To treat as a preventive rather than in a crisis : a new concept of prospective medecine

A doctor, biologist, virologist, Professor Luc Montagnier divides his time between North America and France. Luc Montagnier is especially known by the public for having discovered in 1983 the HIV virus at the root of AIDS, then for having set up in 1993, together with the UNESCO general manager of that time, Federico Mayor, the World Foundation for AIDS Research and Prevention, he presides over. His works on oxidative stress are less known. It is, however, a promising and complementary way of research likely to strengthen immune defence system.

Véronique Anger: You regularly denounce the slackening of public opinion facing with the extension of AIDS throughout the world. How can you explain this demobilization while the epidemic keeps on spreading, more specifically in developing countries?
Professor Luc Montagnier: On the one hand, AIDS' extension has been quite limited in France. Indeed, if thousands of people are infected each year, the number of road casualties is much higher, which explains that this figure is quite hard to keep in mind sometimes. On the other hand, most people believe that there are treatments for curing AIDS. But that is wrong. Furthermore, people seem to get "accustomed" to this disease with the passing of years and they tend to consider AIDS of secondary importance. It is human to fear what is less known, such as the new epidemics of SARS (Severe Acute Respiratory Syndrome or atypical pneumonia) or Influenza H5N1. However, AIDS keeps on spreading over developing countries, particularly in Africa, Asia, India and China but also closer, in Eastern Europe.

Véronique Anger: On the other hand, you highlight the strong mobilization of researchers. What are today the chances of erading AIDS epidemic in the world? What are the most promising treatments, and about prospective vaccines?
Prof. LM: Researchers' mobilization tends to stabilize. The number of teams would even rather tend to diminish, particularly in France. The National Agency of Research on AIDS (ANRS) has less money than before. Its future is at issue. In the other European countries, there is no specific budget for AIDS, which is considered of part of the infectious diseases as well as other pathologies. Untill now, France has appeared as an exception, but that is likely to change.
There is the hope to make all the current treatments available to the patients who need them. Let us take the example of the African continent. It is estimated that 30 million individuals are infected by the virus. Among those, ten percent have reached a rather advanced state and should be treated with tritherapies. To manage to treat them successfully, more facilities and medical training would be necessary on the spot. To lower drugs' prices is a good thing but that is not enough. It is necessary to set up centres focused on research, prevention and treatments. Through our Foundation(1), that's what we've been trying to set up in partnership with local authorities. But this project will fail if political leaders don't get heavily involved in the countries where AIDS is strongly present, which is not always the case.
At the same time, this disease must be demystified. This is also valid for Asia where AIDS remains taboo and strongly feared. The individuals who are carrying the virus don't speak about it and even prefer sometimes to ignore they are infected. It is a very serious problem because the part of the population declared infected is very small (less than one percent of the contaminated individuals). The patients come to be treated only when they are in a critical state. To change this established fact, it is necessary to propose a treatment for all HIV-positive individuals, which is not the case at all today. For this reason, education and prevention are essential. There are still too many mistaken ideas, especially in Africa where some men believe that they will escape AIDS -and even that they will be cured- if they have sexual relations with virgin women.Other ones think that it is a curse spelled by marabouts. It is so absolutely necessary to educate the populations to prevention and particularly to persuade them to use condoms.
Research plays also a key role. It raises the hope that one day cheaper and less heavy treatments than tritherapy will be finalized. Of course, there are projects for vaccines, but I have a vey firm opinion on this matter. I think that current vaccines will not be effective. The tests carried out in Thailand by Vaxgen and Aventis-Pasteur are negative. I have expected this result because these preparations use native surface proteins of the virus. They expose the variable parts of the virus to the immune system, whereas it would be necessary to expose the virus' regions that do not change. As some tests have proved, the solution would consist in modifying the conformation of this surface molecule. Unfortunately, for the moment, pharmaceutical firms do not consider seriously this idea. Such as high-speed trains, they have got up speed and cannot slow down anymore. And they are going straight against a wall... Twenty American scientists or so have co-signed a letter in the magazine "Science"denouncing the money wasted on this wrong track. Tritherapy is an effective treatment, but it is not enough because it does not eradicate the infection. The hope would be to stimulate the contaminated individuals' immune systems so that they can resist and control their viral infections. Therapeutic vaccines added to immuno-stimulants and antioxidants would be a solution.

VA: This brings us to the following question… You preside over the scientific committee of Probiox, a Belgian laboratory specialized in biology related to oxidative stress. Can you explain what oxidative stress is?
Prof. LM:
It is an imbalance between oxidative molecules to which the organism is exposed, i.e.molecules derived from oxygen that oxidize all the components they meet (proteins, DNA, lipids, sugars...), and antioxidants that we ingest and produce. The most known are vitamins C and E, but there are other antioxidants, such as glutathion which are also significant. This imbalance will involve an oxydation of our components, generate changes in DNA, deteriorate the lipids of our cells' membranes and decrease our proteins' life. In small quantity, oxidative stress can stimulate the expression of some genes implied in cellular division. On the other hand, used in too high quantity, it can be harmful for the organism.For most of us, oxidative stress appears normally around 45/50 years. It is more significant among individuals suffering from pathologies such as diabetes, cardiovascular and neurodegenerative diseases, or from infections. It can be also caused by nutritional imbalances, air pollution, or the too intensive practising of sports.

VA: Probiox has carried out some tests on the French football team for example. What are the main effects of oxidative stress on the organism? What are its consequences on ageing?
Prof. LM:
This oxidative stress leads to premature ageing. It also favours the induction of cancers. These diseases can also appear among young people, and especially among professional sportsmen who makes too much physical effort. Treating oxidative stress will not improve their results, but it will improve their capacities of recovery after efforts. The treatment of oxidative stress raises the question of overdoses. In two high quantities, a very same vitamin can become pro-oxydant, which explains the necessity of diagnostic tests. That's what the Probiox firm does for example. From a mere blood test, it is possible to evaluate the deficiencies or overdoses and thus to adapt patients' treatment. The effects are more preventive than curative. The symptoms are treated, not the causes. Of course, we can improve the state of contaminated people, but we cannot cure them. Especially, we can reduce risk factors. It would be possible to prevent diseases thanks to a regular check up every six months and a correction of oxidative stress by using appropriate antioxidants.
I encourage the creation of such centres in order to make more prevention and thus reduce the huge costs related to the treatment of chronic diseases, these "long-term diseases". Life expectancy increasing, more and more old people live in old peoples' homes, as they are victims of the handicapping diseases which are Parkinson, Alzheimer or cancers. Prevention is costly, but it will be always less expensive than hospitalizations. To treat as a preventive rather than in a crisis state is a new concept for everybody.

VA: Some antioxidant plants or products (such as papaya) would make it possible to fight against neurodegenerative diseases. How do you integrate traditional medecine (African or other) into your research on AIDS?
Prof. LM:
Plants, which have been confronted with this problem for ages (they generate oxygen by photosynthesis), contain mixtures of components capable to eliminate oxidative stress and this could be increased by fermentation. For instance, fermented papaya extracts have antioxidants and immuno-stimulative properties and can have effects likely to lead to improvements if they are used in addition to validated treatments.
The tests carried out by Probiox have shown that degenerative diseases (Parkinson's, Alzheimer's...) reveal a great oxidative stress. Knowing that they are few treatments for these diseases, it is logical to test this type of products, not to replacement but in addition to drugs used usually for these diseases. Once again, we treat symptoms and not their causes. But as a researcher, I am interested in the causes. And I think that they are partly infectious. Infectious agents (bacteria, viruses,...) associated with these disease in a latent way will contribute to break out an oxidative stress.Traditional medecine, essentially based on plants, should not be missed. My idea is to integrate it by using the same evaluation criteria than for common drugs. These preparations must be reproducible and clinical trials must prove their efficiency. This medicine, which acts by stimulating immune defence system (and not directly on the causes: infectious agents or tumours), might be used as a complement of our more conventional medicine. It can improve the effects of classical drugs or reduce their side effects but I do not think that it can, used alone, cure serious diseases.

VA: You divide your time between North America and your research in France. Do you feel concerned by the anger that is raging among researchers? Do you feel that France is loosing an irreversible time on the international scene? According to you, why fundamental research is not a priority in France?
Prof. LM:
It is a usual problem in our country. I think that researchers are right to draw public attention. All the more so as there is another underlying issue. Research is not always considered as positive by the public. Certain aspects frighten: cloning, GMOs. People wonder where scientists are going... The public interest in science has never been very strong in France where Arts prevails contrary to the US situation; It is a very key point because politicians often follow public opinion. And if public interest in research decreases, research might disappear through lack of support.
I think that researchers must comply with some ethical rules and not carry out research that could have harmful consequences. But research is essential. Would be this only in biology or physics, to find out solutions to the many problems involved in our civilization (pollution, epidemics, diseases linked to population ageing, ...).
Granting more budgets? Yes. But not anyhow. I think that structural changes should be made in compensation. I've always asserted that the state takeover of researchers in France was a mistake. I agree with five-year research contracts providing they are renewable and better paid than civil servants. Training a researcher takes ten years. So, the five-year contracts should be renewable. This is a way that more and more countries choose today.
In France, we have an objective delay reflected in particular by the relative reduction of the number of patents. Less and less students choose research. Moreover, significant sides of research are missed. That will be truer in the years to come because the generations are not renewed in a certain number of specialities. It is necessary to set up new structures and advanced research institutes, as in the Unites States. In France, the funding of research by private foundations is very low, except for those specialized in genetic diseases. Biotechnology companies are missing too. In France, contrary to the United States, there are no -or very few- links between pharmaceutical laboratories and universities. That obliges researchers to show creativity to convince the public of the interest of what they do. I think that the main issue is, both in the US and in France, the significant scientific conformism, particularly in biology. We rely on fifty-year-old concepts. We use them and we are right to do so... But many enigmas remain to be solved. For example, we have been trying to understand the mechanisms, the "how" of cancers (which genes are implied in?) and some explanations have been found, but all this does not explain why all these genes act at a given time. Scientists still do not know what stimulates the cells to become cancerous. We go back over oxidative stress. It may be one of the factors, combined with infectious factors. We should be interested in the origin, the etiology of cancers, not only in their mechanisms.

*Professor Luc Montagnier is also the author of several works among which: "Virus" (Edition anglaise. Norton. 2000) ; " Des virus et des hommes " (Odile Jacob. 1994) ; " Sida et société française " (Documentation française. 1994) ; " Le sida " (avec R. Daudel - Flammarion. 1994).Biography.

(1) In 1996, the World Foundation for AIDS Research and Prevention set up a centre - CIRBA- in Abidjan (The Ivory Cost). Another centre is in way of installation in Yaounde (Cameroun).

For further information:
Fondation Mondiale Recherche et Prévention SIDA
Oxidative stress
On SARS and Influenza H5N1 : Let's see the website of OMS