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Physics

Versatile Minds

Physicists help to solve problems in genetics, in medicine, and in team leadership

For physicists, there are no frontiers delimiting the space in which they should work. Not satisfied with exploring the entrails of atoms and the most distant stars of the heavens, they have begun to occupy other territories and to solve problems in genetics, biology and medicine – more recently in economics and business administration as well. They are elegant incursions: in search of simple rules that explain the phenomena of nature, they do not hesitate to leave aside details that the specialists from other areas regard as precious. And, endowed with a notable capacity for abstraction, they examine different phenomena – the propagation of tumors or the floating in the price of shares on the stock exchanges – following the same mathematical techniques used in an area of physics, statistical mechanics, to explain the so-called phase transitions, like the transformation of water into ice.

On September 8, a meeting held at the Physics Institute of the University of São Paulo (USP) in homage of the 60 years of José Fernando Perez, FAPESP’s scientific director and a researcher in the area of mathematical physics, threw the spotlight on this versatility, with demonstrations that physicists also understand genes, cancer, or stock exchanges. In the last 20 years, Perez himself has applied the methods of mathematical physics to create models that explained phenomena like the fluctuation in the populations of flies, or the capability of some materials to become magnetic in a spontaneous way. “No phenomenon of nature”, says he, “can, a priori, be excluded as an object of study for physics, which from the epistemological point of view is an arrogant science. Physics claims the right to study any natural phenomenon”. Last year, Perez took advantage of the end of a debate on the 50 years of the discovery of the structure of the DNA molecule to, with a dash of humor, to launch a provocation: “Modern biology should be perceived more and more as a chapter of physics”.

The image of DNA
The desire for intervening in other areas began a little over 60 years ago, when Austrian physicist Erwin Schröedinger published his book What Is Life?, applying concepts of physics to understand the surprising stability of genetic information. Schröedinger also launched the idea that the chromosomes of each cell could contain encoded messages – it was the genetic code, later confirmed experimentally by the biologists. It was another physicist, Francis Crick, who died in June, who interpreted the X-ray images of DNA, which their very author, biologist Rosalind Franklin, would look at without imagining that it was the final evidence of the helicoidal structure of the molecule responsible for the transmission of hereditary characteristics between living beings.

From then until now, the integration of physicists with specialists from other areas has just grown. “Besides employing the principles of physics to understand biology better, we want, in the opposite direction, to use biology to understand physics”, says physicist José Nelson Onuchic, co-director of the Center for Theoretical Biological Physics (CTBP), created in 2002 at the University of California at San Diego (UCSD), in the United States, with funding of US$ 10.5 million from the National Science Foundation (NSF). Physicists and chemists from the CTBP, working with experimental groups, have managed to demonstrate the principles of entanglement, aggregation and recognition of proteins, now employed in the design of drugs, and of the workings of the calcium channels, with potential applications in the regulation of heartbeats.

Out in the lead
But those who do not know what a Hamiltonian or an Ising model is, typical terms in the jargon of physicists, should relax: physicists are more and more trying to understand the language of other areas and make their conclusions clearer – although it is a slow process. One of the speakers at the meeting on the 8th , the Portuguese physicist João Amaro de Matos spent ten years studying social psychology, economic theory and sociology, after graduating in physics at USP and in business administration from the Getúlio Vargas Foundation in São Paulo. It was as a professor at the School of Economics of the New University of Lisbon that he arrived at a mathematical model that suggests how a president of a company or a professor should act, or generally speaking anyone who takes care of many people, using the support or rejection that he receives from the group.

According to this model, drawn up in conjunction with economist Luis Almeida Costa, also from Lisbon, a president or professor of the hard line type who feels himself isolated and without the support of the group who keep quiet about their proposals and communicate only with those responsible for the working groups, until the contrary attitudes begin to be diluted in the midst of growing adhesion. If he enjoys the support of at least one part of the group, the best thing to do is to strengthen the teams and encourage the exchange of ideas. “This model is going to show, for each situation, how to control the interactions between people, in such a way that all of them follow the attitude of the leader of the group”, comments Matos, who studied for his master’s and doctor’s degrees under Perez and lived in Brazil from the age of 14 to 28 – he is 43 years old today.

The president of the company or the professor before his student, as they manage to change the attitude of the group and win over adhesions, behave like the crystals that are formed in water about to be transformed into ice and are capable of rapidly attracting other molecules of water and constitute increasingly larger crystals, until all the water freezes, at 0°C. Published in 2002 in Computational and Mathematical Organization Theory, this theory explained the strategies inspired only on intuition and empiricism, without a single equation. One example analyzed by the team from Lisbon is the Aerospace Engineering Division of General Electric, gripped years ago be a turbulent process of reformulation: in less than two years, three presidents went in and out, until a fourth one managed to establish more suitable communication channels, eliminated the internal conflicts, and went back to the way to profits.

Matos also applies the concept of mood contagion to provide a basis for the mechanisms of the subtle variations in prices on the stock exchanges, governed, in accordance with a relatively new area, econophysics, by imitation behavior: each investor buys or sells shares according to the trend of the moment, to avoid risks and to remain in the group to which he belongs. “In the financial market”, says he, “few people really know what they are doing”. Chain interactions and hierarchies also explain how, in the inside of the human body, enzymes organize themselves and tumors spread.

In search of a way of differentiating normal cells from tumorous ones that facilitates the medical treatment, a team from the Mathematics and Statistics Institute (IME) at USP, and another from the Ludwig Institute for Cancer Research examined the behavior of 376 genes from 99 samples of tissues from healthy persons and from sufferers from cancer of the digestive tract, usually diagnosed at an advanced stage. In a first test, carried out at the beginning of last year, a computer from the IME worked three weeks without stopping on an exhaustive analysis to identify small groups of genes that reveal the distinction between the cells.

Based on the results of this test, the researchers developed alternative search methods, more realistic from the computing point of view, without impairing efficiency in identifying groups of genes that could work as classifiers, capable of differentiating a normal cell from an altered one.

Biochip
“It is very easy to generate classifiers”, comments physicist Eduardo Jordão Neves, the coordinator of the team from the IME, who also presented his most recent results at the meeting at USP on the 8th. “What is difficult is to find those that are really important, that can be extrapolated and used in other situations.” Jordão Neves’ scientific career started with his thesis for a master’s degree, supervised by Perez, with important contributions to the mathematical study of models for magnetic materials.

Analyzing the information generated by glass slides that reveal the more or less intense activity of each gene – or biochips -, the researchers identified 41 pairs and 37 trios of genes that may work together, but in the opposite way: in normal cells, one of them may be produced more and the other or the other two less, while in tumors the opposite happens. “The way for analyzing data generated by biochips requires a strong knowledge of mathematics and statistics that we, doctors, do not have”, says physician Luiz Fernando Lima Reis, head of the group from the Ludwig and co-author of this study, published in February in the Cancer Research magazine. According to him, this work has helped to create molecular classifiers for the early identification of other kinds of tumors of the neck and head, foreseeing which individuals ought to be given one kind of treatment or other.

Red carpet
Something has changed. Physicists, who previously had the habit of going in where they were not called, are now invited and valued, in a time in which molecular biologists, geneticists, biologists in general and doctors see themselves faced by an indescribable volume of information. Ten years ago, one gene a time would be studied, but today a set of biochips analyzes the action of 10,000 genes at a single time. In March 1999, in a speech at the celebration of the centenary of the American Physics Society (APS), the American physician Harold Varmus, then director of the National Institutes of Health (NIH) of the United States, highlighted the value of the methods of work and the equipment created by the physicists, like radiography, PET scans, ultrasonography, magnetic resonance and electron microscopy, which have placed biomedical research on another level.

Next, Varmus recalled that it was a mathematical physicist, Warren Weaver, who first used the term molecular biology in 1932, on the argument that, already in those days, “the distinction between physics and chemistry, and even mathematics, on the one side, and biology on the other, would be as illusory as unfortunate”. Finally, perhaps not to let the ego of the physicians swell too much, the director from the NIH commented that the fight against diseases depends on the energies of specialists from other areas, like engineering, computing sciences, psychology, sociology and anthropology. Evidently, the rapidity and the relevance of the results are proportional to the capacity of interaction between the specialists from the most varied areas, made possible by a common language. “My group was willing to learn a bit more about mathematics, in the same way that Jordão Neves’ team studied biology with more attention”, says Reis, from the Ludwig. “We both yielded, and today we no longer speak 100% Greek to each other.”

At USP’s São Carlos Physics Institute, José Fernando Fontanari advanced more easily in one of his lines of work, about the mathematical models that try to explain the emergence and the organization of the first living beings, when he allied himself to a theoretical biologist, Eörs Szathmáry, from the Collegium Budapest, in Hungary. At USP’s School of Medicine, Eduardo Massad, who graduated in medicine and in physics, is coordinating a group with other physicists and physicians to foresee the possibilities of the dissemination of diseases like yellow fever or dengue, by means of equations that take into account variables like the transmission rate of the causal agents and the number of persons that the transmitting mosquito can sting in one day.

Limits
The physicists know it: their proposals will only really be understood when packaged in the theoretical referentials known by the specialists from other areas. “It’s no good arriving with ready-made models and publishing the results only in physics magazines”, comments Matos. They also know that they have to take care when applying the mathematical models to reality. More realistic formulations abdicate ice, made up just of water molecules, to inspire themselves on materials without defined structures, like glass, formed of elements that are different between themselves, each one interacting with another in its own way. Be that as it may, it is clear that competency in dealing with mathematical structures that describe complex systems can sprawl from ferromagnetism to such diverse environments as the stock exchange or a biochip. Even so, not even the physicists are capable of expressing the complexity of nature in formulas.

In a cell, the network of interactions between the molecules is absurdly entangled. Human sciences also emphasize unforseeability, since people can change behavior driven by their own will, different from an atom. Physicist Christof Koch and biologist Gilles Laurent, from the California Institute of Technology, United States, in an article published in Nature in 1999, indicated a basic difference between the brain and large physical systems like galaxies. “The brain has a function, which is to protect the individual (or his skin) in his environment and to ensure the continuity of his genome”. The agglomerates of stars, on the other hand, have only a brute existence – purely physical.

But the physicists believe that they can still go much further, as says American Robert Laughlin at a conference in San Diego in 2000, two years before winning the Nobel for Physics: more than mere part players and simply doing calculations, it is the physicists who should say what is really important in each area of science. Schröedinger, with What Is Life to hand, would be in full agreement.

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