A Cancer Pioneer

When Prof. Leo Sachs was young, he dreamed of founding a kibbutz in Israel and even spent two years as a farm laborer to prepare for pioneering on the land. Today, however, Sachs, a professor at the Weizmann Institute of Science in Israel, is renowned for pioneering of a very different nature. One of the world's leading scientists in the areas of cell biology and cancer research, Sachs has made fundamental contributions to his field and paved the way for successful clinical treatments.

One recent recognition of his achievements comes from Harvard Medical School, which will present him with its Warren Alpert Foundation Prize in Boston on April 17. Shortly afterwards, Sachs will travel to Sweden, where on May 30 he will receive an honorary doctorate of medicine from Lund University.

These are only the latest in a long list of prizes that have punctuated the illustrious career of the 6'8" researcher, who is quippingly said to be "head and shoulders" above many of his colleagues. His previous honors include the Wolf Prize in Medicine, the Israel Prize in Natural Sciences, the Rothschild Prize in Biological Sciences, the General Motors Cancer Research Foundation Prize, the Bristol-Myers Award for Distinguished Achievement in Cancer Research, the Royal Society Wellcome Prize, and Foreign Associate of the USA National Academy of Sciences.

Prenatal diagnosis

At the very beginning of his scientific career in Israel, Sachs had an idea that ultimately made it possible to diagnose human diseases in the womb.

The year was 1952, and the German-born Sachs, who had been educated in England, had just moved to the new Jewish state. By then, he had abandoned his early dreams of working the land in favor of contributing to the fledgling nation in the way he knew best - through science. He was recruited by the Weizmann Institute and asked to initiate a research program in genetics and development.

Sachs started working on a theory that human amniotic fluid, which bathes the baby in the womb, contains fetal cells that can provide information about the fetus. His studies proved him right. He showed that cells in the fluid can be reliably used to tell the sex of the baby before birth and also reveal other important properties of the fetus. This groundbreaking research formed the basis for human prenatal diagnosis by amniocentesis, a diagnostic procedure used today in millions of expectant mothers.

"I could have made this my life's work. But since I'd already proved the point, I wanted to look at some other aspect of development," Sachs explains. "I wanted to get a broad picture and try and discover general principles of normal and abnormal development."

Improving clinical treatments

Shortly afterwards, Sachs moved to the Institute's newly-created Experimental Biology Department and asked himself two questions that would form the basis of his research over the following years. First, what controls the normal development of different types of blood cells and second, what happens when normal development goes wrong through disease? "I thought that by understanding the normal processes and what happens in disease, I might be able to find a way to control the disease," says Sachs.

In trying to answer these questions, Sachs made discoveries that would serve as a cornerstone for current blood cell research and lead to major clinical applications. He developed the first-ever procedure to grow, clone and induce the development of different types of normal blood cells in a petri dish. Using this process he discovered and identified a family of proteins, among them colony-stimulating factors and some interleukins, that control blood cell production in its various stages.

One of the proteins that Sachs identified, the granulocyte colony stimulating factor, is now used clinically to boost the production of disease-fighting white blood cells in cancer patients undergoing chemotherapy or irradiation. The problem with both of these therapies is that they kill not only cancerous cells but also healthy ones. In many cases patients become dangerously susceptible to infection because their white blood cells have been destroyed. Regenerating certain white blood cells therefore gives these patients a better chance to fight infections. After clinical trials in several countries, this treatment is now widely used around the world.

The same protein was also found to help improve the success of bone marrow and blood cell transplants, as well as a number of other clinical procedures.

Reversing malignancy

Sachs also asked the question: what changes in normal development result in leukemia, and can this process be reversed? Subsequently he demonstrated that the proteins he had initially discovered, and some other compounds, can induce certain leukemic cells to behave again like normal ones both in a petri dish and in the body. Until then, most scientists had believed that malignancy was irreversible. These findings led to a form of treatment, called differentiation therapy, that does not kill cancer cells but instead gently induces them to behave like normal cells again.

Based on these results, researchers in France and China then developed an experimental treatment for patients suffering from acute promyelocytic leukemia. This procedure is now also being tested in other types of cancer.

What keeps cancer cells alive?

A few years ago Sachs returned to a question that had troubled him back in the early days of his scientific work. "When I first put normal blood cells into a petri dish, I found that without the necessary chemicals the cells would die. I decided to see if the materials needed to keep normal cells alive were the same for leukemic cells," says Sachs.

In normal circumstances, a cell is created, lives and then dies, and there is a balance between the creation of new cells and the death of old ones. But in cancer cells this balance is profoundly distorted. Sachs' present research includes studies on the genetic changes which take place in leukemic cells enabling them to live longer, and on finding ways to "switch off" these life-maintaining genes in the cancer cells, so that they die like normal cells that the body no longer needs. This research could provide another new approach to cancer treatment.

Contemplating 45 years of work, Sachs, who holds the Otto Meyerhof Chair of Molecular Biology at the Weizmann Institute, acknowledges that it has not always been easy. "I enjoyed most of it, but not all," he admits. "There have been ups and downs. But overall I'm optimistic and believe that all problems have solutions. One has to be permanently curious and keep on trying."