Special Issue July 2011

Special Issue July 2011

An ancestral picture of the Amerindians New archeological findings and genes retrace how the Americas were populated

Genetically modified mosquitoes to fight dengue 001_capa pesquisa _ingles_2011.indd 1

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YOUNG INVESTIGATORS AWARDS in São Paulo, BRAZIL The São Paulo Research Foundation (FAPESP) is one of the main research funding agencies in Brazil. With a budget of US$ 450 million, it supports more than 11,000 scholarships and 8,000 research awards. FAPESP’s Young Investigators Awards envision the creation of new research groups led by highly promising early-career scientists in any field of knowledge and from any country. Selected candidates receive competitive fellowships and sizable research funding. Candidates are encouraged to develop their projects with higher education and research institutions in the state of São Paulo, Brazil.

Research areas include biodiversity, bioenergy, climate change, neuroscience, cancer, materials science, optics and photonics, urban studies and violence. Proposals in other fields will also be considered. All proposals will be selected through a peer-review process.

For guidance and further information: yi@fapesp.br Additional information: http://www.fapesp.br/en/materia/4479

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WWW.REVISTAPESQUISA.FAPESP.BR

JANuary / APRIL 2011

sections

5 Letter from the editor 50 Art

Interview 6 Former Minister of

cover 12 A new study stating

Science and Technology JosĂŠ Israel Vargas, an advocate of nuclear energy and a critic of corporatism, remembers his career as a scientist and policy maker

that the first Americans looked like Africans reignites the controversy concerning the arrival of man on the continent

scientific and technological policy 16 MEASURING SCIENCE

20 Integration

A study shows that French and German researchers lose influence when they do not publish in English

Researchers interact with Nobel laureates and plan experiments in biology and physics

science 22 Neurophysiology

26 Physiology

28 Geophysics

32 Physics

Corticoids activate inflammation mechanisms in some areas of the brain

Endothelial cells store information about their state when extracted from the donor

Accurate measurements reveal deformities in the shape of planet Earth

A new strategy allows the evaluation of the magnetic interaction between nanoparticles

technology 34 Biotechnology

Transgenic mosquitoes are set free in Bahia to fight dengue fever

38 Biochemistry

An energy alternative for producing electric power

humanities 42 Cinema

How the seventh art depicts mental disorders

46 The history of science

Brazilian researchers find philosopher’s stone recipe at the Royal Society

Cover MAYAN MAIZE GOD STATUE photo PHILIPPE PSAILA / SCIENCE PHOTO LIBRARY

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letter from the editor

São Paulo Research Foundation

Celso Lafer

President

eduardo moacyr krieger

vice-President

The peopling of the Americas

Board of Trustees Celso Lafer, eduardo moacyr krieger, Horácio Lafer Piva, herman jacobus cornelis voorwald, Maria josé soares mendes giannini, josé de souza martins, JOSÉ TADEU JORGE, Luiz gonzaga belluzzo, sedi hirano, Suely Vilela Sampaio, Vahan Agopyan, Yoshiaki Nakano

Executive Board Ricardo Renzo Brentani

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 Arana Varela, José Eduardo Krieger, Luiz Davidovich, Marcelo Knobel, Marcelo Leite, Maria Hermínia Tavares de Almeida, Mariza Corrêa, Maurício Tuffani, Monica Teixeira

Scientific Committee LUIZ HENRIQUE LOPES DOS SANTOS (president), cylon gonçalves da silva, FRANCISCO ANTôNIO BEZERRA COUTINHO, joão furtado, Joaquim J. de Camargo Engler, josé roberto parra, luís augusto barbosa cortez, luis fernandeZ lopez, marie-anne van sluys, mário josé abdalla saad, PAULA MONTERO, Ricardo Renzo Brentani, sérgio 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), maria guimarães (online), Ricardo Zorzetto (Science) Special Editors Carlos Fioravanti, Marcos Pivetta Editorial Assistants Dinorah Ereno, Isis Nóbile Diniz (online) Translator Deborah Neale Reviewer Nature Publishing Group Language Editing Art Editor Laura daviña and Mayumi okuyama (Coordinator) ART ana paula campos, maria cecilia felli Photographer eduardo cesar Contributors alexandre agabiti Fernandez, André Serradas (Data Bank), evanildo da silveira, nana lahoz, nelson provazi Printers ipsis gráfica e editora

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 - brasil FAPESP Rua Pio XI, nº 1.500, CEP 05468-901 Alto da Lapa – São Paulo – SP - brasil

department for economic development, science and technology São Paulo state government

T

he current issue of the English version of Pesquisa FAPESP con­ tains a number of prominent ar­ ticles that appeared between January and April 2011. The cover feature focuses on a new study on the earli­ est Americans, which suggests that they entered the continent more than 15,000 years ago, coming from Asia via the Bering Strait (page 12).

They seem to have had an anatomical structure similar to that of the first population of modern humans that left Africa in search of other lands some 55,000 to 70,000 years ago. The occupation started with Asia, con­ tinued toward Europe and Australia, and finally reached the Americas. The research in question indicated that 10,000 years ago the cranial morpho­ logy of all the Homo sapiens on eve­ ry continent had an African pattern.

This means that the differentiation of physical types, such as Caucasian or oriental, is a very recent phenome­ non that took place after humans had already established themselves on all quadrants of the Earth.

The study was conducted by two Brazilian researchers, one from the University of São Paulo, in Brazil, and the other from the Catholic Univer­ sity of the North, in Chile, together with a Greek researcher from the Uni­ versity of Tübingen in Germany. They compared 24 anatomical features of the craniums of humans who lived 10,000 to 40,000 years ago in South America. The results support the hypothesis that the Americas were colonized by two migratory waves of different peoples that crossed the Bering Strait into the continent at different times. The first is thought to have occurred 15,000 years ago by people with a “pan-African” mor­ phology. These humans with Afri­ can traits are believed to have been

replaced, according to this theory, by a second migratory wave that arrived between 9,000 and 10,000 years ago. A second, older theory advocates that a single group of humans with varying physical types left Siberia for Alaska 18,000 years ago. The third hypothe­ sis proposes that man first arrived in the Brazilian northeast coming from Africa by sea and stopped along the way at several islands at a time when the sea was low. As one can see, the study underlying the cover of this issue expands the discussion on the peopling of the Americas.

Two other articles merit mention.

The first concerns the fight against dengue fever, an infectious disease that is one of the main public health problems in tropical countries, such as Brazil (page 34). Through genetic manipulation, a population of labo­ ratory-raised male Aedes aegypti mosquitoes received a protein that kills the offspring resulting from their crossing with normal females. The objective is to suppress a large num­ ber of individuals of this species, to reduce spraying with insecticides, and consequently to diminish the inci­ dence of the disease among humans.

The genetically modified mosquitoes were released in inner-state Bahia at the beginning of this year.

The second article shows how high precision measurements of the force of gravity appear to point to a deforma­ tion of the supposedly perfect sphere of the Earth as seen from space (page 28). For example, the highs and lows of the ocean surface, which constantly adjusts itself according to the field of gravity, might indicate that “sea level” does not even exist. It is well worth exploring this entire story.

All these researches were directly or indirectly supported by FAPESP. Enjoy your reading.

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Interview

José Israel Vargas

From crisis to opportunity The former minister, an advocate of nuclear energy and critic of corporatism, looks back on his career as a scientist and policy maker Fabrício Marques Published in April 2011

J

osé Israel Vargas, 83, who was born in Minas Gerais state, is not just a privileged witness to the development of Brazilian science in the twentieth century.

As Minister of Science and Technology from 1992 to 1998 – a position he held longer than anyone else has – he became one of the most influential voices in science and technology policy in Brazil.

He graduated from the Federal University of Minas Gerais (UFMG) in 1952 with a degree in chemistry but soon became involved with physics. He gained solid experience in physics at the University of São Paulo (USP) and the Aeronautical Institute of Technology (ITA) and received a PhD in nuclear science from the Department of Physics & Chemistry at the University of Cambridge. He was one of the formulators of Brazil’s nuclear energy policy at the beginning of the 1960s, an activity that was interrupted by the military coup of 1964, which led to Vargas leaving the country and living in exile in France for six and a half years.

While in France, he worked as a researcher at the French Atomic Energy Commission’s Center for Nuclear Studies in Grenoble. Vargas returned to his policy-making career in Brazil under Aureliano Chaves, then Governor of Minas Gerais. In the Figueiredo administration, he became the Secretary of Industrial Technology in the Ministry of Industry and Commerce. Itamar Franco’s presidency saw him moving to the Ministry of Science and Technology, where he remained through Fernando Henrique Cardoso’s first term in office. “Because I’m jinxed, I was always appointed during times of crisis,” says Vargas, who, three years ago, compiled a book, Science at a Time of Crisis, from some of his writings generated over the last thirty years. A defender of nuclear energy and critic of corporatism in Brazilian science, Vargas talked about his career in this interview with Fabrício Marques.

■■You have a degree in chemistry, but you embarked on a career in physics. How did that transition happen?

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——My friends joke that to physicists, I’m a chemist, and to

chemists, I’m a physicist. I think they mean I’m equally ignorant in both areas. The field that most attracted my generation was nuclear physics and nuclear energy, where the biggest technical and scientific advances during and after the Second World War had been made. Brazil had had the good fortune to have a generation that produced a series of great scientists at the USP. This line of scholarship came out of the brilliant Italian school led by Enrico Fermi. At USP, Gleb Wataghin and Giuseppe Occhialini taught Marcelo Damy, Abraão de Moraes, Mário Schönberg, Paulus Aulus Pompeia, César Lattes and Oscar Sala. I came into contact with this generation of scientists when I went to study chemistry at the Federal University of Minas Gerais in 1948. In my second year, I transferred to USP, in Alameda Glete, where I stayed for almost two years. Like every young person at the time, I was a left winger, involved in student protests and the “The oil is ours” campaign, which was led mainly by the Communist youth movement. I made friends with and got to know people there who were to become important scientists.

■■For example?

——Ely Silva, Luís Hildebrando Pereira da Silva, Ernst and

Amélia Hamburger, Fernando Henrique Cardoso, José Goldemberg, Victor Nussenzweig – with whom, as a matter of fact, I was imprisoned during the oil campaign. I went back to Minas leaning towards physics. Although I continued studying chemistry, I became a high-school physics teacher, and I taught physics in a university-entrance-exam preparatory course in the School of Philosophy at UFMG. ■■What was your stay at ITA like?

——At the time, ITA was running a development course for

high-school physics teachers. It was an initiative of the CNPq [National Council for Scientific and Technological Development] organized by Paulus Aulus Pompeia, who was one of the most important figures in Occhialini and Wataghin’s group.

Pompeia had participated in the most remarkable achieve-

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Photos Glรกucia rodrigues

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ments in physics in recent times, the discovery of so-called penetrating showers. That discovery was one of the first to demonstrate that the atomic nucleus is much more complex than had previously been imagined. There were some twenty-odd students from all over Brazil in that course. The prospects that nuclear energy offered for the world’s economy and for science were tremendous. It was natural that young people with scientific inclinations would want to move into that area. The course was especially interesting because Pompeia brought the leading lights of Brazilian physics to lecture and give conferences. There were also two great American physicists in Brazil at that time, Richard Feynman and David Bohm, the latter of whom was fleeing from McCarthyism. Abraão de Moraes, an important Brazilian physicist, suggested that Pompeia recruit me at ITA. So although I had recently graduated in chemistry, I ended up in the physics department.

■■What was the environment at ITA like?

——I was at ITA from 1952 until 1954.

It was an extremely interesting period because ITA had recruited the very best people in Brazil: young scientists and engineers in various areas, but especially in mechanical engineering, materials science, aeronautics and, of course, mathematics. It had hired a large number of scientists, including many from the Massachusetts Institute of Technology (MIT). There were some Germans from Von Braun’s group, along with Belgian, French, Czech and Swiss researchers, who began working on the project to develop the first Brazilian airplane, the seed of what would one day become Embraer.

ITA was a special place, because it offered accommodations, food, a small salary and a minimal work schedule, which allowed people to attend the various courses at ITA. One of those was taught by Walther Baltensperger, from the Zurich Polytechnic, who became a close friend. What’s more, I used to go to São Paulo once a week to attend David Bohm’s seminar at USP, and I frequently stayed with Fernando Henrique Cardoso. Mário Schönberg lived in the same building, which was reason enough for long conversations late into the night. This experience encouraged me increasingly in the direction of physics. I left ITA because my father was sick and went back to Belo Horizonte.

That’s when an opportunity arose for me to take the public-service entrance exam to be chair of the physics department at 8

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The Geisel government appointed me as a member of the board of the National Research Council but wouldn’t give me a passport to leave the country the municipal college. Soon after that, the Institute for Radioactive Research [IPR] was founded in Belo Horizonte, and I was invited by Professor Francisco Magalhães Gomes, its organizer, to do precisely the work I wanted to do, nuclear research.

■■The next step was a PhD from the Uni­ versity of Cambridge.

——Exactly. At that time, the first Latin American course in nuclear chemistry was being given in Chile, at the University of Concepción, sponsored by the University of Cambridge and by Unesco. I received a grant from the CNPq to attend the course; just two of us taking the course were Brazilian. There I met Alfred Maddock, who suggested I should do a PhD at Cambridge and offered to be my tutor.

I started in 1956. Cambridge University had been the main center for the development of nuclear science. There were some five or six Nobel prize winners there at the same time I was. The lead researchers were from the English nuclear-armament program, and many had taken part in the Manhattan Project. A number of scientists were lecturing there at the time, including James Chadwick, who had discovered the neutron, and Otto Frisch, who had developed the first model of nuclear fission.

■■What did you do when you came back to Brazil?

——I went back to my old jobs at the Institute for Radioactive Research and at the School of Philosophy [at UFMG], where I was the acting professor of physicalchemistry and advanced chemistry. I later

passed the public-service exam and formally became the full professor. I made a lot of efforts to get a hold of the necessary resources for doing scientific work; these efforts were very urgent. I subsequently established a strong relationship with Marcelo Damy and took part in numerous working groups organized by the CNEN [National Nuclear Energy Commission], which he presided over. I was appointed a member of CNEN’s board, and, in that capacity, I acted as his deputy on the Board of Governors of the International Atomic Energy Agency [IAEA] in Vienna, where I was on various committees. Two of the more notable ones were the committee that established the rules and safeguards for controlling nuclear activities via inspections and the one that was responsible for formulating the international standards for nuclear data.

■■Why were you relieved of your duties with the CNEN after the 1964 coup?

——Naturally, they remembered that I had been a student agitator; the revolution had a long memory; like all revolutions.

I was subjected to three police inquiries and my laboratory was invaded by an army detachment. I was relieved of my duties, supposedly at the request of the CNEN board; however, I decided not to leave Brazil until things had been clarified, in order to avoid being tried in absentia.

In 1964, I received invitations to go to the United States, Argentina, the Netherlands and France. I chose France, specifically Grenoble, but I maintained close relations with the National Institute for Nuclear Science and Technology, which was located in Saclay, near Paris. I went to Grenoble because one of my friends at the International Atomic Energy Agency, Pierre Balligand, who had been the director for power reactors there, became director of the Center for Nuclear Studies in Grenoble, along with Louis Néel, a Nobel prize winner in physics.

■■What kind of relationship did you maintain with Brazil during that time?

——In 1969 or 1970, I was asked by the CNEN to come to Brazil to suggest policies, presumably new ones. The chairman of the committee was General Uriel Alvim; he wanted to discuss whether or not to resume the famous thorium project that had been started at the IPR in Belo Horizonte.

This project had been initiated at a time when there was no clearly defined Brazilian nuclear policy. In that environment, a group of young engineers, physicists and

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chemists from Belo Horizonte had formulated the so-called thorium project, which aimed to build one type of reactor out of the various possible options, the so-called auto-generating or regenerating reactor, which would use a mixture of enriched uranium and thorium. The project lost support, and I became the black sheep of the program. I have never managed to prove it, but, because of something a well-informed friend let slip, I’m certain that our Nuclear Energy Committee was forbidden to have any relationship with me by a secret decree – apparently a common occurrence in the ’64 regime.

■■To what do you attribute this?

■■Tell us about your return to Brazil.

was 12 years old. Remaining in France at that time would have meant staying there permanently because it’s likely they would have gotten married there. So I came back in 1972. It was an important moment in Brazilian science. In 1972, Finep [the Research and Projects Financing Agency] was headed by José Pelúcio Ferreira, a leader in promoting an extremely active and smart set of scientific policies here that were supported by ample financial resources coming from the BNDES [the Brazilian Development Bank] and then from Finep itself. I didn’t know Pelúcio, but he invited me to talk with him. He wanted me to act as a type of consultant. I told him I was resistant to having any relationship with the military government and said that I was not interested in his invitation. As I was leaving, I asked who had suggested he contact me.

He answered, “Celso Furtado.” I had become friendly with Celso at Cambridge. I said that this changed the whole picture; if the suggestion came from Celso Furtado, it was because it deserved consideration.

“So, what are we going to do?” he asked me.

My proposal was to focus on strategic materials, like nickel, zinc and niobium. Niobium is important because we have 90% of the world’s reserves of it whereas we don’t have nickel; our nonferrous metals are all very altered by tropical storms, so autonomous technology is required. Pelúcio and the Planning minister João Paulo dos Reis Velloso brought about a major reform of the Brazilian science-and-technology system under the Geisel government. To my surprise, I was named a member of the plenary body of the new National Research Council, a presidential commission that coordinated the country’s research and development activities. But at the same time, they would not issue me a passport so I could leave the country.

I had four daughters, the oldest of whom

■■The military government also had a

——My cohort [at CNEN], that of the

Damy administration, had always advocated an independent nuclear program using natural uranium. But the military government signed an agreement with the United States and acquired a readymade turnkey reactor fed with enriched uranium, to which the contribution of Brazilian technology would be practically nil. We did not accept that policy.

We had our independent position on the Board of Governors of the IAEA. Remember that the certainty of a third world war was then current doctrine in the Brazilian government. In the subsequent Geisel government, there was an agreement with Germany, in which I played an indirect part. The João Pi­ nheiro Foundation in Belo Horizonte, of which I was chairman under the Aureliano Chaves government, formulated the Pronuclear Program to be administered by the CNPq, which aimed to train the personnel who would be needed to implement the nuclear agreement with Germany. Oscar Sala, Goldemberg and I, who were wary about the agreement, were invited to visit the German nuclear facilities. I thought then, and I still think now, that the nuclear program should be an instrument for modernizing Brazil.

I considered that agreement to have its positive side. For a long time the nuclear program had been nothing more than an American reactor, Angra 1. We could learn nothing from that reactor about technology – except, to be fair, the technology of safety, management and operations. The first reactor included in the nuclear agreement with Germany was Angra 2, which I supported in the end.

——The time arrived when I had to decide.

modernizing aspect, as can be seen in the way it courted scientists.

——The situation at that time was doubtful. Although I had been appointed by Geisel, certain groups and institutions opposed me, perhaps because, with a view to their own careers, they saw me as a competitor. At the same time, Aureliano Chaves had been appointed Governor of Minas Gerais State, and he knew me. He invited me to organize the Department of Science and Technology in the state government. I told him that I couldn’t accept because I didn’t know the situation in which I would be operating sufficiently well; I had been away for almost seven years. He said to me, “Do you want time to reflect, to think about it, to gather information?” I accepted this suggestion and was appointed chairman of the João Pinheiro Foundation. It was at this time that Embrapa [the Brazilian Agricultural Research Corporation] was created.

■■What were the discussions like that led to the creation of Embrapa?

——I was against the project as it was originally drawn up, until the plan for developing human resources was presented. The plan, designed by Alysson Paulinelli, the Minister of Agriculture, was to send 800 young Brazilians to get PhDs at the best foreign universities, particularly Wisconsin, Purdue, Cornell and other centers with international reputations. That’s when I said I was in favor of the project. I knew that of those 800, 10% would have the competence to be able to understand the advances that had been made in molecular genetics and would thereby be able to reorient the company’s programs in that strategic sector. I remember this issue because it shows that there’s no secret to finding the path to progress. The sequence of policies that led to Embraer and Embrapa is an example of such a suc-

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tution of 1988: the unified-labor-policy regime, which made the salaries of professors at UFRJ, UFMG and Unifesp the same. It also established that the professors at those institutions had the same duties and would receive the same remuneration as the professors at any new universities, such as those the Lula government started founding left, right and center. In addition, there was a provision that, in practice, impeded the hiring of foreign scientists.

It took four years of struggle to eliminate that impediment from the Constitution.

It took a long time, and even after it had been repealed, the university cliques and the unified-labor-policy regime still kept the country’s scholarly communities from being refreshed by people involved in research in interdisciplinary areas.

cess: recruitment and highly competent training, management flexibility and independence from official bureaucracy. We’ve somewhat forgotten today that science is the work of individuals. The people who produce good science are good scientists, and the people who produce great science are great scientists. What is the role of the government, politics or management? It is to create conditions under which quality people can produce quality science. The second principle is that, unlike technology, which can be local and linked to particular natural conditions and natural resources, science is universal. There’s no such thing as Brazilian science; there’s just science.

■■You were opposed to the creation of the MCT [Ministry of Science and Techno­ logy].Why? ——I was always against it because the Ministry has to compete with other cabi­ net-level departments that are obviously more important to politicians, who almost always take a short-term view. So the Ministry of Science and Technology is always treated as being a second- or third-level player. In the Reis Velloso shuffle, Pelúcio put science in the view of the President of the Republic, thereby guaranteeing it priority and a budget. That’s what matters. Why was the Ministry created? For political reasons, Dr. Ulysses Guimarães wanted Renato Archer to be appointed Minister of Foreign Affairs, but Tancredo had a commitment to Olavo Setúbal. So the Ministry of Science and Technology was created for Archer, who was, in fact, a good minister. That shows how vulnerable and unimportant science and technology 10

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are in Brazilian society. They still don’t form part of our system of values.

■■How were you appointed to head the Ministry?

——President Collor was impeached and Itamar, the new president, invited me to the position. I told him that I’d been a little disillusioned with my position as Secretary of Industrial Technology in the Figueiredo government. Itamar said, “Oh, but I need you to help me carry the burden! I’m trying to form a government of national unity.” Because I am jinxed, I arrived in the midst of a crisis, but I was the Minister of Science and Technology, and I lasted longer than anyone in that position. Itamar gave me a lot of support.

The things I managed to accomplish in the beginning were largely the result of the privatization of the Companhia Siderúrgica Nacional [National Steel Company].

The proceeds allowed us to continue a large part of the work that had previously been put on hold for lack of funds.

■■For example?

——I didn’t go there to invent the wheel; I

worked from the assumption that my predecessors were neither imbeciles nor malevolent, but that they were people whose choices represented the opportunities – or lack of opportunities – at a given time to carry through on certain projects and initiate certain others. I spent my time finishing work that had already been started.

Many of the initiatives, either from the military regime or subsequent administrations, came to absolutely nothing because of a disastrous decision under the Consti-

■■What is your assessment of the recent changes in legislation on innovation?

——There are differences of opinion about whether it was Louis XV or Madame Pompadour who was the author of the famous phrase “Après moi, le déluge” (“After me, the flood”). In Brazil, it’s the opposite; it’s “Before me, the flood.” All that had been done before was abandoned. We had two extremely important laws that incentivized the participation of industry in the development of science and technology: Law 8,248, the IT law, and Law 8,661, which allowed companies to deduct up to 8% from their income-tax bill if they invested that money in science and technology. Law 8,248 was very generous; it applied to revenue in the IT sector. Both were altered. One of the reasons for lack of success in building relationships between industry and universities and entities that promote research is that industry wants economically important developments, those that will generate income, to be protected by secrecy. A company that wants to develop a new device will not be persuaded to submit its idea to a decisionmaking bureaucracy made up of scientists at Finep and the CNPq. Nor will it agree to submit the idea to its peers because they are potential competitors. The solution is to award the incentive afterwards. A company declares that it’s going to invest X in science and technology; it invests it, entering into an agreement with a university and doing what it wants with secrecy clauses. When the project is finished, the company shows what it has done to the government, which can either award the incentive or not. It seems trivial, doesn’t it?

It’s essential. But because it runs counter to the desires of the scientific community,

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which wants to have the decision-making power, a tension is engendered between the production sector and academia. One of the changes that occurred with this law was to give a greater role to the decisionmaking bodies. That was a mistake.

■■What is the future of the Brazilian ener­ gy matrix going to look like?

——First, hydroelectric power. Everybody’s talking about megaplants, but when you look at the hydroelectric potential of Brazil, generally speaking, all of the water that has a potential production of less than 20 megawatts is ignored. But miniplants have immense potential. I think we need nuclear energy to replace the generation that today comes from gas, coal and petroleum, which produce greenhouses gases.

■■Nuclear energy lost a bit of ground in the 1980s because of safety issues, which might be coming to the fore again after the radioactive leaks caused by the earthquake in Japan. Is there a mature technology that will allow us to substitute nuclear power for these other means of generation and truly fulfill all of Brazil’s needs?

——No. There’s very little chance of the country resuming activities in that area because the specialists here are now old and because there are no incentives to encourage new people to specialize in it. Over 30 years ago, during the Geisel presidency, a Pronuclear Program was created. When it was active, more than 600 people – engineers, geologists, chemists and physicists – were sent abroad to undertake specialized studies, mainly in Germany. These people have grown old and retired. The only initiative that has survived is the remains of the so-called parallel program, now being directed by Admiral Otto Pinheiro, which is a great success. Thanks to this program, Brazil dominates the technology for the isotopic enrichment of uranium. We have a valuable currency for exchange in this area.

So even though we don’t have the trained personnel, it would be possible to revive the sector through international cooperation.

■■And the safety issue?

——We have to adopt independent and

efficient radiation-protection regulatory systems that will guarantee the safety of the existing power stations and of any future ones. What has so far been done in this area doesn’t seem sufficient to me. Brazil does not separate licensing from the supervision of nuclear-related activities, so it is not complying with the 2003 recommendations of the International Atomic Energy

spending was 6%; by the time I left, it had reached 30%. When Sérgio Rezende left the ministry in 2010, it was at 34%. We tripled the number of PhDs from 1,000 to 3,000, and the last administration tripled it again, to 10,000. In relative terms, the volume of funds has increased very little; in absolute terms, it has grown with the GDP. When I left the Ministry, around 1% or 1.1% of the GDP was being spent on science and technology; now it’s 1.3%.

The GDP has increased, but the relative investment has changed almost not at all. The licensed-patents indicator is still poor; 90% of patents are registered by nonresidents. National scientific production has increased; the number frequently cited is 19,000 annual publications. But there has been a change in the counting method; the current rubric is broader than the previous one used by the ISI.

The science and technology system has been imbued with the official ideological view that Brazil started eight years ago.

But in relative terms, the volume of resources has increased very little Agency – which were approved with Brazil’s vote. This is also despite the warning issued years ago by the scientific community.

An irrefutable example: The accident in Goiânia [1987] led to a bill that would correct this anomaly, but it’s still on the back burner in the House of Representatives today. This inertia is the result of corporatist pressure arising from the utilitarian attitudes of the CNEN. I have no doubt that nuclear energy will be fundamental to filling the world’s energy needs. Naturally, what happened in Japan will hold up the launch of new projects, perhaps for a long time. There has recently been talk of our alleged wind potential. In France, which generates almost 80% of the energy it consumes with its nuclear power stations, it is estimated that wind power from marine generators is four times more expensive.

There’s more potential in biomass, particularly sugarcane bagasse, whether it is burned directly or used as raw material in facilities that generate energy through the enzymatic hydrolysis of pulp.

■■Since you left the Ministry, some of the scientific-production indicators have been steadily growing. How would you assess what has happened in these last few years?

——Unfortunately, the scientific and technological system has been imbued with the official ideological view that Brazil began eight years ago. When I arrived at the Ministry, despite the difficulties I faced, the indispensable participation of the private sector in the science and technology

■■The number of Brazilian journals in the ISI journal database has gone from a few dozen to more than one hundred.

——The number naturally increased when the basis for inclusion changed. In other words, there was not really such a significant increase. This question leads me back to the difficulties I faced – and to some of my achievements. One of them was the creation of the CPTEC [the Center for Weather Forecast and Climate Studies at Inpe], thanks to which Brazil has begun to have its first class meteorological forecasts. The José Pelúcio Ferreira National Scientific Computing Laboratory, which previously operated in Praia Vermelha in Rio, has been set up on a new campus in Petrópolis. The National Light Synchrotron Laboratory also began operations under the Fernando Henrique government, financed with funds that partly came from the privatization of the CSN during the Itamar presidency. As to so-called sector funds, in my administration, we created a royalties fund that came from the revenue from oil concessions. It was earmarked for science and technology, thanks to a proposal from then Senator Eliseu Resende, who reestablished the Government’s oil monopoly. We created the Brazilian Spa­­ce Agency, and two satellites were built at Inpe, in addition to two others that were built in collaboration with the Chinese. The sector has benefited from the continuation of the Scientific and Technological Development Program [PADCT] with the World Bank and from the funding of Centers for Excellence, which have become important platforms for Brazil’s participation in the world’s scientific community. n

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eduardo cesar

Like our parents

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New study argues that the first Americans looked like Africans, which increases the controversy over man’s arrival in the Americas Marcos Pivetta Published in April 2011

Skulls from Lagoa Santa: American with African traces

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omo sapiens was not separated into distinct races with distinctive physical types before settling throughout the Americas, the last great, habitable land block conquered by the species, according to a new study. The initial group of hunter-collectors reached the Americas from Asia more than 15,000 years ago along a path now submerged by the Bering Strait. They had an anatomical structure very similar to that of the first population of modern humans migrating out of Africa between 55,000 and 70,000 years ago. After leaving the cradle of humanity, H. sapiens entered Asia, which served as a base from which to reach Europe and Australia, and then later the Americas. “Until 10,000 years ago all Homo sapiens present on any continent had a standard African cranial morphology,” says bio-anthropologist Walter Neves of the University of São Paulo (USP). “The racialization process had not yet begun.” The appearance of distinct races such as the Caucasians and Mongoloids (Asians with almond-shaped eyes and a flat face) was a very recent biological phenomenon that occurred after man had spread over almost the whole Earth.

Neves defends this controversial hypothesis in an article published in the March edition of the American Journal of Physical Anthropology. He has two co-authors, both of whom are physical anthropologists: Brazilian Mark Hubbe, from the Archaeological Investigation Institute and the Museum of Catholic University of the North (Chile), and Greek Katerina Harvati, from the University of Tubingen (Germany). Neves, Hubbe and Harvati identified 24 anatomical characteristics of the skulls of human beings living between 10,000 and 40,000 years ago in South America, Europe and East Asia. They then compared these characteristics to those of individuals from the present day from these three regions. The fossils were also compared to people currently living in Sub-Saharan Africa, Oceania and Polynesia. In all, 48 ancient skeletons were compared (32 from South America, 2 from Asia and 14 from Europe) to 2,000 present-day skeletons. “Regardless of their geographical origin, members of the ancient populations are much more like their contemporaries from the past than they are like humans of today,” comments Hubbe. In other words, the physical features of those humans who first left Africa and those who settled 40,000 years later in the Americas were practically the same. According to this view, the conquest of the world was a rapid phenomenon; Homo sapiens used coastal routes that were efficient and easily traversed. This rapid spread gave humans almost no time to adapt physically to their new environments.

The results of the study support the settlement model of the Americas that has been defended by Neves (whose work is largely funded by FAPESP) for over 20 years. According to this hypothesis, the Americas were colonized by two migratory waves of distinct peoples who crossed the Bering Strait at different times. The first group crossed 15,000 years ago and was comprised of humans who still possessed a “panAfrican” morphology, to use the term employed by Neves.

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Three views of arrival in the Americas 15,000 YEARS

A MIGRATION

10,000 YEARS

A single group of humans leaves Siberia and enters Alaska.

Individuals of different physical types, some more African and others more Asian, make up the group.

18,000 YEARS

TWO MIGRATIONS

Migrants with African features cross the Bering Strait and settle in the Americas. Later, a new colonizing group with Asian traits arrives in the Americas and becomes dominant.

0

BY THE ATLANTIC OCEAN

100,000 YEARS

Humans arrive in northeast Brazil from Africa. They sail from island to island at a time when the sea was lower.

The idea is defended

by Niède Guidon.

5,000 Kilometers

to have resembled Luzia, the famous 11,000-year old female skull found in the Minas Gerais region of Lagoa Santa.

These humans had broad noses, wide eye sockets, forward-projecting faces and narrow, elongated heads. Although it is impossible to determine with any degree of certainty the color of their skin, they were probably black. All of their descendants disappeared mysteriously at some point in pre-historic times and left no representatives among the tribes present on the South American continent today.

T

he African features of these early humans fit with Neves’ settlement theory. Later, this group of settlers was supplanted by a second migratory movement of humans from Asia to the Americas. This new group entered the New World between 9,000 and 10,000 years ago and exclusively comprised individuals with the physical characteristics of the so-called Mongoloid people, the descendants of whom are like current Asian races and the indigenous tribes still alive today in the Americas. Humans with this Asiatic appearance, which possibly arose as an adaptation to the extremely cold climate of Siberia (and possibly the Arctic), cannot have been part of the first migratory group to the Americas.

Neves, Hubbe and Harvarti claim that the reason is simple: at the time of that

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first migration, this Mongoloid physical type had not yet appeared.

There is far from a consensus on this settlement model of the Americas.

DNA analyses taken from extinct and living indigenous populations of the continent, especially from the sequences contained in the mitochondrial genome (the maternal line, i.e., inherited from the mother) and from the Y chromosome (the paternal line), tell a different story. These results support the hypothesis that there was just one movement of individuals from Asia towards the New World, and that this crossing occurred thousands of years before the date suggested by the archaeological evidence.

“Practically all the biological diversity of current human types was already

THe ProJecT Origins and microevolution of man in the Americas: a paleoanthropological approach III – nº 2004/01321-6 TYPE

thematic research Grant COORDINATOR

walter Neves – institute of Biosciences of usp INVESTMENT

r$ 1,555,665.94 (Fapesp)

present in the single migratory group that entered the Americas,” says geneticist Sandro Bonatto, of the Pontifical Catholic University of Rio Grande do Sul. “Only the Eskimos, a population that represents the most extreme and latest case of the so-called Mongoloid morphology, still had not originated and were not part of this group.”

In October 2008, Bonatto, along with colleagues from Brazilian and Argentinian institutions, published a scientific article in the American Journal of Physical Anthropology, the same journal that published Neves’ work. The study analyzed 10,000 pieces of genetic information and the anatomy of 576 skulls of extinct and current populations from North and South America. According to the article, a fairly physically heterogeneous group of hunter-collectors had already left Siberia and settled in Alaska approximately 18,000 years ago.

This first band contained humans with Asian features and humans with more African features. This model also differs from Neves and Hubbe’s because it maintains that before entering the New World, these colonizers were forced to stop in Beringia, the dry land (now submerged by the Bering Strait) that once connected Asia to the Americas.

This stop on the divide between the two continents occurred between 18,000 and 26,000 years ago, a period in which giant glaciers blocked entry

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he models described, which are only two of the theories about how the Americas were settled, seem irreconcilable. But the Argentinean physical anthropologist, Rolando González-José, of the National Patagonian Center in Puerto Madryn, a frequent collaborator and co-author with Neves and Bonatto, sees strengths and weaknesses in both approaches: “I agree that many variations present in the skull of man are of recent origin, but it also needs to be said that the ancient populations may have been fairly heterogeneous”, says González-José.

“Neves’ model is not totally wrong, but it’s difficult to question the genetic data and it shows that all American Indians descend from a single population.”

There are other views on the settlement process of the Americas, and some of them are even more controversial.

According to archaeologist Niède Guidon, the founder and president of the Museum of the American Man Foundation (Fumdham) and administrator of the Serra da Capivara National Park in Piauí, man was already in northeast Brazil 100,000 years ago. Humans came from Africa by sailing from island to island and taking advantage of times when the sea was far lower than it is today. “Navigation is a lot older than is thought,” claims Guidon. “I don’t believe that Homo sapiens colonized the Americas via the Bering Strait.”

With almost 1,300 pre-historic sites full of beautiful rock paintings, the Serra da Capivara National Park has already supplied 33 human skeletons and more than 700,000 stone artifacts for the museum’s collection. The dates supplied by Guidon indicate a human

The oldest site in the USA

michael waters

to the Americas. When the route finally opened up, the final leg of the migration took place. However, according to this hypothesis, the necessary stop in Beringia produced specific mutations in the DNA of the population of humans imprisoned between the two land masses. These genetic alterations are not found in the peoples of Asia but were passed on to the descendants of the earliest Americans. A recent study, in which Brazilians took part, suggests that one of these mutations favored the accumulation of cholesterol and is found in Indians from the continent.

Stone laminates from Texas A new and important piece of the complicated puzzle regarding when Homo sapiens entered the Americas appeared at the end of March 2011.

A team of researchers led by Michael Waters from the University of Texas A&M publicized its discovery of the oldest trace of human presence in North America. Located in Buttermilk Creek, Texas, the Debra L. Friedkin site houses some 15,500 artifacts made by humans an estimated 15,500 years ago. These artifacts are essentially blade-like objects, many of them unfinished and some two-sided, made from a type of quartz. “The site is in the center of the state, and it must have taken man some time to find this location,” said Waters in an interview with Pesquisa FAPESP. “It’s possible that [man] arrived in the Americas before then, but how much earlier, I couldn’t say. Only time and more hard work can tell us.”

The artifacts were dated using the luminescence technique. This method measures the energy from the last rays of the sun (or from final exposure to intense heat) that were trapped in the sediment of the 20 cm thick geological layer in which the pieces were found. No bones were found in the location, but scientists say that the objects were undoubtedly hewn by Homo sapiens

presence in northeast Brazil for at least 50,000 years, but these findings are questioned by many of her peers.

Guidon does not risk speculating on the physical appearances of those responsible for the park’s prehistoric drawings, although some preliminary studies suggest that they may have been similar to Luzia and her tribe. n

and could have been used as knives or spearheads. They may even have formed part of an assortment of items that ancient humans carried with them in their wanderings.

The study was rolled out with much fanfare. After all, the ancient inhabitants of Buttermilk Creek lived 2,500 years before the so-called Clovis culture, which got its name from an archaeological site in New Mexico where 13,000-year old stone spearheads were found around 80 years ago. Until the 1980s, the predominant and largely unquestioned theory was that the Clovis culture was the oldest in the Americas. However, over the last few decades, the discoveries of other sites as old or older than Clovis, both in North America and Central and South America, have increasingly undermined this theory.

The new findings in Texas seem to bury, once and for all, the theory that the ancient inhabitants of New Mexico were the first to settle in the Americas. Because the blade-like objects from the Debra L. Friedkin site were found close to fragments of Clovis-style spearheads, and because the two objects bear similarities, the researchers believe that the Clovis culture may have derived from the earlier Buttermilk Creek culture.

Scientific article Hubbe, M. et al. Paleoamerican Morphology in the Context of European and East Asian Late Pleistocene Variation: Implication for Human Dispersion Into the New World. American Journal of Physical Anthropology. v. 50, n. 3, p. 442-53. Mar. 2011.

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SCIENTIFIC AND TECHNOLOGICAL

policy

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[ Measuring Science ]

Sacred code Study shows that French and German researchers are not exempt from losing influence when they do not publish in English Fabrício Marques Published in March 2011

illustrations Nelson Provazi

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he language barrier, which is responsible for the small amount of written science published in languages other than English, is a problem that does not only affect researchers from emerging countries such as Brazil. A study led by physicist Anthony van Raan, director of the Centre for Science and Technology Studies at Holland’s Leiden University, found that this barrier also negatively affects the scientific powers of France and Germany, which rank right behind the United States, China, the United Kingdom and Japan on the list of countries with the highest number of published scientific articles. Studies by French and German scientists, however, have less impact when they are published in their respective native languages.

Van Raan, an expert in scientometrics, a discipline that generates information to facilitate overcoming scientific challenges, was involved in the development of the Leiden Ranking, which is a collection of data generated by the Dutch university to analyze the scientific production of countries and of universities and research institutions. In the most recent Leiden Ranking, the University of São Paulo (USP) achieved fifteenth place in the list of universities with the highest volume of scientific production. The study on the language barrier focused on the list of the world’s 500 greatest universities, ranked according to the impact of their scientific articles as reflected in

the Thomson Reuter Company’s Web of Science (WoS) database. The impact factor is a measure reflecting the average number of citations to articles published in science and social science journals.

The Dutch researcher noticed that the modest performance of a number of French and German universities in the rankings was not consistent with their academic prestige. For comparison, he produced a second list in which only the scientific papers published in English-language scientific journals were considered, whereas articles written in the authors’ native languages were not. Van Raan found that the performance of the German and French universities was higher in the ranking of the list on articles in English because the impact of those papers was higher than that of articles published in the authors‘ native languages.

The University of Nantes, for example, ranks 106th on the list of articles published in English and 201st on the list that takes into account articles written in other languages as well.

Germany’s Heidelberg University and Munich’s LMU ranked 109th and 114th, respectively, on the impact list based only on articles in English but dropped to 150th and 166th, respectively, on the list of all articles. “We found a dramatic and underestimated effect in measuring the impact,” said Van Raan. “The articles published in languages other than English dilute the average impact of countries such as Germany, Austria, and France.

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Impact restricted to articles published in the native language weakens the performance of universities in rankings

This effect is particularly pronounced in the applied sciences, such as clinical medicine and engineering, but also occurs in the social sciences and the humanities. Because medicine accounts for a major part of any country’s scientific production, this effect influences the ranking of a university.”

Tool – The basis of Van Raan’s concern

refers to the use of bibliometric indicators linked to impact factors. Because citations carry considerable weight in the rankings of universities, such as those prepared by The Times Higher Education and China’s Shanghai Jiao Tong University, Van Raan suggests that one should be cautious when analyzing these lists and proposes a controversial alternative to remove the bias; he asserts that, for comparison purposes, one must take into account only the English version of the scientific production of the institutions and ignore articles written in other languages.

“Calculating the indicators only on the basis of publications in English is the only fair procedure,” Van Raan states. There is nothing new about the fact that proficiency in English is a basic tool for researchers in all fields of knowledge. This was already true in the 1930s, when German researchers published a study, in German, that associ18

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ated cigarette smoking with a higher incidence of lung cancer. Because of the language barrier, this fact remained almost unknown until the 1960s, when British and North American researchers reached the same conclusion. At present, resisting the supremacy of the English language is counterproductive says Sonia Vasconcelos, a researcher from the Federal University of Rio de Janeiro (UFRJ) and author of a doctoral thesis on the language barrier, which she presented in 2008 (see Pesquisa FAPESP, issue 162). “Countries in which English is the main language have a huge advantage, but there is an international movement among research institutions and scientific editors from various nonEnglish speaking countries to narrow this advantage. In the case of Brazil, it is necessary to train our researchers, especially those working in the fields of science and technology, to write properly in English and to develop some independence in order to be able to communicate with their peers in international contexts,” she states.

“In Germany, currently, a number of post-graduate courses are taught in English, which helps students overcome this barrier. This trend is also observed in France, which has always cultivated its language in academic settings, albeit with a strategic attitude towards Eng-

lish. Brazil has no strategy to deal with this challenge,” Sonia says. Van Raan’s suggestion that scientific papers written in native languages should be ignored to improve international comparisons might lead to another kind of bias that is caused by the absence of contributions in major fields of knowledge. “Production in a local language is a crucial part of the knowledge generated by countries and cannot be disregarded,” states Abel Packer, who is part of the team that coordinates the SciELO electronic scientific library in Brazil. Packer notes that papers on themes related to the health sciences and agrarian sciences have traditionally been written in Portuguese because it is important to convey this knowledge to professionals in these fields.

“The issue involves not only scientists, who generally speak English, but other users of scientific information who are not proficient in the language,” according to Packer. “Multilingualism is part of scientific communication and has its roots in the fact that science is part of culture. Science cannot be placed inside an ivory tower and kept apart from the rest of society; it must be regarded as a source of knowledge for economic and technological development. If the national scientific community doesn’t make an effort to create

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semantics in its own native language, the country and its culture will be unable to absorb ideas and knowledge that essentially serve its society,” he states.

In the opinion of Luiz Henrique Lopes dos Santos who is assistant coordinator at the Human and Social Sciences, Architecture, Economics and Business Administration of FAPESP and a professor in the Department of Philosophy of the School of Philosophy, Literature and Human Sciences at USP, the issue demands compromise because it is not limited to the issue of impact.

“This is also a cultural issue,” he says.

“Language is an essential element of a country’s culture and it is constituted and enriched by the interaction between its more common and more sophisticated uses – as in literature, science and philosophy. No country can afford to totally disregard its native language as a vehicle of knowledge production.”

Packer further proposes that the fact that the number of papers written in Portuguese is growing in the indexed journals must be considered.

Until 2007, the percentage of articles published in Portuguese on the Web of Science database was 8.5%. This fi­ gure has since increased to 22%. “The percentage has increased because the list of indexed Brazilian journals has

It is important to keep in mind that writing a paper in English – although helpful to expand the scope of the scientific article – does not ensure citations and prestige expanded from 34 in 2007 to 133 currently. Therefore, Brazil now ranks 13th in terms of scientific production.

If we disregard the journals in Por­ tuguese, then our ranking drops to 17th,” he states.

Outstanding detail – One must also

consider that writing in English is not sufficient to ensure the insertion of citations and the desired prestige.

A study by Rogério Meneghini, scientific coordinator of the SciELO Brasil library, states that even articles written in English and published in Brazilian journals produce fewer citations. Meneghini invited 9 Brazilian scientists who normally publish their papers in international journals to publish an original article in the May 2008 issue of the Anais da Academia Brasileira de Ciências journal. The intention was to evaluate the extent to which the related authors were able to transfer their prestige to the Brazilian journal, which is published in English. Two years after the publication, he found that the number of citations of those articles was higher than the number of citations of the journal’s other articles, specifically, 1.67 citations versus 0.76 citations from other articles. The 62 articles published by the same authors in international journals in 2008 each achieved an aver-

age of 4.13 citations. According to Meneghini, the difference can be attributed to the fact that the Brazilian journals have less international exposure even though the authors tend to send their best articles abroad. A striking fact was that the 9 authors did not cite articles from Brazilian journals. Only 1.52% of the citations mentioned by the authors in 2008 referred to papers published in Brazil. Meneghini suggests that citating Brazilian journals does not lead to prestige. “It seems that the authors chose to neglect citations from Brazilian journals, assuming that they might convey the impression that the article was inaccurate,” he said.

This does not weaken the consensus that it is crucial to encourage the use of English. “When a researcher makes the effort to cite papers written by his fellow colleagues, it is frustrating to realize that the reference cannot be consulted abroad because the paper is available only in Portuguese,” says Sonia Vasconcelos. In the opinion of SciELO’s Abel Packer, the solution is to invest in the translation of articles written in Portuguese, making them available in English as well. “This would require heavy investments, but I see no other solution to increase the exposure of the work produced by Brazilian scin ence,” Packer states.

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[ inTeGraTiOn ]

The map of light researchers interact with nobel laureates and plan experiments in biology and physics Carlos Fioravanti Published in February 2011

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hose who have already worked with synchrotron light to study proteins, fossil bones, rocks, medicines or computing materials improved their experimental plans as a result of seeing what other research groups are doing. Moreover, those who until recently knew hardly anything about this field have seen that this type of light can have academic and industrial applications. From January 17 to 25, 18 experts from 6 countries, including a Nobel laureate in Chemistry and another in Physics, spent time with researchers and 76 graduate students from 24 countries (13 of whom were Brazilian) during the São Paulo School of Advanced Science (SPSAS) of the National Laboratory of Synchrotron Light (LNLS) held in Campinas. The SPSAS is a funding option that was launched in 2009 by FAPESP in order to finance short courses in advanced research in São Paulo state in various fields of knowledge.

“We want to increase the laboratory’s visibility for potential researchers from overseas,” explained Antonio José Roque da Silva, LNLS director. “At present, when we are beginning the project for a new synchrotron light source we must look ahead to the future and at what others are doing.” Named Sirius, the new ring should have a circumference of 460 meters (the current ring measures 93 meters) and considerably more energy (see “Brilho maior” [Greater brilliance], Pesquisa FAPESP issue 172). The only synchrotron light source in Latin America and one of the only two in the Southern Hemisphere

(the other one is in Australia), the LNLS serves researchers and companies from Brazil and other countries.

Sometimes, Brazil’s use of the synchrotron light source is different from that in other countries. “While many Brazilian companies are still trying to figure out how to use synchrotron light to improve the quality of their products, the Japanese company Toyota already has its own beamline,” says Silva. Formerly a user of the European Synchrotron Radiation Facility (ESRF), in Grenoble, France, the company decided to build its own beamline, which has been in operation in Japan since 2009. Gemma Guillera, a researcher who worked with Toyota, said that this beamline should provide support for the development of new catalysts to reduce pollutants from batteries and fuel cells. “The spectroscopy of the absorption of X-rays [one of the types of analysis conducted by means of synchrotron light that is used by the Toyota team] provides information about the lengths of atomic connections, and the type and the number of atoms,” she explained.

Researchers and students saw how surveys emerge and how long they can take to produce impressive results. Israel’s Ada Yonath said that she worked for almost 30 years in her laboratory at the Weizmann Institute in Israel as well as on synchrotron light sources in the United States, in Germany, and in Brazil until she unlocked the structure and function of cell components known as ribosomes, which are essential for the production of proteins.

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EDUARDO CESAR

In order to make progress, she and other specialists had to obtain crystals of these cellular components, something that had been regarded as impossible for decades but which was finally achieved by cooling the cells. Mastery of this technique and the resulting leap in knowledge about ribosomes earned her and two other researchers (Venkatraman Ramakrishnan from the Molecular Biology Laboratory at Cambridge, England, and Thomas Steitz from Yale University in the United States) the Nobel Prize for Chemistry in 2009. At the end of the presentation, she thanked the Weizmann Institute “for having allowed me to pursue my dreams.”

New memories – The French physicist

Albert Fert, a researcher at the National Center for Scientific Research (CNRS) and one of the winners of the Nobel Prize for Physics in 2007, spoke of the fundamentals and applications of spintronics, a new kind of electronics that does not exploit the electrical charge but rather exploits another property: the spin (direction of rotation) of the electrons. This property is the basis of the more powerful computer memory chips that companies in the United States, France and Japan are expected to launch in the next few years.

Fert and the German physicist Peter Grünberg were awarded the Nobel Prize in Physics in 2007 for their simultaneous identification, in 1988, of giant magnetoresistance. This is a quantum mechanics effect observed in materials made from magnetic and nonmagnetic materials, resulting in an intense variation of the electrical resistance as a function of a magnetic field. Exploiting this effect allowed an expansion in the capacity of computer memory devices and mobile phone handsets, which should now get another boost, thanks to a new generation of devices based on spintronics.

Those who had lunch with Fert noted that he enjoys thinking not only about the computers of the future but also about his holidays. Close to his 73rd birthday, which he will celebrate in March of this year, Fert windsurfs, normally in France or in the Caribbean.

He has already been to Botafogo in Rio de Janeiro on two occasions, not to discuss physics, but to surf. n

The LNLS ring of light: multiple uses

Carlos Fioravanti PESQUISA FAPESP

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SCIENCE

[ neurOpHYsiOlOGY ]

UNEXPECTED

EFFECT corticoids activate inflammation mechanisms in certain areas of the brain Published in April 2011

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he one percent of the world’s population living with the terrible pain of rheumatoid arthritis, a chronic inflammation that causes articulations to degenerate, is well aware of the importance of corticoids in improving the quality of life. Over the last few decades, the millions who suffer from respiratory allergies, skin diseases, brain tumors and a variety of other conditions in which the body’s inflammation response is exaggerated have also benefited from the powerful anti-inflammatory effects of these compounds, which are generally synthetic derivates of cortisone, the main corticoid secreted by the human adrenal glands.

Identified by Edward Calvin Kendall and Philip Showalter Hench at the beginning of the last century (the discovery earned them the Nobel Prize for Medicine in 1950), corticoids do not, however, always work as expected, particularly in the case of synthetic hormones. In some areas of the brain, the effect may be the exact opposite of what is expected, causing increased inflammation, as was suggested by Carolina Demarchi Munhoz and Cristoforo Scavone of the University of São Paulo (USP) and Robert Sapolsky of Stanford

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University in their study published in the Journal of Neuroscience in late 2010.

By means of an intravenous injection of bacteria fragments, this group of researchers induced inflammatory responses in laboratory rats to assess the power of corticoids to modulate biochemical reactions caused by brain inflammations, such as those that occur in the case of tumors or strokes.

It is known that the body’s natural response to inflammation is the secretion of corticoids – and the adrenal glands of rats produce corticosterone, a hormone similar to human cortisone.

Before provoking inflammation, Munhoz removed the rats’ adrenal glands (adrenalectomy) and implanted slow-release corticosterone capsules under their skin. Thus, by controlling the dosages, she was able to investigate whether the anti-inflammatory action varied depending on the different levels of corticoids in the blood of the animals. The rats were separated into three groups, each with a different hormone dose. The first group received a low level of corticosterone, equal to that normally produced by the rodents; the second group received a medium dose, similar to what is found in the body in cases of light stress,

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illusTraTiOn nana laHOZ

such as the sudden fright caused by an unexpected slamming of a door; and the third group received a high dose, which corresponded to moderate levels of stress, such as worry over the inability to pay one’s bills. The control group was composed of rats whose adrenal glands had not been removed.

The relation between levels of corticoids in the blood and levels of stress is important because this adaptive reaction by the body to new or threatening situations also causes the adrenal glands to release corticoids. Years before, this group of researchers had already shown that chronic and unforeseeable stress may cause brain inflammation (see Pesquisa FAPESP issue 129), but their more recent research investigated if and how corticoids mediate this effect.

Using immunology and molecular biology techniques, this study evaluated how each level of corticoids affected two distinct regions of the rats’ brains: the hippocampus (involved with memory, learning and, in pathological situations, the development of epilepsy) and the frontal cortex (associated with more advanced cognitive processes, such as decision-making). They observed a complex pattern of response in the analyzed genes.

Depending on the dose, some genes functioned with the same pattern in the two regions (i.e., being activated or deactivated in both); however, others worked differently (i.e., being active in one and inactive in the other). These changes resulted from control over the activity of the nuclear factor kappaB (NF-kappaB), an intracellular communication molecule that is key to the biochemical process that regulates the inflammation response.

Previously, it had been believed that NFkappaB was always blocked by corticoids, which would then have an anti-inflammatory effect. Indeed, in the highest dose, the corticoids reduced NF-kappaB activity and inflammation of the hippocampus. However, at the low and medium levels, they enhanced the effect of NF-kappaB, thereby enhancing the signal that triggers inflammation.

The relation was different in the frontal cortex; there, the high dose of corticosterone was anti-inflammatory, whereas the intermediary dose made the inflammation more severe.

Although these results are experimental, they may prove to be of clinical importance, particularly for neurology and psychiatry, both of which deal with brain inflammation and its consequences.

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PATRICK LANDMANN / SCIENCE PHOTO LIBRARY / SPL DC / Latinstock

According to Munhoz, the doses used in the tests with rats are close to those administered in human studies.

However, she proposes that the data be examined cautiously: “We showed that the effect of corticoids, even at appropriate doses, isn’t just anti-inflammatory; however, the work was done with rats, using their natural corticoid.”

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he fact that the researchers used a natural corticoid in the experiments can make a considerable difference. The corticoids produced by the body work differently than synthetic corticoids used as medication. One difference is that only 10% of the corticoids secreted by the adrenal glands are in free form in the blood, ready to act on both peripheral tissues and the central nervous system. Synthetic corticoids, however, are readily able to act on peripheral tissues, but they are, to a significant extent, filtered when they enter the brain’s circulation, as a special barrier (hematoencephalic) lines the brain’s blood vessels and controls the passage of various compounds.

Therefore, when treating brain inflammation, doctors must increase the dose of the drug, in hopes that a greater proportion may overcome the hematoencephalic barrier, which operates like a partially impermeable raincoat: if it is only drizzling, it keeps water from getting the person wet, but if it is pouring, a certain amount gets in through the pores of the fabric.

Because of this mechanism, the level of synthetic corticoids in peripheral blood may be substantially different from what reaches the brain. Thus, what doctors estimate as a high dose may actually be high on the periphery but only medium in the brain tissue. As it was the medium doses that increased the inflammatory signaling in the hippocampus and in the frontal cortex, the results may pose a warning of the medical use of these compounds when the target is the central nervous system. Still, further research must be conducted. Munhoz and Scavone plan to soon embark on such research to determine if synthetic corticoids act on the brain in the same way as do natural corticoids. “These data are a warning, indicating that there are variables at play that we still don’t understand regarding how corticoids work,” states Scavone.

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Affected cells in bipolar disorder: neurons in green and neuroglia in blue

Mood changes - Recently, Scavone

began collaborating with Beny Lafer’s team in the Psychiatry Department at the Medical School of USP to identify possible influences of inflammatory processes in the development of psychiatric problems. Lafer is particularly interested in discovering if biochemical changes linked to inflammation may affect the balance of cells and induce their death in individuals with bipolar disorder, which typically causes mood swings between depressive and manic (euphoric) episodes.

Described almost two thousand years ago by Aretaeus of Cappadocia, the most severe form (type 1) of this mental condition (previously known as manic-depressive psychosis) affects approximately one percent of the population. Although it has been treated with relative efficiency in recent decades, its biological origins remain unclear. In the 1990s, international studies identified a considerable reduction in the number of cells (neurons and neuroglia) and a reduction in the cellular protection mechanisms in the brains of bipolar individuals. Associated with inflammation, this cell loss, which becomes stronger during manic

The projects 1. Stress and intracellular signaling in the inflammation unleashed by LPS in the central nervous system: participation of the glucocorticoids and of the glutamate-NO pathway in the modulation of the transcription factor NF-kappaB – nº 2002/02298-2 2. Participation of map kinases, thermal shock proteins and apoptosis pathway in the adverse effects of glucocorticoids upon the central nervous system – nº 2004/11041-0 3. Evaluation of the involvement of the Wnt signaling pathway in the physiopathology of affective bipolar disorder – nº 2008/08191-1 Type

1, 2 and 3. Ordinary Research Grants Coordinators

1 and 2. Cristoforo Scavone – icb/usp 3. Beny Lafer – fm/usp Investment

1. R$ 191,086.25 (FAPESP) 2. R$ 229,197.46 (FAPESP) 3. R$ 57,564.57 (FAPESP)

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and depressive crises, affects the frontal cortex and possibly the hippocampus as well, which are two of the regions studied by Munhoz and Scavone. Loss or malfunctioning of frontal cortex neurons may help explain patients’ difficulties controlling their impulses during manic episodes.

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n a review study published this year in the journal Progress in NeuroPsychopharmacology & Biological Psychiatry, Lafer and Scavone proposed a model that attempts to explain how inflammation mechanisms may change the pathway of intracellular signaling activated by Wnt, a protein that regulates the proliferation, migration and specialization of cells. To a greater or lesser extent, all of these processes seem to be jeopardized in mood disorders, such as bipolar disorder and depression. In individuals suffering from these psychiatric problems, strong evidence that something is amiss in the chain of chemical reactions triggered by this protein is the fact that two of the drugs most commonly used to treat bipolar disorder (lithium and valproate) act upon this pathway of intracellular communication, reestablishing the channel of information transmission and eventually avoiding neuron death. “The discoveries about the workings of mood stabilizers have changed the focus of the research from the receptors in the cell membranes and the neurotransmitters that connect with these receptors to what happens in the intracellular world,” explains Beny Lafer.

This new way of looking at psychiatric problems, which brought together the teams of Scavone and Lafer, may lead to new treatments. Among the molecules that may become good therapeutic targets for bipolar disorder in the future, Lafer highlights the brainderived neurotrophic factor (BNDF).

Among its many roles, this molecule regulates the survival and ramification of neurons, which are functions that involve Wnt signaling and that are somehow poorly regulated during depressive and manic episodes.

Although it has not yet been determined, there truly appears to be a molecular link between mood disorders, the action of corticoids and the

At moderate concentrations, corticoids increase inflammation in the hippocampus and in the frontal cortex

influence of stress. Researchers suspect that this link may be NF-kappaB, which is involved both in the brain response to corticoids and in Wnt signaling, which is altered in bipolar disorder.

In their quest for answers to these questions – and, if possible, new forms of treatment – Lafer and his PhD student, Li Wen Hu, in conjunction with Eliza Kawamoto, are investigating changes in the Wnt pathway. They hope to compare levels of proteins in this biochemical chain in the blood of (1) those with the disorder who have been treated with lithium from the study’s outset, (2) individuals with the same condition who have not taken lithium and (3) healthy individuals. To date, they have obtained samples from 20 individuals in the first group, 17 from the second and 36 from the third. “We still don’t know whether the dysfunction

of inflammation processes is the cause or the consequence of the episodes of the disease, which improve with mood stabilizers,” states Lafer.

The suspicion that corticoids worsen brain inflammation is based on clinical observations. Bipolar patients on corticoids to fight inflammation present a worsening of their psychiatric situation. Moreover, medication for depression that acts contrary to corticoids is currently in its initial trial stage.

Although lithium has a different action mechanism to corticoids, researchers do not disregard the possibility that they may act upon intracellular targets in common. Still, it is difficult to know the answer to this question. “It’s a complex biochemical waterfall effect, finely regulated by the body in response to stress and to inflammation processes,” comments Scavone. “Interfering with this system might unleash consequences that we aren’t aware of yet.” n Scientific articles 1. Munhoz, C. D. et al. Glucocorticoids exacerbate lipopolysaccharide-induced signaling in the frontal cortex and hippocampus in a dose-dependent manner. Journal of Neuroscience. v. 30 (41), p. 13.690-8. 13 Oct. 2010.

2. Hu, L. W. et al. The role of Wnt signaling and its interaction with diverse mechanisms of cellular apoptosis in the pathophysiology of bipolar disorder. Progress in NeuroPsychopharmacology and Biological Psychiatry. v. 35 (1), p. 11-17. 15 Jan. 2011.

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[ Physiology ]

Memories of origin The endothelial cells store information in the state in which they were extracted from the donor Ricard o Zorzet to Published in February 2011

C

ells have memory. Possibly not all cells have memory, but some are able to remember, at a later point, the conditions of the organism and the environment from which they were extracted. This ability to retain and transmit information to the descendants has not been observed, as one might expect, in neurons, the brain cells that transport information in the form of electric signals from one point to the other within the organism and store this information in the brain. A team led by the pharmacologist Regina Pekelmann Markus identified cell memory in the endothelium, which is the layer of cells that lines the interior surface of blood vessels.

Currently observed in rats, this form of remembering, described in an article published in November in PLoS ONE journal, is expected to arouse medical interest because it may represent a means to influence organ transplants and to develop tissues in the lab that could substitute natural tissues. “If these findings are confirmed in human beings, it will become necessary to pay attention to cell memory in order to obtain more homogeneous tissue cultures and reduce the risk of rejection in the case of transplants,” says the researcher from the University of São Paulo (USP).

The discovery of cell memory occurred quite unexpectedly. At the Chro-

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nopharmacology Laboratory of USP’s Biosciences Institute (IB), the group led

by Regina was cultivating endothelial cells of healthy rats in acrylic recipients.

The researchers were also cultivating, in the same manner, endothelial cells of animals that underwent a test simulating an acute infection, which was triggered by the injection of lipopolysaccharide (LPS) molecules from the bacteria’s cell walls. After reproducing both groups of cells in vitro for nearly three weeks, the researchers observed that the second set of cells behaved just like their great-great-grandparents.

The cells extracted from rodents with the inflammation reproduced the physiological processes that occur in the endothelium of an injured part of the body: they attracted and retained the defense cells, especially the neutrophils, which are the most abundant immune cells in the organism and one of the first cell types to reach the inflamed region.

The endothelial cells that stemmed from the cells removed from the rats without inflammation behaved as if they were in a healthy environment.

If this phenomenon occurs in rats, the experimental model of various diseases, it is possible that it occurs in human beings as well because the physiology and structure of human organs and tissues and those of rodents are similar. If cell memory is identified in human beings, this memory might

explain, at least in part, the rejection of transplanted organs. Immediately after a heart attack, for example, the endothelium cells produce and expose molecules that attract neutrophils to their surface. Normally dragged at high speed by the blood stream, the neutrophils adhere to the endothelial cells that slow them down until they stop.

Next, the neutrophils squeeze through the endothelium cells, cross the blood vessel and move through the tissues until they reach the damaged cells. This process, which is the same process that occurs in bacterial infections, causes swelling, temperature increases, and pain in the affected area.

According to Regina, this process also leaves a molecular scar. This is why it is possible that a cell that is removed from a person who had a heart attack might carry the memory of this inflammation in its cells, thus increasing the risk of rejection. “This is an important concept and, in principle, might affect the result of transplants; however, we still don’t know if this actually happens,” says immunologist Mauro Teixeira of the Federal University of Minas Gerais.

Salvatore Cuzzocrea, a researcher at the University of Messina in Italy, is a specialist in inflammation. He says that “the idea of monitoring the activation state of the donor’s cells seems like a good beginning to reduce the risk of rejection. We must keep in mind that

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J. ZBAEREN / EURELIOS / SCIENCE PHOTO LIBRARY

Endothelial cells: a record of inflammation

damage to the endothelium is the main cause of unsuccessful transplants.”

The suspicion that cells might retain the memory of a state for long periods of time first surfaced in 2008. In the laboratory headed by Regina, biologist Eduardo Tamura, who was enrolled in the doctorate program at the time, was also working on the standardization of inflammation tests and was trying to discover whether the production of a compound - nitrous oxide (NO), synthesized by the endothelial cells during inflammation and which relaxes the

The projects 1. Pineal gland and melatonin – timing mechanism of neural responses and inflammatory process – nº 2002/02957-6 2. Immune-pineal axis – endocrine and paracrine production of melatonin in conditions of injury – nº 2007/07871-6 Type

1 and 2. Thematic Research Grants Coordinator

1 and 2. Regina Pekelmann Markus – IB/USP Investment

R$ 523,465.57 (FAPESP) R$ 932,222.87 (FAPESP)

blood vessels by increasing the flow of blood to the injured area – varied during the day. Some years before, Regina and pharmacologist Cristiane Lopes had demonstrated that the intensity of the inflammation swings in 24-hour cycles; the intensity is higher during the day and milder at night. The swinging is controlled by the melatonin hormone, the production of which increases after sunset. Synthesized by the pineal gland, which is located in the brain, melatonin tells the organism that it is dark outside and that its cells have to execute the tasks they normally carry out at night.

Physiologist Celina Lotufo, a resear­ cher at the Federal University of Uberlândia and a former student of Regina, verified that melatonin inhibits inflammation because it acts on the endothelium: melatonin prevents the neutrophils from adhering to the endothelial cells and beginning the inflammatory response.

However, the researchers still had to detail this interaction from the biochemical standpoint. Tamura noticed that the melatonin blocked the production of nitrous oxide, reducing the relaxation of the vessels and the arrival of blood and neutrophils to the site of the injury.

In 2008, because of a winter course organized by the Department of Physiology of the IB, Tamura changed the time during which he prepared the rodents for the experiments and was surprised by the result. Instead of in-

jecting the inflammatory compound during the day, he started injecting it at night. When comparing the responses, he noticed that the animals that were injected with the LPS at night produced less nitrous oxide, a sign of less intense inflammation. The anti-inflammatory effect, he noticed, resulted from the action of melatonin, which reduces the production of nitrous oxide by the neutrophils and by the endothelial cells.

When cultivating the endothelial cells for longer periods of time, Tamura and biologists Marina Marçola and Pedro Fernandes noticed that they stored the memory of the health conditions of the rats for up to 18 days; in fact, the cells extracted from rats with inflammation behaved as if they were still living in an inflamed organism.

Under certain conditions, this memory was deleted by melatonin. “When melatonin was given to the animal before the inflammation was stimulated, it prevented this kind of recollection,” says Regina. “But we still don’t know whether the action of this hormone on the endothelial cells is direct or indirect or whether it is possible to revert the memory of the n in vitro inflammation.”

Scientific article TAMURA, E. K. et al. Long-lasting priming of endothelial cells by plasma melatonin levels. PLoS ONE. v. 5 (11). 12 Nov. 2010.

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The Earth

is molded by gravity

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[ Geophysics ]

Accurate measurements deform the idea of the perfect sphere seen from space Carlos Fioravanti Published in March 2011

eduardo cesar

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ravity is still exciting the imagination and leading to bewildering conclusions as it did for Newton. One example: someone traveling by ship from Cape Town, South Africa to Belém, Pará will go downhill without noticing it. Because of differences in the mass of the planet along the route between these two places – and, therefore, variations in the Earth’s field of gravity – the sea level in the port in the south of South Africa is 70 meters higher than the sea level in the port of Belém.

“No one notices this change in level because the distance between South Africa and Brazil is very large, almost 8,000 km,” states geophysicist Eder Cassola Molina, a professor at the Institute of Astronomy, Geophysics and Atmospheric Sciences (IAG) of the University of São Paulo (USP). “Furthermore, the surface of the sea is curved, because our planet is approximately shaped like a sphere.” Last year he made a map of the South Atlantic that comes to these conclusions. He made the map to pass the public admission exam for full professor. Now a smaller A4 version is pinned to one of the cupboard doors in his ample laboratory.

Gravitational force expresses the physical attraction between bodies, which varies according to the mass. An everyday example of the action of this force is the tides. They are the result of the gravitational interaction between the Earth, the Moon and the Sun, which deforms the Earth on a daily basis. Capable of acting at any point in the universe, the force of gravity means that bodies in freefall close to the earth’s surface accelerate at approximately 9.8 m/sec2, i.e., the speed of their fall increases by 9.8 m/sec every second. The acceleration of gravity varies subtly at each point on the Earth according to the relief and density of the rocks because the distribution of the Earth’s mass is heterogeneous. This distribution gives rise to an interesting effect, as described by Molina: “The distribution of the mass of the Earth controls the level at which seawater is going to be found at a

given instant, since the momentary surface of the sea adjusts according to the field of gravity. Therefore, we have highs and lows on the ocean’s surface. The sea level is not constant and varies with the weather and geographical location. In fact, there’s no such thing as sea level, but a mean level or momentary sea level.”

On one of his computers, Molina shows another map that details the variations in the height of the water along the coastline of Brazil. On this map, published in December 2010 in the Journal of Geodynamics, a red stain northeast of Brazil represents an area where the seawater must be 10 meters higher than in the areas that surround it, areas that are marked in green and blue. “With a map like this in your hands,” says Molina, “the pilot of a boat could skirt round the highest areas, even though he cannot see them, to save time and fuel”. While useful, this image is nevertheless a challenge to the imagination, particularly for those who are most skeptical. They will say that they have never seen a slope with water running down it in the middle of the sea.

In the sea and on land – Fernando Paolo, who is now doing a PhD at the Scripps Institute of Oceanography in the United States, prepared this map in 2010, while Molina, his supervisor, prepared the bigger one. The two images result from two sources of information, one local and the other global. The first are the apparati that measure the variation of the field of gravity, gravimeters, which are placed on buoys dragged behind 300 ships that have sailed along the coasts of Africa and Brazil for the last 30 years. The others are sea level variation meters installed in two satellites, the Geosat, which the United States Navy launched in 1986, and the European Remote Sensing Satellite (ERS-1), which has been in orbit since 1995. Molina says, “Using the two sources of information, we developed a methodology that allows us to see what the Brazilian continental platform is like in some areas better than the researchers who study this same region using just satellite data.”

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nasa

Representation of the Earth expresses the force of gravity, which is more intense in the areas in red

Measurement of variations in the sea level by means of satellite, perhaps strange for novice sailors to consider, may indicate valleys or hills on the ocean’s surface that go undetected by other methods because not everywhere that the satellite examines has been evaluated by the various expensive and laborious bathymetric surveys. On land, this type of leveling, which uses GPS (global positioning system) devices and demands a good knowledge of the field of gravity, substitutes relief measurements by classic geometric leveling, which is obtained using a theodolite. Each measurement indicates relief variations at distances of approximately every 100 meters and covers just a few kilometers per day.

“Every work of engineering needs accurate altitude data,” says Denizar Blitzkow, a professor at USP’s Polytechnic.

The apparatuses with which he began to measure gravity variations in São Paulo in the 1970s are soon to be displayed at the Museum of Civil Engineering, which should open later this year.

This way of measuring variations associated with the field of gravity, when added to other techniques, has indicated oil deposits in regions of the northeast of Brazil, for example.

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to this mass – can also indicate where there may be unexplored ore deposits or caves. This technique clarifies the previously inexplicable details of geological maps, reveals differences in the thickness of the lithosphere (the Earth’s crust), and shows how and where the amount of water in the underground deposits of the major aquifers may vary throughout the year. “Until a few years ago,” says Molina, who began working with gravimetry in the early 1980s, “all this was impossible.”

Information coming from the two new European satellites Grace and Goce has been providing details of the variations in the field of gravity since 2003, as

THE PROJECT GNSS: Investigations and applications in geodesic positioning in studies related to the atmosphere and in precision agriculture – nº 2006/04008-2 TYPE

thematic project COORDINATOR

joão Francisco Galera Mônico – unesp INVESTMENT

r$ 1,279,880.42 (Fapesp)

well as allowing for a more exact, albeit somewhat uncomfortable, picture to be built of the shape of the Earth. The Greeks imagined the Earth to be a perfect sphere, but this perfection crumbled when the possibility that the planet turned continuously was consolidated during the Renaissance. Newton stated that, as a consequence of its rotation, the Earth must be flat/oval.

Seen from space, the planet still seems to be an almost perfect sphere, though maps based on the acceleration of gravity represent a deformed Earth, sometimes assuming a shape reminiscent of a heart. “The satellites are showing that we were wrong. Using the most recent measurements we saw that the Earth is not very flat,” says Blitzkow.

The measurement of the axis of the Earth at the equator has shrunk by 250 meters, from 6,370,388 meters in 1924 to the current 6,370,136.5 meters.

Since 1982, Blitzkow has been working with teams from the IBGE on maps of variation in the field of gravity throughout Brazil. The most recent version, which includes other South American countries, came out in 2010. It shows that the force or acceleration of gravity is smaller in an area that includes Ceará, some of the neighboring states and the central region of the country, and as far down as the area north of the State of São Paulo.

Andes and the Amazon – A few days before Christmas 2010 and one week prior to the deadline, Gabriel do Nascimento Guimarães presented Blitzkow with the fourth version of a more detailed map. This one included variations of the field of gravity in the State of São Paulo – the result of 9,000 measurements points on land, complemented by information from the Grace and Goce satellites. This study forms part of the PhD thesis of Guimarães and of a larger project coordinated by João Francisco Galera Mônico, from Paulista State University (Unesp) in Presidente Prudente, for use in socalled precision agriculture, which looks for the best cultivation and harvesting conditions.

Geodesic maps made from differences in elements of the field of gravity smooth out the differences in relief. On the map of the geoidal height of the

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-70o Longitude

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Variations of up to 70 meters in the mean level of the sea reflect differences in the Earth’s field of gravity

State of São Paulo, the relief varies by just six meters in height between east and west, with no sign of the mountains that are 1,200 meters high, close to the coast. On the map of South America, the highest regions are in the Andes, but just 40 meters above level zero, which corresponds to the height of the Amazon.

The concept that the acceleration of gravity reflects the distribution of mass helps when it comes to understanding these now small differences.

“The Andes, although 6,000 meters high, do not have much more mass than the Amazon,” says Blitzkow. “If we could weigh a cylinder of the surface of a mountain in the Andes and another from the Amazon, we would see that the difference in weight is not as great as the variation in altitude.” On the map of the geoidal heights of the Earth, the Himalayas chain is no more than a low hill.

Constructed by Germans and North Americans, Grace, an acronym

Geoidal height (m)

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The force of gravity gains new applications.

All that’s missing is to discover where gravity comes from of Gravity Recovery and Climatic Experiment, is a set of twin satellites. They are 200 km apart and were placed in space in 2002. Because they are in a low orbit, just 250 km up (other satellites with similar functions have been at least 1,000 km high), they measure the most subtle interferences in the Earth’s mountains and valleys on each

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of their trajectories: on-board equipment records variations of thousandths of a millimeter in the distance between them. Goce, an acronym for Gravity Field and Steady-state Ocean Circulation Explorer, was built by the European Community and launched in 2009 to record something complementary: the variation in the various elements of the field of gravity relative to three pre-established axes.

The acceleration of gravity is constantly gaining new applications. The origin of gravity, unlike that of other forces like electricity and magnetism, is still a mystery. No one knows how the Sun attracts the Earth and, to a lesser de­­ gree, how the Earth attracts the Sun. n Scientific article Paolo, F. S.; Molina, E. C. Integrated marine gravity field on the Brazilian coast from altimeter-derived sea surface gradient and shipborne gravity. Journal of Geodynamics. v. 50, p. 347-54. 2010.

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[ PHYSICS ]

Restless neighborhood Strategy allows evaluation of the magnetic interaction between nanoparticles Ricard o Zorzet to Published in February 2011

S

ueli Hatsumi Masunaga and Renato de Figueiredo Jardim, physicists at the University of São Paulo (USP), have developed a relatively simple strategy for measuring a phenomenon that affects the storage and transmission of information registered on magnetic media, such as computer hard drives (HD). If this method of evaluating the characteristics of the material that comprises computers’ magnetic memories proves to be economically feasible, it may become possible to produce, using the same material used currently, hard drives with a storage capacity up to five times higher than the current capacity.

The hard drive of a standard computer, which registers information in films of small magnetic particles of cobalt (Co), chromium (Cr) and platinum (Pt) covered with isolating material, stores 200 gigabytes of data on a surface comparable to that of a matchbox. “If the manufacturing of this component is optimized, the same area would be able to store 1 terabyte,” states Jardim, director of USP’s Physics Institute (IF).

Expanding the storage power of this material, which features an exact composition and capacity that are not commonly disclosed by the industry, depends on the control of the influence that the nanoparticles exert on one another, a phenomenon of the atomic world known as dipolar interaction because the nanoparticles behave like tiny magnets (magnetic dipoles). “This interaction, the inten-

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sity of which increases as the space between the particles decreases, occurs even at distances that are considered as being long in the nanometric world,” says Sueli.

When one hits the “enter” key of a computer to save a text file, for example, a small coil (head) that floats tenths of a millionth of a millimeter from the hard disk converts electrical pulses into magnetic ones and guides the nanoparticles’ magnetic field in a specific direction or in the opposite direction, which requires turning 180 degrees. The direction of this magnetic field (imagine an arrow pointing upward or downward) functions as a unit of information, the bit, represented by the numbers 0 and 1. Once the save command is activated, a long sequence of zeroes and ones is coded in the magnetic direction of the nanoparticles. This magnetic coding does not change when the computer is turned off.

Increasing the storage capacity of this kind of memory, which was created by IBM in the 1950s, requires accommodating a higher number of particles in the same area. However, this process is complicated by dipolar interactions, among other factors. As the nanoparticles come closer together, the magnetic fields generated by them interact with each other until, depending on the distance, they provoke the inversion of the nanoparticles’ direction, or, as physicists refer to the phenomenon, they flip. In this case, a flip is synonymous with instability, which is not desirable when information is stored.

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resin was crushed and heated again in an atmosphere of nitrogen to eliminate impurities. The result was the formation of sphere-shaped nickel nanoparticles immersed in a matrix of carbon and silica. With an average diameter of five nanometers, each nanoparticle is actually a group of nearly 6 thousand atoms organized in the form of cubes that behave as if they are a single dipole.

Interaction – By increasing the con-

Metallic cube: organization of nickel atoms at room temperature

THE PROJECT Study of intra granule phenomena in ceramic materials – nº 2005/53241-9 TYPE

Thematic Research Grant COORDINATOR

Reginaldo Muccillo – Ipen/SP INVESTMENT

R$ 945,914.22 (FAPESP)

In January, Jardim and Sueli proposed a way of avoiding this problem, which they explained in the Applied Physics Letters journal. They suggest using two sets of characteristics of the material to estimate at which point the dipolar interaction becomes relevant. The first set, of a structural nature, takes into account the size of the particles and the distance between them. The other measure is magnetic susceptibility, that is, the material’s response to a magnetic field.

The two researchers devised this strategy by investigating the behavior of a material containing nanoparticles of nickel that had been synthesized by Sueli as part of a thematic research grant supported by FAPESP and coordinated by physicist Reginaldo Muccillo. Nickel (Ni) is a model metal for the study of magnetic properties because it is naturally magnetic at room temperature, as are iron (Fe) and cobalt (Co).

In the lab, Sueli mixed an acid (citric acid), an alcohol (ethylene glycol) and a salt (nickel nitrate), maintaining the liquid at a temperature of 80 degrees Celsius until it had gelled; this gel was subsequently put inside an oven for a period of three hours at a temperature of 300 degrees Celsius. The resulting

centration of nickel, which ranged from 1.9% to 12.8% of the compound’s mass, Sueli observed through the electronic microscope that the distance between the nanoparticles had decreased from 21 to 11 nanometers. Concurrently, the magnetic susceptibility revealed a higher level of interaction among the particles. From a certain distance onward, the magnetic susceptibility was no longer organized as expected for independent particles, an indication that the nanoparticles’ magnetic fields had begun to interfere with each other. “The dipolar interaction became important at distances of less than 14 nanometers,” says Sueli, who described her findings in an article published in Physical Review B journal in 2009 and in another article scheduled for publication in the Journal of Applied Physics.

A set of HD-containing nanoparticles organized so close to each other would behave in a manner similar to a memory affected by Alzheimer’s disease: it could lose the information immediately after acquiring it.

“This characteristic, which renders the material inappropriate for data storage, could be interesting for phenomena that do not require the preservation of the state, such as the transmission of information,” says Jardim. According to the physicist, the strategy could be applied to any material, a property that could attract the interest of the industry. “The method”, he says, “could be adopted as a protocol to monitor the construction of computer magnetic memories and test their quality.”

■ Scientific article MASUNAGA, S.H. et al. Increase in the magnitude of the energy barrier distribution in Ni nanoparticles due to dipolar interactions.

Applied Physics Letters. v. 89. Jan. 2011.

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TECHNOLOGY

Genetic

solutions

Evanild o da Silveira Published in February 2011

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James Gathany / CDC

Transgenic mosquitoes are set free in Bahia to fight dengue fever

16.09.11 17:00:27

[ Biotechnology ]

F

The elimination of female mosquitoes in the larva stage is a strategy that is currently being tested

or animals, mating is a way to perpetuate the species. In the case of Aedes aegypti, the mosquito that transmits dengue fever, this basic process is being inverted. By means of genetic manipulation, a population of lab-raised male mosquitoes was given a modified gene. This gene produces a particular protein, killing the offspring that result from mating with normal female mosquitoes. The release of such males could lead to the reduction of a significant number of these insects, reducing the spraying of insecticides necessary to eliminate them and thus reducing the incidence of dengue fever in human beings.

The first genetically modified mosquitoes were set free in December 2010, after Brazil’s National Biosafety Technical Committee (CTNBio) granted approval. The transgenic strain of the Aedes aegypti mosquito, which was developed by the British company Oxford Insect Technologies (Oxitec), is to be released this month in Brazil’s Juazeiro region, in the state of Bahia. This work will be done by biologist Margareth Capurro of the Biomedical Sciences Institute (ICB) of the University of São Paulo (USP) in partnership with Moscamed Brasil, a company headquartered in the town of Juazeiro.

Dengue fever is one of the world’s leading public health problems, especially in tropical countries like Brazil. According to the World Health Organization (WHO), 50 million people are infected every year, resulting in 550 thousand hospital stays and 20 thousand deaths. Currently, the only sure way to control this disease is to eliminate the insect that transmits it – namely, the Aedes aegypti mosquito. The transgenic mosquitoes developed by Oxitec could become a possible answer for this problem. The males of the OX513A strain – the name given by Oxitec – are set free to mate with wild females. The offspring

inherit a lethal protein and die when they are still in the larva, or pupa, stage. They are modified to survive when given tetracycline, an antibiotic, so that they can be reproduced in the lab. Without this antidote, which represses the synthesis of the lethal protein, no survivors would be left to be released into nature. The transgenic strain contains a fluorescent genetic marker that becomes visible when the mosquitoes are exposed to ultraviolet light. This ensures better quality control of the production of these mosquitoes and their dispersion in the field. The continuous release of these genetically modified insects in large quantities is expected, in time, to reduce the wild population of mosquitoes, in hopes of reducing the spread of the disease.

The story of Capurro’s work with these mosquitoes began with a chance encounter during a conference in 2007. At the conference, Capurro met British scientist Luke Alphey, from the University of Oxford, the founder of Oxitec. He proposed a test, in Brazil, of the transgenic mosquitoes he had developed. At the time, the Brazilian researcher did not believe the experiment would be feasible because of legal and bureaucratic obstacles. A short while later, she changed her mind and decided to conduct the experiment.

To this end, she requested permission from CTNBio, the entity responsible for the regulation of transgenic products in Brazil, to import the insects. “The permission to import the insects was granted on September 21, 2009,” Capurro recalls. “One week later, we received an envelope with 5,000 eggs from Oxitec, at no cost.” The researcher started to raise the modified Aedes aegypti in her insect lab at the ICB. However, it became necessary to raise the insects on a large scale to set them free and test them in the wild.

In addition, the need arose to find an adequate site to do so; the site must be isolated and have a population of wild mosquitoes. Aldo Malavasi, PESQUISA FAPESP

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Danilo Carvalho-ICB / USP

eduardo cesar

a former professor at USP and founder of Moscamed, proposed producing the transgenic mosquitoes in his biofactory, free of charge, and suggested that the mosquitoes be released in isolated towns in the region of Juazeiro. Capurro accepted the proposal, and the company and USP made an agreement to conduct the trial. “These tests will provide us with exposure, technical training and, at the same time, we will have an alternative to control these insects,” Malavasi explained. Through cobalt radiation, the company produces sterile males of the medfly (Ceratitis capitata) and of the New World screwworm fly (Cochliomyia hominivorax). These flies were set free in the regions of Juazeiro and Petrolina, in the Vale do São Francisco river valley, state of Pernambuco, to compete with wild males for females (see Pesquisa FAPESP issue 133).

Masses of insects - “As we have been

raising a mass of insects for some time already, we are going to conduct the experiment, with the help of the infra structure provided by Moscamed, to multiply the transgenic mosquitoes,” Malavasi explains. “To this end, we have built a laboratory to work with the transgenic insects. Our lab has already been approved by the CTNBio.” Moscamed’s team has chosen the appropriate places to conduct the field tests, which will take place in the semidry climate of the region that surrounds Juazeiro. “The tests will be conducted in five isolated sites that are separated from the town of Juazeiro by plantations, highways or unpopulated areas, and where there is a high incidence of the Aedes aegypti,” says Capurro. “In the 36

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water storage tank of a single house we found 300 larvae of the mosquito.” The researcher emphasizes another advantage of working in the chosen places.

“Because of Moscamed’s work in the region, the local population is already accustomed to insects being set free in the environment,” she explains. “This is why the local inhabitants are not afraid of the mosquitoes that we are going to release.” Capurro emphasizes that only the male mosquitoes, which do not bite and do not transmit the disease, will be set free. Now that the CTNBio has granted permission, the next step will be to conduct a dispersion study to assess the size of the local Aedes aegypti population. This is necessary to calculate how many transgenic mosquitoes will have to be set free. Capurro explains that 5 to 10 transgenic mosquitoes need to be released for each wild male. The researcher does not expect a significant reduction of the wild population after the first lab-produced mosquitoes are released. “We will have to set the trans-

The project Promoting mortality in Aedes aegypti infected by the dengue fever virus – nº 08/10254-1 Type

Ordinary Research Grant Coordinator

Margareth Capurro – USP investiment

R$ 347,263.34 (FAPESP)

Larvae of transgenic Aedes with fluorescent genetic marker

genic mosquitoes free for at least two summer seasons to significantly reduce the existing population,” she says.

There are good reasons to expect that this experiment will be successful in Brazil, especially based on the results of trials in other places where Oxitec’s transgenic mosquitoes have been released. Tests conducted last year in the Cayman Islands, which involved the release of 3 million genetically modified mosquitoes, showed an 80% reduction in the wild mosquito population. Similar results were obtained in Malaysia. These successful results have led other countries to use the British company’s transgenic mosquitoes in trials as well. Oxitec claims on its web site that France, India, Singapore, Thailand, the United States, and Vietnam have already approved the importation of these insects.

The path chosen by Oxitec to develop genetically modified mosquitoes is just one of many that are being taken around the world. An example of such work was cited in early 2010 in an article in Proceedings of the National Academy of Sciences (PNAS). The article was written by a team of international scientists, including Brazilian biologist Osvaldo Marinotti, a former researcher of USP and currently a professor at the

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eduardo cesar

University of California, Irvine (UCI).

Instead of producing Aedes aegypti males that leave a mortal gene for their descendants, they developed a transgenic female that is unable to fly.

The males remain – The muscles that

support the mosquitoes’ flying ability are stronger in females. Nobody knows exactly why this is so, but it is believed that this occurs because the female mosquitoes draw blood from other animals, including human beings, and carry the eggs. The females carry more weight and therefore need to have stronger wings.

On a genetic level, the explanation for this difference is that the muscles that drive the flight of the female depend on a protein, called actin-4, which is coded (produced) by a gene that is much more active in the females than in the males.

The males have the same gene, but its expression is milder.

The males carry another kind of acting, which also acts on the flight muscles. Scientists, aware of this difference, created a gene that produces a toxic substance for actin-4, preventing this protein, which is found in the flight muscles, from performing its function.

This modification results in females that develop normally until the larva phase, but are unable to fly once they reach the adult phase. Subsequently, they are unable to leave the water, and they die without reproducing or feeding on blood. This way, they can neither have offspring nor transmit dengue fever. The transgenic males are able to fly, but this is not a problem because the males only feed on nectar and plant juices. They do, however, remain sexually active and mate with wild females, thus transmitting the gene that prevents female offspring from flying.

Professor Capurro has also studied other strains of genetically modified mosquitoes. One strain involves the mosquito that transmits malaria, and another strain involves the mosquito that transmits dengue fever. In the first case, Capurro takes a gene from ticks responsible for the production of an antimicrobial peptide – a protein fragment – called microplusin. “This gene is modified so that it can be inserted into a mosquito,” she explains. “Once the gene is inside the insect’s genome, it produces the microplusin, which

Aedes: the male, on the left, is harmless; the female transmits dengue fever

The use of transgenic mosquitoes will reduce the use of insecticides.

Consequently, the insects do not acquire resistance to these poisons

eliminates the Plasmodium protozoa, a single-sell microorganism that is the agent of malaria, before it is transmitted to a human being.”

In the case of the other strain of modified dengue fever mosquito, a project funded by FAPESP, Capurro’s genetic manipulation leads to the disease-carrier’s death via apoptosis (cell death) after feeding on blood “The existence of the dengue fever virus

activates the protein that induces the apoptosis, thus causing the cell death of all the tissues in the infected mosquitoes, and leads to the female’s death.

As a result, the viral transmission is 100% blocked,” Capurro explains. Several gene introduction techniques are currently being tested with the aim of releasing new transgenic mosquitoes into the wild. One of these techniques is referred to as Medeia, because it induces, by means of biotechnological systems, the death of the non-transgenic offspring resulting from the mating of the normal females with the genetically manipulated males. “Only the offspring that carry the transgenic gene survive. The introduction of the transgenic gene into a population of mosquitoes through the Medeia technique takes only eight generations.” An additional benefit will be available if time and research studies prove that these strategies of using genetic engineering to create transgenic mosquitoes are efficient. This form of control will reduce the need to use insecticides and larvicides, which, while less expensive in the short term, result in insects becoming resistant. For this reason, the use of transgenic and sterile mosquitoes seems to be a promising option for the future. n

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Sugarcane juice in biocells Energy alternative to produce electric power Marcos de Oliveira Published in April 2011

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ugarcane juice, which people in São Paulo often drink when eating deepfried pastries at street markets, is a strong candidate as a source of electric power in a small plastic box that can be used as a battery for mobile devices, MP3 players and even notebook computers. The device that allows sugarcane juices to act as a fuel, called a biocell, is one of the latest developments in the field of alternative energy sources. In 2007, Sony displayed one of these prototypes – there are various such prototypes around the world – using it to supply power to a small music player fueled by glucose. In addition to sugars, other fuels such as ethanol, methanol, and sewage water can be used for this purpose. With respect to sugarcane, the first demonstration was conducted by a research team from the Federal University of the ABC Region (UFABC), in the city of Santo André, located in the Metropolitan Region of São Paulo, Brazil. The team was able to produce electric power from sugarcane juice by synthesizing an enzyme in the laboratory. This enzyme increases the chemical reaction that converts the sugar into electric power.

photos eduardo cesar

[ Biochemistry ]

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Biocell with sugarcane juice is measured at UFABC laboratory

Fuel biocells have gained scientific and technological importance in the last few years. Studies involving these devices, which began in the early 1990s, increased from five articles published in scientific journals in 1989 to 240 articles in 2010, according to a survey by Professor Adalgisa de Andrade of the Chemistry Department at the School of Philosophy, Sciences and Letters of Ribeirão Preto at the University of São Paulo (USP).

These studies are usually conducted jointly by several institutions. For example, Andrade, who works on the development of ethanolfuelled biocells, has partnered with Professor Chelley Minteer from the University of Utah in the United States. Professor Minteer is the coordinator of a group that has conducted several studies in this field. Frank Nelson Crespilho, coordinator of UFABC’s Materials and Advanced Methods Group, which uses sugarcane juice in biocells, has partnered with the University of South Korea, the University of Grenoble in France, and the Federal University of Piauí under the National Institute of Organic Electronics Science and Technology (Ineo).

One of the challenges of the studies on fuel biocells is that the power generated by biocells is still too low, which is an obstacle for commercial implementation. For example, the UFABC study finds that sugarcane and its new enzyme generate 60 milliwatts (mW) per square centimeter (cm2) running at 0.39 volt (V), which is equivalent to 26% of the voltage of a AAA 1.5-volt battery. “The voltage can be increased by placing various cells to function sequentially,” states Professor Crespilho, coordinator of the study. This was the formula that Sony used in its prototype, which generated 1.5 milliwatts per cm2 and a total of 0.8 V. The company’s experiment enjoyed the scientific support of Professor Kenji Kano of Japan’s University of Kyoto.

The current technological challenge is to increase the power and the operating time of biocells, which can currently run for more than 10 hours. Other lines of study in the field include electric power generated by sewage, in which electrons are extracted from the organic material and then miniaturized, a process that would enable installing these cells in humans.

In this case, the fuel might be blood glucose PESQUISA FAPESP

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Biocell with a membrane Electrodes with microorganism and enzyme dipped in sugarcane juice and solution

Anode

e-

Cathode O2 or h 2O 2

e-

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CO2 eCarbon tissue with Saccharomyces cerevisiae

Carbon tissue with enzyme H+

H+ H 2O Saline solution

Sugarcane juice

Injecting sugarcane juice into biocell

rather than sugarcane juice. “One of the current challenges concerning biocells is to put them into microchips, to produce a micro biocell or nanobiocell that could be implanted to work like a pacemaker battery, to release medication in the body or to detect glucose levels,” says Crespilho, who, at the age of 32, is also the head of the Intellectual Property Division of the Technological Innovation Center at UFABC. To measure very low currents of tiny biocells, Crespilho and his team developed a software program and, with FAPESP funding, purchased equipment that eliminates noise from the cables of electronic appliances.

since, like their older cousins, they are highly energy-efficient and use little fuel to convert energy, as compared to gasoline or diesel-fueled engines, for example. This conversion is silent and does not produce large amounts of gases or pollutants.

THE PROJECTS 1. Interaction between biomolecules and cell systems with OD, 1D, 2D nanostructures, using electrochemical methods nº 2009/15558-1 2. Development of a fuel biocell using ethanol dehydrogenases enzymes immobilized by selfassembly - nº 2008/05124-1

High efficiency – The biocells work like

batteries; that is, they convert chemical energy into electric power in a manner akin to fuel cells that produce electric power. The related equipment can be made to order by several companies, including in Brazil, and it is hydrogenfueled. The power of this equipment corresponds to more than five kilowatts, which is enough to provide electric power for a home that comfortably houses four people. The fuel biocells currently undergoing scientific and technological research have the potential to become an alternative form of electric power, 40

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Type

1 and 2. – Ordinary Research Grant Coordinators

1. Frank Nelson Crespilho – UFABC 2. Adalgisa Rodrigues de Andrade – USP Investment

1. R$ 92,262.80 and US$ 50,821.57 (FAPESP) 2. R$ 73,622.30 and US$ 29,031.76 (FAPESP)

The benefit of these small devices is the biological aspect found in organic catalysts produced with enzymes or microorganisms. They produce the necessary chemical reaction to generate electric power and can replace the expensive platinum used in fuel cells. Crespilho’s team has developed a synthesized enzyme in the form of a compound comprised of iron oxyhydroxide nanostructures and an organic polymer called poly diallyl dimethyl ammonium chloride (PDAC). This compound is applied in the cathode, one of the terminals of an electrolytic system, similar to a battery, that produces electrons or allows them flow.

The electrons, in this case, are extracted from the sugars of cane juice on the anode (see illustration). The group also used polyamide in the structure of the cell To understand this bioelectrochemical area of study, which is being referred to as nanobioelectrical chemistry because it uses nanotechnological compounds, one must keep in mind that the fuel and biocells need oxidizing and reducing elements to gain and lose electrons. A polymeric membrane called a proton exchange membrane is sandwiched between the biocell’s anode and cathode. Given that the current is direct, the electrons flow from

infographics mario kanno

Proton-exchanging membrane

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Biocell without a membrane Solution with electrodes and enzymes produces electric power

anode

Cathode

e-

h 2O 2

e-

eeGlucose Enzyme glucose Oxidase

Artificial enzyme: iron oxide nanoparticles stabilized in an organic polymer

Gluconic Acid H 2O Saline solution

one side to the other and are received at the other end. Only the protons – the non-electron atoms – pass through the membrane. Crespilho also studies biocells without membranes between the two terminals. “In this case,” he explains, “we produce a biocell in which the electrons are placed in a solution of glucose, water, hydrogen peroxide (H2O2), and two kinds of natural enzymes – a glucose oxidase and our enzyme with iron oxide nanoparticles.

The biocell proved to be effective, as the electrochemical reaction achieved a higher speed than some cells described in scientific literature,” says Crespilho.

“The synthetic enzyme that we developed mimics the natural mechanism of enzymes of the peroxide class. When electrons are extracted from the sugars for the anode, other electrons are injected into the cathode and the synthetic enzyme accelerates the breaking of the hydrogen peroxide molecules.” According to the researchers, a biomimetic enzyme is cheaper, more stable and more efficient than natural enzymes. The work, which was developed by Marccus Victor Martins, a doctoral student, consists of coating the iron oxide with a layer of a synthesized organic polymer in the shape

of needles. The immobilized enzyme, placed over an electrode containing carbon tissue fibers, is placed inside a saline solution with sugarcane juice and other additives that then form the enzyme’s natural environment.

“The biggest problem is to maintain the enzyme’s stability for more than 10 hours. If it degrades, the current weakens,” says Crespilho.

Without disturbing – The experi-

ments conducted by Crespilho’s group also focus on another possibility of the biocell world, namely, the use of microorganisms such as the Saccharomyces cerevisiae yeast, which is used to ferment ethanol, bread and beer.

“They digest the sugar,” says Crespilho.

“The biggest difficulty is to extract the electrons without disturbing or killing the Saccharomyces.” By means of various chemical strategies, the researchers were able to maintain the microorganism and to produce electric power while the organism was immobilized in a carbon electrode. According to the scientific literature, more than 20 microorganisms, especially bacteria, have already been used successfully in experiments with biocells.

The use of electrodes with microorganisms was not part of the studies

conducted by Professor Andrade of the USP at Ribeirão Preto, author of an article that summarized the worldwide activities conducted in 2010 concerning enzyme biocells. She develops ethanolfueled biocells comprised of enzymes that break up the alcohol, such as the dehydrogenases found in the liver to digest alcoholic beverages. Her group’s most recent accomplishment is the development of anodes with immobilized nanostructures. These anodes, which contain more stable organic polymers and dehydrogenases, have a higher electric current density and function for as long as 90 days.

“Our work consisted of mixing the enzymes and the polymers and placing them on a carbon surface prepared to receive electrons; we guided the electrons so that the electrode would become more stable and powerful,” says Andrade. A postdoctoral student, Juliane Forti, also participated in the study. As a result of these new arrangements, Andrade’s group produced a battery with 0.28 milliwatts per cm2 that worked with ethanol. Adalgisa and Crespilho are among a select group of researchers who inherited the development of biocells from Professor Michael Potter of the University of Durham in the United Kingdom. In 1912, Potter demonstrated the production of electric power by Escherichia coli bacteria in an organic substrate.

The first biocell with enzymes was announced more than 50 years later, in 1964, by a group of researchers from the Space-General Corporation, California, United States. It has been a long journey, one that might lead to a new power alternative in the not very disn tant future.

Scientific articles 1. Martins , M. V. A.; Bonfim, C.; Silva, W. C.; Crespilho, F. N. Iron (III) nanocomposites for enzyme-less biomimetic cathode: A promising material for use in biofuel cells. Electrochemistry Communications. v. 12, n. 11, p. 1.509-12. 2010.

2. Aquino Neto, S.; Forti, J. C.; Zucolotto, V.; Ciancaglini, P.; Andrade, A. R. Development of nanostructured bioanodes containing dendrimers and dehydrogenases enzymes for application in ethanol biofuel cells. Biosensors and Bioelectronics. v. 26, p. 2.922-26. 2011.

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HUMANITIES

Dali’s madness in Spellbound

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[ cineMa ]

How the seventh art depicts mental disorders

ARTISTIC MADNESS

Alexandre Agabiti Fernandez Published in February 2011

M

ore than any other form of art, cinema lends itself to the representation of mental disorders.

Paranoids, psychotics, and other mentally unsettled people fascinate or disturb spectators because mental madness shatters the inherent order of the world and one’s usual perceptions of it. Cinema e loucura – Conhecendo os transtornos mentais através dos filmes [Cinema and madness – Learning about mental disorders through movies] (Artmed), by J. Landeira-Fernandez and Elie Cheniaux, is the first published work that systematically classifies the mental disorders of movie characters. Each chapter describes the clinical aspects of a given mental disorder, followed by the presentation and discussion of cinematic examples of the said disorder. The authors discuss a total of 184 movies, many of which are well known. “The book is an academic tool for the teaching of psychopathology and psychiatry, providing concrete examples that are treated in a more abstract manner in lectures,” states J. LandeiraFernandez, a professor at the Psychology Department of PUC-Rio. “Using movies motivates the student and is especially interesting in the case of students that have no access to actual patients,” notes Elie Cheniaux, a professor at the UFRJ Psychiatry Institute.

The relationship between cinema and the human psyche is highly evident, as the seventh art represents humans in all their forms, from the most cheerful to the gloomiest. On the other hand, the very situational environment in which movies are shown (i.e., the cinema, a dark room in which images are projected for a relatively passive and immobile spectator) fosters an artificially regressive, dreamlike state, implying that the

individual draws away from reality and becomes involved with the images of the films. In cinema, a similar phenomenon takes place. The experience of a dream, with its free associations, is comparable to cinematographic construction, which enables apparently heterogeneous worlds to coexist.

Beside these analogies, one should keep in mind that cinema and psychoanalysis, which was born out of psychiatry, came about at almost the same time – the end of the nineteenth century and the start of the twentieth century – and revolutionized how reality is addressed.

For example, Hanns Sachs, one of Freud’s disciples, was among the first psychoanalysts to show an interest in cinema. In his seminar, Jacques Lacan, another psychoanalysis pioneer, analyzed the main character in Luiz Buñuel’s This strange passion, a notorious case of paranoia.

“The script is based on conflict. A film, according to the classic model, has three acts: an introduction to the characters, the development of conflicts amongst them and the resolution of these conflicts, many of which are of a mental nature. A movie with ‘normal’ characters, who are at one with themselves and conflict-free, would not arouse the interest of the audience. However, a movie with disturbed characters, outside normality, depicts conflicts that drive the plot forward. A ‘crazy’ character is more cinematographic. Deviation seduces; normality does not,” argues Flávio Ramos Tambellini, professor and coordinator of the Darcy Ribeiro School of Cinema in Rio de Janeiro.

In Cinema e loucura [Cinema and madness], movie characters are regarded as clinical cases. Lost Weekend (1945), by Billy Wilder, vividly depicts the wealth of symptoms of abstinence from alcohol. Annie Hall PESQUISA FAPESP

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Nicholson’s lunatic in The Shining

(1977), by Woody Allen, presents dysthymia, characterized by depressive symptoms that are weaker than those of typical depression, and a generalized anxiety disorder.

H

owever, mental disorders are often misrepresented because movies are not educational, but instead follow artistic and commercial dictates.

“Screenwriters and movie makers are not obliged to be true to reality. Cinema is not required to be educational. It’s an art, not a science,” Cheniaux notes.

However, these distortions do not mean that the author’s form of addressing such issues as proposed should be disregarded. In Ron Howard’s A Beautiful Mind (2001), a biography of John

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Nash, a mathematician and Nobel Prize laureate in Economics, John Nash’s schizophrenia is poorly described.

“He has visual, kinesthetic and hearing hallucinations. This is wrong, because schizophrenics have single-mode hallucinations, of which the hearing type is the most common one. Actually, this was the only form of hallucination that Nash suffered from. Although wrong, the representation of the symptom works as a negative example,” says Landeira-Fernandez.

In other cases, the character’s behavior does not fit any diagnostic category. Frequently, this “madness” reflects common sense and is very different from the symptoms of a real mental patient. The book also includes movies with such distortions. In Roman Polanski’s Repulsion (1965), Carol, the character played by Catherine Deneuve, has a horror of penetration and

behaves in a very strange way. What mental disorder might these characteristics show? Carol’s disturbances do not fit the categories described by the DSMIV-TR (the Diagnostic and Statistical Manual of Mental Disorders), which guided the authors.

The problem of mental illness diagnosis, however, is far from being specific to movies. “In medicine, diseases are defined based on their causes. However, in psychiatry the categories are described only by their symptoms, a fact open to criticism. Often a given patient meets the diagnostic criteria for more than one category of disorder at the same time. It is difficult to believe that he has three or four psychiatric illnesses at the same time. So things are arbitrary, to some extent,” states Cheniaux.

In the first decades of the last century, those who were “mad” were generally limited to the fantastic and weregene­ rally considered criminals. With Robert Wiene’s German expressionism classic, Das Kabinett des Doktor Caligari, mental madness is first cinematographically represented. As in other expressionistic movies, the sets were strongly stylized, and the abrupt gestures of the actors symbolically translated the mentality of the characters and the state of their souls.

The character Caligari is a mad doctor who hypnotizes Cesar, his assistant, and directs to him to commit crimes, which reflects a paranoid need for power. Another perverse and intelligent figure of that time was the central character of Fritz Lang’s Dr. Mabuse (1922), a psychiatrist who also resorts to hypnotism to manipulate people to commit crimes.

Mabuse is driven by the desire to govern by money, whereas Caligari’s thirst for power is abstract. Mabuse’s madness and the morbid passivity of his victims point to the decadence of German society at that time and to the chaos that was overtaking the country.

Another Fritz Lang movie, M (1931), focuses more realistically on the psychology of its characters. The central figure is a murderer of girls who is depicted with humanity in the horror he commits. Nevertheless, society is no better: in the face of the police’s inability to arrest him, he is “judged” by other delinquents, pointing to what was to become true in Germany a few months later when the Nazis rose to power.

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n the 1940s, the media gave more room to psychoanalysis. During this era, psychoanalytic thrillers appeared, and the filmmakers resorted to the psychoanalysis arsenal clumsily and naively. The prototype of such movies is Alfred Hitchcock’s Spellbound. Constance (played by Ingrid Bergman) is a young psychiatrist in an asylum who falls in love with the new director. However, she soon realizes that the man she loves (played by Gregory Peck) is mentally ill and is pretending to be Dr. Edwards. Based on the sick man’s dreams and a session of analysis, Constance discovers that he has lost his memory, and she understands why he had shouldered the burden of guilt for a crime he had not committed: he had witnessed the death of the real Dr. Edwards, who was murdered by the asylum’s former director, just as the patient himself, during a game as a child, had pushed his younger brother to his death. Beside anguish in the face of madness, the movie depicts the anguish of madness by showing the character’s fear through dreams (as drawn by Salvador Dalí) that reveal a world full of hallucinations and symbols supposedly produced by

After the 1940s, psychoanalysis gained popularity in movies and psychological thrillers appeared, such as those directed by Alfred Hitchcock

the unconscious. In this and in other movies of this period, psychoanalysis is reduced to a method that can resolve obscure conflicts by deciphering a set of generally clear signs.

Starting in the 1950s, under the impact of the horrors of World War II, movies began questioning the confinement of mental patients. Concurrently, new psychiatric drugs appeared

that caused severe side effects, which led many patients to refuse treatment.

In reaction to psychiatry at that time, anti-psychiatry arose and grew during the 1960s, when this counterculture peaked. Some movies show this movement very well, such as Family Life (1971), by Ken Loach, A Woman Under the Influence (1974), by John Cassavetes, and One Flew Over the Cuckoo’s Nest (1975), by Milos Forman.

These works criticize the society that chose to confine its mentally ill people and offer them only straitjackets, electric shocks and drugs, rather than help them mitigate their suffering. These movies reflect a new view of cinema that regarded madness with more concern regarding the burden society put upon its individuals. Some questioned the “madness” of this society and of the family, which raised the issue of defining normalcy.

The great precursor of this line of movies is the cinematographer Ingmar Bergman, one of whose obsessive themes was mental madness. Despite the transformations of the representation of madness in cinema occurring during that time, most movies continued to portray madness as banal, with old clichés that turned the mentally ill into criminals in thrillers or fools in comedies. n

Scene from Repulsion

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ALCHEMIST’S LABORATORY, 1570 – JAN VAN DER STRAET / PHOTO: ERICH LESSING / ALBUM/ALBUM ART / LATINSTOCK

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[ The history of science ]

Documents worth their

weight in gold

R

Alchemist’s laboratory

esearchers Ana Maria Alfonso-Goldfarb and Márcia Ferraz, both from the Simão Mathias Center for Studies on the History of Science (Cesima) at the Catholic University of São Paulo (PUC-SP), took the Royal Society’s motto, Nullius in verba (“Do not believe anybody’s word”), literally. This motto conveys the idea that scientific knowledge needs to be experimentally tested rather than assumed to be true. Thanks to their literal interpretation of the Society’s motto, the two researchers made an astonishing discovery in 2008. While going through piles of documents in the archives of the British institution, they came across a formula for alkahest, the alleged “universal solvent” of alchemists that supposedly dissolves any substance by reducing it to its primary components (see Pesquisa FAPESP issue 154).

However, certain questions needed answering before the case could be closed. Specifically, it was necessary to identify the author of the copy of the discovered formula. Alfonso-Goldfarb and Ferrazwent back to the archives, solved that mystery, and then came upon an even more enticing one: the discovery of a formula for the notorious philosopher’s stone that, according to popular belief, transformed ordinary metals into gold.

Alfonso-Goldfarb explains, “It was an astonishing surprise and, in a way, an uncomfortable one because, as historians of science, it has become increasingly difficult to verify to what extent alchemy was important for the consolidation of the new science in the eighteenth century. It is important to point out that this continuous search for transmutation was viewed within the context of chemistry – especially as an instrument for medical progress – rather than within an esoteric context.

This becomes very apparent in the concerns of such men as Boyle or Newton, among other heavyweights, who believed in the existence of the philosopher’s stone.” She and Ferraz believe that the work on the philosopher’s stone was conducted within the scientific context of the eighteenth century, although there are divergent views as well. As the historian Theodore Hoppen, a professor at the University of Hull and author of a paper entitled “The nature of the early Royal Society,” points out, “Baconism was introduced into the Royal Society distorted by the views of a group linked to Samuel Hartlib, one of the institution’s founders. This group took Bacon’s precepts of studying ‘that which is new, rare, and strange’ in nature to

Brazilian researchers find philosopher’s stone recipe at the Royal Society Carlos Haag Published in April 2011

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the limit, mixing it with the persistent interest in discovering ‘useful’ inventions, without disregarding hermetic ideas, and going back to the works of Paracelsus and Helmont. Suffice it to see how Boyle maintained an embarrassing – to say the least – interest in issues related to natural philosophy and was willing to accept any kind of phenomenon, as long as it could be explained along mechanical lines. This included the philosopher’s stone. Newton, in his letter to Henry Oldenburg, the Royal Society secretary, complained that his colleague should ‘keep silent’ and refrain from disclosing ‘the secrets of a true hermetic philosopher.’”

At the Royal Society in the seventeenth century, brilliant men believed in the existence of the philosopher’s stone to ‘unlock gold’,” says Alfonso-Goldfarb

Latin – Oldenburg, that same Royal So-

ciety secretary, is in fact at the center of the new mystery uncovered by the Brazilian researchers. After several attempts to identify the handwriting of the alkahest formula, they came across a document in Latin with marginal comments in French.

“The handwriting looked familiar to us, and we realized that it was Oldenburg’s handwriting; he wrote his personal comments in French. So that mystery was solved: it was he who had transcribed the alkahest formula. However, when we read the text in Latin, written in another kind of handwriting, we realized that it was a formula for the philosopher’s stone,” the professors explain. The title of the text, whose date they were able to pinpoint as

1659, was Processus de bois. Right from the start, the two researchers believed that this referred to experiments related to burning wood (bois is French for “wood”).

However, when they verified the existence of elements in the philosopher’s stone formula, they realized that the same person who had written the alkahest formula was involved. They checked in France if someone called Du Bois had anything to do with the famous transmutation; after a detective-like search, they came upon the story of Noel Picard, also known as

ALCHEMIST / ETCHING, 1625 / ALBUM / AKG-IMAGES / LATINSTOCK

Preparing the philosopher’s stone

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Du Bois, who was hanged in the Bastille in 1637 at the order of Cardinal Richelieu.

The reason? Picard had tried to fool Louis XIII’s powerful minister by claiming that he was able to produce gold from lead.

After an adventurous life of travels and after having converted from a Capuchin priest to a Lutheran one, Du Bois, now back in Paris, was taken under the wing of Father Joseph, Richelieu’s confessor. “The cardinal saw this as a chance to increase France’s wealth and solve the kingdom’s financial problems. So he asked Du Bois to use his ‘projection powder’ to produce gold in the presence of the king, the queen, and other noteworthy guests, including Richelieu,” recounts Ferraz. Carrying a cupel and a crucible, Du Bois went to the Louvre and set to work, asking the guards to bring him some musket gunpowder.

He heated the gunpowder, sprinkled a powder on it and then covered it with ash.

The enthusiastic king insisted on blowing on the mixture himself to reveal what he hoped would be gold, thereby covering himself, the queen and all the guests in ash. However, the glimpse of gold in the bottom of the pan more than made up for the inconvenience. Louis XIII hugged the ill-fated Du Bois, immediately granting him a noble title and the privilege of hunting on royal lands. Richelieu, who was very pleased, took Father Joseph aside and told him that he would nominate Father Joseph for cardinalship.

The court goldsmiths helped sustain the jubilant mood by verifying that the material was indeed 22-karat gold. Du Bois confidently told the goldsmiths that this transmutation was merely a small example of alchemy’s possibilities.

Richelieu told Du Bois that the king needed “only” 800 thousand francs worth of gold every week and granted him 20 days to begin this large-scale production. Richelieu added that this newfound source of gold would allow the king to stop collecting taxes and make him the most powerful ruler in Europe.

However, Du Bois spent the 20 days hunting with his friends. The cardinal became suspicious and ordered that Du Bois be watched. Finally, irritated with the delay, Richelieu built a laboratory for the alleged alchemist to execute his “great work,” this time as a prisoner in the castle of Vincennes. Du Bois failed, and the “nobleman” was taken to the Bastille where he was tortured and hanged for

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ARTWORK OF AN ALCHEMIST CREATING LIFE / JEAN -LOUP CHARMET / SCIENCE PHOTO LIBRARY / SPL DC / LATINSTOCK

failing to provide the formula for the philosopher’s stone to his captors. In spite of the alchemist’s evasive behavior, Du Bois’ executioners believed that he really was capable of producing gold but did not want to disclose the secret. Twenty years later in 1659, Oldenburg was in France and came across Du Bois’ formula. He sent it to England, where it seems to have been enthusiastically received. As Alfonso-Goldfarb notes, “In the seventeenth century, at the Royal Society, those brilliant men actually believed that Du Bois had really been able to ‘unlock the gold,’ in other words, that he had been able to dissolve it in order to prepare other materials, which was the function attributed to the philosopher’s stone.”

Stones – Alfonso-Goldfarb explains,

“The core of the matter was the concern in dealing with health problems, especially the dissolving of stones in the body, one of the leading causes of death at those times.

The belief was that the perfect solution was to dissolve them with mineral acids, without killing the patient. It was necessary to find something with the power of acid without the problems. This is where alkahest and the philosopher’s stone together would be the perfect medication.”

Alkahest would reduce the negative effects of the acid remedies, and the philosopher’s stone was its perfect complement. The stone was powerful enough to dissolve a noble and resistant metal such as gold, yet not powerful enough to damage the body. “Of course,” Ferraz adds, “this didn’t keep people from believing that the Stone was able to produce gold for financial purposes, even though the monetary reasons were neither the only nor the most important ones.” Everything was interconnected. If, as alchemists believed, the stone had the power to “perfect” the metals by converting them into gold, then this metal “medicine” could be extended to medicine and similarly “improve” human subjects. This belief in alchemy’s purifying power explains why so many people referred to the stone, and its gold-producing power, as a panacea for all illnesses and capable of prolonging life. As gold did not corrode, it came to be viewed as a symbol of immortality. Thus, ancient physicians and Chinese alchemists seeking life-prolonging elixirs came to believe that gold could be used for medical purposes.

Ironic portrait of an attempt at “the great work”

The chemistry historian Paulo Alves Porto, a professor at the Chemistry Institute of the University of São Paulo, expands on the medical implications of alchemy: “The work of Paracelsus and Van Helmont, among others, was developed at a time when Galenic medicine was being questioned. In addition, there were other new diseases that required more effective solutions. The search for such solutions by resorting to such remedies as alkahest, for example, reveals this medical concern.”

In his article “Alchemy and Iatrochemistry,” the American historian Allen Debus contends that “the meaning of chemistry, in the sixteenth and seventeenth centuries, must be viewed in the context of its relationship with medicine, even though transmutation remained a constant issue until the Age of the Enlightenment, even when the separation between chemistry and medicine had already begun.” According to Debus, the early proponents of the chemistry-medicine divide were rivals of the Galenic camp. They primarily sought to explore chemical explanations for physiological processes, and their advancements formed the basis of the work

of Van Helmont. His work led to a separation between chemistry and medicine in every area except pharmaceuticals. “The work of Lavoisier did not need to resort to chemistry based on medicine because of this long process. The importance of medicine in the rise of modern science was not discussed much,” Debus adds.

As a result of these shifting conceptions, transmutation lost some of its power in the late seventeenth century. “A movement was started at the Academie Royale de Sciences in Paris to sideline practice in order to domesticate chemistry, turning it into a respectable subject which would be included in academia. It was necessary to break away from the alchemistic past and start everything from scratch to provide chemistry with a new identity and status. Even so, this movement was not entirely successful,” notes historian Lawrence Principe from Johns Hopkins University, the author of Alchemy Tried in the Fire. Alfonoso-Goldfarb believes her discovery will lead to more revelations: “The network of documents and people intimately linked to transmutation, that our research work has exposed, gains more data and ramifications every day.

This could be the tip of an enormous documental iceberg.” n

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art

Restoration of

War and Peace

Invited to produce panels for the United Nations (U.N.), the painter C창ndido Portinari represented war and peace as pain and happiness. The powerful works of art came back to Brazil 53 years later, in 2010, for restoration. With the dust now removed and the colors renewed, they are expected to be exhibited in S찾o Paulo in early 2012.

Above, War before restoration.

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Eduardo Cesar

POST DOCTORAL FELLOWSHIPS in São Paulo, Brazil

affiliated with higher education and research institutions in the state of São Paulo.

FAPESP’s PD Fellowships are granted for 24 months and can be renewed for 12 months.

It includes a monthly stipend, travel to and from Brazil, expenses for the selected candidate and family, and overhead for small research expenses.

For additional information, see http://www.fapesp.br/en/materia/ 5427/scholarships/post-doctorate-fellowship.htm For guidance write to pd@fapesp.br

Gustavo Tílio / LNLS

The São Paulo Research Foundation (FAPESP), one of the main research funding agencies in Brazil, invites talented researchers with a recent PhD degree and a successful research track record to apply for postdoctoral fellowships. In 2010, 66 positions were opened, in virtually all fields of knowledge (see http://www.oportunidades.fapesp.br/en/) Fellowships may also be requested through specific proposals presented by a candidate and a supervisor from any research group

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