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Bernardo Galvão: The battle against Aids and other fights

Held in Salvador from November 22 to 25 last, the 16th National Virology Encounter was presided by Bernardo Galvão Castro Filho, a very special Brazilian researcher. Galvão, as everyone calls him, was 32 years old, when he came back from Geneva, with a doctorate in immunology concluded under the supervision of Professor Paul Henri Lambert, when he was given a grant by the World Health Organization (WHO) to implant a Parasite Immunology Center. The amount of this assistance: US$ 1 million. It was money way beyond reasonable for a young Brazilian researcher, even more so in 1977, in Bahia.

The difficulties encountered in his home town to implant the center he dreamt of ended up taking Galvão, in December of the same year, to the Oswaldo Cruz Foundation, the well-respected Fiocruz, in Rio de Janeiro. There, with the fine amount from the Tropical Disease Research (TDR) program, he started the history of the institution’s Immunology Department, which was soon to transform itself into a magnet for young and talented researchers, and, a few years later, was to play a decisive role in the control of Aids in the country. Under the command of Galvão, the team isolated the HIV virus in Brazil, worked against its diffusion, defining the bases for blood triage and for its quality control, amongst other important contributions both to scientific research and to public health in Brazil.

But Galvão always tries to minimize his role in the feats of this department or in his most recent works at the Fiocruz center in Salvador, to which he returned in 1987, and today, at the age of 60, finds himself grappling with HTLV virus research, new public health programs, and always countless projects with a strong social commitment. As if that were not enough.

This cordial and generous Bahian, simultaneously Christian and communist, was born in the elegant Corredor da Vitória, not for being the son of a rich family in Salvador, but because his father, a teacher and educator the whole of his life, ran a lodging house for youngsters from the hinterland who went to study in the capital, at the famous Sofia Costa Pinto College, located in that street. The lodging house was also the home of the Galvão family, which thought that it was absolutely normal to share the daily lunch table with some 40 persons. Married to Aninha for 35 years, the father of Karina and Verena, grandfather of Thiago and Bernardo, Galvão told many delicious stories in the long interview he granted Pesquisa FAPESP. Below, the main passages from it.

I would like you to talk, without false modesty, about your role in the strategy for the National Aids Control Program, when it began back in the 1980’s.
I think that the most important contribution of the group I led at Fiocruz was to implant the bases for the triage of blood for HIV in Brazil. And also to implant the bases for the quality control of the blood and the quality control of the laboratories. Aids was and still is a very great ill, but in the wake of this ill many important things have happened. Because since Aids is a disease transmitted by blood, and as the bag of blood supplied by an infected donor can infect various persons, if there were no control over blood transfusions, if there were no screening of blood since those days, I think that the dimension of the disease in the country would have been far greater. That is why I believe that, within what we did, the most important contribution was to have started this triage in 1985. The disease was recognized as a syndrome in 1981.

That is to say, in that period when Robert Gallo and Luc Montagnier isolated the virus?
No, that was afterwards. The syndrome was notified, publicized and recognized as a syndrome in 1980/1981, thanks to the epidemiological surveillance of the United States, which is very good, although the healthcare system, generally speaking, is not. What happened then? I explained this in an article that Ênio Candotti, the editor of the Ciência Hoje [Science Today] magazine, asked me to write. We got together, me, Hélio Pereira and Euclides Castilho, and we wrote an article about Aids. But it was César Benjamim, an associate editor, who put everything into an easy and accessible language. On the one hand, there was this syndrome that the CDC (Center for Disease Control and Prevention), of Atlanta, and other researchers had begun to note and to see if there was anything different there. What was to be seen was that young adults, previously healthy, without anything to indicate innate immunodeficiency, and that they would unexpectedly show an immunodeficiency. In the United States, to start with they saw five or six cases of youngsters who suddenly showed what people call opportunist infections, prompted by pathogens that normally do not cause diseases in man.

The organism has to be very debilitated for them to install themselves. Well, it was found in Los Angeles, soon afterwards in New York, that they had these diseases, pneumonia from Pneumocystis carinii. And then these cases were reported to the CDC, which noticed a few things in common to all of them: immunodeficiency, a sharp drop in lymphocytes, and what called attention was the fact that they occurred in men, all of them homosexuals. That kept spreading all over the United States, afterwards all over Europe, Brazil and other place…

In 1982, we were running Fiocruz’s Immunology Department, which had resulted, as I have already told you, from that TDR project. And as this syndrome was characterized by a very serious immunological deficiency, it had to do with us.  In the meantime, a colleague from the department, Claudio Ribeiro and I were called by a desperate father, whose son was with Aids in hospital, down in Rio. And we went to see this guy. He was very young, some 26, 27 years old, and he was coming to an end, which left us very impressed, very mobilized. At that moment, you didn’t have to be a visionary to imagine that this disease was going to spread all over the world, was going to spread over Brazil, that there characteristics of behavior and culture that would allow this. So we did a project that was immediately approved by the CNPq (the National Council for Scientific and Technological Development) to study cases of Aids in Brazil. We wanted to see whether the immunological alterations found in the Brazilian patients were similar to those found in patients from other countries.

Was the project done right away in 1983?
Yes, 1983. And to do so, we needed the blood of infected people, to be able to evaluate various parameters, such as lymphocyte counts. This blood came to the laboratory, and it was processed. There was then a very strong reaction from researchers who thought that we ought not to work with this biological material. After all, it was a problem of fear, for a lack of adequate biosafety. I left my room to transform it into an Aids research laboratory, because we had to fulfill the main mission of Osvaldo Cruz Foundation, which is to do research and teaching, without bothering about what, whenever questions of public healthcare have to be answered. There was a demand, and we had to give a response.

Did the resistance occur amongst the researchers from the foundation itself?
Inside the very department where the things were happening. Because we had a group of youngsters who accepted this research and its challenges, but in actual fact almost everyone was afraid of manipulating biological materials without proper biosafety. In 1983, the first report on the identification of the virus was made. Who isolated the virus, as you know, was a woman, Françoise Barré-Sinoussi, whom we will have the pleasure of receiving to do the opening conference at the Virology Encounter. She is part of the group of Luc Montagnier and was the first author of the first article about the identification of the virus, published in the Science magazine. When the article came out, Robert Gallo thought that that was not fair to him…

He felt ‘bypassed’.
I don’t even know if it was ‘bypassed’, he thought it wasn’t fair because he really contributed a lot towards the isolation of the virus. Except that he didn?t manage to isolate it first. The two groups, French and American, contributed equally.

The work had to be signed by the two, in fact.
Logically. Gallo’s big mistake was to deny this possibility. He ought to have accepted. Things happen like that. If you take a look here at a work that I did for the Academy of Medicine [Origin of HTLV-I in Salvador, Bahia: possible post-Colombian introduction], about another retrovirus, you’ll see that there have been studies about retroviruses since 1908, without it being known that they were retroviruses. And, for example, Peyton Rous demonstrated in 1911 that avian sarcomas were caused by retroviruses, which two Japanese researchers confirmed three years later. But the importance of Peyton Rous’s discovery was only recognized 55 years later, when he was honored, in 1966, with the Nobel Prize in Medicine.

What you mean to say is that up until the isolation and identification of the Aids virus, Gallo contributed a lot for this to have become possible.
I mean to say that the case of the retroviruses is a clear demonstration of how basic research keeps on contributing little by little, without any visibility for the public at large, to an important discovery. Visibility occurs when a problem of the same kind as Aids happens, which calls attention. In the history of the retroviruses, we have various researchers who won the Nobel Prize. In 1970, for example, Howard Temin and David Baltimore identified in neoplasias caused by retrovirus the reverse transcriptase enzyme, which is what characterizes the retrovirus, and they won the Nobel in Medicine in 1975. Gallo contributed with a lot of things, except that he was not the first to isolate the HIV. His group isolated a virus in 1980, which was an HTLV, a close relative of the HIV, but with several different characteristics. Both are transmitted in human beings in the same way, but with different intensities.  While HIV causes a devastating disease, HTLV, at least from what one knows up until now, only causes disease to develop in 5% of the individuals infected. HIV is a pandemic, it occurs all over the world, and HTLV occurs in certain geographical regions, and, with the exception of Japan, only in the poor countries. [please see Pesquisa FAPESP, issue 114, of August  2005. The odd thing is that in the 1970’s there was a lot of work on retroviruses, when Gallo made many contributions, and in 1980 there was a certain discouragement, until HIV arose. Luc Montagnier’s group identified the virus in 1983, and, in April 1984, Gallo also identified it. There was then that great dispute over who had actually identified the virus first.

And when did you do the isolation here?
Long before that, before 1985, two researchers, very famous in the world of virology, a fantastic couple – she was English, called Margueritte Pereira, Peggy, and he, Hélio Pereira, a Brazilian-born naturalized Englishman -, became interested in the work on Aids that we were doing here. She was a director of the public health laboratory in London, he was head of department in English universities, and they often came to Brazil. We became great friends, thanks to their interest in our work. They knew the dimension that all this was going to have. Because when in April 1985 they came into the laboratory, they asked for me, with two little bottles of culture, which were the cells infected by the HIV, which Gallo had given them, for them to be able to bring them to Brazil. And then, from that moment onwards, everything changed. Our work went up a level, the objective changed, because we began to try to install a technique of serological diagnosis, to make it possible to do epidemiological work, knowing which groups were affected etc., and to begin to create kits for diagnosis.  So, in those days, we had everything, we were in a referral center that had all the equipment, all the modern technologies, because a lot of resources were applied for studying parasite immunology. Once again it was demonstrated that, when you invest in basic science, sooner or later you can get a response. We were able to do what we did because we had mastery of the methodology and of the technique.

But when the two little flasks were brought by Hélio Pereira…
And Peggy, hey! We cannot forget her. We began to expand, to do cultures. We could do cell cultures.

And then you isolated the virus here as well.
Not in that year, not yet. In 1985, we focused our attention on things with more priority, more urgent, which was to create the screening bases in the blood banks. With this is mind, we began to try to develop a methodology that would make it possible to detect donors that were HIV bearers. Why? Because HIV causes a chronic infection. The individuals are healthy, without a test you cannot see that they are infected until they show Aids, an easy syndrome to diagnose. It was as if it were an iceberg, the tip of which was the individuals with Aids, and the great submerged mass of ice was the infected individuals, who unfortunately did not know and would donate blood, something that many did to help their fellow men. And that is how they would spread the virus. This was the great problem in those days: without screening of the blood, this infection was going to spread rapidly. We began to try to develop a methodology, actually not at all original, because the tests already existed, we just had to adapt to HIV the methodology we had already mastered for Chagas and leishmaniasis. So from the virus culture we would prepare the viral antigens and we would adapt the techniques. And then we started to try to make the Elisa, which is more difficult. Brazil had a lot of experience in a technique called immunofluorescence, extremely laborious and subjective. But it was what we had at the moment, all the blood banks were equipped to do fluorescence, because they did it for Chagas and other infectious agents. It was then that the great idea came that it was easier for us to produce immunofluorescence kits. The problem is that we begun to do this on a production scale, and we transformed the research laboratory into a factory. A very homemade factory, with a very young working group, working in shifts of two hours. At that moment, my office had come to be a corridor.

With those techniques, wasn’t the false positive result a big problem?
It was, because one of the principles of serological diagnosis is that, once the first reaction is done by some method, the result has to be confirmed by methods with a different principle and/or antigen. Strictly speaking, the question involved two problems: one, was the screening, at a public health level, where what one was trying to do was to protect a community from being infected. That’s where any sign of a positive result had to be taken into account.  But another problem was showing itself, more individual, but which did not fail to be a problem that was ours too, because you had to tell someone that the first result was positive, you had to confirm, because you weren’t going to tell someone that he was infected with HIV when you weren’t sure.  You can’t destroy someone else’s life. So we had to have confirmatory tests. It was when the World Health Organization (WHO) pressed hard and even managed to import Elisa tests for Brazil. The fluorescence technique resolved the Brazilian problem a bit, but it was very laborious. There were thousands of bags to test in a very handmade way, very subjective. The problem with Elisa was its prohibitive cost, and what happened then was that the World Health Organization managed to buy large quantities of the test for a much lower price and to distribute it, of course with a contribution from several countries. From that moment on, these tests were implanted for the blood banks. But the confirmatory test most widely used in the world, the Western blot, continued to show the same problem: it was very expensive to import. And then Brazil and the state of California, which had experience in the use of fluorescence for the same purpose, started to use it, which was much contested in the major international forums, in the World Health Organization etc. But Brazil uses it to this date. At a given moment, production became so big that there was a decision to transfer it to Bio-Manguinhos, which would start to take care of this on an industrial scale. And Bio-Manguinhos still distributes immunofluorescence to the blood banks from the public network. We signed an undertaking that we could at no moment use that material for profit-making purposes. We could only use it in the area of public health. The fact is that I think that Aids brought horrible, terrible, devastating things, but at the same time it forced society to organize itself to fight it.  And, together with it, other problems started to be more controlled, because the means of transmission are the same. It was following Aids that a law regulated all this question of transfusions, donations, the control over hepatitis came, etc.  I think that this is extremely interesting, a mobilization of the whole of society such as had never happened before.  Today, it is said that Brazil has an exemplary program for controlling and treating Aids.

However, I have doubts whether it will be possible to maintain it in the long term due to its high cost.
For example, as we go not produce certain consumables here, I don’t know if it will be possible to maintain free distribution in the long term. But the mobilization about Aids was a remarkable happening, and it wasn’t the government that took the first step, but citizens who were demanding their rights, showing the strength they have when society is organized. Why have other serious diseases not had a similar repercussion? In my interpretation, what happened is that in the West the groups affected by Aids were already very well organized for other reasons.

You are talking about the homosexuals, basically.
Yes, they already had a practice of organization, particularly in the United States, and in this case they joined together to demand their rights.

But the quality of the program in Brazil also has to do with the way it is run, with the good vision of public health of the researchers involved – and here I’m also talking about Fiocruz, about its group in the Immunology Laboratory.
No doubt, but researchers are part of society. And when I said that society organized itself with regard to the problem of Aids, it is worth recalling that, when the epidemic started, it hit mainly people of the upper middle class, intellectuals, artists, opinion makers and extremely organized groups, with power of mobilization. In parallel, there really is this extremely important question of the role of Fiocruz, its greatest mission, which is to solve public health problems. Never mind what you do inside Fiocruz, it’s always to respond to public health questions. So the fact of having these researchers already motivated by this social commitment helps. But there was also all the favorable international environment, because Aids soon showed itself as a very serious problem worldwide, and at that moment there were funds from external institutions, like the World Bank, which brought about the implantation of the program with people trained at various levels, not only researchers from the basic area, but epidemiologists and other specialists. I want to recall that the person who really started and wrote all this Brazilian project for the World Bank was Lair Guerra de Macedo, a woman from the northeast, from the state of Piauí, who stayed six or seven years at the CDC and who, coming back to Brazil, in 1985, came very well trained for these great epidemiological battles, with the mission of setting up the program. Actually, it was her, who organized all this. And she succeeded. Unfortunately, losses also occurred, many, during this process. For example, Hélio and Peggy Pereira had a car accident, she died in 1987, he died later. Lair had a car accident, she faced a very difficult situation to go back to work. We worked together a lot. I took part in the first Aids commission of the Ministry of Health, together with Hebert de Souza, Betinho, which was very active and diversified. We, the researchers, the “scientists” normally enclosed in their ivory towers, with extremely sophisticated knowledge and thinking, suddenly began to live with segments that we were not used to. It was very interesting. Luís Roberto Castelo Branco liked to recall that I was once coming back from a meeting of the commission, in Brasilia, and my traveling companion was the representative of the prostitutes of Rio de Janeiro. We came back together, in the plane, talking very friendlily, she now a lady, retired. So this familiarity was very interesting, you saw the groups affected take a position within the policies, like targets, and they themselves were participants in drawing up and implanting this policy. One of the great problems that was still showing itself was the problem of national autonomy for developing tests. From 1983 to 1985, all the developed countries had already isolated their viruses. We received many proposals for collaboration, but in actual fact they were unilateral.  We like international collaboration a lot, but not of the kind proposed, in which a group from abroad would come, collect blood samples in the country, and isolate the virus, and we would continue without competence for this. We could indeed, this way, have isolated the virus sooner, but we took another route.

Which one?
We took the decision that it was better to wait to acquire national autonomy. The big problem in isolating the virus was not the lack of expertise or of knowledge. Any virology laboratory with a cell culture could isolate it. The problem was to identify the virus, you had to carry out detection by reverse transcriptase. Then, together with a group of youngsters, we decided to isolate the virus.

Actually, you headed it up, with a group of youngsters. It’s only for modesty that you put it another way.
It’s not quite like that. I think that it was the whole group, I may have been the oldest leader… We had everything to isolate it, and we succeeded. That had an enormous repercussion, the laboratory was totally transformed. We were solicited by the media on a daily basis, but we had to carry on with our duties.

And you were on television almost every day.
That was a very serious problem for us, because we could not abide the truncated news. But it was a very interesting moment at Fiocruz because, as the journalists got in touch with  us, we would argue a lot, but at the same time we liked it a lot. And an idea of doing courses ended up arising. The researchers mobilized themselves to organize molecular biology courses for the journalists, and from all that the relationships became excellent.

That was in 1986, 1987?
In 1987, I believe. I think that something remained from this process. Today, far more news of this area comes out in the press.

What is the date the virus was isolated?
I can say the date of the publication of the article: May 1987. It was just an isolation, but it had an impressive repercussion. I remember I did a collective interview, I was young those days, I wasn’t to it, I got very tense, but I managed to come through all right. And it was very funny, because [Sérgio] Arouca was with us and would say “how patient you are!” Because at a certain moment, one of those reporters from the television asked me like this: “Can you catch the virus with tweezers?” And we came to be recognized on the street… that was difficult.

You became stars.
I remember that I was once with my wife in a line for the movie theater, and a person came and asked for an autograph. For me that was… I was shattered, mortified. I said, but I’m not an artist, how am I going to do that? It was a difficult moment, but very rich.

You learnt to deal with many publics.
Yes… And I remember that in 1987, with all that stuff, the Banco do Brasil Foundation looked us up to do a project. We did it, and Banco do Brasil, I think that it was to approve it quickly, set up a committee. On this committee, there was a doctor who voted against the project. We were proposing to isolate more viruses, because certain viruses vary from region to region, and we had to do a characterization, even thinking of a future vaccine, specific to Brazil. That was extremely important in those days. The foundation itself did not accept the doctor’s refusal and demanded that I went to talk with him. We spent a whole afternoon in his office, discussing the importance of the project. He argued that this had already been done in the United States and that it was not important. In actual fact it was pure prejudice.

What a horror!
It was a horror. And then, even recognizing that the project was important, he gave it low priority. The project remained in a drawer at Banco do Brasil. And do you know who finally took the project out of the drawer?

Dom Eugênio Sales (The Cardinal of Rio de Janeiro). There was a program of the Bank of Providence in the Mangue region [a traditional district for prostitution very close to the center of Rio de Janeiro] for prostitutes, transvestites, beggars. Two doctors who were working on the program looked me up and we began to work together. The result of that was a study of the prevalence of HIV, syphilis and hepatitis in beggars who donated blood. In those days, donations were paid for in certain private blood banks, and the beggars would donate to have some dough to eat. Well, Dom Eugênio knew of our existence, so he invited me and I went to meet him. We spent an entire afternoon talking, I spoke about the veto of the project at Banco do Brasil and he telephoned the president of the bank, Camilo Calazans.

It’s the power of the Church leading to the encounter between science and religion.
He asked why the project was in a drawer, he said it was extremely important and so on, and the project came out of the drawer.

Let go back in time. All that history of yours at Fiocruz begins with you, a young researcher, setting up the institution’s Immunology Department, with available funds of no less than US$ 1 million, which in those days was worth far more than a million today. Let’s talk about that.
It was a challenging experience, very enriching. What happened is that this grant from the WHO’s Tropical Disease Research program made it possible for us set up an infrastructure and, with this structure in place, the Immunology Department became a center of attraction for youngsters, with recent doctorates, who were coming back to the country. In a speech at the ceremony for the 25 years of the department, at which they paid homage to me, Claudio Ribeiro said the following: “When you received the funds from the WHO, a colleague from the Brazilian community of immunologists made a comment that you didn’t like (nor, by the way, did we): ‘You are going to have to render an account of this money to society, Galvão’. We are here commemorating 25 years of the department, which you created, and paying homage to you, I think they are a report and a rendering of accounts that speak for themselves”. Logically, it wasn’t me that created it, it was a group. What I meant to say is that it was a very challenging thing, but that perhaps it has allowed me some success. My wife defines this thing well, the fact is that I’m a stimulator I like people around me. I like a phrase of Norberto Odebrecht: he says that the true leader has to annul himself for the benefit of the enterprise. It’s true that there are sometimes conflicts, you let loose some ideas, and people appropriate them, there are jealousies, when you recognize that that idea that was originally yours is yours no longer… But, on the other hand, that?s a very wholesome thing. For me, it’s very important that the others grow, because I believe in the dissemination of knowledge and in the sedimentation of groups and individuals working.

How many disciples did you help to transform into scientists?
I don’t have disciples, I have colleagues who have worked or who are working with me. In the Immunology Department, there were about 20 persons. I supervised their master’s degrees, doctorates… And one of the things that left me very happy is that, when I decided to go back to Salvador, I saw that the department had a lot of brilliant people to run it.

So you went back to Salvador in 1987, at the peak of your work at Fiocruz in Rio.
Yes, at that moment I had a very good infrastructure, but we went back for one more challenge. We thought at the time that Salvador, due to the sociodemographic characteristics that were very similar to those of African cities, with more or less 80% of Afro-descendents in its population, would have a pattern of dissemination of the disease similar to the African one, where it had already been demonstrated that infection by HIV had begun many years ago. Also at that moment, Arouca, who was Fiocruz’s president, had a very great interest in decentralizing the foundation’s actions and wanted to reinforce the center in Bahia. But the progression of the disease did not take place as we then thought.

And so your challenge no longer existed.
But we had the surprise of seeing that Salvador is the Brazilian city that has the highest prevalence of HTLV in Brazil. So today we have a lot of work with this virus, which affects needy people, with little schooling, has a predominantly heterosexual transmission, and affects women more. In the old days, two diseases were associated with HTLV: leukemia and a neurological disease that disables people from walking and ends up putting them in a wheelchair. Today, we realize that infection with HTLV is systemic and affects many other organs, like the lungs, eyesight, joints etc. Today, we have a Center at the Bahian Medicine and Public Health School of the Foundation for Development of Science, resulting from an agreement with Fiocruz, which attends to the infected individuals, in an integrated manner, in the biopsychosocial aspects.