51.

J. Lederberg and E. C, Levinthal - Relevance of Current Program of Instrumenta-

3)

4)

1)

2)

3)

4)

tion Research Laboratory to Problems of
Molecular Biology.

Cells which can be reproducibly obtained and maintained with good
viability.

Cells which can be divided into subclasses according to biological
function, subclasses which might be related to cell volume or cell
fluorescence, For these reasons, we chose to work on thoracic duct

populations of lymphocytes, which are:

Divided into at least 3 size subclasses.

Naturally obtained in single cell suspension and do not form clumps

of 2 cells or greater.

Can be maintained in a viable state with appropriate media for as

long as 24 hours. |

Have at least two significant biological criteria for size-subclass

separation:

a) DNA synthesis: Large and medium thoracic duct lymphocytes are
in a continuous cycle of cell division. At least 80% of their
cell cycle is devoted to DNA synthesis, and therefore short-term
incubation of thoracic duct lymphocyte population with radioactive
DNA precursors will selectively label large and medium cells.
Small lymphocytes only rarely divide.

b) Small lymphocytes are “immunologically competent cells", whereas
populations of large and medium lymphocytes are not. We have
developed rapid and easy methods for testing immunological com-

petence,
J. Lederberg and E. C. Levinthal - Relevance of Current Program of Instrumenta-

tion Research Laboratory to Problems of
Molecular Biology.

c) Both of the above assays detect these biological functions in
viable cells only. Therefore, since we have a system (described
previously) in which only viable cells fluoresce, we can test

the fluorescent cell separator's action also.

The following are a few of the medically and biologically significant

experiments we hope to perform:

1)

2)

3)

Test purified cell populations for cell-cell interactions in the

induction, development, and execution of the immune response (in

conjunction with Professor L. Herzenberg and Dr. I. Weissman).

a) Isolation of antigen-processing cells by phagocytosis of fluoro-

genic substrate.

b) Isolation of immunologically competent cells by size.

c) Isolation of antibody-forming cells by size following adherence
of large antigenic particles.

Isolation of cells in mitosis by size criteria in order to establish

cell lines in vitro which are synchronously cycling. These will be

useful to determine the actual cellular and molecular events which

determine the differential sensitivity of cells to radiation and

certain drugs as a function of their place in the cell cycle (in con-

junction with Prof. George Hahn, Department of Radiology).

Detection and isolation of cancer cells in the blood stream (meta-

stases) in order to determine the type of cancer therapy most appro-

priate for the patient (in conjunction with Prof. H. S. Kaplan, Execu~

tive Head of Radiology and Radiotherapy Prof. R. Kallman, Radiology

Department).
53.

J. Lederberg and E. C. Levinthal - Relevance of Current Program of Instrumenta-

4)

5)

tion Research Laboratory to Problems of
Molecular Biology

Isolation and testing of cell types in Hodgkins Disease, (a cancer

of the lymph node system) in order to determine:

a) The malignant cell, its biochemistry and radiosensitivity

b) The cell type (in these patients) responsible for widespread
immunological deficiency, and how this deficiency is maintained
in conjunction with Professor H. S. Kaplan.

Isolation and testing of the cell type in the bone marrow theoreti-

cally designated as the "stem" cell, which is responsible for

redevelopment of normal blood cell types following irradiation

In conjunction with Dr. Weissman.
54.

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55.

Crabbé, P.,E. Santos and B. Halpern, 1968. Cotton effect of dimedone conden-
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from Bacillus subtilis (in press).

Garnett, J. L., S. W. Law, J. 0. Keefe, K. Turnbulland B. Halpern, 1968.
Tritium labelling of optically active amino acids by the Wilzback Procedure.
Chem. Comm. submitted for publication.

Halpern, B., J. Ricks and J. W. Westley, 1966. Biochemical applications of
gas liquid chromatography. I. The stereospecific hydrolytic action of
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Halpern, B., and J. W. Westley, 1966. Chemical resolution of secondary (+)
alcohols. Aust. J. Chem. 19, 1533-1534.

Halpern, B., and J. W. Westley, 1966. High sensitivity optical resolution
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Halpern, B. and J. W. Westley, 1966. High sensitivity optical resolution of
poly-functional amino acids by gas liquid chromatography. Tetrahedron
Letters, 2283-2286.

Halpern, B., J. W. Westley, P. J. Anderson and J. Lederberg, 1966. Demonstra-
tion of the stereospecific action of microorganisms in soil by gas liquid
chromatography. Anal. Biochem. 17, 179-181.

Halpern, B., J. Ricks, J. W. Westley, 1967. The stereospecificity of a-
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56.

Halpern, B., L. Chew, and J. W. Westley, 1967. Investigation of racemization
during peptide bond formation by GLC of diastereoisomeric t-BOC-amino acid
amides. J. Anal. Chem. 39, 399.

Halpern, B., J. W. Westley, and B. Weinstein, 1967. Chemical shift of a
magnetic non-equivalent isopropyl group due to steric hindrance. Chem.
Comm. 160.

Halpern, B., and J. W. Westley, 1967. Correlation of absolute configuration
of a-alkylphenylacetic acids by GLC. Chem. Comm. 237.

Halpern, B., D. Nitecki, and B. Weinstein, 1967. The steric purity of model
peptides by N.M.R. spectroscopy. Tetrahedron Letters, 3075.

Halpern, B., L. Chew, and B. Weinstein, 1967. Measurement of racemization in
peptide synthesis by N.M.R. spectroscopy. J. Am. Chem. Soc. 89, 5051.

Halpern, B., A. Wegman, V. Close, and J. W. Westley, 1968. GLC of amino acids
as N-thiocarbonyl ester derivatives. Tetrahedron Letters (in press).

Halpern, B., J. W. Westley, D. Nitecki, 1968. The configuration of Echinulin
by thin layer chromatography. Tetrahedron Letters (in press).

Halpern, B., J. W. Westley, E. C. Levinthal and J. Lederberg, 1967. The
Pasteur Probe: an assay for molecular asymmetry in Life Sciences and Space
Research (COSPAR). (M. Florkin and A. Dollfus, eds.) p. 239-249.

Herschkowitz, N. H., G. M. McKhann, and E. M. Shooter, 1966. Metabolism of
lipoproteins in the developing brain. J. Pediatrics 69, 948-949.

Herschkowitz, N. H., G. M. McKhann, and E. M. Shooter, 1967. Studies on the
water soluble lipoproteins in rat brain. J. Neurochem. 15, 161-168.

Herschkowitz, N. H., G. M. McKhann, S. Saxena, and E. M. Shooter, 1968.
Characterization of sulfatide-containing lipoproteins in rat brain. J.
Neurochem. (in press).

Herzenberg, L. A., 1966. H-2 and immunoglobulin isoantigens (allotypes) in
somatic cell genetics, (Antigenic variations of somatic cells and cytogenetic
aspects of cell antigenicity-introduction), p. 363-65. In Genetic Variations
in Somatic Cells, Proc. Symp. Mutational Process. Praha, 1965. Academia.

Herzenberg, L. A. and L. A. Herzenberg, 1966. Suppression of a yG-globulin
allotype in mice by anti-allotype antibodies, p. 227-32. In Genetic
Variation in Somatic Cells, Proc. Symp. Mutational Process, Praha, 1965.
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Herzenberg, L. A. and H. L. Warner, 1967. Genetic control of mouse immuno-
globulins. In Regulation of the Antibody Response, Chapter XV. C. C.
Thomas, Springfield, Illinois (in press).

Herzenberg, L. A., and L. A. Herzenberg, R. C. Goodlin, and E. C. Rivera, 1967.
Immunoglobulin synthesis in mice: suppression by anti-allotype antibody.
J. Exp. Med. 126, 701.

Herzenberg, L. A., J. D. Minna and L. A. Herzenberg, 1967. The chromosome
region for immunoglobulin heavy chains in the mouse: allelic electrophoretic
mobility differences and allotype suppression. Cold Spring Harbor Symp.
Quant. Biol. 32, 181-186.

Herzenberg, L. A., H. O. McDevitt, and L. A. Herzenberg, 1968. Genetics of
antibodies. Amn. Rev. Genetics, 2 (in press).

Herzenberg, L. A. and M. Tyan, 1968. Genetics of antibody formation: Role of
the thymus in the evolution of the immune response. 12th Int. Congress of
Genetics, Tokyo, 1968.

Herzenberg, L. A., 1968. Suppression of antibody production by anti-allotype
antibody. 12th International Congress of Genetics, Tokyo, 1968.

Huehns, E. R. and E. M. Shooter, 1966. Further studies on the isolation and
properties of a-chain subunits of haemoglobin. Biochem. J. 101, 843-851.

Huehns, E. R. and E. M. Shooter, 1966. The properties and reactions of haemo-
globin F, and their bearing on the dissociation equilibrium of haemoglobin.
Biochem. J. 101, 852-860.

Karger, B. L., R. L. Stern, W. Keane, B. Halpern, and J. W. Westley, 1967.
GLC separation of diastereoisomeric amides of racemic cyclic amines. J.
Anal. Chem. 39, 228.

Karlin, S., J. McGregor and W. F. Bodmer, 1967. The rate of production of re-
combinants between linked genes in finite populations. Proc. Fifth
Berkeley Symp. Probability and Statistics. p. 415-438.

Klein, Jan., J. Martinkova and L. A. Herzenberg, 1967. Analysis of the histo-
compatibility-2 (H-2) locus of NZB mice. Transplantation 5, 1335-37.

Klein, J. and L. A. Herzenberg, 1967. Congenic (genetically similar) mouse
strains with different immunoglobulin allotypes. I. Breeding scheme,
histocompatibility tests and kinetics of yG2, globulin production by trans-
ferred cells for C3H.SW and its congenic partner CWB/5. Transplantation 5,
1484-1495.
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Laird, C. D., L. Wang and W. F. Bodmer, 1968. Recombination and DNA replica-
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Lederberg, J., 1966. Experimental genetics and human evolution. American
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Lederberg, J. 1966. Planetary exploration and biological research. Impact
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Lederberg, J., 1967. Biology and the rational animal. The Sciences (New
York Academy of Sciences) 7, 28-32.

Lederberg, J., 1967. Eutechnics - a motif for technology. Technology Week,
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Lederberg, J., 1967. Biochemical research - its side effects and challenges.
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Lederberg, J. and E. A. Feigenbaum, 1968. Mechanization of inductive inference
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Lederberg, J., 1967. A geneticist looks at contraception and abortion.
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Minna, John D., G. Michael Iverson and L. A. Herzenberg, 1967. Identification
of a gene locus for yG, immunoglobulin H chains and its linkage to the H
chain chromosome region in the mouse. Proc. Nat. Acad. Sci. 58, 188-194.

Nitecki, D. E., B. Halpern, and J. W. Westley. A simple route to sterically
pure diketopiperazines. J. Org. Chem. 33, 864.

Papermaster, B. W. and L. A. Herzenberg, 1966. Isolation and characterization
of an isoantigenic variant from a heterozygous mouse lymphoma in culture.
J. Cell. Physiol. 67, 407-20.

Payne, R., W. Bodmer, G. M. Troup and R. L. Walford, 1967. Serologic activities
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Sagan, C., E. C. Levinthal and J. Lederberg, 1967. Contamination of Mars.
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52

Shooter, E. M., S. Varon and J. Nomura, 1968. The nerve growth factor protein
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Smith, A. P., S. Varon and E. M. Shooter, 1968. Multiple forms of the nerve
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Sved, J. A., T. E. Reed and Walter Bodmer, 1967. The number of balanced
polymorphisms which can be maintained in a natural population. Genetics
55, 469-481.

Tyan, M. L., L. J. Cole and L. A. Herzenberg, 1967. Fetal liver cells: A
source of thymus-dependent specific immunoglobulin production in radiation
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Warner, N. L. L. A. Herzenberg and G. Goldstein, 1966. Immunoglobulin iso-
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Welton, J., S. R. Walker, G. C. Sharp, L. A. Herzenberg, R. Wistar and W. P.
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Westley, J. W., Anderson, P. J., Close, V. A., Halpern, B. and E. M. Lederberg,
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Westley, J. S., and B. Weinstein, 1967. Magnetic nonequivalence of the methyl-
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