A proposal for submission to

National Science Foundation

(Italy/U.S. Science Cooperation)

An Exchange Program in Genetics and Molecular Biology
Between Research Scientists from the Departments of Genetics of the

Universities of Stanford and Pavia

May 1, 1967 - April 30, 1968

Submitted by:

\ fem Gon

Gpshue Lederberg, Principal Investigator
rofessor and Executive Head

Department of Genetics

Stanford University School of Medicine
Palo Alto, California

Area Code 415, 321-1200, Ext. 5801

Approved:

7 i
fod. (Lal
Vhnot J. Glaser “™..

Earl G. LS Cilley
Associate Research Administrator
Stanford University
Stanford, California

    

Vice President for Medical Affairs and
Dean, School of Medicine

Stanford University

Palo Alto, California
Italy/U.S. Science Cooperation

An Exchange Program in Genetics and Molecular Biology
Between Research Scientists from the Departments of Genetics of the
Universities of Stanford and Pavia

May 1, 1967 - April 30, 1968

The Departments of Genetics of Stanford and Pavia, Italy, respectively,
wish to undertake a formal collaborative project in genetics and molecular biology.
The present proposal from Stanford closely parallels one submitted by

Pavia to the Consiglio Nazionale delle Ricerche of Italy.

The two departments have enjoyed a very close de facto relationship in
the past, as exemplified by the exchanges listed on page 3. These repeated
exchanges have resulted in the elaboration of a number of joint research projects
in genetics and molecular biology in which both U.S. and Italian scientists par-
ticipate. It will be very useful for the continuation of these projects if they
could be corroborated by an even stronger exchange of people and ideas from the
two departments. |

These enterprises have been financed vy charges to regular research budgets,
funds which are becoming more difficult to release for this purpose. The coopera-
tive program would enable us to move from an occasional interchange to a systematic
coordination of research programs.

There should be two research units involved in this collaborative research,
one at Stanford and one at Pavia. Each of the two would be engaged mostly, but
not exclusively, in one of the two major research programs which are explained
below. In particular, at least one pair of visits each year will involve the
head of one department or his deputy, making an intensive consultation with the
entire research program of the other. However, because of teaching and other
duties, the senior scientists would be able to spend only comparatively short

periods of time away from their main laboratories. On the other hand, younger
2.

scientists could spend longer periods of time in the other department. In
addition, other people may be engaged on a more or less permanent basis in
either laboratory to ensure the continuity of the work.

Stanford, then, will furnish one or more senior and associate scientists
so that the Pavia laboratory will have, on the average, one or two visitors in
residence at any one time, and correspondingly will offer the facilities of the
Stanford laboratory to two visitors, one a senior scientist, who may be different
individuals during different parts of the year. The respective departments will
endeavor to identify and certify scientists from other institutions as well who
might go under Stanford's (or Pavia's) auspices, to represent special skills and

interests needed to fulfill the program,
3.

The following faculty and staff members from the Genetics Departments
of Pavia and Stanford have been associated with the other department for periods
of time ranging from a few weeks up to two years:
Dr. J. Lederberg (Stanford) in Pavia in 1962;
Dr. L. L. Cavalli-Sforza (Pavia) in Stanford in 1962, 1964, and 1965;
Dr. W. Bodmer (Stanford) in Pavia in 1963 anda 1966;
Dr. A. Edwards (Pavia) in Stanford in 1964;
Dr. 0. Ciferri (Pavia) in Stanford in 1966,
Presently, one junior scientist from Pavia, Dr. S. Barlati, is working in the
Stanford Department of Genetics.
Further exchanges have taken place between Pavia and Stanford:
Dr. A. Falaschi, presently in Pavia, has spent four years in the Stanford
Department of Biochemistry;
Dr. H. M. Cann, formerly a fellow in the Stanfora Department of Genetics and
now in the Stanford Department of Pediatrics, has spent one year in Pavia;
Dr. G. Milanesi will soon be spending several months in the Stanford Biochemistry
Department.
Dr. Ruth T. Gross, then at Stanford, spent part of 1959-60 at Pavia. She is

now Chief of Pediatrics at Mount Zion Hospital.
PROPOSED JOINT RESEARCH PROGRAMS

Molecular Genetics (MG, to be carried out mostly at Stanford)

It is proposed to study the integration of synthetic deoxypolyribonucleo-
tides and of DNA of widely different biological origin into the genome of Bacillus
subtilis, and their genetic translation in vivo. Two models can be given as examples
of a first experimental approach:

1) the uptake and integration of synthetic deoxypolyribonucleotides such as poly-
aAdT into the genome of Bacillus subtilis;

2) the uptake and translation of synthetic ribopolynucleotides such as poly-rU into
Bacillus subtilis.

Among other things, the second type of experiment, if sutcessful, could
permit the verification of the validity in vivo of the genetic code.

The ultimate goal of this research is the controlled modification of the
genome of an organism.

Scientists from Pavia have already made an important contribution to the
foundations of this problem, through their earlier visits having become familiar
with the biochemical techniques developed mainly in the U.S. for molecular biology
research. |

A special laboratory and office has been designated at Stanford for the
regular use of the Italian visiting scientists. In addition, the experimental
facilities of the Department will be freely available, including modern analytical
instrumentation for biochemical genetics, library, information retrieval aids, and .
access to a time-shared, remote-terminal computer system, with system programming

support.
Human Populations Genetics (HPG)

A theoretical analysis shows that for an understanding of human variation,
in particular of the mechanism of action of selection and genetic drift, work
on populations must be conducted:

1) at a larger scale than so far, with the adoption whenever feasible of auto-
mated techniques for the analysis of a large number of characters;

2) refining further the mathematical and numerical tools presently available
for the study of human populations.

The program is to set up a collection center starting with what techniques
‘are already available and use it for the study of populations on which the Pavia
and Stanford Departments are already engaged. Such an analysis is at present
carried out in part in other departments for lack of the required facilities at
Pavia and Stanford. One of the major aims in mind is to carry out the study of
the inheritance of complex quantitative characters by way of linkage to the
standard chromosome markers. This seems to be one of the best ways, so far un-
tried, to study the inheritance of characters which otherwise escape analysis,
such as behavioral ones. This will also involve much computer work.

While Pavia will be the primary center for these activities during its
operational phase, Stanford has a specially competent instrumentation development
laboratory. This is mainly dedicated to instrumentation for experiments in space
biology, but its engineers and physicists will be available for consultation for
the development of specialized automated equipment for immunological survey work.
Stanford also has one of the most advanced computer systems in the world dedicated

to medical research laboratory work, and its facilities will also be available

for this project, giving Italian scientists an unusual opportunity to become familiar .~ —

with these advanced techniques.
Other research support:

NSF

NIH

NIH

NASA

-GB-4430X1

AI-5160-09

FR 00311-01

NsG 81-60 S7

(Jointly with faculty members of Genetics Department )
A Program in Genetics and Molecular Biology
10/15/66 - 10/15/67 $63,600

Genetics of Bacteria 9/1/66 - 8/31/67 $52,174
(Jointly with Medical School faculty)
Advanced Computer for Medical Research

9/1/66 - 7/31/67 $444 534

Cytochemical Studies of Planetary Microorganisms.
9/1/66 - 8/31/67 $448 850