Introduction
Texte intégral
1Today’s inaugural lecture is on cancer, the “emperor of all maladies”, as it is called in the title of a book that I recommend to anyone both terrified of and fascinated by cancer.1 It is terrifying because it has always been mysterious and multifarious. Its causes were long unknown and the remedies to treat it were empirical and radical: empirical for they were applied blindly, as the disease’s mechanisms were unknown, and radical for doctors were incapable of targeting the cause of the ailment, and therefore sought to fight it through brute force, either by means of surgery or the use of toxic drugs whose collateral effects often killed the patient.
2I speak in the past tense as the situation is currently changing, given that, thanks to molecular biology, decisive progress in our understanding of the disease has been made in recent decades. This is where cancer becomes fascinating. Through a series of fundamental discoveries, we have learnt that it is actually a deregulation of our “normal self”, a disease whose profound cause is endogenous, linked to dysfunctions in the very mechanisms of life. The history of all the cells in our body is steered by genes that programme their differentiation, control the speed of their divisions and even decide when they end by organizing their death. Mutations in these regulatory genes can disrupt the normal cell division process. Some so-called “oncogenic” genes which, in normal life, control the rhythm of cell division, start giving accelerated orders, like an accelerator pedal stuck to the floor of a car, leading to an indefinite multiplication of cells and to the growth of tumours or, in the case of leukaemia, to a growing number of abnormal white blood cells invading the bloodstream.
3If other genes, called “antioncogenes” and whose normal mission is to inhibit cell division, become deficient, again an abnormal acceleration of cell division occurs. Once the disease has begun, yet other genes conspire to its propagation: those which, in a normal process, control the vascularization of organs, also support that of tumours by supplying them with the blood necessary to their growth; and those which manage the vital transport of certain cells from one part of the body to another, for example to fight infections, can foster the migration of cancerous cells and lead to the appearance of metastases.
4Hence, understanding cancer and understanding life itself are two sides of a same coin. Cancer is not outside of us, caused by exogenous agents like infectious diseases, but inside us, potentially present in our genes, which are themselves likely to mutate at any moment. This does not mean that external agents cannot play a role in triggering the disease. By modifying genes, chemical substances and radiation can cause cancers. Likewise, by parasitizing our DNA, some viruses can introduce altered versions of normal genes therein and trigger cancerization. In fact, our genome’s sensitivity to external agents long concealed the profound nature of cancer, leading researchers down wrong exogenous tracks.
5Of course, doctors did not wait to understand the profound nature of cancer to fight it. A cancerologist illustrated this fight with a metaphor, arguing that it is not because one does not understand how the digestive system works that one should refuse to eat. This metaphor is fitting, as chemotherapy was long a sort of cookery exercise, with the development of treatments using one or several molecules whose effects were assessed following a long series of trial and error. They would give patients hopes that were often disappointed, but sometimes miraculously fulfilled. Nor has it been necessary to understand the nature of the disease to establish the role of triggering agents. The causal correlation between cigarette addiction and lung cancer, for example, was irrefutably established as early as the fifties.
6We have good reasons to believe that we are now coming out of a long period during which empiricism prevailed. The increasingly precise understanding of the genetic and biomolecular deregulations that induce cancers is revolutionizing cancer research by steering it towards the search for molecules which operate according to mechanisms that we now understand. This enables treatment to specifically target a certain stage of the cancerization process without affecting normal vital functions. In the longer term, genetic engineering to repair defective genes will perhaps add to the range of therapies available, in a personalized medicine procedure, tailored to each patient. The hope, not so much of eradicating a disease that is but a mirror deforming life itself, but rather of controlling it or making it a chronic condition with which we will live up to an old age to eventually die with cancer and not from it, is no longer a utopia.
7When it comes to health, it is impossible to dissociate fundamental research from its applications. Biologists and doctors are driven as much by the need to understand as by the desire to treat. These two motivations are not independent of each other. The effectiveness of treatments is contingent on the acquisition of fundamental knowledge on the disease, which is often unpredictable. Studies as unexpected as those on sea urchins’ reproduction or on a rare sarcoma affecting hens have led to crucial progress in the understanding of cancer mechanisms. The history of cancer research offers a lesson that also applies to other scientific fields: even when there is strong demand from society, it is impossible to short-circuit fundamental research and to limit funding to applied research projects.
8This was attempted in the 1970s in the United States with the launch of a great cancer plan, announced triumphantly by President Nixon and supported by hundreds of millions of dollars in funding. The plan prioritized mass clinical trials and the search for hypothetical cancer viruses. The intention was to overcome a disease whose mechanisms were unknown, in order to eradicate it so to speak with the brute force of money and technology, a little bit like setting out to conquer the Moon without knowing Newton’s laws. Measured against set goals, it was a failure. Fortunately, a small part of the allocated funds went to researchers who were working freely on the sidelines of this grandiose project, on questions that they themselves had asked. These researchers were the ones who made fundamental discoveries on the nature of the disease, paving the way for innovative therapies. It is worth pondering this lesson, should we imagine that fundamental research is a luxury and that, in times of urgency, it is possible to programme the acquisition of results, be it regarding a public health issue, the renewal of energy sources, or global warming.
9Hugues de Thé, the oncologist whom we welcome to the Collège de France today, started his career at the Institut Pasteur and pursued it at Inserm, before being appointed as a professor at Paris VII University and heading a laboratory at the Hôpital Saint-Louis. His work, crowned with many prizes and recognized with his entry to the French Academy of Sciences in 2011, illustrates the promising facets of cancer research that I have just mentioned. His research on the treatment of a rare form of leukaemia is one of the remarkable successes of the new therapeutic approach, which consists in using simple molecules to target a very precise biological phase of the cancer process. The paradoxical use of a poison, arsenic, as a remedy is a weapon of traditional medicine – cure evil with evil –, but now positions it in a resolutely scientific context by clarifying the mechanisms that cause this poison, combined with retinoic acid, to be a powerful and effective medicine. The treatment against this form of leukaemia can serve as a model for therapeutic approaches to other forms of cancer. Throughout his work, Hughes de Thé has shown how fundamental research and the development of treatments could be combined into an exemplary translational approach. Like all great doctors, he sees the physician’s curiosity as inseparable from the clinician’s compassion.
10Cancer research draws on biology, genetics and chemistry, and even on statistics and informatics. Hugues de Thé, at the Collège de France you will have the opportunity to collaborate with colleagues working in fields complementary to yours. Your Chair’s relations with those of Experimental Medicine and Epigenetics, as well as the Liliane Bettencourt Annual Chair of Technological Innovation, are clear to see. You will also build ties with other teams: those of the Centre for Interdisciplinary Research in Biology (CIRB), of the Chair of Chemistry of Biological Processes, and perhaps of the Chair of Informatics. These ties, which will grow all the stronger as you will set up a laboratory at the Collège de France, will once again illustrate the fact that pooling knowledge from different sciences is mutually enriching. I now leave the floor to you, to deliver the Inaugural Lecture of your Chair of Cellular and Molecular Oncology.
Notes de bas de page
1Siddhartha Mukherjee, The Emperor of All Maladies: A Biography of Cancer, New York, Scribner, 2010.
Auteurs
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Serge Haroche
Administrator of the Collège de France
- Liz Libbrecht (trad.)
Le texte seul est utilisable sous licence Licence OpenEdition Books. Les autres éléments (illustrations, fichiers annexes importés) sont « Tous droits réservés », sauf mention contraire.
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