhabditis briggsae Dougherty and Nigon, 1949 (Nematoda: Rhabditidae). J. Exp Zool, 112:488-503.

Nigon, V. and E.C. Dougherty. 1950. A dwarf mutant of a nematode. A morphological mutant of Rhabditis briggsae, a free-living soil nematode. J. Heredity 41:103-109.
Riddle, D.L., T. Blumenthal, B.J. Meyer and J.R. Priess. 1997. C. elegans II. Cold Springs Harbor Press.

Venette, R. C. and H. Ferris. 1997. Thermal constraints to population growth of bacterial-feeding nematodes. Soil Biology and Biochemistry 29:63-74.