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Interview. Manuel Elkin Patarroyo

Manuel Elkin Patarroyo colombian scientist, who was developed a vaccine that marks an important stage in the struggle against malaria. [WHO, Geneva]

In 1986 Colombian physician and biochemist Manuel Patarroyo made a synthetic vaccine, SPf66, which has since shown considerable efficacy in the struggle against malaria, one of the world’s most widespread diseases. In this interview with Flor Romero he looks back to the day when he vowed to follow in the footsteps of Louis Pasteur.

‘Science with conscience”

· How did you first become interested in science?

Manuel Patarroyo: I think my scientific curiosity was whetted for the first time when I was five years old, on the day when my aunt Alicia turned up in Ataco, the village where I was born, with two little dog-shaped magnets. It was then that I heard the word magnetism for the first time. I insisted on being told what it meant. Ever since then I have always needed to understand. Whenever I went fishing and came back with a catch, it wasn’t to cook the fish but to open them up and see what was inside.

When I was eight years old, I read a biography of Louis Pasteur in a book my father gave me. From that day on, Pasteur became my hero, my model. I decided that I too would make vaccines to serve humanity. I have devoted my life to fulfilling this childhood dream.

I don’t know how much credence should be given to what the ancient Greeks called fatum, the destiny that shapes a person’s life and leaves little room for freedom. But the fact is that even as a child I already knew what I wanted to do. I have never been tempted to leave my chosen path.

· But how did you manage to develop a chemical vaccine against malaria in a country without a scientific tradition and without the necessary infrastructure for such an important discovery?

M.P.: The story of this vaccine, SPf66 (Synthetic Plasmodium falciparum, 66th tested formula) began in 1978 after we had mastered the methodology developed by Bruce Merrifield, who won the Nobel Prize for Chemistry in 1984. The first step in our research was to isolate Plasmodium falciparum, the deadly parasite that causes malaria, from cultures of infected blood. Then we had to isolate the proteins of which it is composed. After vaccinating Amazonian monkeys with these molecules, we exposed them to the parasite. We succeeded in defining four molecules that were immunologically useful. We established their molecular structure and then synthesized them and endeavoured to find the combination that protected the infected monkeys. The 66th combination was the successful one. This was how SPf66, the first entirely synthetic antiparasite vaccine, was discovered in January 1986.

And yet I would be incapable of explaining in detail why the product works. No one knows parasites’ pathogenic mechanisms.

· Was this why the scientific community reacted oddly to your discovery?

M.P.: We were blamed for having discovered this vaccine empirically, in a situation involving multiple combinations of falciparum molecules.

We first of all tried the vaccine in the owl monkey, Aotus trivirgatus, which is one of the few animal hosts of the human malaria parasite and is plentiful in Colombian Amazonia. The results, published in the scientific journal Nature, met with considerable scepticism from the scientific community, and so did the first human trials in 1987.

I understand this scepticism, not only because of the synthetic nature of the vaccine but also because my country has no scientific tradition. But no one can deny that in Colombia we have discovered a vaccine which is revolutionary on two counts - as the first antiparasite vaccine and as the first totally synthetic vaccine. And while for the moment it is only partially effective, SPf66 can prevent around a million deaths each year.

· Can a higher standard of protection be achieved?

M.P.: Since 1986, we and other research teams have discovered other molecules on the surface of the parasite. In order to maximize the vaccine’s efficacy, we have tried to find out more about these parts of the parasite which enable it to adhere to the cells and invade them. We are continuing to work along these lines so that, hopefully, the vaccine can one day be administered orally.

At present the vaccine’s efficacy in Latin America varies between 38.9 per cent and 60.2 per cent, depending on patients’ age. The vaccine seems to be much more effective on children under five. The side-effects (which do not affect more than 5.6 per cent of patients) are limited and require no medication. It is an absolutely safe vaccine without any of the problems associated with biological vaccines.

Under the auspices of the World Health Organization (WHO), the vaccine has been tested in the most malarious areas of the planet, the United Republic of Tanzania, and Gambia. In late 1994, the prestigious medical journal The Lancet published the results of vaccinations in the United Republic of Tanzania, after a two-year trial between 1992 and 1994 whose objective was to determine the efficacy of the vaccine on children aged from one to five in an area of intense malaria transmission. The results showed that the protective efficacy of SPf66 was 31 per cent.

The epidemiological situation in Tanzania provided a particularly stiff test for SPf66 because people living in this part of the world are a hundred times more exposed than those living in Colombia to the bites of the mosquito that harbours falciparum. In these conditions, as Nicholas White of the Oxford Tropical Medicine Research Programme pointed out, the protection obtained with our vaccine is a positive and important result.

But we must be realistic. This vaccine will make it possible to reduce the incidence of malaria, but will not eradicate it completely. We must continue to control the disease, diagnose it and use medicine and insecticides. Only a pragmatic and multifactorial approach to the problem will make it possible, if not to eradicate this scourge, at least to reduce the number of victims.

· How do we stand with regard to malaria today?

M.P.: Malaria currently kills more people than any other disease. It occurs in hot, humid tropical regions, i.e. where the vast majority of people in the developing world live. It affects 40 per cent of the world’s population and causes between 2 and 3 million deaths each year, far more than Aids, for example.

But malaria is not equally virulent everywhere. Some ethnic groups are more resistant to infection than others. Susceptibility to malaria is related to blood group. In Africa, for example, the epidemic is particularly intense and can worsen during the rainy season. It is the world’s malaria hot spot. One and a half million children under five die of malaria in Africa each year.

· You have developed a top-level scientific laboratory in Colombia...

M.P.: Yes, and I am extremely proud of the team I work with. Most of its dynamic young researchers (average age thirty) are Colombian chemists, physicists, bacteriologists, molecular biologists and medical doctors.

In the grounds of Bogota’s San Juan de Dios hospital, where I worked, there was a derelict building constructed at the beginning of the century by a Colombian architect who had studied in France. Incredible though it may seem, in a kind of delayed-action response to my childhood dream, this building was an almost identical reproduction, albeit in ruins, of the Pasteur Institute in Paris. I was able to take it over and use it as the premises of the Bogota National Institute of Immunology, where thousands of doses of SPf66 are made today.

· What was the most difficult time in your life as a researcher?

M.P.: The most anxious moment of my life was when I administered the vaccine to thirteen volunteer soldiers. Experiments had already been carried out on monkeys, but their kidneys and brains are not identical to those of human beings. For nine months I woke up at three o’clock in the morning feeling sick with anxiety. I said to myself that if their kidneys were damaged a transplant was always possible. But if their livers were damaged these young men would be exposed to incurable hepatitis. The thought that these thirteen boys might die was a nightmare.

When the time came to introduce the parasite into their veins, for eleven days I was unable to sleep. I visited the hospital at all hours of the day and night to see how they were.

One day, in Cartagena, I went to the beach and threw myself into the water. I was so panic-stricken that I wanted to drown myself. Fortunately everything turned out all right. The results of the tests turned out positive.

As a child you saw the ravages of tuberculosis at close quarters. Have you ever thought of trying to find a synthetic TB vaccine?

M.P.: There are currently 27 million cases of tuberculosis in the world, and two and a half million people die of the disease each year. Tuberculosis is my wife and malaria my mistress. I can say that I have spent as much time with the one as with the other.

After a long spell of secret work at the San Juan de Dios Institute of Immunology, we succeeded in identifying the molecules exclusive to the tuberculosis bacillus and synthesized them chemically. I hope it will be possible for this vaccine, which we will call COLTU VAC (Colombian Tuberculosis Vaccine), to be used on a massive scale by the year 2000.

· You have given the patent of the malaria vaccine to humanity via the World Health organization.

M.P.: I received very tempting offers from a number of American, European and Asian laboratories. But the vaccine should be made available to governments so that they can organize massive vaccination campaigns. It should not be sold and I do not want to earn money from it. That is why I offered it to WHO for nothing, because in my opinion WHO is the most suitable organization to distribute it in the countries where it is needed.

· Didn’t you think of using proceeds from your discovery to develop your Institute and improve its research facilities?

M.P.: Giving is giving, not a form of exchange. To ask for something in return would tarnish the gesture. But Pasteur said that though the results of science are universal, the scientist has a country and his merits belong to that country. That is why I wanted the vaccine to bear the name of Colombia. I also want the main production plant to be in Bogota and the price of the vaccine to be very low so that it will be accessible to the needy. So far the price has been calculated as thirty U.S. cents for the three “adult” doses and half as much for a child’s dose.

· It’s your way of fulfilling your cherished dream of becoming a benefactor of humanity...

M.P.: One should fight to fulfil one’s childhood dreams. The world we live in has lost the capacity to dream. We should teach children to dream and encourage them to work for the good of their fellows. Aptitudes are fostered in the home during childhood, not in universities.

· You have often talked of demystifying science. What do you mean by this?

M. P.: One of the problems of science is that it tends to lock itself up in an ivory tower and invent a coded language that only initiates can understand. That is a mistake. The scientist is a product of society and must act in and for society. Knowledge must help to free and elevate the human being. If it does not, we are condemned to suicide.

We must vaccinate the world against selfishness and pessimism. Solidarity, goodness and generosity must not be empty words. Researchers have a moral responsibility to work for the welfare of all humanity. “Science with conscience” should be their watchword.