Special Issue 2012 - Edition 1

PESQUISA FAPESP 2012 _ EDITION 1

2012 _ EDITION 1

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CANCER

Antihypertensive medication halts tumor growth ENERGY

Biodiesel can be made from vinasse DEMOGRAPHY

Migrants to São Paulo no longer go there to stay INTERVIEW LAURA DE MELLO E SOUZA

History with imagination and rigor

Parkinson’s Disease Mistaken for stem cells, fibroblasts hinder cell therapy

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2012 _ EDITION 1

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12 COVER Stem cell contamination may be the cause of poor results in the treatment of Parkinson’s disease

SCIENTIFIC AND TECHNOLOGICAL POLICY 18 Ecology

CREDIT MEDICALRF.COM/ GETTYIMAGES

From basic research to public policy, FAPESP has been investing in biodiversity studies for five decades

INTERVIEW

SCIENCE

6 Laura de Mello e Souza For historian Laura de Mello e Souza, there is a lack of innovative researchers who can reach the general public

24 Medicine

SECTIONS

32 Astronomy

Cover photo Artistic interpretation of a neuron, cell affected by Parkinson’s disease

5 Letter from the editor 98 Art

Antihypertensive medication halts tumor growth, indicating new therapeutic targets

28 Evolution

Unlikely cross-breeding can create new species of plants and animals An alternative mechanism may explain the formation of larger-than-normal stars from neutrons

TECHNOLOGY 35 Immunization

Butantan develops technology to increase production and lower costs

40 Intelligent packaging

Sensitive film warns consumers about food deterioration

44 Energy

Production waste from ethanol may be used to produce biodiesel

HUMANITIES 48 Digital library Cartographic material reveals Portuguese colonial ambitions 52 Demography The profile of migration from Sao Paulo is underscored by comings and goings and by internationalization 56 Ranking

humanities

Brazilian courses distinguish themselves on the international scene

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SÃO PAULO RESEARCH FOUNDATION

CELSO LAFER PRESIDENT EDUARDO MOACYR KRIEGER VICE-PRESIDENT BOARD OF TRUSTEES ALEJANDRO SZANTO DE TOLEDO, CELSO LAFER, EDUARDO MOACYR KRIEGER, HORÁCIO LAFER PIVA, HERMAN JACOBUS CORNELIS VOORWALD, JOÃO GRANDINO RODAS, MARIA JOSÉ SOARES MENDES GIANNINI, JOSÉ DE SOUZA MARTINS, JOSÉ TADEU JORGE, LUIZ GONZAGA BELLUZZO, SUELY VILELA SAMPAIO, YOSHIAKI NAKANO EXECUTIVE BOARD JOSÉ ARANA VARELA PRESIDENT DIRECTOR CARLOS HENRIQUE DE BRITO CRUZ SCIENTIFIC DIRECTOR JOAQUIM J. DE CAMARGO ENGLER ADMINISTRATIVE DIRECTOR

ISSN 1519-8774

EDITORIAL BOARD Carlos Henrique de Brito Cruz (President), Caio Túlio Costa, Eugênio Bucci, Fernando Reinach, José Eduardo Krieger, Luiz Davidovich, Marcelo Knobel, Marcelo Leite, Maria Hermínia Tavares de Almeida, Marisa Lajolo, Maurício Tuffani, Mônica Teixeira SCIENTIFIC COMMITTEE Luiz Henrique Lopes dos Santos (President), Adolpho José Melfi, Carlos Eduardo Negrão, Douglas Eduardo Zampieri, Eduardo Cesar Leão Marques, Francisco Antônio Bezerra Coutinho, João Furtado, Joaquim J. de Camargo Engler, José Arana Varela, José Roberto de França Arruda, José Roberto Postali Parra, Luis Augusto Barbosa Cortez, Marcelo Knobel, Marie-Anne Van Sluys, Mário José Abdalla Saad, Paula Montero, Roberto Marcondes Cesar Júnior, Sérgio Luiz Monteiro Salles Filho, Sérgio Robles Reis Queiroz, Wagner do Amaral, Walter Colli SCIENTIFIC COORDINATOR Luiz Henrique Lopes dos Santos EDITOR IN CHIEF Mariluce Moura MANAGING EDITOR Neldson Marcolin EXECUTIVE EDITORS Carlos Haag (Humanities), Fabrício Marques (Policy), Marcos de Oliveira (Technology), Ricardo Zorzetto (Science), SPECIAL EDITORS Carlos Fioravanti, Marcos Pivetta EDITORIAL ASSISTANT Dinorah Ereno ART EDITOR Laura Daviña ART Ana Paula Campos, Maria Cecilia Felli PHOTOGRAPHER Eduardo Cesar, Léo Ramos ELETRONIC MEDIA Fabrício Marques (coordinator) PESQUISA FAPESP ONLINE Maria Guimarães (Executive editor) Isis Nóbile Diniz (Editorial assistant) CONTRIBUTORS Bel Falleiros, Daniel das Neves, Evanildo da Silveira, Márcio Ferrari, Mayumi Okuyama, Miguel Boyayan, Nelson Provazi, Salvador Nogueira PRINTERS Editora gráficos Burti Ltda.

THE REPRINTING OF TEXTS AND PHOTOS, IN WHOLE OR IN PART, IS PROHIBITED WITHOUT PRIOR AUTHORIZATION

PESQUISA FAPESP Rua Joaquim Antunes, no 727, 10O andar, CEP 05415-012, Pinheiros, São Paulo-SP FAPESP RUA PIO XI, NO 1.500, CEP 05468-901 ALTO DA LAPA, SÃO PAULO-SP

DEPARTMENT FOR ECONOMIC DEVELOPMENT, SCIENCE AND TECHNOLOGY SÃO PAULO STATE GOVERNMENT

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LETTER FROM THE EDITOR

A powerful producer of Brazilian science Mariluce Moura EDITOR IN CHIEF

S

tem cells are, perhaps, the biological entity that has given rise to the most dreams, hopes, frustrations and deceptions among scientists, physicians, people with complex medical conditions and their family members in the past decade. In May 2011, findings about stem cells and Parkinson’s disease by a group of scientists from São Paulo were featured on the cover of the Brazilian version of Pesquisa FAPESP, a monthly publication. Because these findings continued to be among the most important studies originally published in 2011, we selected this study for the magazine’s special English language issue and again as the cover story. The article on page 14 presents an important clue that may partially explain the failure of stem cell transplant treatments and of older cell-based therapies that involved the transplantation of material from the adrenal glands or the brains of aborted fetuses.

In the original article published on April 19, 2011, in the online issue of Stem Cell Reviews and Reports, the São Paulo group suggested that one of the villains in this story might be fibroblasts. Fibroblasts are skin cells that are similar to certain stem cells but have different properties. When implanted in mice with Parkinson’s disease in combination with mesenchymal cells derived from the umbilical cords of newborns, the fibroblasts not only reversed the beneficial results observed when the mice were implanted with pure stem cells but also exacerbated the symptoms in the test animals.

What might one deduce from this finding?

“Perhaps many of the poor results of scientific work on cell therapies were due to this type of contamination,” stated geneticist Mayana Zatz.

In other words, fibroblasts may have been mistakenly identified as stem cells and may have been included with stem cells during implan-

tation, which could cause new problems in patients who receive poorly controlled transplants.

“And patients should be warned about this,” said Zatz. Furthermore, contamination could result in erroneous conclusions about the potential of cell-based therapies. A positive aspect of this story is that, once again, a window has opened for experiments on treating Parkinson’s disease with pure and well-controlled mesenchymal stem cells.

In another field, the human and social sciences section of the magazine carries an article on the changes in São Paulo’s migration profile. The findings of this study provide a better understanding of the impressive population dynamics of the largest city in South America. São Paulo currently has just over 11 million inhabitants, but the São Paulo metropolitan area has 19 million. During most of the twentieth century, São Paulo was absorbed vast numbers of internal and external migrants, who were drawn to the city mainly because of the strength of its industrial growth and its formal jobs. However, in the twenty-first century, the city joined the international migration route.

According to the article on page 56, São Paulo has now become a destination for highly qualified individuals and for workers without documents or specific training. These workers are being absorbed by more flexible forms of production that are aligned with the mobility of the capital’s population.

The pieces highlighted here are good examples of Brazil’s capacity to generate diverse scientific knowledge. The second article brings our readers closer to the demographic reality of one of Brazil’s major science production centers – the state of São Paulo, the capital of which shares the same name, accounts for half of Brazil’s scientific production.

Happy reading!

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INTERVIEW LAURA DE MELLO E SOUZA

A country called the past For the historian, there is a lack of innovative researchers able to reach the general public Carlos Haag PUBLISHED IN MAY 2011

PHOTOS BY EDUARDO CESAR

“H

istory requires imagination and a lot of effort, a lot of discipline, like a rehearsed stage show: the curtain rises, everything appears in its place, so harmonious and so fluent.

But months and years go by before this stage is reached. That’s why I’m fascinated by ballerinas—how much effort goes into every gesture beneath the apparent naturalness.” This statement is from historian Laura de Mello e Souza, a Full Professor of Modern History at the University of São Paulo (USP). Laura has recently published a biography of the conspiracy poet Cláudio Manuel da Costa (Perfis Brasileiros [Brazilian Profiles] collection, published by Companhia das Letras) that represents a beautiful historical entrechat from the researcher, who has constructed a portrait of the man and the age from minimal information about da Costa’s personality. This project was a jeté that demanded long searches in historical archives, a hallmark of Laura’s work. Similar to ballet, however, the work does not reveal her effort, but rather the beauty of the text. “I come from a family of storytellers,” she explains. She was not burdened when her teachers invariably asked, “Oh, so you’re the daughter of Antonio Candido and Gilda de Mello e Souza?” Laura belonged to a

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family of intellectuals that was first and foremost a family, albeit one surrounded by books. “My relationship with my father was always good. They are special people. They have a good idea of their role but are modest and have a very nice relationship with knowledge.”

Before turning to history, Laura flirted with architecture, psychology and medicine. She united these passions in history, adding a substantial dose of social concern and political awareness. She was the first person to address marginalized people, in Desclassificados do ouro (1983) [The outcast], and her books maintain a strong relationship with and an engaged interpretation of Brazil without compromising documentary rigor. Although Laura says that she “lives” between the sixteenth and eighteenth centuries, her work helps to explain Brazil as it is today, including areas previously overlooked by academics, such as religiousness and witchcraft (discussed in O diabo e a Terra de Santa Cruz (1986) [The devil and the land of Santa Cruz] and Inferno atlântico (1993) [Atlantic hell]). More recently, she has considered how to write Brazil’s history. “The historian cannot cling only to the particular. It’s the history of the forest: if we see the tree, we have to see the forest. Otherwise, our understanding will be impaired.” Hence, her dedication to examining empires as a way to solve the dilemmas of the colony that Brazil once was is an important temps levé. This effort resulted in an FAPESPsupported project, Dimensões do império português [Dimensions of the Portuguese empire], which Laura coordinated, as well as books, such as O sol e a sombra (2006) [The sun and the shadow]. Below are extracts from my interview with Laura de Mello e Souza.

How did your voyage “to the foreign land that is the past” begin?

I love that phrase from The Go-between by [British writer Leslie Poles] Hartley, which I believe is a great definition of what history is. Since I was young, I’ve had a passion for history. History and stories. I had a dream of pursuing medicine, which I believe is not far removed from history because of its fascination with fragments that allow you to reconstitute something. Medicine doesn’t seem to me to be an exact science. We go to the doctor, and

he asks a series of questions to be able to build a hypothesis. I think that the historian does the same thing. We never have direct access to the past, and, therefore, the past is a foreign country. It would be great if we could have a direct line to the past, but we always have to consider that the past has to be looked at carefully via the traces it has left. Time ensures that these differences are considerable. We feel the difference between generations, between parents and children, so imagine between various generations, like the ones I deal with—remote periods going back as far as 400 years ago.

How does your way of writing history differ from other styles?

It was heavily influenced by my storytelling parents. My father is a great storyteller. But when I went to college, that type of history was highly discredited, above all at USP, where there was a pre“There are historians dominance of structural who write for the general history. I think that before television, the great public and do not innovate, media transformation, people told many stories. and there are those who I grew up in the countryside, where I lived with innovate but who do my grandparents in a runot write for the general ral environment. People had many stories to tell. public. It’s necessary to find So the history I always liked was narrative hisa middle road.” tory. In the 1990s, it came back into fashion. A more analytical history is very important. It makes fewer mistakes, but for me, it is less attractive. I think there’s an issue of temperament at play here. I’m not only interested because of historians. I love anthropology—above all, the classic dissertations that are narratives. I like the history of art and literature a lot. So these tastes led me to another type of history, which is perhaps more capable of making mistakes but maintains a stronger link to other disciplines.

How did your parents influence you?

I think that the family environment is very influential. Of course, the fact that I grew up in a house in which the intellectual environment was very marked

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had an influence, with its conversations and the presence of books, which I think are the most important things. We don’t read all the books we have, but that business of dealing with books, going to the bookcase and looking at them—it’s very important. My parents were very low profile people, so I only became aware of the weight they carried in the university environment when I went to college. I did not have much of an idea. Because I grew up during the military dictatorship, the situation was the opposite. Having the parents I had was a bit uncomfortable. For 10 years, we heard rumors that my father was going to lose his position.

There was a very heavy atmosphere of insecurity, which wasn’t something I’m proud of, but belonging to that environment was rather marginal. I then started noticing that they were respectable and prominent people. I don’t believe they had very great expectations concerning me; they always gave my sisters and me room to be what we wanted to be. I even tried to drop out, to do other things, like architecture and medicine, but I didn’t manage to. I’m traumatized about not having become a doctor.

You were the first researcher to deal with the ‘marginalized people,’ and in your books, a vision of political engagement is noticeable.

When I went to college, the dictatorship was at its height. That was reflected in my work.

I think it’s impossible to be otherwise, unless you live in the stratosphere. Historians live with their heads in the clouds a bit, particularly those who deal with remote periods. I think that I live with my head in the clouds more than I’d like to, but that was inevitable coming from a leftist environment. Even people like me, who had no vocation for political militancy, tried to write the type of history that, in one way or another, posed important questions for the country. I did this with a social history on the problem of inequality, which was an issue that was present at the beginning of my career. I think that it’s something that marks a generation; it’s an attempt at reaching an agreement with the past that started with Florestan Fernandes, from the time when he worked with Roger Bastide.

I think that Brazilian historiography is now becoming emancipated, somehow. It’s opening up a greater range of themes. My current research, for example, which was funded by FAPESP, is on the history of Brazil, but from a very European perspective, trying to understand the history of our country within the history of Europe. Nowadays, national history makes increasingly less sense. I’m no longer very interested in national history. One of the good aspects of globalization is the possibility of writing total history.

What do I mean by total history? It’s not just the history of Brazil, but the history of Brazil in relation to other histories, other contemporary and correlated historical processes. I think we write about national or regional history for a thesis. It’s like a young girl who, to do ballet, must start with classical ballet, must dance on her points, must work at the barre. Then, later, she can deconstruct that and do modern ballet and contemporary dance.

How were you gripped by what you call the “document fever”?

I began working with documents because I chose a theme on which there was nothing. In fact, I have a vocation for the abyss, for working with topics that are practically impossible to work with, like that book on Cláudio Manuel da Costa. I didn’t write a biography, but I ended up doing something that gives that idea. But in the case of the ‘marginalized’, people said I wasn’t going to manage to write it because there was no documentation. And there really wasn’t.

I worked with published documents, but the cream of it was the handwritten documentation.

So I delved into the archives to see what there was, and there I discovered this extraordinary documentation that had been largely ignored before I started working on it, and that gave me a possible view of this socially marginalized layer of society. It was the same thing in the case of witchcraft; I had no alternative because there was no work on the subject, so I had to read the Inquisition proceedings. It was like fishing with a rod: you threw in the line and didn’t know whether you were going to catch a fish.

Then, before I realized it, I’d become an archive historian. I’m an archive historian, I continue being one, and I won’t ever give up being one.

I don’t know how to work if I don’t work with manuscripts; it’s what gives me great pleasure.

Is it in this sense that you say that the function of the historian has more to do with understanding than explaining?

I think that understanding comes from what you mentioned at the beginning; the past is a foreign land, so it’s difficult for us to explain it.

We have to understand it. On the other hand, it’s necessary to look for an explanation. There’s a margin of explanation we can’t set aside; if we do, we can’t understand it. There’s a margin of generalization we have to establish as well; if we don’t, we can’t convey the message.

How does this generalization work in the case of Brazil?

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bad, we’re already dealing with an issue that is being posed in Europe now, namely, miscegenation. The problem of the blacks in Brazil is still very serious.

People of African descent continue to be heavily excluded socially. But, in any event, Brazil is a country that could not have existed without immigration, that could not have existed without slavery, and that exploited the indigenous labor force atrociously. Even so, there are Indians trying to have an increasingly more active say in things. So Brazil is a phenomenon that has been stitching together its cultural diversity since it was colonized. It couldn’t have maintained its unity if it hadn’t stitched together its cultural diversity. We’re the only country in the Americas that is authentically multi-cultural to the extent that it is experienced. It’s not survival—it’s a living experience. There’s no Indian survival, no survival of Africa here; it’s all a living experience. It forms part of our own experience, our DNA, which is basically indigenous. On the other hand, I think that it’s a false issue to give up our European tradition because we’re also Europeans. So I think that nationalism, precisely, and the need to create a body of intellectuals and original thinking for a young country meant that a series of explanations were constructed that go against the grain of this idea of continuity, which was always sold as a reactionary idea. But it may not be. I think that the history I wrote, including that biography of Cláudio, is always faced with the dilemma that Sérgio Buarque de Holanda expressed so clearly when he said, “We’re homeless

outcasts in our own land,” in Raízes do Brasil [Roots of Brazil].

The evils of Brazil are often attributed to our colonization, the “heritage of the deportees.” How do you view this?

It’s all true, and it’s not. It’s true because all this really happened. The most dramatic thing isn’t being a land of deportees, because they all were: the USA, Australia, etc. The most terrible thing is that we had slavery until 1888 because that indeed generated virtually irreversible social dynamics. So the problem is not colonization, but slavery. Were we the only country to have slavery? No. But we’re the one that dealt with the issue of slavery in the most perverse way. When a child today goes into his room, takes off his clothes and leaves his pants in a mess on the floor just the way they came off his body, I say, “That’s a slave-based society.” This disqualification of less qualified, less highly regarded work, for example, which exists to this day in Brazil. All workers are basically equal; we have to believe that. That’s not the way it is in Brazil. Now, to attribute all the ills to colonization has to do with the affirmation of independence. Because Brazil underwent a different independence process, with a slave Empire, when the Republic arrived, those early republican generations had to attribute Brazil’s ills to Portuguese colonization. I don’t think that explains very much. That is why historians are always studying slavery; it explains things to us better.

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Along with slavery, do the elite also help us understand Brazil?

I don’t know if the Brazilian elite are worse than any other elite. They are more stubborn concerning a certain type of privilege, depending on the region in Brazil. Look, the São Paulo elite are completely different from the northeastern elite. At least, I’m from São Paulo, and I see that the São Paulo elite today are no longer what they were at the time of my grandparents. They’re different, but they reproduce the vices of the former elite. It seems to me that in the northeast and the north of Brazil, they’re the same. I mean, we find the same names in the northeast and the north of Brazil. Not in the south. Who are the elite in São Paulo today? They’re no longer the Paes Leme, etc. Where are these people?

They no longer exist. So the elite turn over much faster in São Paulo and in the south in general because of capitalistic development, “There are no longer of course. It turns intellectuals who over far faster because of the idea operate in society. I believe that society is open to anyone who has that this is connected to money and knows what to do or who the fact that there is no more has talent. I think courage and frankness to that the elite are equally terrible in produce explanations.” the United States, like the Brazilian elite. I think that what characterizes the Brazilian elite is a great reluctance to give up their privileges. This has to do with the type of relationship that they established with the state machinery throughout history. The fact is that the Portuguese state is such an old one and that from the seventeenth century, it really opened up its coffers to its elite.

I mean, the Portuguese nobility, especially in the eighteenth century, was a nobility that depended either on service to the Empire or money from the king’s purse for its upkeep. Far more immediate attention was paid by the state to the needs of the dominant players, it seems to me. But I think it is a bit risky to say what I’m saying.

We’ve had great intellectuals that thought about history holistically.

What about today?

This is something that worries me a lot, more so every day. If someone asks me, “Laura, I want to read a general history of Brazil, what should I read?” I have nothing to tell them. The last great history of Brazil is História geral da civilização brasileira [General history of Brazilian civilization] by Sérgio Buarque de Holanda. This is a very serious problem in my mind because it’s a global phenomenon, but there are certain historiographic traditions that continue maintaining general history. I think it’s sorely lacking. When we want to have a particular general perspective of Brazil, we go back to Caio Prado Júnior or Sérgio Buarque de Holanda or to Capistrano de Abreu. No book written today and during the years after the arrival of the royal family will be better than Dom João VI no Brasil [Dom João VI in Brazil] by Oliveira Lima. I think we’ve jumped stages. We’ve glossed over a particular stage of historical knowledge, which in Europe was very well founded, which is historicity, the mass publication of document collections, the exhaustive description of certain ages.

We skipped a stage and went straight into essayism, into university history, which demands that you focus on portions of things. Today, Brazilian historiographic production is good—according to FAPESP, in the humanities, it is the most prolific—with some absolutely extraordinary books, but it always has a very narrow focus. This has to do with the crisis of paradigms: that it’s impossible to explain, that it’s impossible to construct general explanations, that to understand a general phenomenon you always have to start from a specific angle, the impact of micro-history, of post-modernism.... I think we need to get over this phase, that it’s possible to carry out monographic studies but also to provide general explanations—summaries that are more all-embracing.

What we’re seeing today is that there’s an audience that’s very hungry for history books, and it isn’t always being served by professional historians but by individuals who do research without having any particular specialization. Those who have a more specific background but who chose to sell a lot PESQUISA FAPESP | 11

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generally reproduce; they don’t innovate. They do something that’s correct, but they don’t innovate. Those who are innovating are not writing for the general public. The next step needs to be taken by those who are doing original research and who should start writing for the general public.

You often criticize young historians who discard the classics merely to look for new things. Why? When I was young, I was also someone who liked new things. I thought I was going to invent the wheel. Now, there are certain problems that are false and are attractive merely because they’re new. Students come up to me and say, “I’ve read everything. It’s all rubbish.

No one is saying what I want to say.” I say to them “So, explain to me why it’s rubbish.” Then, in the end, what rubbish remains is not such rubbish after all, and that great new aspect they wanted to talk about is not so new after all.

Another important point is the absence of intellectuals acting in the public sphere.

I view this with great sadness. I think this is a very serious problem. It’s one of the most serious signs of this crisis of paradigms. I think that it must have been very good for those generations that had absolute certainty and truths.

I have none, and this is very disheartening. On the other hand, it’s provocative;

it leads to an environment of creative freedom. Our university production is very good, but there are no great intellectuals any more like there used to be, and that is a loss. I think it’s a very big loss. I was very impressed in 1998, when I was a professor at the University of Texas, and I read The New York Times and found that the whole of the front page was a photo of the coffin of Octavio Paz with a headline that read, “The greatest thinker in the Americas has died.” Perhaps he was the last great Latin American thinker. Now there aren’t any. I think it has something to do with the fact that no one has the courage and frankness to produce explanations any longer. When I suggest The Labyrinth of Solitude, one of the most extraordinary books I’ve ever read, to my students, they complain, “No, for God’s sake, don’t give me Octavio Paz; he’s a reactionary, fiction.” It would be the same thing if I were to take Raízes do Brasil [Roots of Brazil]. Caio Prado Júnior is one of the biggest whipping boys of my generation.

Several colleagues say they no longer talk about Caio Prado Júnior in their lessons because he’s racist. The life of a university professor can be thoroughly dry and uninteresting. Very much so. I struggle desperately for mine not to be.

But if I were strictly a university professor as I should be, my life would be no fun at all because I have to write a load of reports, I have to write a lot of opinions for Capes, CNPq, FAPESP, I

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have to represent my area at Capes, the CNPq, at FAPESP, as I have done, because I have to supervise scientific initiation courses, master’s degree courses, PhDs, post-doctoral studies. I have to go to I don’t know how many congresses a year to be able to be recognized by the agencies that fund research. This creates a certain distortion. I’ve seen opinions saying that suchand-such a high-level historian only publishes books; he doesn’t publish articles, and it’s not good that he only publishes books. The fact that we’ve become professional takes us out of public life. Today, people who work in universities, with a few exceptions, are not involved in public life. Those who are heavily involved in public life end up investigating less.

Why a book on Cláudio Manuel da Costa?

He was a man divided, a man torn, who felt that who he was and what he did were not aligned with the world of the kingdom, but he was also unable to take a step outside it. So I think that he’s very typical of the Portuguese-Brazilian world before independence, when it was neither one thing nor the other. There’s a phrase in his confession in which he says that despite having said everything that he did, he does not think that informers are any better than those who fought, than those who were informed against. In other words, he says, “I informed, but I’m meaner and smaller than those who conspired against the king.” It’s one of the elements that makes me believe he killed himself, that he was sick about what he had done. It was also important to review the Minas Conspiracy and how, towards the end, they were putting on the brakes. They didn’t want anymore. But the movement was headed toward generalized dissemination and a more radical path than it had been initially. For years, they used to go and say to the governor, “Oh my God, it could be better.

And what if we had more representation? And what if Portuguese-Brazilians were listened to more?” And the governors [responded], “No, I don’t think you’re right.” Then, the governors wrote to the Overseas Council, “Look at the things that are going on. You’re seeing it from afar, while here, close to things, they aren’t as you think they are from there. I’m here, and I’m seeing things. There’s no way you can apply things the way you’re ordering them to be applied.” So the issue of trying to reach a compromise to maintain colonial domination went hand-in-hand with the desire for “light” participation on the part of the elite. It was in this type of situation that the governor was changed in 1784, and this special group decided to see if things really could be changed, perhaps even declare independence. I think that in the mid-

dle of the process, everything shifted into another type of movement, one that was more adversarial, more popular in character, more demanding, and that’s when the literary men pulled the handbrake.

And the person of Tiradentes?

If someone is justly entitled to be called the hero of the Republic, I think he is it. I think he was really a great agitator; he was a political agitator.

He was irresponsible and crazy, like all political agitators. He was a political agitator, and that’s when he began to believe that things could really fall into place and become an emancipation movement, at least in the region. Nowadays, there are various studies that suggest that there was an attempt at organization between São Paulo, Rio and Minas, that the elite were trying to defend the economic interests that were heavily tied to these three regions. n You said that you live between the sixteenth and eighteenth centuries. What’s your view of Brazil today?

I have a very positive view of Brazil today, and I think we all have reasons for this because I think we’re the only country in the Americas with its own project, despite what the press says, that we are always on the brink of the abyss and that no one has any project whatsoever. I think Fernando Henrique and Lula produced two very important governments. I think that everything began with the FHC government because he was Fernando Henrique, a respected man, a great intellectual at a moment of enormous international mediocrity. If we think about who the political leaders in the world are, we can wipe the floor with them, whether it’s with Fernando Henrique, Lula, or Dilma. But the problems in Brazil are still the same, though on a smaller scale now because of the distribution of income and education. I think the biggest challenge for Brazil is the challenge of education, quality public education for elementary schools because nowadays, for better or for worse, we have a competent university system. The challenge going forward is education. I think even health is a consequence of education; as education gets into gear, health goes along with it. There is, however, the question of income distribution.

There we go back to the issue of the Brazilian elite. There has to be greater motivation, greater participation, and that’s where there’s a lack of great public figures, which unfortunately we no longer have. There’s a lack of great causes, great standards. But I’m optimistic about Brazil and pessimistic about the world because I think the world’s coming to an end. In the world of today, I view Brazil with optimism. n PESQUISA FAPESP | 13

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The weakness of stem cells Contamination may be the cause of poor results in treating Parkinson’s disease

Marcos Pivetta PUBLISHED IN MAY 2011

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uring the last three decades, cell therapy has become a source of enthusiasm and deception for patients suffering from Parkinson’s disease, an illness characterized by the progressive death of the neurons responsible for the production of an important chemical substance, the neurotransmitter dopamine.

In the 1980s, a controversial approach to treating the disease, i.e., the transplanting of cells extracted from the adrenal gland or immature brain tissue of aborted fetuses, initially seemed promising and was tested on animals and humans in countries such as Sweden, the United States and Mexico. The rationale underlying these surgeries, which were debatable even from an ethical perspective, was to supply the brain structure known as black substance (which is damaged in Parkinson’s disease patients due to the progressive loss of dopaminergic neurons) with a new population of cells capable of producing dopamine.

In this manner, the main symptoms of Parkinson’s disease, including tremors, muscular rigidity, slowness of movements and speaking and writing difficulties, should have been eliminated.

The results of this approach were disappointing. In cases that showed an improvement in the well-being of the patients, this change was short-lived. In others, no improvement occurred, and the attempted treatment worsened the disease in certain cases, leading to the death of some individuals.

A group of biologists and neuroscientists from São Paulo may have discovered one of the reasons for the failure of these prior cell treatments for Parkinson’s disease and perhaps have determined why the more modern and re-

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fined versions of this type of experimental treatment, now based on the use of so-called stem cells, continue to yield inconsistent results. The transplants tested in pre-clinical studies in laboratory animals may contain a significant number of fibroblasts, a type of skin cell that is very similar to stem cells but that has completely different properties.

On April 19, researchers from the University of São Paulo (USP) and the Federal University of São Paulo (Unifesp) published a study in the on-line issue of Stem Cell Reviews and Reports showing that in rats with induced Parkinson’s disease, the presence of human fibroblasts cancels out the possible positive effects of implanting mesenchymal stem cells obtained from the umbilical cord tissue of newborns.

“When we administered just stem cells, the symptoms of the disease in the rats improved,” says geneticist Mayana Zatz, one of the authors of the article and coordinator of the Human Genome Studies Center at USP, one of the Centers of Research, Innovation and Dissemination (Cepid) funded by FAPESP, and the National Institute of Stem Cell Science and Technology in Human Genetic Diseases. “But when we also injected fibroblasts, the beneficial effects disappeared, and there was even some deterioration. It’s possible that many poor results in scientific work with cell therapy are due to this type of contamination.” According to the researchers, their work is the first to demonstrate both the positive effects of using mesenchymal stem cells against Parkinson’s disease and the harmful effects of contamination by fibroblasts in the same animal model.

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The signals that control body movements are transmitted by neurons that move from the black substance to the caudate nucleus Caudate nucleus

Dendrites Lateral ventricles

Putamen

Axon Nigrostriatal neurons

Black substance

Terminal

NORMAL NEURON NORMAL MOVEMENT

NEURON AFFECTED

BY PARKINSON’S DISEASE

Dopamine

Receptors

MOTOR PROBLEMS

In addition to presenting an advance in the basic knowledge on the possible benefits of cell therapies in an organ as complex and delicate as the brain, the result of this study presents a warning to the families of people with Parkinson’s disease. In no country in the world is there any officially approved treatment based on stem cells for combating this or any other neurodegenerative disease.

“Stem cell research needs to be looked at carefully, and false promises of a cure mustn’t be made,” says the author of the article, neuroscientist Esper Cavalheiro, from Unifesp, who is a lead researcher the work at the National Institute of Translational Neuroscience, a joint project of FAPESP and the Ministry of Science and Technology (MCT). “Before proposing therapy, we need to understand the entire differentiation mechanism of stem cells in the various tissues in the organism and understand what the brain does to ‘talk to’ and direct the operation of these cells.”

Currently, the only diseases that have

a stem cell-based treatment are blood diseases, including cancers (e.g., leukemia). When faced with this type of problem, for decades, doctors have resorted to the transplant of bone marrow rich in hematopoietic stem cells, which are the precursors of blood.

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arkinson’s disease continues to lack a cure and is currently controlled with the help of medications, such as levodopa, that the brain can convert into dopamine. In more serious cases, a second alternative may be used: the implantation of electrodes in the brain of patients who are not responding well to the treatment or who experience multiple side effects from the drugs. The electrodes, which are connected to a small generator implanted under the skin, are used to attempt to improve the communication between neurons. The delicate surgery for implanting the electrodes is known as deep brain stimulation, or simply DBS. With the exception of these

two approaches, all other procedures against the disease remain in the trial stage and have not been approved by medical authorities.

Dopamine, a chemical messenger produced by less than 0.3% of the nerve cells, belongs to a class of substances called neurotransmitters. The basic function of neurotransmitters is to pass information from one neuron to another in the form of electrical signals, a communication process known as a synapse. Dopamine acts specifically on brain centers linked to the sensations of pleasure and pain and has proven roles in the mechanisms that generate dependence and addiction as well as the control of movement. In the case of Parkinson’s disease victims, motor function is clearly affected due to the lack of the neurotransmitter.

Mixing up fibroblasts and mesenchymal stem cells is very easy, and this confusion may be at the heart of the inconclusive or contradictory results of many attempts to treat Parkinson’s disease using cell therapy. Fibroblasts and mesenchymal stem cells have the same origin. They are derived from the mesenchyme, the main connective tissue of the embryo, from which various types of cells are formed. Despite their common origin, fibroblasts and mesenchymal stem cells have different properties. Fibroblasts, which are responsible for the synthesis of collagen, form the basis of the connective tissue in adults.

Accordingly, fibroblasts are specialized and differentiated cells. Mesenchymal stem cells, however, are very non-differentiated and can generate many types of tissue, such as bone, cartilage, fat, support cells for the formation of blood and connective fibrous tissue. “It’s almost impossible to distinguish these two types of cells if we simply examine them under a microscope,” commented biochemist Oswaldo Keith Okamoto from the Human Genome Studies Center and principle investigator of the study published in Stem Cell Reviews and Reports. “They grow in vitro under the same conditions, and we only distinguish them with the help of markers and specific tests.” Mesenchymal stem cells also have an important peculiarity: they have immunosuppressive properties and can minimize the need to take medication to avoid the rejection of transplanted organs and tissues.

ILLUSTRATION BY DANIEL DAS NEVES BASED ON NIH MATERIAL

Brain circuit in Parkinson’s disease

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There is no hard evidence that mesenchymal stem cells can generate the neurons that are lacking or somewhat dysfunctional in Parkinson’s disease patients. Nevertheless, mesenchymal stem cells seem to improve the environment in which the lesions associated with the disease occur, reduce local inflammation and favor the preservation of nerve cells. According to Okamoto, “their effects might be indirect, reducing the inflammation in the brain.” This effect was observed by researchers from São Paulo in their experiment with rats. They injected stem cells into the brain of a group of ten rodents with induced Parkinson’s disease and, one month later, found that the rats had no symptoms of the disease and were as healthy as the animals in the healthy control group. This result coincides with the conclusions of similar studies conducted both here and abroad.

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he more novel discovery resulted from the second part of the experiment. The scientists inserted a culture of fibroblasts into another group of ten rats, which also had Parkinson’s disease. The result was a disaster. One month after the procedure, the animals started exhibiting additional motor problems, and the number of dopaminergic neurons in the black substance decreased by half. A third group of sick rodents was given a mixture of the two cell types in equal proportions. In this group, no improvement was observed, and it appeared that the fibroblasts cancelled out the anticipated beneficial effects of the stem cells. As stated by Mayana, “the fibroblasts seem to be neurotoxic.”

In India, a group of doctors and scientists from the BGS-Global Hospital in Bangalore is testing the use of mesenchymal stem cells in seven human patients aged 22 to 62 who are suffering from Parkinson’s disease. Mesenchymal stem cells obtained from the bone marrow of the patients themselves were injected into the damaged brain in accordance with a local protocol designed by the Indian researchers. In an article published in February of last year in Translational Research, the researchers reported a reduction in the symptoms of the disease in three of the seven patients and said that the approach appeared safe. The results, however, remain preliminary and must be viewed with reservation. “Mes-

Image of a normal brain with more neurons that produce dopamine (left) and of a brain affected by Parkinson’s disease.

Injection of fibroblasts led to a deterioration in the symptoms of the disease in rats with Parkinson’s and cancelled out the benefits of the stem cells

enchymal stem cell transplants may not become a definitive treatment for Parkinson’s, but perhaps a complementary one, such as neuroprotection,” Okamoto considers. “This type of study can help us understand how to mitigate the degenerative environment in the brain and maybe how to create new drugs against the disease; who knows?”

GENES, ENVIRONMENT AND MYSTERY

Although there are cases of young individuals with Parkinson’s disease, such

as the famous Canadian actor, Michael J. Fox, who was diagnosed at the age of 30, this neurological disorder appears more often in people older than 50 or 60 years of age. “Patients under 50 are seen as precocious and represent some 20% of the total,” says the neurologist Luiz Augusto Franco de Andrade from the Teaching and Research Institute at the Albert Einstein Hospital in São Paulo. “But I’ve already treated a boy of 13 who had Parkinson’s.”

There is growing evidence that environmental and genetic factors may be implicated in the appearance of the disease, at least in certain cases. A study

by Harvard Medical School researchers, published in October of last year in Science Translational Medicine, showed that hundreds of genes linked to the function of the mitochondria, organelles that are the organism’s power plant, are less active in Parkinson’s disease patients.

Even people who are in the initial or pre-Parkinson’s disease stage appear to have these changes. If this connection between the mitochondria and the disease is confirmed, drugs that act on these genes may become useful in treating the problem.

TWICE AS MANY PATIENTS BY 2030

Along a similar line of investigation, a study published in September 2010 by the National Institutes of Health (NIH) of the United States suggested that individuals with a certain version of the GRIN2A gene might benefit from the consumption of coffee and tea. In a person with this genetic profile, the intake of beverages containing caffeine might act as a protective factor against ParkinPESQUISA FAPESP | 17

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urrently viewed as a nation of young people, Brazil’s demographic profile will change dramatically over the next few decades. A report from the World Bank published last month indicates that its population of persons 65 or older will increase from the current 11% to 49% by 2050. Thus, in a period of 40 years, the number of old people will triple, surging from fewer than 20 million to approximately 65 million persons.

“The speed of population ageing in Brazil will be significantly greater than that in more developed societies in the last century,” say those responsible for the report, Envelhecendo num Brasil bem mais velho [Growing old in an older Brazil]. In France, it took more than a century for the population of persons 65 years or older to increase from 7% to 14% of the total population. “Over the last few years, modern gerontology has emphasized the increase of the ageing process more than its physical and mental losses,” says anthropologist Guita Grin Debert from the State University of Campinas (Unicamp), who studies issues linked to women and old age. “We have experts in diseases but not many in the ageing process.”

A review paper published in January 2007 in the scientific journal Neurology analyzed data from 62 different studies and concluded that the number of

MARIANE SECCO

son’s disease. The search for substances that help to maintain neurons is a strategy adopted by many research groups.

The administration of the GDNF protein, which acts in this manner, has been the target of long-term tests to examine its possible action against the disease.

Despite localized advances in our understanding of the possible mechanisms implicated in its genesis, Parkinson’s disease continues to maintain its general status as a neurodegenerative disease with a cause that is both mysterious and unexplained. No one knows for certain why the neurons that produce dopamine begin to die or stop functioning correctly at a particular point in the life of certain people. The only concrete knowledge is a palpable fact of the current reality: an ageing population is a great risk factor for Parkinson’s disease. This issue is of particular concern for developing nations, which have an age structure that is rapidly changing before they become more wealthy.

Mesenchymal stem cells (left) and fibroblasts: it is difficult to distinguish between these types of cells.

The number of cases of the disease is growing faster in developing countries than in richer nations

cases of Parkinson’s disease in people older than 50 should double over the next 20 years in 15 countries throughout the world. This review analyzed statistics from the world’s most highly populated nations, including Brazil and the five largest countries in Europe. In 2005, this group of countries had between 4.1 and 4.6 million patients with Parkinson’s disease. In 2030, there will be between 8.7 and 9.3 million cases of the disease.

During this same period, the number of individuals with Parkinson’s disease in Brazil will increase from 160,000 to 340,000. According to this review article, the estimated growth rates of the incidence of Parkinson’s disease in developing countries such as China, India and Brazil, whose populations are only now undergoing an ageing process, will be greater than 100%. In developed economies that already have a large number of old people, such as Japan, Germany, Italy and the United Kingdom, the number of people with Parkinson’s disease is expected to increase by less than 50%.

Overall, an estimated 1% of the planet’s inhabitants older than 65 suffers from Parkinson’s disease. However, this figure may vary according to the characteristics of the population analyzed.

A study conducted in 2006 in Bambuí, Minas Gerais, found a high incidence of Parkinson’s disease, i.e., a rate of greater than 7.2% in a group of 1,186 individuals older than 64. This figure is three to four times higher than that reported in similar studies performed in Europe, Asia and the United States. Approximately half of the cases of the disease in Bambuí have been caused by the uncontrolled use of drugs against psychoses and dizziness. “We currently believe that the

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DRAWINGS: INSTITUT SANTIAGO RAMÓN Y CAJAL / WIKIMEDIA

duce good results against Parkinson’s disease without the need for open-brain surgery. In an article that was featured on the cover of the scientific journal Science on March 20, 2009, Nicolelis reported a successful experiment on rats and mice with induced Parkinson’s disease. The installation of small electrodes on the surface of the spinal medulla of the animals helped them recover their normal locomotive capacity. According to the report, the procedure for placing the electrodes takes 20 minutes, is not excessively invasive (only the skin of the animal is cut) and is safe. This new approach, which is now being tested on monkeys, was the first attempt at treating Parkinson’s disease without directly acting on the brain.

number of cases of the disease arising from the uncontrolled use of drugs has decreased,” says Francisco Cardoso from the Federal University of Minas Gerais (UFMG), coordinator of the study. “Control of the sale of drugs in the country has improved.”

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cientists are not betting on stem cells alone to improve treatments for Parkinson’s disease. There are no prospects of a cure in the short-term.

However, researchers hope that preventing the evolution of this neurological disturbance, or at least slowing its progress, will be possible by developing new drugs and more effective and less invasive surgery. “At present, we try to offset the effects of Parkinson’s by administering oral medication,” says Cardoso. “But the way in which we replace dopamine is not good.” For example, when the patient takes the drug levodopa, a precursor of dopamine, his brain comes into contact with high concentrations of the neurotransmitter. As time passes, the amount of the substance decreases. Consequently, the treated patient experiences cycles of excesses and shortages of the neurotransmitter, i.e., a type of chemical see-saw, with dopamine highs and lows.

Several drugs have been developed in an attempt to regulate the moment at which dopamine, produced artificially via the ingestion of levodopa, becomes available for use by the brain of the patient. However, the control of this process requires further refinement, and the imitation of the physiological mechanism is imperfect. The situation becomes even more complicated when the drugs no longer control the Parkinson’s disease symptoms or produce side effects. The prolonged use of dopamine precursors can occasionally causes involuntary and repetitive movements, called dyskinesia, which may cause patients to bite their lips, poke out their tongue or blink rapidly. In these cases, deep brain stimulation (DBS) surgery may be indicated.

Two years ago, the team of the Brazilian neuroscientist Miguel Nicolelis from Duke University (USA) and founder of the Edmond and Lily Safra International Institute of Neurosciences of Natal (IINN-ELS), suggested that electrical stimulation might pro-

Less invasive surgery to improve communication between neurons is another bet against parkinson’s disease

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he prediction of whether new Parkinson’s disease treatments will arise from studies such as those of the teams of Mayana Zatz at USP and Esper Cavalheiro at Unifesp. For the time being, this work and that of other scientists still continues to comprise lines of research that should be explored rather than considered as immediate treatment possibilities. Nonetheless, doctors who care for people with Parkinson’s disease see no cause for pessimism. Patients are living with the disease for an increasingly long time, even up to decades, although the side effects of the medication continue to be an important issue. Nevertheless, the electrodes and batteries used in DBS surgery are becoming smaller and more efficient. “We still don’t know how the neurons ‘talk’ to each other, but today we can record the activity of a larger number of brain cells,” says neurosurgeon Manoel Jacobsen Teixeira, a professor at USP and member of the Institute of Teaching and Research at the Sirio-Libanês Hospital in São Paulo. n

Scientific articles 1. PEREIRA, M. C. et al. Contamination of mesenchymal stem cells with fibroblasts accelerates neurodegeneration in an experimental model of Parkinson’s disease. Stem cell reviews and reports. Published online on April 19, 2011.

2. VENKATARAMANA, N. K. et al. Open-labeled study of unilateral autologous bone-marrowderived mesenchymal stem cell transplantation in Parkinson’s disease. Translational Research. v. 155 (2), p. 62-70. Feb. 2010.

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 S&T POLICY _ ECOLOGY

Ecological path From basic research to public policy, FAPESP has been investing in biodiversity studies for five decades Fabrício Marques PUBLISHED IN AUGUST 2011

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undreds of São Paulo researchers in disciplines connected with the study of biodiversity met in São Carlos in early July to discuss the progress of their work. Concurrently, an evaluation committee composed of foreign scientists analyzed the results presented and suggested possible paths for the upcoming years. The two events highlighted the seventh evaluation of the Program of Research on the Characterization, Conservation, Recovery and Sustainable Use of the Biodiversity of the State of São Paulo, better known as Biota-FAPESP, an effort that began in 1999 and that involves 1,200 professionals in the identification of biodiversity in São Paulo.

The program has promoted more than 100 research projects and has enabled the pursuit of knowledge, including the identification of 1,766 species (1,109 microorganisms, 564 invertebrates and 93 vertebrates) and the publication of more than 1,145 scientific articles, 20 books, 2 atlases and several maps that have begun to guide public policy. At present, São Paulo State has 6 governmental decrees and 13 resolutions that mention the guidance provided by the program. In the area of training human resources, the program

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ILLUSTRATION ANA PAULA CAMPOS, WITH REPRODUCTIONS FROM THE BOOK FLORA DO ESTADO DE SÃO PAULO

has led to 190 Master’s degrees, 120 PhDs and 86 post-doctoral fellowships. FAPESP has invested R$ 82 million in only the first 10 years of this program.

According to its coordinator, the botanist Carlos Alfredo Joly, a professor at the State University of Campinas (Unicamp), Biota-FAPESP is the first Brazilian scientific program to receive investments regularly for more than 10 years.

When the program reached its 10th anniversary, its organizers proposed a new scientific plan to FAPESP for the next 10 years. “This evaluation meeting is very special because it is the first to be held since FAPESP renewed its support for the program up to 2020,” says Joly. “A long-term outlook is fundamental for scientific research,” he stated. Biota-FAPESP is the principal example of the heavy investment by the Foundation for research in the fields of natural sciences and ecology, all of which started long before the name biodiversity was coined. In its early years, FAPESP was already supporting studies of marine algae, at first along the São Paulo coast (1962-1963) and subsequently along the northern, northeastern and eastern coasts of Brazil (1964-1965), conducted by the Department of Botany at the former

School of Philosophy, Sciences and Literature at USP, which was subsequently incorporated into the Institute of Biosciences (IB). The survey conducted along the coast of the state led to several research studies published in scientific journals, the training of marine biologists specializing in algae and the expansion of the algae herbarium at the Department of Botany. The survey of the algal flora of the remainder of the Brazilian coast was part of an international cooperation project that had the support of the Section of Oceanography of Unesco. The combined results of these projects comprise the first version of the Marine Phycological Flora of Brazil.

A key investigator involved in this line of research was Aylthon Brandão Joly (1924-1975), a University of São Paulo professor who began to study algae in Brazil in the 1950s. In 1957, he published the book Contribuição ao conhecimento da flora ficológica marinha da baía de Santos e arredores [Contribution to the knowledge of marine phycological flora in the bay of Santos and surroundings], the first planned survey of algae in a specific area of Brazil. “Up until about 1960, Joly worked by himself at the university.

Afterward, he formed a veritable school in the PESQUISA FAPESP  21

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PERSONAL ARCHIVES

Department of Botany of USP. Directly or indirectly, he was the advisor of most of the first generation of Brazilian phycologists and also of phycologists from other Latin American countries,” wrote Carlos Bicudo, a researcher at the Institute of Botany of São Paulo, in the article “O estudo de algas no estado de São Paulo” [“The study of algae in the state of São Paulo”], published in 1998.

Aylthon Joly left many descendants – one of them in both the literal and the academic sense of the term. His son, Carlos Alfredo Joly, the coordinator of Biota-FAPESP, followed his father’s example. “There is a generation of marine algae researchers that are my father’s academic grandchildren,” says Joly.

“Professor Mariana Cabral de Oliveira from USP, a member of the coordination of the Biota-FAPESP Program, is a good example of this new generation because, in addition to incorporating DNA bar coding techniques into her research, she has shown the same innovative spirit that has always characterized Brazilian phycologists.”

WATER RESERVOIRS

In the 1970s, when FAPESP took the initiative to organize special projects, the Foundation decided to dedicate one project to the field of ecology and commissioned a proposal from Professor José Galizia Tundisi who, even then, was already an expert on water studies.

The result was the project “Typology of the Water Reservoirs in the State of São Paulo”, which involved 70 researchers from the Laboratory of Limnology at the Federal University of São Carlos (UFSCar), the Institute of Biosciences of USP, and the Institute of Fishing at the Agricultural Bureau of the State of São Paulo. “At that time, a researcher from Spain had conducted a study on the profile of 104 water reservoirs in that country, taking into account the biology of the waters, contamination and pollution; I proposed a similar design,” says Tundisi. The project yielded robust scientific data. The project expanded the understanding of the workings of water reservoirs, clarifying the differences between them and lakes. The project also enriched the collections of aquatic organisms maintained at research institutes and led to 150 published studies in Brazil and abroad, 4 books (3 in other

countries), and 10 PhDs and 15 Master’s degrees. The project also enabled, for example, the development of an unprecedented methodology for comparing the aquatic ecosystems of Brazil. Additionally, the project generated information about the geographic distributions of aquatic organisms and the characteristics of the reservoirs that had effects on the use of hydrographic basins. Today, this information continues to furnish the basis for new studies. Finally, the project set parameters for the management of reservoirs. “We managed to determine that the ideal amount of time to retain water in the reservoirs must be less than 10 days to ensure the quality of the water and the health of the ecosystems. If the water in a reservoir takes too long to be replaced, the retained pollutants, nitrogen and phosphorus have an im-

Aylthon and Carlos Joly: from marine algae to Biota-FAPESP

pact on the maintenance of the species in the reservoir. This information was fundamental for the planning of new hydroelectric power stations,” states Tundisi. Once the project was approved, Tundisi sought out the scientific director of FAPESP, William Saad Hossne, and stated that he had a new requirement. “I asked for 15 young investigator awards to train new researchers within the project.

This turned out to be a success. Of the 15 young researchers, 13 are now head professors,” says Tundisi.

DESCRIPTION

Whereas the study of water reservoirs trained leaders and created competence in the field, the Phanerogamic Flora of

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ANTONINHO PERRI / ASCOM / UNICAMP

the State of São Paulo project was a landmark in terms of learning how to function in a multi-institutional environment.

Subsequently, this project involved acquiring a broader outline that involved networks of institutions and researchers under the Biota-FAPESP program. The project, which began in 1993, brought together experts from the three state universities – Unicamp, USP and Paulista State University (Unesp) –, from three research institutes – Botanical, Forestial and Agronomical – and from one municipal body – the Department of Parks and Green Areas of the São Paulo City Government. As one of the chief contributions to the knowledge of the diversity of the Brazilian flora, this project has already yielded six volumes with descriptions of the species of phanerogamic plants, i.e., those that produce seeds. The goal is to publish another 10 volumes in addition to updating the earlier works on the Internet.

The aim of the project was to fill the gap in environmental conservation in Brazil, which was being discussed by the members of SBB (the Botanical Society of Brazil); the Brazilian flora, acknowledged as having the largest number of species, was also among the least known and most threatened on the planet. “In 1992, at the National Congress of Botany, held in [the city of ] Aracaju, [state of ] Sergipe, the principles for the preparation of the Flora of Brazil were consolidated and approved. This not only provided for the study of vegetation but also for the training of human resources and the establishment of botanical expedition programs in the country’s different ecosystems,” recalls Maria das Graças Lapa Wanderley, a researcher at the Institute of Botany who now coordinates the project. The following year, with FAPESP’s first public call for thematic projects, the botanists at a congress in the city of São Luís in the state of Maranhão decided to submit a proposal using the plan of the flora of São Paulo State as a pilot project. The coordination of this was undertaken

by Professor Hermógenes de Freitas Leitão Filho (1944-1996) from the Department of Botany of Unicamp, one of the few Brazilian experts on the Compositae family, which has some 10,000 species, including daisies, chamomile and several medicinal plants.

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Hermógenes Leitão: Phanerogamic Flora

In the early 1990s, the Brazilian flora was simultaneously among the least known and the most threatened in the world.

The first two years constituted the planning phase, including a survey of the collections at herbariums, which enabled the creation of the project’s database.

The second phase consisted of the scientific expeditions, most of them conducted between 1996 and 1997, which resulted in approximately 20,000 plants that are distributed in the state’s herbariums.

When Hermógenes Leitão died suddenly in February of 1996 while leading a field trip, the project coordination was transferred to Maria das Graças Lapa Wanderley and George Shepherd from Unicamp and Ana Maria Giulietti from USP. The third phase led to the reporting of the results, with the expectation of the publication of 16 volumes. FAPESP continued to support the project until 2005. The six volumes published to date describe 132 families, including 655 genera and 2,767 species, or 37% of the 7,058 referred species of São Paulo State. “All of the researchers who want to study a phanerogamous plant consult our databases. The impact of the project extends to all of the fields of botany,” says Maria das Graças Wanderley.

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The Phanerogamic Flora project inspired Biota-FAPESP. In 1995, the Bureau of the Environment of the State of São Paulo attempted, in vain, to involve researchers in work that went beyond preparing a list of the state’s threatened species. “There were many gaps in our knowledge, but the researchers resisted commitment, fearing that eventual political changes at the bureau might jeopardize the work’s continuity,” says Carlos Joly, then an advisor to the secretary of the Environment, Fabio Feldmann. At the time, Joly was also a member of the Coordination of Biological Sciences at FAPESP, working with Professor Naércio Menezes. “The idea of a research program about biodiversity was maturing in FAPESP. I had talked a lot with Professor Hermógenes at Unicamp and was highly familiar with the Phanerogamic Flora project. However, unlike this project, which was a thematic project centered on just one taxonomic group, we wanted to encompass all of the biodiversity of the state, which, obviously, wouldn’t fit under a single thematic project,” recalls Joly. The idea of creating a program with a set of articulated thematic projects was presented by a scientific director of FAPESP, José Fernando Perez, at a workshop held in the town of Serra Negra in 1997. The group in charge of coordination at the time (see details at www.biota. org.br/info/historico) decided to use the Internet to create tools to integrate and share data. Thus, the Virtual Institute of Biodiversity (another name used for Biota-FAPESP) came into being.

The data accrued by Biota-FAPESP now provides guidance for the criteria to create new conservation units and for the authorization for the removal of native vegetation. It also forms the bases of the agroecological zoning for the sugarcane plantations in the state of São Paulo.

Government decrees and the resolutions of the Bureau of the Environment mention and take into account the maps of the priority conservation and restoration areas of the São Paulo biodiversity that are produced by the Biota Program.

Although the first 10 years of BiotaFAPESP were underscored by the progress of the characterization of biodiversity in the use of the database as a tool for the improvement of public policies, the program now aims to broaden its

MIGUEL BOYAYAN

GAPS

The Biota-FAPESP Program data provide guidance for the criteria used to create new conservation units in São Paulo

scope. The subprogram BIOprospecTA, which identifies compounds or molecules of economic interest, merits particular emphasis. Additionally, the Biota-FAPESP program now also produces educational material for elementary, junior high and high schools and studies connected with ecosystem services and with the functioning of terrestrial ecosystems. “Professor Arthur Chapman, from the Australian Service of Information on Biodiversity and a member of the international evaluation committee, praised the program, saying that it strives to implement the suggestions that the committee had previously made,” says Joly. “In 2008, the evaluators criticized the small number of marine biology and microorganism projects. Now, there are 10 new marine biology projects; in the case of microorganisms, for which there was only one thematic project, more than 40 proposals were submitted after the last call for proposals. These are capable groups, and the coordination has had the sensitivity to listen to the wishes of the São Paulo scientific community. That is why these things are occurring so quickly,” says Joly. n

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 SCIENCE _ MEDICINE

The fight against cancer Antihypertensive medication halts tumor growth, indicating new drug targets

Carlos Fioravanti PUBLISHED IN MAY 2011

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ILLUSTRATIONS BEL FALLEIROS

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osartan, one of the most commonly used drugs worldwide to control arterial hypertension, halted the growth of skin tumors in murine experiments conducted in the laboratories of the School of Medicine at the University of São Paulo (FMUSP), Brazil. Thus, an old drug has acquired a new application, potentially advancing the quest for new cancer treatments. However, it is too risky to conclude that this drug is ready for human use for this purpose merely because there is a generic, unbranded version available in Brazil and because its side effects are well known.

“Now, we must learn to use this drug to improve tumor treatment,” comments physician Roger Chammas, an FMUSP professor and one of the coordinators of this study, which was presented in detail in the May 2010 issue of Cancer Chemotherapy and Pharmacology.

Andreia Otake demonstrated that Losartan blocked the action of angiotensin II, a protein fragment (or peptide) that helps control blood pressure, along with other molecules produced by the body. The current study and others studies have shown that angiotensin II may have another, lesser-known and less-explored function:

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helping tumors to form or attract the blood vessels that carry the nutrients required for their survival. With less angiotensin available, fewer blood vessels will develop within the tumor, and tumor death may subsequently occur because of malnutrition. According to Chammas, these studies strengthen the premise that not only the tumor but also the molecules with which the tumor interacts (the tumoral micro-environment) are targeted by the new drugs.

In recent years, several studies have indicated that angiotensin II encourages the migration and proliferation of endothelial cells, which form the innermost layer of blood vessels and, therefore, take part in regulating the inflammatory processes that often underlie the onset or development of tumors. “A tumor can be seen as persistent inflammation, a wound that does not heal and that attracts blood vessels, which, in turn, help to disseminate the cancer throughout the body,� comments Chammas. The existence of angiotensin receptors at the surface of endothelial vessels that feed tumors opens up the possibility of new uses for anti-hypertensive medications, such as Losartan. Preliminary trials that are underway (with limited numbers

of individuals) in the United States attest to the antitumor effect of this medication, either used alone or in conjunction with antihypertensive drugs that have similar mechanisms of action, such as captopril.

Discovered in 1986 by a group of young researchers at DuPont, losartan was the first in a new class anti-hypertensive drugs called angiotensin II receptor antagonists. Produced by Merck, the drug has been acquiring new applications, although it has become a generic medication in Brazil. One such application is the treatment of chronic kidney diseases. Since the late 1980s, the FMUSP physician Roberto Zatz has conducted studies that show high doses of losartan help to deter the damage caused by chronic kidney disease in rats. Zatz has participated in international clinical studies that have led to the relatively common use today of losartan in the treatment of many kidney diseases. Moreover, it was Zatz who suggested the skin tumor experiment to Chammas; he had hypothesized that tumor growth could be halted by using the ability of this medication to reduce blood pressure, blood vessel growth and inflammatory processes.

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At the Federal University of Minas Gerais (UFMG), Robson dos Santos has begun exploring the therapeutic applications of angiotensin 1-7, a derivative of angiotensin II and so named because it has seven amino acids rather than the eight found in angiotensin II. When formulated in cyclodextrin (a sugar) formation, angiotensin 1-7 given orally to rats diminishes the heart cell damage induced by infarction of the heart, as detailed in a study published in the March 2011 issue of Hypertension. According to this author, the same formulation can regulate the glucose and lipid (fats) levels, based on laboratory animal experiments. Santos further states that angiotensin 1-7 taken intravenously demonstrated positive effects in the treatment of women with pre-eclampsia, a severe problem that can appear during the second month of pregnancy and is associated with hypertension and liquid retention. According to Santos, trials of this formulation (taken orally) are scheduled to start soon. “We expect to

get results within six months,” he says.

“In pre-eclampsia, exogenous angiotensin 1-7 helps to normalize the level of angiotensin 1-7 in the blood.”

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long with these promising results, recommendations on the careful use of anti-hypertensive medication for off-target purposes have emerged. According to a study published in the June 2010 issue of Lancet Oncology, individuals who submitted to experimental therapies involving antihypertensive drugs acting on angiotensins to treat cardiovascular diseases and diabetes for at least 1 year had a risk that was 1.2 times greater than that of untreated individuals who had developing cancer, particularly lung cancer.

Although this risk is small, this finding did attract attention.

In principle, the same drug may combat or spur tumors because cancer is actually a broad set of different diseases; experts have identified some 200 different types of cancer, although all are char-

acterized uncontrolled cell growth that invades neighboring tissues. Increased attention is being given to the unique aspects of each cancer to guide diagnosis and treatment. “Lung cancer in one person can be very different from lung cancer in another person, even if they originated in the same type of lung cell.

These differences are evidenced in the different molecular signatures of the tumors and are akin to a fingerprint, as they indicate which molecular pathways have been altered in a given type of cancer,” comments Chammas. “We’re trying to understand these signatures better in an attempt to improve the diagnosis and treatment of different types of cancer.

We must think differently and regard the tumor as an organ that has its own way of working.”

The possibility of antihypertensive drugs being evaluated as antitumor medication in Brazil in controlled human trials is remote, given the labyrinth that the researchers and physicians in public institutions face using laboratory data to solve public health problems. The chief complaint is that the approval of a proposed study by the federal bodies can take one year or longer, whereas in the United States or even South Africa, the approval process averages three months. Santos, from UFMG, says that he had to wait for 6 months to obtain all of the approvals required to carry out the angiotensin 1-7 trials with intravenous cyclodextrin to treat women who suffer from severe pre-eclampsia. As

“We must think differently and regard the tumor as an organ,” suggests Roger Chammas.

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“We aren’t winning the battle against cancer.

We must speed things up,” says Paulo Hoff.

for the request to test the oral formulation, it took 1 year for the commission of research ethics at the university and from Conep (the National Commission on Research Ethics) at the Ministry of Health to respond. “It’s a discouraging reality,” he states.

“I

n Brazil, there is no spirit of urgency,” notes Paulo Hoff, the director-general of Icesp (the Cancer Institute of São Paulo), which is tied to the FMUSP medical school and opened in 2008. Icesp currently serves 12,000 new cancer cases every year. “The bureaucracy could be speedier, more efficient and transparent, with no loss of control,” says Hoff, one of the authors of an article published in 2010 in Lancet Oncology. Hoff proposed joining the governmental, medical and academic interests to plan and execute the initial stages of trials for drugs in countries such as Brazil, primarily to validate the results obtained in countries where the regulation process is speedier.

Hoff explains that the interest of the federal government representatives in supporting clinical trials in Brazil seems to be growing. “We must be flexible in our actions,” he suggests. “We cannot enter a negotiation imagining that our point of view will be predominant.”

Max Mano, an Icesp physician, believes that improved speed in the approval of clinical trials for new drugs or for new applications of older drugs may be particularly beneficial for treating rare tumors, which can appear in any body part and be easily confused with other conditions. In a 2010 article, Mano and Hoff warned that rare tumors account for 25% of all cancer deaths in the United States and possibly in Brazil as well. “A rare tumor is not harder to treat,” says Hoff.

“What is difficult is finding a doctor who can recognize it and who knows how to treat it.”

Certain types of cancer, such as stomach cancer, have become rare in Europe because of the implementation of sanitation measures, improved eating habits and early diagnosis; however, they are still common in Brazil and other Latin American countries. “Many tumors are linked to chronic infectious processes that are not properly addressed,” says Mano. “Research is not advancing as fast as the disease.” Hoff stresses that there has been progress in standardizing diagnostic tests for different types of cancer, although he acknowledges that “We aren’t winning the battle against cancer.

We must speed things up.” ■

Scientific articles 1. ARAI, R. J. et al. Building research capacity and clinical trials in developing countries.

The Lancet Oncology. v. 11. Aug. 2010.

2. OTAKE, A. H. et al. Inhibition of angiotensin II receptor 1 limits tumor-associated angiogenesis and attenuates growth of murine melanoma.

Cancer Chemotherapy and Pharmacology. v. 66, n. 1, p. 79-87. May 2010.

3. MARQUES, F. D. et al. An oral formulation of angiotensin-(1-7) produces cardioprotective effects in infarcted and isoproterenol-treated rats. Hypertension. v. 57, p. 477-83. Mar. 2011.

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_ EVOLUTION

When hybrids are fertile Unlikely cross-breeds can create new species of plants and animals Carlos Fioravanti

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n addition to being talented, Darwin was lucky. Upon arriving in the Galapagos Islands in the Pacific Ocean, he found a rich variety of tortoises and birds living under unique environmental conditions, such as geographic isolation and diet, which must have strongly influenced their evolution over millions of years. The probable cause of the occurrence of so many animals that were so similar to each other – birds, for example, with shorter or longer bills, depending on what they eat – seemed clear. However, the entire world is not precisely similar to the Galapagos. Even if they study areas rich in biodiversity, such as the Atlantic Forest, biologists today do not always encounter evolutionary histories and closely related species that display such marked differences. Nevertheless, when working with specific strands of DNA sequences known as molecular markers, biologists can now identify the genetic bases of species diversification. A mechanism for the formation of new species that has been gaining recognition among researchers is the possibility of plant and animal species that are genetically similar to one other crossing naturally and generating fertile hybrids.

Previously, this idea was not widely accepted, because, in general, different species have dif-

ferent numbers of chromosomes, the structures within cells that contain genes. This difference can prevent the normal development of the embryo, as each chromosome that came from the male parent must be aligned with an equivalent chromosome from the female parent when the fertilized cell divides for the first time. Without this proper alignment, the cell usually cannot divide and, thus, dies. However, there are exceptions, and such exceptions appear to be less rare than was previously thought. The crossing between plants – or animals – of closely related species can produce offspring that, although of hybrid origin, are fertile, even though some chromosomes do not encounter their respective partner in the initial phases of cell division.

With sufficient time and favorable environmental conditions, such hybridization events can generate species that are different from both of those from which they originated.

Today, the word “hybrid” defines the sterile mule, which is the result of a donkey crossing with a horse, but it also defines fertile organisms, such as the hybrid orchids from the Atlantic Forest that are maintained in a plant nursery at the Botanical Institute of São Paulo. This hybrid orchid has 38 chromosomes and resulted from a natural cross between two wild species, Epi-

EDUARDO CESAR

PUBLISHED IN JULY 2011

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A hybrid orchid from the Atlantic Forest

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EDUARDO CESAR

A hybrid with a flower in two colors: red like Epidendrum puniceolutem and yellow like E. fulgens

dendrum fulgens, which has 24 chromosomes, and Epidendrum puniceolutem, which contains 52 chromosomes. Externally, the differences between these two species are subtle: the flowers of the socalled parental species are red or yellow, whereas the flowers of the hybrid can be orange with red spots.

Genetic information alone is insufficient to identify fertile hybrids. Nevertheless, fertile hybrids are now identified with relative ease because, in addition to comparing the number of chromosomes, experts initially examine the most visible aspects of the environments inhabited by the hybrids and the species that gave rise to them. The history of the landscape is then considered by studying the geological maps and climatic variations, which may indicate previous displacements of rocks, past earthquakes or prolonged variations in rainfall or temperature. These historical changes may increase or decrease the proximity of plants or animals with each other, which may or may not influence the formation of new species.

In the case of the above-mentioned orchids, the hybrids inhabited both the restinga, the typical environment of Epidendrum puniceolutem, and dunes, sites where E. fulgens is found. “This versatility suggests that some regions of the genome can be exchanged among these species, giving the hybrid a greater capacity to utilize the habitat,” says botanist Fábio Pinheiro, research associate at the São Paulo Botanical Institute. “Natural hybridization is probably one of the explanations for the high degree of di-

Hybrids can arise most easily under conditions that bring together populations of closely related species of plants or animals

versification that we observe in the genus Epidendrum, which includes almost 1,500 species.”

As a precaution, in a presentation in May 2009 at the Royal Botanic Gardens, Kew, London, Pinheiro did not mention the number of chromosomes present in the hybrid, for fear of the reaction. “But the orchid specialists at Kew asked, and, when they saw the orchid, they didn’t believe it. They said something was wrong, but then they accepted it,” Pinheiro says. The prevailing view is that different species do not interbreed naturally and that any hybrids that do form, are sterile. The argument is that the germ cells are not compatible and are thus unable to combine and form viable offspring.

“However, most plants are in fact the result of natural or induced hybridization events between closely related species”, says Fábio de Barros, coordinator of the project at the Botanical Institute.

Induced hybridization is used to create unique species of orchids and plants used in food production, such as corn and sugar cane. Usually hybrids have an advantage: in the case of food plants, they tend to be more disease resistant and more productive than either of the parent species. “Darwin had already written that hybrids may be sterile or fertile but could not prove it because, at that time, there was no such thing as using molecular markers to identify the genetic signatures of fertile hybrids,” says Barros. “Apparently hybridization is quite abundant and seems to have a much larger role in evolution than we ever imagined.”

Botanists have already observed other such cases. Orchids of the genus Ophrys, from the Mediterranean region, regularly form hybrids that are highly fertile.

Moreover, a cross between two short plants with yellow flowers from Europe and the United States, Senecio squalidus and S. vulgaris, produced a hybrid that attracts more pollinators and could produce more fruit than either of the parental species.

MIXED SPACES

Animals also form fertile hybrids.

Thales Freitas, a geneticist at the Federal University of Rio Grande do Sul (UFRGS), observed that two species of subterranean rodents known as tuco-tucos – Ctenomys minutus, with 42 to 50 chromosomes, and C. lami, with 54 to 58 chromosomes – are able to cross and sometimes produce fertile offspring. The result depends on the species of the male and female parent: if the female is Ctenomys minutus and the male is Ctenomys lami, the offspring can be fertile, whereas the reverse combination, male Ctenomys minutus crossed with female Ctenomys lami, results in sterile hybrids. A similar situation has been observed for the Atlantic Forest frogs of the genus Phyllomedusa. At the State University of São Paulo (UNESP) and the University of Porto, Portugal, Tuliana Brunes studies the formation of species of Phyllomedusa, the genetic identification of

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TATIANE NOVISKI/UFRGS

hybrids, and the historical origins of hybrid zones.

The most likely places in which hybrids can arise are in areas where populations of closely related species of plants or animals that were once separated, come into contact. “We have discovered hybrids most frequently in zones of ecological transition, known as ecotones, in which two distinctive types of vegetation mix and facilitate the chances of contact between populations of plants and animals that are otherwise geographically isolated,” says Jão Alexandrino of the Federal University of São Paulo (UNIFESP).

Years ago, when he was at the University of California, Berkeley, Alexandrino verified this phenomenon while studying fertile hybrids resulting from the cross between two closely related species of salamanders occurring in riparian woodland habitats in California.

Thus far, he, Tuliana, and Celio Haddad (of Unesp) have verified that the resident frogs form hybrids where two types of Atlantic Forest, one more humid and the other drier, are adjacent in the interior of São Paulo State. The hybrids of orchids and tuco-tucos were also found in habitats occupied by groups of species that now coexist. It is probable that this outcome was the result of climatic variations that brought together previously isolated areas or influenced changes in the geographic distributions of certain plants and animals over thousands of years.

A consequence of the processes that lead to the separation of species, thus resulting in crossing or hybridization between closely related species, is that forests with high levels of biodiversity, such as the Atlantic Forest, become “a cauldron of new species in continuous transformation,” in the definition of Nuno Ferrand of the University of Porto.

“The wealth of biological diversity is not only measured by the number of species but also by the processes that may give rise to new species,” said Clarisse Palma da Silva from the Botanical Institute.

The best known mechanism for the formation of new species of animals or plants is the accumulation of genetic mutations in the offspring of the same species. Although it is clear that new species may also result from the clustering of populations of different species that were once separated, not all of

Tuco-tuco: hybrids in the sands of the south

these issues have been resolved. “The rules governing the emergence and differentiation of species are not entirely clear because evolution is a continuous process that follows different paths for long periods of time,” said Craig Moritz, a biologist at the University of California, Berkeley.

EFFECTS OF ISOLATION

One of the principles that has survived since Darwin is that isolation promotes genetic diversity and the divergence of species over thousands or millions of years. A well-known example is the two species of pit vipers restricted to the islands off the southern coast of São Paulo – Bothrops insularis, which only occurs on Queimada Grande Island, and Bothrops alcatraz, which is found only on Alcatrazes Island, located less than 50 km away – that began to differentiate in complete isolation from one another approximately 18,000 years ago (see Pesquisa FAPESP No.132).

However, much more may still be learned about these species. The research of Ana Carolina Carnaval, a Brazilian biologist now working at City College of New York, indicates that variations in the climate (from dry to wet) and altitude (from zero to 1,600 meters) along a strip of coastline 5,000 km long in the Atlantic Forest favored the isolation, emergence, and development of new species with a greater intensity than in the Amazon, a region where the varia-

tions in climate and elevation are not nearly as pronounced. These isolated areas that separate and protect plants and animals form so-called refugia, stretches of forest that survived the intense climatic changes over the millions of years that caused a reduction in nearby forests and the consequent elimination of the animal populations that lived there.

Luciano Beheregaray, a Brazilian biologist who teaches at Flinders University and Macquarie University in Australia, indicated that researchers from the United States, Great Britain and France lead the increasing global scientific efforts in this area, which is called phylogeography and combines genetic, geographical, geological and historical analyses. In the survey by Beheregaray, Brazil, despite its status as the richest country in terms of biodiversity, ranked 15th among the 100 countries examined.

“We can go much further, making more complete analyses of our data, instead of dying on the beach,” warned Celio Haddad. “We collected the data, but it is the specialists from other countries that analyzed these data. We should be leaders in this area and not merely towed along.” n

Scientific article PINHEIRO, F. et al. Hybridization and introgression across different ploidy levels in the Neotropical orchids Epidendrum fulgens and E.puniceoluteum. Molecular Ecology. v. 19, No 18. p. 3981-94. 2010.

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_ ASTRONOMY

The heavyweights of the Universe Alternative mechanism may explain the formation of neutron stars that are more massive than normal Salvador Nogueira PUBLISHED IN AUGUST 2011 The Crab nebula is bathed in particles emitted‌.

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… by a neutron star (right) at its central region

NASA / JPL

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magine compacting the Sun until it is the same size as a city. Is that radical thinking?

It might be, but nature performs the same experiment when it creates the so-called neutron stars, which are among the smallest and densest objects in the Universe. Astronomers know basically how this process happens, but there are few who admit that a great deal of work remains before science can explain what is out there. One of the mysteries is how neutron stars appear that have a greater mass than that forecast by the theory of stellar formation and evolution. A group of researchers in Brazil is attempting to illuminate the subject by reviving a controversial hypothesis. In general terms, they are suggesting that there must be more than one way of creating neutron stars.

Neutron stars appear because of the death of stars that have very large mass, at least eight times greater than the Sun’s mass. To understand what happens, it is necessary to first consider what astronomers know about how stars live and die.

Made from concentrated gas (mostly hydrogen) and dust, stars begin to shine when the concentration of material makes the atoms in the central region of these heavenly bodies join together, a process known as nuclear fusion (see text on

page 60). The transformation of two hydrogen nuclei, each with one proton, into a helium nucleus, which has two protons, is accompanied by a subtle reduction in the total mass. Part of the mass is converted into energy and escapes from the star. This escaped energy is the source of a star’s power, which can bathe an entire planetary system in radiation. This energy generated inside the star offsets its gravitational force, which acts in the opposite direction. Because of this equilibrium, the star remains approximately the same size throughout most of its life.

Over millions of years, however, the fuel available for nuclear fusion gradually runs out. Without hydrogen, heavier elements, such as helium, carbon, and oxygen, are used until a limit is reached: iron. This is the final frontier: the fusion of iron nuclei consumes more energy than the energy released at the end of the process. At this stage, the production of energy in the central region is interrupted, and gravity begins working unimpeded without any force to offset it.

COSMIC BOMB

At this point, the star collapses, triggering a complex sequence of events. The result is the explosion of the outermost layers of the star, when 90% PESQUISA FAPESP  35

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of its mass is launched into space. What remains after this violent episode, known as a supernova, is a very compact stellar core. If the mass of the core is relatively small, this compression produces what is normally called a neutron star. If the mass is larger and the compression continues, a black hole is formed, an object so dense that nothing escapes its attraction, not even light.

A

ccording to the currently accepted theory, neutron stars (so called because they have high proportions of uncharged particles (neutrons) inside them) should all have the same dimensions: a mass almost 40% greater than that of the Sun compressed into a sphere less than 20 km in diameter.

“But no one knows exactly what mass a star needs to have during its life to die and leave a neutron star or a black hole,” says astronomer Jorge Horvath from the Institute of Astronomy, Geophysics and Atmospheric Sciences (IAG) at the University of São Paulo, coordinator of a group that is investigating the characteristics of neutron stars.

“Until recently, it was believed that all neutron stars had this pattern,” says João Steiner, another astronomer from the IAG. “But last year, a case was discovered that is clearly bigger.”

The name of the object is PSR J1614223, a neutron star located 3,000 light years away from Earth that was discovered by a group from the National Radioastronomy Observatory (NRAO) in the United States. Presented in an article published in Nature, this star appears to have two solar masses – it is mammoth, in terms of objects of this type.

This finding obliged the astronomical community to accept the fact that there is significant variation in the size of neutron stars. This realization fits well with the forecasts made recently by Horvath’s group, which were published in the June issue of the journal Monthly Notices of the Royal Astronomical Society. In this work, Horvath, Eraldo Rangel and Rodolfo Valentim conducted a statistical analysis of the mass of 55 heavily studied neutron stars and found there are two common patterns: one is formed by stars with a smaller mass (approximately 1.37 times that of the Sun) and with little variation, as expected; the other is a more variable type with

Life and death of stars Stars with a mass eight times greater than that of the Sun shine for millions of years until they exhaust their nuclear fuel and explode in the form of a supernova. The outer layers are launched into space, and the central core generates a neutron star or a black hole

SUPERGIANT

MAIN SEQUENCE

PROTOSTAR

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a larger mass that is approximately 1.73 times the solar mass.

Why do these two different groups exist? “The results point to more than one mechanism for neutron star formation,” says Horvath.

This idea seems compatible with the distribution of neutron stars in places like globular clusters, which are inhabited principally by very old stars with a smaller mass than the mass that would be necessary to give rise to neutron stars, according to the star formation theory.

Recent observations by astronomers from various countries have shown there are many more neutron stars in these regions than would be expected if they were the exclusive product of the explosion of large-mass stars.

Stars that originally have a mass that is less than eight times that of the Sun do not generate neutron stars when they collapse. Instead, they generate another class of object: white dwarves, with the mass of a sun compressed to a volume such as that of the Earth.

THE PROJEC TS 1. Hadronic matter and QCD in astrophysics: supernovas, grbs and compact stars – nº 2007/03633-3 2. Investigation of high energy and high density astrophysical phenomena nº 2008/09136-4 TYPE 1. Thematic Project 2. Young Investigators Awards Program COORDINATORS 1. Jorge Horvath – IAG/USP 2. German Lugones - UFABC INVESTMENT 1. R$ 154,250.00 (FAPESP) 2. R$ 91,207.65 (FAPESP )

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SUPERNOVA

BLACK HOLE

NEUTRON STAR SUPERNOVA REMNANTS

This is how the Sun will likely end its days. In some binary systems, the white dwarf uses gravity to rob mass from its companion star until it reaches a limit that induces a new collapse. This event is explosive and produces a specific type of supernova, called Ia, in which the entire mass of the star is violently launched into space.

H

owever, some astronomers suggest a different process can occur.

Instead of resulting in a supernova, the rapid growth in mass of a white dwarf might cause it to become a neutron star. “This is an idea that has been around for 20 years, and there are those who hate it,” says Horvath. “But there are also those who say that it works. It’s difficult to imagine a better alternative to explain how certain neutron stars end up where they do.”

Recent data complicate the situation by indicating there are neutron stars with a mass smaller than that of the Sun that were not formed by collapse.

The definitive answer is yet to emerge, but it is almost certain that future research will involve reformulations in the theories of how neutron stars arise and behave.

INSIDE AND OUT

If there is mystery regarding the size and mass of neutron stars, it is no simpler when the subject is their composition.

The level of compacting of these objects is so high – the density of a neutron star is greater than that of the nucleus of atoms and 100 trillion times that of water – that the matter may appear in forms that are not found in any other place in the Universe.

At densities greater than that of the atomic nucleus, particles such as protons and neutrons break down into their fundamental units: quarks, which are generally never seen alone. It is difficult to reconcile these predictions with observations, but it is believed that these conditions exist in certain neutron stars that presumably harbor a soup of quarks at their core.

At the Federal University of ABC in Santo André, in the Greater São Paulo Metropolitan Region, Germán Lugones’ group has been performing calculations and simulations of how different internal compositions of these stars would affect their mass, radius, evolution and other properties. One of the team’s results is that certain phenomena that arise when matter is found in the form of quarks – such as the transition to a superconductor state – naturally explain the existence of stars with masses much greater than the classic 1.4 times the solar mass. This is why the discovery of PSR J1614-223 was an important sign that researchers may be on the right path. Lugones believes that a more radical version of quark stars – the strange star, or autolinked quark star, in which the entire star is composed of these particles – should be considered a candidate if stars with a mass even greater than that of PSR J1614-223 are observed.

“According to theoretical studies carried out over the last few years by our group, the density necessary for particles of matter to break down into quarks is 5 to10 times greater than the density of the inside of an atomic nucleus,” says Lugones, emphasizing that this density may be reached quite easily in the center of neutron stars with greater mass.

No one knows if this occurs. There are gaps in understanding of both the physics behind these processes and the observable properties of neutron stars.

Manuel Malheiro, a researcher at the Aerospace Technological Institute and a collaborator with Horvath and Lugones, has been at the University of Rome since 2010, where he is investigating the composition and other characteristics of another type of neutron star: magnetars, which have a high magnetic field.

Advances in theory and observations will be necessary to arrive at a more cohesive picture. The only certainty is that there are interesting problems regarding these stars that are, accidentally, ideal laboratories for studying the most extreme properties of matter. ■

Scientific article VALENTIM, R. et al. On the mass distribution of neutron stars. Monthly Notices of the Royal Astronomical Society. v. 414 (2), p. 1.427-31.

June 2011.

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 TECHNOLOGY _IMMUNIZATION

The increased production of vaccines Butantan develops technology to increase production and lower costs Fabrício Marques PUBLISHED IN JULY 2011

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ILLUSTRATIONS NELSON PROVAZI

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ith the capacity to produce 20 million doses, the flu vaccine plant at the Butantan Institute became fully functional in March and should ensure Brazil’s self-sufficiency in the prevention of influenza in the elderly in 2012. This plant was inaugurated in 2007, but the plant’s processes were validated only recently. In three to five years, the country could potentially become an exporter of influenza vaccines. Two technologies developed by researchers at Butantan promise to increase production without the need to expand the plant or purchase more raw materials. Each dose requires the use of a fertilized chicken egg for the reproduction of the virus, and the plant uses 20 million eggs per year to produce viruses. One of the new technologies permits the whole virus to be isolated, including all of the proteins. Current vaccines against the influenza virus are based on one protein, hemagglutinin A. The remaining proteins are discarded, but they can also provide protection.

In addition, these other proteins accumulate fewer mutations over time than hemagglutinin A. “When we produced this new vaccine, we found that production per egg increased from two to seven times, depending on the serotype of the

virus,” says Isaias Raw, a researcher at the Butantan Institute.

The second technology, already patented by the institute, allows for the isolation an adjuvant substance, monophosphoryl lipid A (MPLA), which enhances the body’s immune response by stimulating the production of appropriate antibodies or lymphocytes. Other adjuvant substances have already been created, but they are expensive or inaccessible. MPLA, curiously enough, is the byproduct of another line of research by Butantan that involves the development of a new type of pertussis vaccine that is considered safer due to the removal of lipopolysaccharide (LPS), which causes inflammatory and toxic reactions, from the bacteria. “We convert pounds of LPS into MPLA, which in small quantities can increase the responses to several vaccines so that they can be used in lower doses,” says Isaias Raw. Tests on mice showed that MPLA can allow the vaccine to protect against influenza using just a quarter of the currently used dose. This effect has already been demonstrated in human beings.

This substance is being tested against various diseases. Butantan demonstrated that MPLA has the potential for use in canine leishmaniasis vaccines. These vaccines can break the transmission cy-

cle of the disease, which can be deadly to humans. MPLA is also the subject of investigations by researchers at the Ludwig Institute in New York, who seek to enhance the effect of a vaccine against ovarian cancer, and researchers from Ribeirao Preto, who are working on a vaccine against tuberculosis. “Soon, it will also be evaluated with a hepatitis B vaccine that is now ineffective in people over 50 who are awaiting kidney or liver transplant,” says Isaias Raw. By increasing the immune response, MPLA also makes the vaccine less specific, and cases in which a flu vaccine immunized against serotypes not included in the vaccine have already been detected.

MPLA is also inexpensive. “We can produce enough MPLA to manufacture 1 billion doses at a cost of just pennies.

This makes Brazil immune to pressure from large pharmaceutical companies that do not want to sell the adjuvant but only the complete vaccine itself,” says the researcher. The results, which must be validated in new clinical trials before the vaccine reaches the production line, were published in the journal Vaccine in an article by Raw, Cosue Miyaki, Wagner Quintilio and Eliane Miyaji, among other researchers at the institute. “The research does not end with the publication of the article but with the producPESQUISA FAPESP  39

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tion of vaccines to meet public demand,” says Isaias Raw. Butantan believes that both technologies have the potential to increase the plant’s production capacity for the influenza vaccine from 20 million to 160 million doses. Such growth, after the completion of clinical trials, will naturally depend on market conditions, which have varied greatly in recent years. The plant was designed in 2004, when avian flu was a threat. Caused by the H5N1 virus, the flu outbreak in 2005 resulted in the death of thousands of birds and hundreds of humans in Vietnam, Thailand, Indonesia, China, Egypt and Cambodia. At that time, an old building at the Butantan Institute was converted into a pilot laboratory to start experimenting with small-scale production of the influenza vaccine. Simultaneously, funding was obtained from the state of São Paulo to build a plant and from the Ministry of Health to import the necessary equipment. The technology for vaccine production was transferred to the Charles Merieux laboratory, now called Sanofi-Pasteur, and is based on the reproduction of the virus in fertilized chicken eggs.

The picture changed radically in 2009 with the emergence of the H1N1 virus,

The WHO estimates that the alarms sounded regarding the severity of H1N1 were exaggerated, but then this organization launched a joint effort to provide vaccines.

which causes swine flu. This virus appeared in the United States, infected thousands of Mexicans, and quickly caused a pandemic. The pandemic strains were similar to those that caused the 1918 influenza pandemic, the so-called Spanish flu that killed 40 million people. Both viruses primarily affect young children and pregnant women, a sector of the population that was not previously targeted by vaccination campaigns. Suddenly, the demand for immunization increased 10 fold. The World Health Organization (WHO) now believes that the degree of alarm regarding the lethality of H1N1 was exaggerated, but at the time, the WHO launched a joint effort to provide vaccines. “The WHO had to prepare a vaccine and give it to producers, including the institute. There would not be vaccines for everyone, but the agreement between the Butantan Institute and Sanofi guaranteed the priority of acquiring vaccines manufactured overseas and allowed the immunization of some 80 million people, “says Isaias Raw. Even before the application of new technologies, Butantan may be able to export influenza vaccines to countries in the Northern Hemisphere. Today, the productivity of the plant is seasonal.

Manufacturing begins around September, when the WHO defines the three types of flu virus that are most prevalent in that period and sends samples to the manufacturers. For Butantan, the level

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MARCELO VIGNERON

Ministry of Health and the Butantan Foundation. “These figures become irrelevant relative to the millions of dollars in savings that Brazil will realize when it does not need to buy products from international laboratories,” said Jorge Kalil, director general of the Butantan Institute, in an article published

by Folha de São Paulo newspaper. “This tremendous advancement in science and technology turned Brazil into the only country in Latin America that currently produces influenza vaccines.”

GLOBAL ALLIANCE The production of the vaccine is based on the use of fertilized chicken eggs.

of production is high until April, when actual vaccination begins, and then the plant suspends all activity until the following September. “In this period, we could produce the combination of vaccines of the Northern Hemisphere and supply them to people who live above the equator in Brazil as well as in countries like Venezuela, Colombia and Guyana,” says Isaias Raw. “Today, immunization arrives too late in these regions and is not really effective.”

VIRUSES AND EMBRYOS

It took 7 years to complete the factory because it was necessary to overcome a series of obstacles. In addition to bureaucratic issues related to choosing a construction company for the project and importing special equipment, such as centrifuges, it was also necessary to develop a machine that destroys what is left of the eggs after the liquid full of viruses has been isolated. This leftover material has to be reduced to a powder to be safely transported and incinerated. This material must be destroyed to prevent it from becoming food for birds and other animals – a few live viruses would be sufficient to accidentally spread the disease. ““It is a very complex process, which involves a specific technique for injecting the virus into each egg, separating the liquid in which the virus reproduces, and then purifying and re-purifying it to allow the environmentally friendly treatment of the waste material,” says Hernan Chaimovich, superintendent of the Butantan Foundation. The vaccine immunizes

“This giant step forward has made us (Brazil) the only country in Latin America that is currently producing influenza vaccines,” said Jorge Kalil.

against three types of influenza, but the production process is concentrated on one strain at a time. Before moving to the next strain, the plant must stop all activity for a few days and undergo a rigorous disinfection process. Sanofi monitored the production of the first batches and testified that the plant had been validated within the rules of the European Union. Investments for the implementation of the project exceeded R$100 million, with funding from the state government of São Paulo, the

The vaccine production capacity of public institutions in Brazil caught the attention of the Bill and Melinda Gates Foundation, which has also made contact with institutions in other countries.

Last year, Butantan was visited by Tachi Yamada, president of the Global Health Program of the Gates Foundation, who was interested in learning more about the production capacity of the institution in São Paulo. The Gates Foundation, a charitable organization started by the founder of Microsoft, is seeking partners to produce vaccines at a low cost so that these vaccines can be provided to developing countries. A proposal for collaboration with Butantan, the Serum Institute of India, and BioManguinhos in Rio de Janeiro was recently formalized. The partnership aims to produce approximately 30 million doses of a pentavalent vaccine against diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (which causes meningitis and other diseases).

Butantan delivered a proposal to provide 100 million doses at $1.50 each, which is scheduled for delivery in 2014, and this proposal is currently awaiting approval.

The partnership of the Bill and Melinda Gates Foundation with the Global Alliance for Vaccines and Immunization (GAVI) has already produced remarkable effects in its search for new suppliers. Last month, four pharmaceutical giants, GSK, Merck, Johnson & Johnson and Sanofi-Aventis, agreed to sell GAVI vaccines against diarrhea and rotavirus at cost. This represents a 70% reduction in the retail price of the vaccine.

Furthermore, two companies in India, the Serum Institute and Panacea Biotec, committed to providing the pentavalent vaccine at just $1.75 per dose. n PESQUISA FAPESP  41

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_INTELLIGENT PACKAGING

Color in fungi Sensitive film warns consumers about food deterioration Evanildo da Silveira PUBLISHED IN MAY 2011

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PH + BASIC

BASIC PH

NEUTRAL PH

ACID PH

PHOTOS EDUARDO CESAR

T

he traditional manioc (also known as cassava), a native plant from the southeast of the Amazon Region and the staple food of Brazil’s indigenous people, had been used as food long before the arrival of the Portuguese explorers.

Cassava now has new and advanced technological functions. Biodegradable plastic films made from the starch of this vegetable can be used to produce active packaging, capable of preventing the growth of fungi, or intelligent packaging, which changes color when the food product begins to spoil. This polymer is also being tested in heart surgery to coat venous implants and provide them with higher resistance during the initial phase or to release drugs.

The studies that resulted in the plastic films made from cassava, a polysaccharide whose main function is storing the energy produced by photosynthesis, began in 2004 at the University of São Paulo (USP). The films, developed by the research group coordinated by Professor Carmen Cecília Tadini from the Food Engineering Laboratory of the Chemical Engineering Department of USP’s Polytechnic School, share a common element, which is the addition of glycerol during the composition of the film. Glycerol is a plasticizing substance, commercially referred

to as glycerin. A low-cost compound, glycerol is a by-product of biodiesel.

This research group has conducted studies on three types of plastic films, each one characterized by the substances in their compositions.

Two of the films contain clay nanoparticles to make them more resistant. In the case of the antimicrobial film, the substances include clove and cinnamon oils, which provide protection from microorganisms. Laboratory tests with the polymer containing these oils revealed that the polymer prevents the growth of fungi. “Nowadays, anti-fungi substances are applied to the packaged product for protection,” says Carmen.

“The assays we conducted on the films that we developed showed that this protection lasts for up to seven days.”

One of the challenges that the researchers had to address to produce the film was to establish the specific doses of the clove and cinnamon oils.

If they were too high, the characteristic scent of these spices could seep into the packaged foods; if too low, the spices would lack the necessary efficacy to prevent microbial growth. The challenge of solving this problem was handed over to doctoral student Ana Cristina de Souza, who had been an intern at the High Pressure and Supercritical Technology Laboratory at the UniverPESQUISA FAPESP  43

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a vein begins to act like an artery is the objective of the line of research being developed by Krieger at InCor. “We want to know which genes and proteins are involved in this process,” he explains.

O

The pink film contains grape extract in its composition, whereas the transparent film contains cinnamon extract

sity of Coimbra, in Portugal. While an intern in this laboratory, Ana Cristina learned how to employ carbon gas using the supercritical state technique to incorporate the said oils into the polymers. She explains that the supercritical state is achieved when the temperature and the pressure of a substance are above its critical point, which occurs when a specific pressure is achieved and the liquid-vapor balance no longer exists.

A substance in this state has many applications in chemical separation and extraction processes.

The other plastic is also made from cassava starch, glycerin, and clay nanoparticles. However, unlike the first plastic, it has a fourth compound, anthocyanin, a natural component of purple or purplish fruit, such as grapes, açaí palm, jaboticabas (Brazilian grapes) and blackberries.

“Anthocyanins have the ability to change their color as their pH changes, which is the characteristic that we take advantage of in our work,” Carmen explains. “As changes in the pH are one of the first signs that a food product is beginning to deteriorate, we use this component to produce a film for intelligent packaging. It changes color when the food inside the packaging starts to spoil.

A palette of colors on the packaging can

tell the consumer whether the product is still good or not.”

The third polymer is being tested together with the team headed by Professor José Eduardo Krieger, director of the Genetics and Molecular Cardiology Department of the Heart Institute (InCor) of the School of Medicine of USP. This plastic is employed to improve the efficiency of the vein grafts used in coronary artery bypass graft surgery.

In this case, the film does not contain clay nanoparticles because it is meant to be absorbed by the patient’s body. In addition to cassava starch and glycerol, the film contains a substance called carboxymethyl cellulose (CMC), a polysaccharide extracted from cellulose that improves the mechanical properties of plastic.

NATURAL RESISTANCE

In coronary bypass implants, when the saphenous vein is removed from the leg and is placed inside the heart to function as an artery, the demand for resistance is higher compared with that of the vein’s natural function. Krieger explains that the speed of the flow is slower and that the pressure of the blood running in the veins is lower than in arteries, which is why the walls of veins are thinner than those of arteries. When a vein such as the saphenous vein is implanted in the heart, its function undergoes an abrupt change, and the vein has to adapt quickly to its new role. Understanding how this process works and what happens when

nce the process is understood, one can conceptualize new interventions to improve performance and to enable the coronary bypass to last longer. Krieger explains that 50% of coronary bypasses become nonfunctional after 10 years, as if “the warranty had expired in one half of all the cases.” The work being conducted by the team seeks to find an alternative to increase this “warranty.” To this end, the film developed by Carmen and her team is being tested for two functions. In the first, it is used to envelop (i.e., to coat) the coronary bypass externally, giving it more resistance and support during the initial stages after the surgery. Then, the vein that is now functioning as an artery acquires its own support. Therefore, the film loses its function, and its capacity for being absorbed by the body becomes an advantage.

The second function entails using the film as a platform to release drugs or other substances. “If we discover the genes or proteins involved in this process, which is different in each patient, we will be able to interfere in the process using therapeutic means,” says Krieger. “Thus, if a gene is more active than it should be, we can switch it off with drugs, for example.” For the film developed by Carmen to be able to perform this function, it has to be infused with drugs, just like other plastics are infused with anti-microbial or color-changing substances. For the time being, the tests conducted in Krieger’s lab are in vitro

THE PROJEC T Active biodegradable packaging based on cassava starch and natural edible additives: preparation, characterization and evaluation - no. 2005/51038-1 TYPE Regular Research Grant COORDINATOR Carmen Cecilia Tadini - USP INVESTMENT R$ 85,401.19 and US$ 58,250.00 (FAPESP)

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The films developed at USP are infused with various substance types according to the function they are to perform

tests using vascular segments and cells and in vivo tests on experimental models using rats. The next step will be to conduct tests on rabbits and pigs.

The project for the development of the film to envelop the heart veins is more recent. It started in 2009 as a doctoral project conducted by Helena Aguiar with funding from the National Council for Scientific and Technological Development (CNPq) and with the participation of a group of researchers from USP’s Chemical Institute in São Carlos, headed

by Professor Douglas Franco. The most advanced project in this respect is the development of a plastic with anti-microbial properties, a project initiated in 2004. “We are already at the point of making production feasible on an industrial scale,” says Carmen. This project was funded by FAPESP. The group received grants from the CNPq and the Coordinating Office for the Improvement of Higher Education Personnel (Capes).

HOMOGENEOUS AND BIODEGRADABLE

The evolution related to the integration of clay nanoparticles includes the work of doctoral student Otilia de Carvalho, who attended an internship program at France’s University of Strasbourg, specifically at the Engineering and Polymers and High Technology Laboratory (the acronym in French is Lipht). “My main objective during the internship was to prepare a film from starch and a nanocompound with clay, plasticized with glycerol,” she says. “As there is low

Intelligent packaging for grapes shows if they start spoiling

compatibility between starch and clay, I tested two modifications and obtained a more homogeneous material.”

A research study presented in April

by Germany’s Fraunhofer Institute also describes the use of films that change color when foods such as meat and fish have deteriorated. A study conducted by Professor Anna Hezinger used chemical sensors on plastic packaging. These sensors respond to amines, molecules found in deteriorating meats, and they change the color of the film that envelops the product. Anna’s research studies were funded by the German Ministry of Education and Research. Anna is currently looking for colleagues with whom to partner to produce the chemical sensors for food packaging.

The general field of biodegradable plastics is being developed around the world. Many types of such films are being produced in countries such as Japan, the United States, Holland, and Brazil. These films are produced from various sources, such as cassava, corn, potatoes, soybeans and cellulose. In Brazil, a biodegradable plastic made from sugar cane is being produced on a pilot scale. This biodegradable plastic’s properties are similar to those of propylene. This product, called Biocycle, was developed through a partnership between the Institute of Technological Re-

search (IPT) and the Copersucar Technology Center (CTC) in the early 2000s.

“Nowadays, the production technology is consolidated,” says general manager Eduardo Brondi, of the PHB company that produces this bioplastic. “The company’s total production is geared towards development and applications testing in conjunction with a number of partners around the world.” These applications include automotive parts, toys, drinking glasses and cutlery.

According to a study conducted by European Bioplastics, a trade association established in 2006, whose members include manufacturers, processors and users of bioplastics, biodegradable polymers and by-products, the latest available data (from 2007) show that the global production capacity of bioplastics corresponds to approximately 0.3% of the world’s plastics production, which is derived mostly from petrochemical sources. The forecast is that the production of bioplastics will correspond to 2.33 million tons in 2013 and 3.45 million tons in 2020. n

Scientific articles 1. KECHICHIAN, V.; DITCHFIELD, C.; VEIGASANTOS, P.; TADINI, C.C. Natural antimicrobial ingredients incorporated in biodegradable films based on cassava starch. LWT - Food Science and Technology. v. 43, p. 1.088-94. 2010.

2. VEIGA-SANTOS, P.; DITCHFIELD, C.; TADINI, C. C. Development and evaluation of a novel pH indicator biodegradable film based on cassava starch. Journal of Applied Polymer Science. v. 120, p. 1.069-79. 2011.

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_ENERGY

Alternative vinasse Production waste from ethanol may be used to produce biodiesel Marcos de Oliveira PUBLISHED IN AUGUST 2011

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FOTOS EDUARDO CESAR

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ombining microalgae and vinasse to produce biodiesel is the challenge that has been undertaken by the São Paulo enterprise Algae Biotecnologia.

Although companies in the United States have been successful in producing biodiesel from algae, the use of vinasse by this company is a new feature. The waste produced in the manufacture of ethanol is characterized not only by the highly noxious smell it emits but also its richness in mineral salts, mainly potassium, and its high levels of acidic organic material. Also called dunder, in the mid-1970s, vinasse became the villain of Proálcool, the government program that introduced ethanol as a fuel. Thrown into rivers and lakes as an effluent, this byproduct killed fish and polluted water and even reached the water table in some locations. After 1978, specific rules and legislation at the federal and state levels, prepared mainly by the Companhia de Tecnologia de Saneamento Ambiental (Cetesb) [Environmental Sanitation Technology Company] of the State of São Paulo, forced producers to develop an environmentally sound and commercially appealing use of the waste. The solution that was developed was to use vinasse to fertilize sugar cane plantations. Since then, vinasse has been sprayed onto plantations using irrigation piping, in a process called ‘fertirrigation’, or taken by truck to be put directly onto the crops. Although this process is fairly common in the sugar and alcohol industry, the volume of vinasse has been growing exceptionally quickly. For each liter of ethanol that is made, at least 10 liters of vinasse are produced. In 2010, 25 billion liters of ethanol were produced and consequently yielded more than 250 billion liters of vinasse from the distillation of the ‘wine’ obtained from the cane juice fermentation process. The large volume indicates that alternative uses besides fertilizer should be identified. However, to produce more profitable ethanol on some large properties that incur

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PHOTO EDUARDO CESAR

in favor of the microalgae is the fact that the CO2 produced by the distilleries during fermentation, which is absorbed by the sugar cane plantation itself, can be used during the production of biomass because the microalgae require CO2 to multiply. Any surplus protein produced in the process can be used as feed for fish farming, providing an additional benefit for the producers. To produce biodiesel, any type of oil, including oil from the microalgae, goes through transesterification, a chemical reaction between one type of alcohol – methanol or ethanol – and a lipid, which results in biodiesel.

RIGHT CHOICE

Experimental cultivation of algae at the biotechnology company

large expenses transporting the vinasse, a new process, developed by Fermentec from Piracicaba, in upstate São Paulo, has emerged to reduce the amount of waste by increasing the level of alcohol in the fermentation phase. “With this increase, it’s possible to cut vinasse production by half”, says agronomist Henrique Amorim, a Fermentec partner and retired professor from the Higher School of Agriculture Luiz de Queiroz (Esalq) at the University of São Paulo (USP).

However, although the volume of vinasse is reduced in this new process, at least 160 billion liters will be left over every year. This large excess represents a raw material that can be used to produce biodiesel from microalgae, a process that has been proven to be effective in Algae’s laboratories. “We’ve already had great results, and the challenge now is to scale up oil production in pilot plants until 2012 and then start testing in a distillery in 2013 and 2014,” says Sergio Goldemberg, the company’s technical manager.

The oil is extracted from the biomass that is formed by the multiplying microalgae cultivated in the vinasse. The microalgae consume the nutrients from the liquid and grow. Some species double their population in just one day.

To extract the oil, a centrifugation system is needed to separate the lipids (fats) from the biomass. The material then goes to a drier, and the oil is ex-

tracted using mechanical or chemical techniques. The level of lipids from the microalgae biomass reaches 30%, compared with 18% from soybeans or 40% from jatropha. Microalgae also have another advantage. Their productivity can reach 40,000 kg of oil per hectare (kg/ha), while the productivity of soybeans reaches 3,000 kg/ha and that of jatropha reaches 3,500 mil kg/ha. Also

Goldemberg explains that the researchers involved in the project are now trying to develop studies and solutions to improve the entire system’s effectiveness. The search begins with the choice of microalgae or cyanobacteria, organisms that are similar to algae. “We’re researching a lot of species, mainly those that live in fresh water,” says Goldemberg. “Afterwards, we select some to find out which ones adapt best to the vinasse and produce microbial biomass with a high lipid content,” says Professor Reinaldo Bastos, from the Center of Agrarian Sciences in Araras, at the Federal University of São Carlos (UFSCar), an Algae partner in the research, along

Path to biodiesel Vinasse produced in the distillery is transformed into biomass by algae

VINASSE

ALGAE

BIOMASS

OIL

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with a group led by Professor Eduardo Jacob-Lopes, from the Federal University of Santa Maria, in Rio Grande do Sul. “We already have some 20 species, many collected from the environment, that are being tested in cultures with vinasse,” says Bastos.

Vinasse works as a culture for growing and multiplying microalgae. In experiments in other countries, particularly in the United States, companies that grow algae must add mineral salts and nutrients to the water during the production process. “We have advantages relative to them because we have really economic waste for production,” says Goldemberg.

In the United States, various companies use algae to make biofuels, including aviation biokerosene, although still not on a commercial scale. Examples include: Solazyme, which has investments from the large oil and energy corporation, Chevron; Algenol, which has partnerships with Dow; and Sapphire, which has an investment from Cascade, a company belonging to Bill Gates, Microsoft, and the Rockefeller Foundation. All three companies also receive funding from the United States Department of Energy. Initial studies in the use of algae to produce biofuels took place during the 1980s at the National Renewable Energy Laboratory (NREL) in the United States.

“But at the time, the energy problem and excess CO2 were not important,” says Goldemberg, who is an agronomist and has already worked with vinasse in ethanol distilleries, before establishing Algae. The wave of projects with government support, mainly in companies in the United States, began in the 2000s.

THE PROJEC T Selection of tolerant yeasts in fermentation processes with a high alcoholic strength to reduce vinasse and save energy – nº 09/52427-2 TYPE Technological Innovation in Small Businesses (Pipe) COORDINATOR Henrique Amorim – Fermentec INVESTMENT R$ 202,923.42 and US$ 135,310.28 (FAPESP)

“We verify which genes are related to the capacity of the organism to remain viable with a high alcohol content,” says Márcio Silva Filho, from USP

“We could have repeated what is done abroad, although there are still no products for sale, but we decided to have our own ideas and follow a new path with vinasse,” says Goldemberg, who is the son of José Goldemberg, a professor from the University of São Paulo (USP), former Education Minister and former Secretary of the Environment of the State of São Paulo. Algae receives R$ 2.5 million in funding for its research from the Studies and Projects Funding Agency (Finep), in an Economic Grant Program project, and has received a second grant for R$ 3.2 million over three years from the National Economic and Social Development Bank (BNDES), from its Technology Fund (Funtec), to be used with UFSCar, which also received R$ 400,000 from the company. Algae was set up in 2007, and since 2009, the company has been a joint venture with the Ecogeo Group, a conglomerate that operates in the areas of consultancy and environmental engineering and had revenue of R$ 50 million in 2010.

ALCOHOLIC YEAST

Biodiesel production from vinasse, in addition to leading to new benefits in the end product, may also eliminate additional expenses for the ethanol producers from pumping or carrying this waste transformed into fertilizer over long distances. Fermentec’s proposal to cut vinasse production by half may

lead to savings for distillery owners.

“Taking vinasse up to 35 km away from where it is produced pays for the fertilizer, mainly potassium chloride, which is mostly imported. More than this distance, it produces a loss,” says Amorim from Fermentec. The company’s goal is to increase the level of alcohol to 16% from the average 8% by the end of the fermentation process, the phase at which Saccharomyces cerevisiae yeast transforms sugar into alcohol. Afterwards, in the distillation phase, the alcohol is separated from the vinasse.

The company, which has revenues of R$ 10 million per year, has been selecting strains of Saccharomyces since 1990 and uses almost 80% of the yeasts used in Brazil’s distilleries. For the last six years, the company has been studying the temperature of the fermentation process, particularly as it relates to the selection of these microorganisms. To do so, it has brought together researchers, such as professors Luiz Carlos Basso and Márcio de Castro Silva Filho, from Esalq, Pio Colepicolo, from the Institute of Chemistry at USP, and Boris Stambuck, from the Federal University of Santa Catarina. Coordinated by Silva Filho and with funding from the National Council for Scientific and Technological Development (CNPq), a study was performed to understand how yeasts can adapt to the high alcohol levels during fermentation. By analyzing 6,000 genes of these yeasts, it was possible to identify the genes that are related to the organism’s capacity to remain viable at high alcoholic strengths. “We’ve already identified a series of genes, and in the long-run we’ll be able to introduce or modulate the expression of these genes in yeast strains,” says Silva Filho. To select new yeasts that operate at high alcoholic strength, in 2009, Fermentec requested a project from FAPESP’s Technological Innovation in Small Businesses (Pipe) Program.

“We want to find better yeasts than the current ones that can function at an alcoholic strength of 18% for use in the new fermentation process,” says Amorim.

A study was successfully performed at the Pedra Distillery in Serrana, São Paulo. With fermentation at 16%, a saving on vinasse of R$ 7 million per crop in this distillery was estimated. “We’re now ready to market the process,” says Amorim. n PESQUISA FAPESP  49

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 HUMANITIES _ DIGITAL LIBRARY

A mine of maps Cartographic material reveals Portuguese colonial fantasies Márcio Ferrari PUBLISHED IN MAY 2011

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DISSEMINATION

P View of Brazil that reveals exploitation

recious cartographic material has been given unrestricted visibility because of the work of a group of researchers from the University of São Paulo (USP). This group has organized the Digital Library of Historical Cartography with free online access at http://www.cartografiahistorica.usp.br. The website, the result of a concept developed by the Laboratory of Historical Cartography Studies (Lech), houses a collection of rare maps printed between the sixteenth and nineteenth centuries.

With the plurality and speed of the Internet, the site makes cross-referencing, comparisons and interpretative keys possible. After all, a single map alone is not much use, says Iris Kantor, a professor at the History Department of the USP and one of the project’s coordinators. The collection offers considerably more than geographical information; it also discloses how fantasies were created over time, as revealed by images of Brazil created abroad. The project was part of a

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Previous page, World Map according to navigations, showing the Southern Continent, part of Geography by Claudius Ptolemaeus, edited between 1597 and 1598.

On the side, Atlas sive Cosmographicae Meditationes de Fabrica mvndi et fabricati figvra, produced in Amsterdam in 1606, showing the American continent in the two hemispheres, but without the connection with Asia.

major theme-related project called Dimensões do Império português [Dimensions of the Portuguese Empire], coordinated by Professor Laura de Mello e Souza with FAPESP support.

T

he collection was developed from two main sources. The first was a set of notes written over a period of 60 years by Admiral Max Justo Lopes, a leading expert on cartography in Brazil. The second source was the private collection of the Banco Santos, a bank that was under Brazil’s guardianship during the intervention process in 2005 and that involved the assets of former banker Edemar Cid Ferreira. A court decision transferred custody of the former banker’s collection to the Institute of Brazilian Studies (IEB) at the USP. This initiative was praiseworthy, as this collection, according to Iris Kantor, “was stored in very insecure conditions in a warehouse, with no concern about suitable storage.”

Approximately 300 maps were retrieved. It is widely known that the original private collection was significantly larger, but the locations of the remaining maps are unknown.

The first step entailed recovering and restoring the retrieved maps. These maps arrived at the USP “totally naked,” and the initial work included such steps as identifying and dating the maps and establishing their authors. During 2007 and 2008, the Digital Reproduction Laboratory of the IEB researched, acquired, and

used the appropriate technology to reproduce the map collection in high resolution. Various attempts were made to achieve the desired accuracy of the colors and lines. The Information Technology Center, located at the USP’s campus in São Carlos (Cisc/USP), then developed specific software that enabled the building of a database capable of interacting with the USP library’s general catalog (Dedalus) and of collecting and transferring data from other Internet databases. An inspirational source for the researchers was British collector and graphic artist David Rumsey’s website, which houses 17 thousand maps (http://www.davidrumsey.com).

Another inspiration was the pioneering Virtual Historical Cartography Library of the National Library, a collection of 22 thousand digitized documents (http://bndigital.bn.br/cartografia).

In the future, the USP’s cartography collection will become part of the Digital Library of Historical Cartography. Priority has been granted to the maps of the Banco Santos collection because they do not belong to the university, and at any time, the court may request that they be returned to erase the bank’s debts.

The Digital Library has “cartographic and bibliographic information, biographies, data of a technical and publishing nature, and explanatory entries that contextualize the production, circulation and appropriation process of cartographic images.” “There are no naive maps,” says PESQUISA FAPESP  89

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Carte tres Curiese, from 1719

Dutch map based on Jean de Léry Carte tres Curiese, from 1719

Iris Kantor, indicating that this information must be obtained to understand what lies beneath the surface of the maps’ geographical contours and toponymy. “Historians assume that all maps lie; manipulation is important information in any cartographic element.”

G

eopolitical and commercial interests of a given era and the interests of those who produced or ordered the maps were part of this manipulation. In the early 2000s, Historian Paulo Miceli from the State University of Campinas (Unicamp) was invited by Banco Santos to provide consulting services concerning how to organize the collection. He states that the first cartographic record of what is now known as Brazil was a map prepared by Spanish navigator Juan de la Cosa (1460-1510). The map is dated 1506 and shows “the demarcation line of the Treaty of Tordesillas, a very accurate portrayal of Africa, and, to the left, a tiny triangle depicting South America.” “Brazil surfaced from out of a kind of fog of documents, conditioned, among other things, by the rigor of the Portuguese crown over the work of the cartographers, who were subject to the death penalty.” Brazil’s gradual “apparition” in the empire’s geopolitical scheme is the topic of Miceli’s post-doctoral thesis, appropriately titled O desenho do Brasil no mapa do mundo and scheduled for publication this year by the Unicamp publishing press. The title refers to Theatrum orbis terrarum (Theater of the World), written by the Flemish geographer Abraham Ortelius (15271598) and considered to be the first modern atlas.

Contrary to widespread belief, the main and practical function of these ancient maps was not to guide explorers and navigators. Until the nineteenth century, explorers and navigators used written scripts, or “nautical charts,” written on parchment without concern for beauty or ambiguity. These nautical charts, perforated by compasses and other instruments, became wrappers of document files in cartographic collections,” according to Miceli. “Maps were objects of ostentation and prestige, with ornamental and fruition value for noblemen and scholars,” says Iris Kantor. “One of the treasures of the Vatican is its cartography collection.” The nautical charts were handwritten, while maps were printed, which granted maps the status of special documents. The original metal plates, with alterations performed over a period of many years, lasted up to 200 years and were always in the hands of “families” of cartographers, publishers, and bookstore owners. Sometimes, these families were related by blood and were thus the heirs of said plates.

Highly specialized studios also owned maps.

Experienced cartographers did not travel but collected their information from “navigators who were often illiterate,” according to Miceli.

An example of the prestige attributed to cartography is the Atlas maior, produced by the Dutchman Willem Blaue (1571-1638); decorated with gold ink, it was considered the most expensive book during the Renaissance.

A criterion of the Historical Cartography Digital Library is the search for “schools” of car-

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tographers, including the French, Flemish, and Venetian schools. The basic knowledge of cartography originated from Portuguese navigators and cosmographers. Iris Kantor believes that the schools intermingle, so she plans to replace the word “school” with “style.” The team also plans to reconstruct the genealogy of map production for the corresponding historical period.

The study of these documents includes identifying documents with voluntary errors as a counter-information effort, which Miceli refers to as “patriotic adulteration.” Examples of the latter are maps that incorrectly identify the location of natural resources, such as rivers, to benefit the Portuguese or the Spanish under the division of the Treaty of Tordesillas.

E

vidence of cartography’s function as propaganda can be found on the map Brazil, which was created by the Venetian school in 1565 and illustrates the beginning of this article. Geographic accuracy is not a key feature of this map.

“The toponymy is not outstanding, even though the entire coastline had already been named at that time,” says Iris Kantor. “This map was made for the laymen, perhaps for traders, as indicated by the boats with the crests of the French and Portuguese crowns. The map depicts the brazilwood trade, with no identification of political sovereignty. Brazil is shown as a region of free access. The portrayal of the indigenous people and their contact with the foreigners transmits cordiality and reciprocity.”

“The fact is that maps represent us,” says the USP professor. “For example, the study of post-independence Brazilian cartography calls “Maps were our attention to a view of national objects of identity based on a romantic, liberal and naturalist geographical culture, ostentation which represents the country as a geographical continuum stretching with ornamental from the Amazon Region to the La Plata River. In those times, the idea of and enjoyment a national people was not that homovalue for geneous. It is no coincidence that the men who declared the independence noblemen and and designed the legal framework of our country were linked to the natuscholars,” says ral sciences, to cartography, etc. Geography was crucial in the creation Iris Kantor. of the national identity.”

A different example of the use of digital resources for the study of maps is being pursued at Unicamp and is derived from the project Trabalhadores no Brasil: identidades, direitos e política, coordinated by Professor Silvia Hunold Lara with FAPESP support. This study, Mapas temáticos de Santana e Bexiga, focuses on the daily life of urban workers from 1870 to 1930 (http:// www.unicamp.br/cecult/mapastematicos). According to Professor Lara, one can reconstruct the daily lives of urban dwellers “without disassociating them from their mode of work and their claims for their rights.” n

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WILSON PEDROSA / AGÊNCIA ESTADO / AE

‘

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_ DEMOGRAPHY

The mobile metropolis The profile of migration from Sao Paulo is underscored by comings and goings and by internationalization Márcio Ferrari PUBLISHED IN JUNE 2011

I

t is a reasonably well-known fact that the metropolitan region of São Paulo is no longer a center of attraction for immigrants from abroad or from other parts of the country, as was the case during most of the 20th century. In the first decade of the 21st century, there was a significant negative balance between the number of people who came to the metropolitan region and the number of people who left; specifically, one hundred thousand newcomers came to the city, while eight hundred thousand people left for other towns in the state. A little-known fact is the new migration profile that these numbers obscure to some extent. The flow of newcomers is no longer explained by the dynamics of industry and by the employment opportunities that previously attracted newcomers. What is new is the phenomenon of reversibility, i.e., the length of time that people stay tends to be shorter, and the movement is characterized by comings and goings as well as definitive departures.

The task of describing these new demographic configurations and consequences in detail has been undertaken by the Observatory of Migration in the Center of Population Studies (Nepo) at the State University of Campinas (Unicamp), funded by FAPESP and coordinated by Rosana Baeninger, Professor in the Department of Sociology at the Institute of Philosophy and Human Sciences, also at Unicamp. The research project has an extensive chronological scope, extending from 1880 to 2010, and an interdisciplinary perspective, which means that new themes of

study (currently totaling 16) will develop as the research project moves forward.

“Our objective is to allow each researcher to reveal processes that the bigger numbers do not show,” says Rosana. “Our challenge is to look for new data sources—the census does not provide information on domestic migration, for example.”

The end products are expected to be a themed atlas and a database. In addition to new sources, the researchers are also utilizing national and foreign bibliographies to help them understand the overall situation. One of the starting points of the project is that “the understanding of migration processes only becomes meaningful if we consider the spatial and territorial aspects.”

The researchers have concluded that in the 21st century, as had already been envisioned since the 1990s, the metropolitan region of São Paulo has been incorporated into the route of international migration. “The city’s characteristics are now much more closely focused on the international market, as part of a chain of global cities,” says Rosana. Within this broad scenario, economic processes multiply in terms of space while time becomes globalized. This is what British sociologist Anthony Giddens refers to as “disembedding mechanisms.”

São Paulo is now a destination of both highly qualified and unskilled and undocumented workers, both of whom are already part of flexible production mechanisms and fit into the capital city’s mobility. The highly qualified professionals are typically Argentines and Chileans who come to work in the city in upper-level management posiPESQUISA FAPESP  57

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of most of the garment industries that employ Latin American labor.

This activity is international even at the beginning of the production chain because the textiles come from South Korea. In the last few years, this sector has been implementing elaborate systems that allow the Bolivians to work seasonally, according to specific demands related to fashion launches (in summer and winter), which reinforces the general coming and going pattern of the migrants. Many Bolivian laborers come from urban regions and are professionally trained.

Working seasonally has also intensified among domestic migrants, especially those coming from the northeast region of Brazil. For example, a fairly large contingent of people earn money as street vendors, selling lottery tickets.

They work for a couple of months and then go back to their home states during the high season to work in the area of tourism. Another reason for the short stays of these migrants in the metropolitan region is the fact that the cost In La Paz, a Bolivian walks by a sign offering employment, 2007 ANTÔNIO GAUDÉRIO / FOLHAPRESS

tions and have a two-year work permit that can be extended. According to the Ministry of Labor, the number of these professionals is currently estimated at twenty thousand. The unskilled workers are predominantly from Bolivia, who come to Brazil because of problems in their native country; this contingency is not accounted for in official statistics.

It is estimated by private entities, such as the Pastoral do Imigrante church organization, that unskilled laborers from Bolivia total approximately two hundred thousand. Thus, says the sociologist, “100 years after the European migration, São Paulo has once again become the port of entry for international migration, this time without any government subsidies.”

As has been widely known for thirty years, most of the Bolivian immigrants are employed in the garment industry, which is controlled primarily by Asian immigrants or their descendants. Bolivian immigration is already in its second generation and has had a significant urban impact, such as through the well-known changes in the demographic profile of the Bom Retiro neighborhood, which had traditionally been predominantly Jewish and today is the center

of living in São Paulo has risen significantly in recent years. In the past, the neighborhoods in the city’s outskirts had the potential to absorb new inhabitants.

However, according to Rosana, “the outskirts are no longer separated from the city; these regions have become denser and are being re-shaped.” Departure is another characteristic of the migration profile of the 21st century in the metropolitan region of São Paulo. This is the region in Brazil that loses the highest number of people per year, especially due to domestic migration. In contrast, it is the region that receives the highest number of skilled workers.

NETWORKS

Social networks are an important element of the country’s social structure because they facilitate the movement of domestic and foreign migrants. Social networks are articulated groups that provide support to migrants who are in the metropolitan region temporarily. These groups are comprised mostly of the relatives of migrants. As a result of these networks, it is possible for migrants to leave their children in their home states while they work at seasonal jobs. Social networks operate at both ends of migration and are not a new phenomenon (some of these networks have existed for 60 years), but they have gained key importance in supporting the temporary nature of migrations between far-flung regions. These networks have resulted in the creation of organized and dynamic transportation systems, such as the buses that leave from the region of São Miguel Paulista, on São Paulo’s East Side.

The State of Goias is currently the main destination for migration in Brazil.

“It is the biggest,” says Rosana. Agribusiness has even attracted qualified labor from the State of São Paulo. In addition, grain-producing regions, such as the city of Rio Verde, offer public administration courses that attract people from outside the state.

The expansion of agribusiness in the State of São Paulo also continues to attract migrants from other regions, from the capital city, from neighboring towns, and, on a smaller scale, from abroad.

Agribusiness is joined in this respect by the growth niches in the economy involved in exporting, which various regions have managed to consolidate. Ex-

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DANILO VERPA / FOLHAPRESS

amples of this can be found in the region of Franca, which has a flourishing shoe manufacturing industry; Limeira, which has a leading jewelry industry; the furniture industry in the region of Votuporanga; and the hotel industry, supported by rodeos in Barretos. The road network is efficient enough to allow many professionals to live in one town and commute to another town for work, which results in the increase in “population density in small towns previously characterized by a shrinking population.”

Is this a return to rural regions? “No,” says Rosana. “Even though some jobs are performed in rural areas, people live in towns or in what we refer to as nonregistered urban extension zones, that is, areas with urban characteristics without being officially considered as such.” This standardization has led to an increase in short-distance migration and regional commuting to the extent that a theoretical question is being asked: should people who commute such short distances be considered migrants? The professor says that, according to the related criterion in effect in the 1960s, a rural migrant’s adaptation to the modern urban environment took about ten years. In the State of São Paulo today, urban and consumption patterns are virtually identical in all regions.

IMPACT

The way in which research studies are conducted at the Observatory of Migration, which focuses on interdisciplinary interaction and cooperation with

South Koreans in front of a second-hand furniture store in Bom Retiro

other Brazilian and foreign academic institutions, has resulted in studies on phenomena that do not entail very high numbers yet are very important from the sociological and anthropological points of view. For example, the researchers plan to conduct a pioneering study on the social impact of the transfer of prison facilities to small towns in the State of São Paulo and on the resulting movement of groups.

A study currently underway sheds light on the migration of refugees in the metropolitan region in this century. A significant number of Colombians (and some Cubans), who left their native countries because of internal conflicts, have settled here. “Brazil has one of Latin America’s most lax rules for refugees, which has provoked this influx,” says Rosana. It is estimated that the city of São Paulo is currently home to 1,800 refugees. Among these are Colombians with families, many of whom have Brazilian spouses or children. In general, these refugees are professionally qualified but have difficulties in terms of blending in because they do not have valid diplomas.

For comparative purposes, most of the refugees in the city of Rio de Janeiro are single Africans who arrive in Brazil as students and then ask for refugee status.

According to Rosana, the influx of refugees and immigrants without identity

documents has created a situation that demands the development of social policies to protect their rights and to protect them from discrimination. Such social policies have not yet been implemented.

A particularly interesting study conducted by the Observatory of Migration was headed by sociologist Marta Maria do Amaral Azevedo, also of Unicamp.

The study focused on the existence of the indigenous Guarani people in São Paulo. At present, there are 20 Guarani communities in the eastern part of the state and four communities in the capital city. The migration process, which originated in what is now the State of Mato Grosso do Sul in Paraguay and in Argentina, started in the second half of the 19th century. However, this process is still under way, “often creating stalemates for public policies and for the land ownership issue.” Among other issues, the study seeks to quantify this population and elucidate its genealogy.

“Existing studies point to religious and economic reasons, such as the search for a land without evil, a place where it would be possible to live in the Guarani way, or according to the guarani reko, the way of life of this indigenous people,” says Marta. “Nowadays there are broad structured social networks based on family and religious ties. The communities engage in economic barter and practice the oguatá concept: walking, which can be a visit to a relative or a trip to consult a pajé (witch doctor), or even to go to a family reunion.” n PESQUISA FAPESP  59

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_ RANKING

Excellence in the humanities Brazilian courses distinguish themselves on the international scene Mรกrcio Ferrari PUBLISHED IN AUGUST 2011

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ILLUSTRATION BY BEL FALLEIROS

A

t the beginning of July, QS (Quacquarelli Symonds), which has evaluated and classified universities around the world every year since 2004, published the first global university rankings that rated the top institutions in each of various areas of knowledge (these rankings are available at www.topuniversities. com). Brazilian universities are relatively highly ranked, appearing among the top 200 institutions for various topics, particularly in the broad categories of the “social sciences” and the “arts and humanities.” For each field, the top 50 universities are listed in rank order; the institutions in the 51-100 range are then listed in alphabetical order, followed by an alphabetical listing of the universities in the 101-150 range and an alphabetical listing of the universities in the 151-200 range. Six Brazilian institutions appear in the list of the top 200 institutions for the human sciences as a whole: two state universities (USP and Unicamp), two federal universities (UFRJ and UFMG), the Getúlio Vargas Foundation (FGV) and the Pontifical Catholic University

of Rio (PUC-Rio). This list also includes two universities from other Latin American countries (Universidad Nacional Autônoma do México and PUC-Chile).

USP appears in the 51-100 group for philosophy and sociology and is in the 151-200 group for geography and international relations. Unicamp is included in the 101 – 150 group for philosophy and in the 151 – 200 group for statistics and operational research, whereas UFRJ has the converse rankings for these two fields of study. FGV and UFMG appear in the 151-200 group for international relations and philosophy, respectively.

For comparison, in the exact and biomedical sciences, only three Brazilian universities are ranked: USP (agronomy, 51-100; civil engineering, 151-200), Unicamp (electrical and electronic enPESQUISA FAPESP  61

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gineering, 151-200) and PUC-RJ (civil engineering, 151-200).

“The criteria that guide these rankings cannot be considered unique or infallible, but it would be absurd to ignore their usefulness and the visibility they afford,” states Modesto Florenzano, deputy dean of the School of Philosophy, Literature and Human Sciences (FFLCH) at USP, which houses three of the departments that were mentioned in the QS rankings (namely, philosophy, sociology and geography).

“The main purpose of these lists – and this is their economic basis – is to offer people who intend to enter these institutions a panorama of the universities.

That is why carrying out research by discipline is very useful,” explains Rogério Meneghini, a specialist in scientometrics, the study of the quantitative aspects of science and scientific production. “The rankings weren’t produced to give a broad view of the quality of the universities, but they ended up serving this purpose.”

QS, which is headquartered in the United Kingdom and has offices in various countries, prepares its rankings to be used as guides by students who wish to study outside their own cities or, in particular, their native countries. This objective is the reason that special attention is devoted in the rankings to the degree of

internationalization of the institutions that were evaluated. The recent rankings are based on three major criteria: academic reputation (professors are invited to evaluate courses and universities other than their own), reputation among employers (the quality of the professionals that graduate from each institution) and the number of citations of the academic publications from each institution.

QS considers its inclusion of the “employability” criterion to be the primary distinguishing factor of its rankings.

However, this criterion is criticized because it represents an index that is not necessarily related to the quality of universities’ intellectual production. “For our target audience, it would be disproportional if we were to place more emphasis on academic research than we already do,” says Ben Sowter, head of the information unit of QS. “Furthermore, the other rankings already provide this emphasis, in part because of the type of data internationally available and in part due to the history of how the rankings

Latin America in the QS university rankings: social sciences INSTITUTION

STATISTICS AND OPERATING RESEARCH

SOCIOLOGY

POLITICS AND INTERNATIONAL RELATIONS

LAW

ECONOMICS AND ECONOMETRICS

National Autonomous University of Mexico

—

44

—

—

151-200

University of São Paulo

—

51-100

151-200

—

—

Federal University of Rio de Janeiro

101-150

151-200

—

—

—

Pontifical Catholic University of Chile

151-200

—

—

51-100

—

Getúlio Vargas Foundation

—

—

151-200

—

—

State University of Campinas

151-200

—

—

—

—

Pontifical Catholic University of Rio de Janeiro

—

—

101-150

—

—

SOURCE QUACQUARELLI SYMONDS

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QS world university global rankings: philosophy INSTITUTIONUniversidade Harvard

COUNTRY

ACADEMIC

EMPLOYABILITY

CITATIONS POINTS

1

Harvard University

United States

99,6

96,3

50,3

94,3

2

University of Oxford

United Kingdom

100,0

95,4

41,0

93,6

3

University of Cambridge

United Kingdom

94,5

100,0

51,9

90,8

4

University of California at Berkeley

United States

88,4

65,4

73,3

84,6

5

Princeton University

United States

80,1

39,7

81,6

76,2

6

Australian National University

Australia

73,8

52,8

95,1

73,8

7

University of Toronto

Canada

77,1

60,6

36,1

71,4

8

Stanford University

United States

74,8

46,0

56,7

70,1

9

Yale University

United States

73,2

64,4

22,1

67,2

10

University of Chicago

United States

71,1

50,4

13,8

63,3

51-100

University of São Paulo

Brazil

26,8

5,9

5,0

–

101-150

State University of Campinas

Brazil

16,1

0,0

9,8

–

151-200

Federal University of Minas Gerais

Brazil

10,7

0,0

8,5

–

151-200

Federal University of Rio de Janeiro

Brazil

14,4

0,0

0,0

–

2

first appeared. The first international classification was created by the Chinese government [via the University of Shanghai] to highlight the performance of scientific research in their own universities in comparison with those in the West.”

The QS rankings are also not free from bias. A quick glance at the lists is sufficient to reveal the predominance of universities from English-speaking countries (not only the United States and the United Kingdom but also Canada and Australia). For instance, the philosophy rankings feature very few institutions from France and Germany, the countries that historically (and currently) have contributed most to this field of knowledge, and the universities from these nations that do appear are not particularly highly ranked. “How can the University of Frankfurt, which has Jürgen Habermas and Axel Honneth, be low on the list?” asks Ricardo Ribeiro Terra, a professor from the Department of Philosophy at FFLCH-USP and the coordinator of the human and social sciences department of FAPESP (which includes philosophy).

Terra also observes that although certain Brazilian universities are highly ranked with respect to various disciplines, such as sociology, the QS rankings consider very few of the articles in international publications that are produced

by Brazilian researchers in these highly

ranked subject areas. “This raises doubts as to the journals chosen and makes one suppose that they are limited to analytical philosophy of the type that predominates in the United States,” he says.

We started out being international, and we came from a strong humanist tradition, says Florenzano from FFLCH.

FUNDING

Unsurprisingly, the international parameter of the English language is impossible to ignore. “There is a noticeable interest from foreign students wishing to study in Brazil, largely because of the possibility of obtaining funding for research at a very early stage in their academic careers. Even the scholarship seems attractive, but most of them don’t come because Portuguese is seen as a barrier,” says Meneghini.

Because of this situation, the weight placed on internationalization in the QS assessments is considered to be appropriate, and there is general agreement among various Brazilian academics that there continues to be a dearth of foreign students in Brazilian universities.

“The main universities have always been meeting points for the best minds in the world,” says Sowter. “A large part of the drive for internationalization is conducted not only by institutions individually but also by government policies. Recently, universities have become centers for economic policy because governments have PESQUISA FAPESP  63

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realized that research and innovation play key roles in stimulating growth.”

However, it is not easy to use quantitative criteria of internationalization to assess the quality of educational offerings. “In the social sciences area, the majority of the studies refer to Brazilian issues, and these are naturally not published in foreign publications,” says Terra. “Criteria should be considered that also evaluate domestic impact.” At the same time, regional characteristics may be the basis for the high prestige of certain areas of Brazilian research.

“The highly complex territorial and social characteristics of Brazil demand the creation of a sophisticated theory,” says Antonio Carlos Robert de Moraes, a professor in the Department of Geography at FFLCH-USP and the coordinator of the human and social sciences area at FAPESP (which includes geography).

Observers of international rankings are unanimous in stating that the criteria for these recently created rankings continue to require improvement and refinement.

QS itself agrees with this, and its decision to create a ranking that categorized institutions by subject area represented an attempt to make these classifications more specific and useful.

“The most delicate question has to do with the possibility of producing criteria that are compatible with the different ways of producing knowledge in the various disciplines,” says Paula Montero, a professor from the Department of Anthropology at FFLCH-USP and the assistant coordinator of the Scientific Department at FAPESP. She believes that peer review (academic reputation) criteria are the most important: “When an area of knowledge is sufficiently developed and diversified, this type of external evaluation works very well.”

Despite its status as the most widely established criterion, the criterion of citations in academic publications is also the target of criticism. “I’ve never seen a

measure that tries to evaluate the quality of research,” says Meneghini. Furthermore, in the QS rankings, cumulative rather than per capita data are considered for this item; thus, huge universities, such as USP, have an inherent competitive advantage over smaller institutions with respect to this criterion.

MODESTY

The high ranking of the FFLCH-USP courses is not surprising. “Modesty aside, USP’s Department of Geography educates the rest of the country and sets the tone for the discipline in Latin America,” says Robert de Moraes. “Our presence abroad is very significant and we play host to a fair number of international meetings,” Terra continues. To a degree, this eminence stems from the origins of FFLCH, which was founded by foreign professors, particularly French academics, who immigrated to Brazil.

FFLACH subsequently formed the basis for the creation of USP in the 1930s.

“We began our existence in an international way, and we come from a strong humanist tradition,” says Florenzano.

“The social sciences in Brazil have always been of a relatively good standard

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for historical reasons,” says Paula Montero. “However, the decline in the quality of public schools, the growth of higher education, the lack of performance assessment in universities and the relative isolation of human sciences with regard to international debate were factors that acted against the expansion and consolidation of this quality.”

The effects of tradition are reflected even for recent educational initiatives that are not part of the FFLCH, such as the course offerings of the Institute of International Relations (IRI). “I’m going to be very sincere with you. I think that in this ranking, we hitched a ride from the Department of Political Science, which is a lot older and better known than the IRI, which was created in 2004 and only has two years of graduate studies,” says Maria Hermínia Brandão Tavares Almeida, the director of the institute. Obviously,

The best universities have always been meeting points for the best minds in the world, says Sowter from QS.

however, the quality of the IRI’s courses is reflected in its ranking.

For these reasons, the presence of institutions in the QS rankings and similar lists is both important and relative.

“Only universities that are not very consistent allow themselves to be directed by demands for this type of survey, but they can be an element to be taken into account in academic guidelines,” says Marcelo Ridenti, who graduated with a degree in sociology at USP and is both a professor at Unicamp and the coordinator of human and social sciences at FAPESP (which includes sociology).

“The assessment procedure has to start with the university itself, like the surveys that USP has undertaken periodically,” says Meneghini, who has participated in university assessment committees that involved contributions from foreign specialists. Florenzano agrees: “We mainly need to diagnose the quality of graduate courses, and this is the most important starting point.” n

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ART

Like a glove PUBLISHED IN NOVEMBER 2011

Glove Trotter, 1991 Steel mesh and balls of various sizes, colors and materials, 25 x 520 x 420 cm

The installation above, a steel mesh that involves balls of various colors and sizes, is one of the most attractive creations of the Brazilian artist Cildo Meireles, who named it Glove Trotter. Meireles’ work was one of the featured attractions of the 32nd Panorama of the Arts at São Paulo City’s Modern Art Museum (MAM). The artist now plans to take another installation, Abajour, to the Serralves Museum in Porto (Portugal) in 2013. Abajour, which was one of the highlights of the 29th São Paulo Biennial Art Show in 2010, will then travel from Porto to Madrid (Spain).

Cildo Meireles’ work was the subject of an article in the Art section of the November 2011 issue of Pesquisa FAPESP.

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