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IF THE DISTINCTION between
basic and applied research is some-
times a hazy one, this is especially
true in the life sciences. It is widely
appreciated today that many of the
scientific efforts made over the years
devoted to an improved theoret,cal
understanding of the complex pro-
cesses of living organisms are, one
day, likely to be converted into
treatments or detection proce-
dures for disease.
The path of basic research towards
solutions for improving the human
condition may not alwayi be direct
or quick, but it is a sure one
nevertheless.
Biomedical research, which has
developed considerably at the Weiz-
mann Institute mainly in the last 20
years, focuses on many fields: the
nervous and muscular systems, re-
production, the process of ageing, the
immune response, the circulatory
and endocrine systems and others.
At the hub of the Institute's life
science research is the challenge of
cancer, which is addressed in no less
than nine departments.
Fundamental research in biology
and in cancer in particular began at
the Institute in 1950, with the arrival
from Oxford of Prof. Isaac Beren-
blum, a pioneer in the cancer fields.
Some of the numerous develop-
ments in cancer research at the In-
stitute were explained by Prof.
Michael Feldman, Head of the
Department of Cell Biology and
Dean of the Faculty of Biology.
He noted that one of the impor-
tant discoveries in cancer research
made by Berenblum, now a profes-
sor emeritus, was that the conversion
of normal cells into cancerous cells is
a two-stage process. The normal cell
is first converted into a dormant
tumour cell, and may remain dor-
mant for a very long time until it
receives another chemical "signal"
which converts it into an active pro-
liferating tumour.
Another landmark in cancer re-
search at the Institute was the work
of Prof. Leo Sachs in the late 1950s
and early 1960s. Sachs was one of the
first scientists, Feldman noted, to
convert normal cells to cancer cells
in an incubator, outside of a living
organism. This opened the way to a
wider range of studies that could not
be performed on intact laboratory
animals.
Since the early days of cancer
research in Rehovot, this field has
expanded and branched out, with
those scientists who first served in
junior positions on the research
teams of the founding professors
later coming to direct their own
projects. Research teams including
senior professors, young scientists
and lab technicians can range from
anywhere between two and 20 peo-
ple.
This development reflects the na-
ture of scientific inquiry itself, Feld-
man explained: "A scientist asks a
question and designs a lab experi-
ment to provide an answer. But
typically, each new lab discovery not
only solves one question but raises
many others. Some of these may
have an immediately apparent ap-
plied relevance, but the applications
of other discoveries may be
approachable only after many more
stages of basic inquiry."
This process is illustrated in the
later work of Prof. Sachs and his
associates. They sought to gain a
better understanding of what makes
cancer cells replicate. Normal cells
grow by developing into specialized
cells that form the building blocks of
the organs of the body, and then stop
proliferating. Cancer cells, however,
continue to proliferate without any
final stage of specialization.
Sachs' research has shown that

Getting cancer
under control

Charles Hoffman surveys the Weizmann
Institute's ongoing battle against cancer.

Prof Michael Feldman.

specific chemical signals sent to a cell
are required for it to specialize and
hence to stop multiplying. This
raises the tantalizing possibility that
such signals could also be applied to
cancer cells in order to make them
stop proliferating. It takes little im-
agination here to see the possibilities
for clinically controlling the growth
of cancers.
But the jump from discovery to
application is never simple. The
Sachs research group first managed
to use chemical signals to stop the
proliferation of cancer in blood-
forming cells, that is, in certain types
of leukemias. But this was done in
tissue cultures taken from lab anim-
als and humans. The next stage,
which is now under way, is to deter-
mine if such processes also work on
living organisms.
Feldman noted that even though
many of the questions being
asked today in cancer research were
posed 30 years ago, gaps in scien-
tific knowledge and the relatively
simple level of experimental techni-
ques at that time made it impossible
to investigate them.
"There have been dramatic de-
velopments in cellular and molecular
biology since then. For example, we
now have the capacity to grow cells
outside the organism and direct their
development. And we have • the
capacity, which was virtually science
fiction then, to isolate single genes,
study their precise structure and
function, thereby tracing the precise
molecular processes that regulate
normal and cancerous growth in
cells."
Physicians can often treat their
patients successfully without know-
ing exactly why a certain medication
has a positive effect. Scientists,
however, can never be content with
simply matching two sets of external
observations made on lab animals,
cells or some other experimental
object.
In order to know what makes
normal and cancer cells tick, Feld-
man explained, it is necessary to
analyse the chemical processes that
take place in the molecules of the
cell. This takes us into the role of
genes and their main chemical com-
ponent DNA in sending out growth
instructions to the cell.
About seven years ago it was dis-
covered that viruses can convert nor-
mal cells into cancer cells because
they have one unique gene, called
the "oncogene". Later it was deter-
mined that viruses had actually

"stolen" the oncogene from one site
in the normal cell and reintroduced it
into another site, thus triggering the
cancer.
Research at the Institute by Dr.
Eli Kena'ani, Prof. David Givol and
their colleagues has located the pre-
cise site of the resettling of the gene
responsible for the conversion of
normal blood forming cells to certain
types of leukemias.
Identifying the gene that is the
"culprit" in triggering cancers is only
part of the solution to the puzzle,
however. Genes contain chemically
coded instructions for many bodily
developments and functions. Before
clinical application of the discovery
of the oncogene and its wanderings
about the cell can be considered,
more has to be known of the other
functions of this gene.
An important advance in this
direction has been made recently by
Dr. Ben-Zion Shilo, a young Insti-
tute scientist. He found that this
gene is widely distributed through-
out nature, appearing, for example, in
humble but durable organisms like
the fruit fly. It must therefore have
other important functions, which are
not yet known.
Other work on tracing the charac-
teristics of genes which influence the
formation of cancer cells has been
carried out by Dr. Varda Roter and
Dr. Moshe Oren, who have used the
recently developed techniques of
genetic engineering in their ex-
periments. They have investigated a
unique protein which appears pre-
dominately in cancer cells.
Prof. Feldman's own research is
linked to the "migration" of cancers
from their primary site of generation
via the blood and lymph systems to
other parts of the body, where they
form new centres of growth.
Born in 1926 in Tel Aviv, Prof.
Feldman was educated at the Gym-
nasia Herzliya and received his Ph.D.
at the Hebrew University. He joined
the Institute in 1955 and has served
as Chairman of the Scientific Coun-
cil of the Institute and as Dean of the
Institute's Feinberg Graduate
School. Feldman is a member of the
Israel Academy of Sciences and
Humanities.
Despite the manifest importance
of understanding the process of can-
cer migration, or metastasis – if
cancers remained at their original
site, surgical cures would be relative-
ly simple – this field has been neg-
lected until the last few years.
Feldman's research group has

special while blood cells called
shown that within a given tumour,
lymphocytes. Attempts were
some of the cells are "programmed"
to stay there and proliferate, while therefore made to remove such
others get instructions to move out.
`killer' lymphocytes from the bone
The differences in their behaviour
marrow prior to their injection into
are related to the presence of diffe-
the patients.
"This was acheved by Dr. Yair
rent antigens (molecules that can
evoke an immune response in the Reisner, a young scientist at this
Institute. He then collaborated with
body) on the cell surface. The team
found that changing the antigens on physicians at the Sloan-Kettering In-
the surface of cancer cells induces stitute in New York, who applied
changes in their capacity to generate Reisner's method to treating
leukemic children, and the initial
metastasis.
It has also been found that the results are promising."
The Institute is seeking to form a
tumour at the original site has a
suppressing effect on the growth of cancer research centre modelled af-
ter the other interdisciplinary cen-
secondary tumours sent out from
there. This was discovered when it tres on campus. Such a centre would
achieve greater cooperation be-
was noted that surgical removal of a
tween the research groups in the
tumour that had already generated
various departments now working on
metastasis caused the growth of the
cancer-related subjects, and would
latter to speed up.
Can we unravel enough of the also provide a framework to host
visiting scientists from abroad work-
secrets of the process of secondary
tumour formation in order to check ing in this field, Feldman noted.
the spread of cancer throughout the Such a centre could also provide a
regular source of funding for new
body? One approach to this problem
that has been investigated is whether equipment needed to keep abreast
a person can be immunized against . of the field.
The Institute authorities have
his own cancer, which would then be
rejected by the body in the way that determined that it would take $5
grafted or transplanted organs are million to establish an endowment
rejected.
fund to support such a centre.
Feldman said that two factors
Clinical trials of this method,
Feldman said, have so far not holding back progress in the field of
cancer research, as well as in others,
yielded the hoped-for results.
are a decrease in funds available for
Another immunological approach
to cancer treatment is being de- basic research in recent years and the
veloped by Institute president Prof. high cost of new equipment. "The
only way to get to applied research is
Michael Sela together with Prof.
Ruth Amon. As Feldman described to start with basic work, and unfortu-
it, this approach involves the use of nately young scientists have found it
"guided missiles." Drugs lethal to much harder lately to get funding for
certain cancer cells are coupled to their work from sources in Israel and
antibodies which specifically abroad."
recognize cancer cells. It is hoped
Feldman smiled when asked to
that such antibodies — drug con- compare the equipment needed now
jugates — will see out the cancer to do basic research in cancer with
cells, lead the drugs to them and the tools used by Prof. Berenblum
when he initiated the field at the
subsequently destroy them.
If this technique can be de- Institute: "All he he needed then
veloped, it will have clear-cut was a syringe to inject the lab anim-
advantages over standard che- als and a cage to keep them in.
motherapy, which has a negative Neither he nor anyone else then
influence on normal cells as well as could manipulate genes or sort cells
on tumours.
to analyse what actually happens at
When a promising avenue for can- the molecular level.
"Today, for example, we need a
cer treatment like this one crops up
in the lab, an impatient public usual- new machine for sorting out various
ly badgers scientists with questions types of cells. It costs about $300,000
like: When can you try this on hu- and requires constant attention by a
technician. The lack of funds for
mans?
"Not so fast," is Feldman's such equipment is becoming a se-
emphatic reply. The decision to rious bottleneck in our research.
shift the focus of research from the Lacking specific equipment, we are
lab to the clinic is a complicated simply unable to apply for some
one involving several time- research grants."
Starting from "scratch" 30 years
consuming stages.
"From initial observations made
ago, the Institute has built up an
in the lab on animals, the researcher internationally-respected tradition
must decide if the discovery has an of cancer research that includes top-
effect on human cells grown in a notch scientists; an inventory of in-
tissue culture. The new therapeutic teresting avenues of inquiry; mas-
approach involved is then tested on tery of the latest experimental tech-
normal animals to see if there are niques (such as genetic engineering);
fruitful interdisciplinary coopera-
any harmful side-effects. Only then
tion ; skilled technicians and coop-
can a clinical test be designed.
"This requires joint efforts by sci- eration with doctors and hospitals
entists and doctors and cooperation for clinical tests of promising ther-
between the Institute and hospitals apeutic ideas.
It thus seems ironic that today the
in Israel and abroad. During the last
few years there has been greater most serious obstacle to progress
collaboration on these levels in de- towards new treatments and detec-
tion procedures for cancer is lack of
signing and conducting clinical tests
money.
for Institute techniques.
Prof Berenblum holds the Jack
"One example is a discovery made
at the Institute, which led to clinical Cotton Chair of Cancer Research,
trials in patients with cancer of the Prof Feldman the Philip Klutznik
blood-forming cells, namely leuke- Chair in Developmental Biology, Prof
mias. Theoretically, had we been David Givol the Oscar H. and Anne
able to destroy the diseased cells and Altschuler Chair of Immunochemistry
replace them by normal blood- and Prof Sachs the Otto Meyerhof
forming cells taken from the bone Chair of Molecular Biology.
Dr. Yair Reisner holds the Dr. Phil
marrow of healthy donors, the dis-
Gold Career Development Chair in
ease could have been cured.
"We can destroy these cancer cells Cancer Research, Dr. Varda Rotter
by x-rays, but the injection of nor- the Norman and Helen Asher Career
mal bone marrow cells results in a Development Chair and Dr. Ben-Zion
lethal process in which the injected Shilo the Charles H. Revson
cells 'attack' the cells of the patient. Foundation Career Developmental
Chairs.
The attacking cells were found to be

