MARIE CURIE PRIZE - LOW RADIATION

Maurice Tubiana was born on March 25 1920 in Constantine (Algeria). He completed his secondary school education in Algiers and studied medicine in Paris (degree received in 1946). He also has a M.S. in physics and worked in the labs of Frédéric Joliot-Curie at the Collège de France and of John Lawrence at Berkeley.

He spent most of his career at the Institut Gustave Roussy in Villejuif. He began in 1951 as head of the isotope laboratory developing their use in cancer treatment; in 1959 he became head of the department of radiation; in 1978 director of research and director general from 1982-1989. In parallel, he was professor at the Paris University medical school (1963-1989), Chairman of the commission on cancer of the French Ministry of Health (1975-1981 and 1988-1994), President of the Committee of cancer experts of the European Action Against Cancer (1986-1994), Expert-Consultant to the World Health Organization and member of its board (1978-1982), member of the scientific committee and the board of the International Agency for Research on Cancer, member of the main commission of the International Commission on Radiological Protection (ICRP) (1953-1958) and vice-chairman (1958-1969) of the International Commission of Radiological Units (ICRU).

He has received numerous national and international distinctions, among them: Barclay’s Medal for Radiobiology (London 1977), L.H. Gray’s Medal (Washington 1981), Breur’s Medal (Stockholm 1985), Roentgen Medal (1986), Janeway Medal (1991), Pezcoller Prize (1991), Raymond Bourgine Prize (2007).

He is Doctor honoris causa of several universities and an honorary member of eleven academies. He was elected member of the French Academy of Sciences (1982) and of the French Academy of Medicine, of which he was President in 2002.

M. Tubiana was one of the leaders in the development of the study of proliferation kinetics and growth rate of human and experimental tumors. His works have had major consequences for cancer management.

Radiosensitivity and chemosensitivity of tumors are influenced by the proliferative status of the cells since quiescent cells repair more effectively potentially lethal damage.
In a large proportion of human tumors, an insult by ionizing radiation or drugs triggers into proliferation surviving tumor cells previously quiescent. This so-called tumor repopulation has a strong impact on the overall results of a fractionated treatment either by radiotherapy or cytotoxic drugs. New successful schemes of fractionation have been based on this concept.
The rate of tumor cell proliferation is for all tumors a prognostic factor and is correlated with the probability of early metastatic dissemination.
The analysis of the growth rate and progression of human tumors helps to understand their natural history. There is a strong correlation between the size of a tumor, its growth rate and the probability of metastatic dissemination; thus an early diagnosis can avoid a large proportion of dissemination. This is the rationale for screening, in particular breast cancer screening by mammography which has markedly improved the prognosis of breast cancer.
Conversely, in some tumors the dissemination occurs before diagnosis. In a large proportion of these patients the size of the metastases at the time of diagnosis is small so they cannot be detected, but due to their smaller size they can be controlled by relatively low doses of cytotoxic drugs or radiation. This is the basis of adjuvant chemotherapy or radiotherapy. M. Tubiana developed these two concepts in the 1970s and provided in the late 1970s and early 1980s the scientific evidence which substantiated them. More recently, he demonstrated that occult residual tumor after initial treatment can be a nidus for distant dissemination. This is the rationale for post-operative radiotherapy.

Another major contribution to cancer treatment has been the study of hematological complications of radiotherapy and chemotherapy. The investigation of their mechanisms led M. Tubiana and his group to carry out fundamental research on the regulation of bone marrow stem differentiation and proliferation. He showed that partial body irradiation triggers hemopoietic stem cell differentiation in the shielded bone marrow and thereafter proliferation. Thus iterative partial body irradiation can deplete the stem cell pool of the protected areas. The analysis of this phenomenon led to the study of growth factors (M. Tubiana was among the first to study them) and inhibitors (his group was the first to study these and isolated, identified, and synthesized one of them).

In radiobiology he has published several papers on late effects of ionizing radiation on hemopoietic tissue. He assessed the probability of second cancers after treatment by radioactive isotopes and external radiotherapy. He showed in mice that after an irradiation repeated bleeding increases the probability of leukemia.

He has recently devoted several reports and articles to the carcinogenic effect of low dose irradiation and challenged the validity of the linear no threshold relationship (LNT) for assessing the carcinogenic effect low doses.