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USP 70

A monument to health

The trajectory of the School of Medicine of the University of São Paulo (USP), one of the most vigorous centers of health care and scientific research in the country

Arnaldo Vieira de Carvalho (1867-1920), a surgeon and gynecologist, and Enéas de Carvalho Aguiar (1902-1958), a hospital administrator, both died prematurely, in their 50s, and were able only to glimpse the birth of the institutions they founded: respectively, the School of Medicine of the University of São Paulo (FMUSP), created in 1913, and its hospital arm, the São Paulo Hospital and Clinics (HC), inaugurated in 1944. The memory of these two doctors is recalled every day, even by people who hardly know who they were. Dr. Arnaldo and Dr. Enéas are the names of two busy parallel avenues, in the western district of São Paulo, which contain the quadrilateral made up of the FMUSP, the HC, and their various institutes. These are the most famous and productive addresses for health services, teaching, and research, applied to medicine, in Brazil.

Inhabitants of São Paulo, city and state, look to the services of the Hospital and Clinics in cases of emergency, and for humdrum ailments as well, attracted by the efficiency of its doctors, a safe haven in the midst of the deficiencies in public health.  Brazilians from all the corners of the country, have become used to traveling thousands of kilometers to be treated at the HC – many are suspicious of the idea that there are centers of excellence in almost all the regions. The largest hospital complex in Latin America, the HC attended to 1.5 million outpatients last year alone, and to 550,000 emergencies. Its 2,492 beds received 60,000 patients.  45,000 operations were carried out, amongst which 500 transplants and 6 million laboratory tests. As the school and the hospital make up a complex and inseparable weave, accompanying the noteworthy diversity of patients makes all the difference in training new doctors and researchers. The FMUSP currently houses 1,422 undergraduate students (the faculty is ranked A), and 2,055 students for a master’s of doctor’s degree (70% of the FMUSP’s postgraduate programs were very well assessed by the Committee for Postgraduate Courses in Higher Education (Capes).

The tradition of being a great school of medicine goes back to the 1940s and 1950s – when a chair professor was just as respected as the Governor of the State, and the students, submitted to an iron discipline, would go to the lessons wearing suits and ties. Today, the profile of the 344 members of the faculty at the FMUSP has changed a lot. “The field of knowledge of medicine has expanded, and it no longer fits within the old professorial chairs. Doctors specialize earlier and earlier”, says Ricardo Brentani, the president of the school’s Research Commission.  Another change, this one more recent, is the increasingly greater dedication to scientific research. In the last ten years, there has been progressive growth in the productivity of the 62 Medical Investigation Laboratories (LIMs), the FMUSP’s research arms.  Just take as a point of reference the original works published in magazines indexed on the database of the Institute for Scientific Information (ISI). In 1993, there were 72 works from the LIMs on the ISI database. In 2002, this figure had leapt up to 338.  In relative terns, the advance is also significant. The LIMs were responsible for 1.6% of all the Brazilian publications on the ISI database in 1993.  In 2002, this slice had reached 3%.

This change was brought about by a set of measures that stimulated the research activity. A 2% fraction of the money that the HC receives from the Public Health System (SUS in the Portuguese acronym), equivalent to R$ 2.6 million in 2002, came to be set aside for the LIMs – and distributed according to criteria of productivity, like publication in high-impact scientific magazines, and the capacity for attracting foreign funds for research. The laboratories are assessed annually. According to the marks given, each LIM receives a larger or smaller portion. This money is spent autonomously, on, for example, the purchase of material, or air tickets so researchers can take part in congresses. The 126 faculty members who devote themselves exclusively to the school have also won the right to a variable supplement to their pay.  They are assessed with marks from A to D. Those marked A can get as much as an extra R$ 3,000 on their paycheck. Those marked D get nothing.  “The assessment takes into consideration several of the professor’s activities, but, above all, the dedication to research”, says José Eluf Neto, the LIMs’ executive director.

The development agencies have also had an important role in this new profile. “The line of thinking is simple”, says Maria Mitzi Brentani, a dentistry associate professor.  “With the funds from the agencies, the laboratories equipped themselves to do research, taking the burden off the budget of the school and of the HC, which can be spent on salaries and attending to the public”, she says. In 2002, these funds amounted to R$ 15.6 million. The main sources were FAPESP, with R$ 8.6 million, and the National Council for Scientific and Technological Development (CNPq), with R$ 1.8 million. “In the context of biomedical research, the FMUSP takes part in all of FAPESP’s major programs. It participated in all the genome programs. And many of the professors have thematic programs with the institution”, says Eduardo Massad, a professor of Medical Information Technology. Massad coordinates a LIM that has stood out by drawing up mathematical models capable of assessing the dissemination of diseases, and by the creation of strategies for fighting them. Recently, its research foresaw an outbreak of yellow fever in a region of the interior of São Paulo scourged by dengue and populated by the mosquito that spreads the two diseases – which happened straight away.

Stem cells
One example of the expansion of the research activity is the Genetics and Molecular Cardiology Laboratory, which occupies the 10th floor of the new building of the Heart Institute, the Incor. With its architectural project inspired on the laboratories of Harvard University, since the first half of the 1990s, the institution has been leading research into mapping the chromosomal regions linked to hypertension.  Another line of research is seeking to understand how genetic and environmental factors interact to increase cardiovascular risk – and showed that hypertrophy in the hearts of mice much more serious the greater the number of copies of the gene responsible for the production of the angiotensin converting enzyme (ACE). The genetic alteration, for sure, is not a direct cause of the problem, but it appears when another trigger overloads the heart. The Laboratory, which joined the effort to map the Xylella fastidiosa bacterium, houses today a vast collection of research, which ranges from the genetics involved in the resistance of the saphenous veins used as bypasses in the heart to the application of stem cells to rebuild regions of the cardiac muscle affected by infarction. There is speculation that the stem cell research may have an effect in rallying public opinion similar to the effect with the advent of heart transplants at the end of the 1960s. Ten heart attack victims have now been given injections of these cells that are capable of transforming themselves into any tissue.  They reacted well. The research is now going to go ahead with another 60 patients, to assess the effectiveness of this procedure on the capacity for reconstituting vessels and tissues.  “There are immense opportunities for new treatments related to cell therapy and to gene therapy”, says Professor José Eduardo Krieger, who is responsible for the laboratory.

The Incor laboratory is far from being an isolated example. Recently, researcher Ana Claudia Latronico, the Endocrinology of Development Unit of the Hospital and Clinics, won the Richard E. Weitzman Memorial Award, granted in June by The Endocrine Society, of the United States, for her participation in pioneering studies that describe new genetic mutations that cause hormonal diseases. The team led by Maria Mitzi Brentani, a professor in oncology at the Radiology Institute, is taking part in investigations like the one looking for molecular markers related to the response to chemotherapy in breast cancer patients. The team recently presented at a congress the genetic characteristics that supposedly make even patients that have advanced tumors react well to doxorubicin, a chemotherapy drug. The discovery, now being submitted to broader studies, may have an important role in choosing the treatment for each patient, according to the peculiarities of their DNA.  “Our long term objective is to find a broad spectrum of tumor markers”, says Professor Maria Mitzi Brentani. Another line of research is investigating the relationship between low levels of vitamin D in the blood and the outbreak of breast cancer in women over the age of 65.  One hypothesis is that low exposure to the sun and poor nutrition have a role in vitamin D deficiency and in the consequent appearance of the disease.

In the Lung Medicine Laboratory, assistant professor Marcelo Amato has developed a piece of equipment capable of producing images, through the emission of electrical pulses, of the pulmonary conditions of ICU patients submitted to artificial respiration.  It is common for forced ventilation to cause damage to the lungs, and doctors have tools that are very imprecise for detecting these problems. Certain moves, like physiotherapy and calibrating the equipment, may help to prevent this side effect. In 1998, the lung group published a study showing the damage from mechanical ventilation in the scientific magazine The New England Journal of Medicine.  “One famous case is the case of President Tancredo Neves, who after several weeks in hospital and breathing artificially, suffered irreversible damage to his lungs”, says Marcelo Amato. The equipment consists of a belt tied to the chest, full of electrodes, which emit pulses in the direction of the lungs, at frequencies that are imperceptible to the human body. On a monitor, the pulses are transformed into images that reveal the movements of the lungs – the air that goes in and out is an electrical insulator. The apparatus will be assessed in the ICU at the Hospital and Clinics.

Teaching and research are inseparable in the FMUSP’s trajectory, but, historically, the scales have been tipped in favor of professional training. The school started working in 1913 and acquired its current headquarters, an architectural complex in front of the Araçá Cemetery, eighteen years later.  The building was incorporated by the Historical Heritage in 1981, for embodying a concept of a model medical school for the time – two large departments (the laboratories and the clinics) installed in just one block, in a “teaching hospital”.  As the professors should dedicate all their time to the school, the architectural equivalent was the creation of offices for the teaching staff and their assistants. The complex was built with money from the Rockefeller Foundation, and reproduced the medical teaching practiced in the United States, strongly bound up with research. But the medicine that was practiced in Brazil in those days had a French accent – a more empirical and less investigative model. Until the Second World War, when the professors from the FMUSP wanted to recycle themselves, they would go to Paris.

Second hand
In 1934, with the foundation of USP, the School of Medicine was officially integrated with the body of the University. The creation of the Hospital and Clinics, in 1944, and the gigantic proportions that it soon took on, molded the school’s nature of providing assistance and forming good doctors. Research ended up in the background. “If you analyze the biography of the great professors of the school  in those days, you will see they were great clinicians or surgeons, great professors, but today they would be seen as not very productive researchers”, says Professor Eduardo Massad. The research that was done for a long time in the FMUSP, and still occupies a space inside, has been the kind that takes advantage of the diversity of the patients and of their diagnostics to test medicines. “But it is a sort of second hand research. The drugs are not developed here”, Massad adds.  The 1969 university reform meant a blow to research activities. With the transfer of the basic chairs from the FMUSP to the USP campus, the school felt the blow from losing researchers and laboratories.  The reaction came in 1975, with the creation of the Medical Investigation Laboratories, the LIMs, the protagonists of the current escalation of research.

Also going back to the 1970s is an experience in management that was to have an impact on the institution. Backed by the popular support that he won over by carrying out the first heart transplant in Brazil, surgeon Euryclides Zerbini (1912-1993) managed to get support and money to create an appendix to the Hospital and Clinics linked with his specialty, the Heart Institute (Incor). From the state government, he achieved a gift of a plot of land on Dr. Enéas Avenue, in those days a steep bank at the back of the Emílio Ribas Institute. Besides the competence of its clinics and surgeons, Incor was innovative in its management model. The institute is managed by the Zerbini Foundation, a private entity by law, which instituted a model for raising private funds, setting aside 20% of Incor’s beds for health insurance and private patients. The other 80% are vacancies of the public system.  The model generated a financial balance that guaranteed the continuity of research projects in the 1980s, when the company’s economy stagnated. The foundation handles the hiring of staff and complements the salaries of employees of the HC. The doctors are required to work full time – and may even attend to private patients in offices at the institution.  Incor’s example inspired the creation in the 1980s of USP’s School of Medicine Foundation, which also seeks to raise private funds for the institution, but does not have as much flexibility as the Zerbini Foundation.

“We created an environment in which doctors and staff work motivated, and turnover is very low, at 3% of staff a year”, says Professor Sérgio Almeida de Oliveira, the director of the Thoracic and Cardiovascular Surgery Division. The Zerbini Foundation sets aside funds for the doctors from the hospital to submit their researches to international magazines and to take part in congresses. In 2002, there were 463 research projects under way. The institution’s comfortable financial situation, though, comes from attending to patients. Incor’s second building, recently inaugurated, was conceived to house only research activities.  But when the Zerbini Foundation put pen to paper, they saw that they would have to attend to more patients in order to take in more money from the public system and the health insurance plans. So they decided to set aside the 6th, 7th, and 8th floors for inpatients. Today, the hospital has 510 beds.

One paradox permeates the history of the FMUSP.  There is not a professor, a student, or a member of staff who does not complain about overcrowding at the HC and its disturbing impact on the teaching and research environment. But it is the demand from the population that supplies the complex with a diversity of diagnoses and treatments that are a fundamental raw material for teaching and research. The institution’s prestige comes from its capacity for doing cutting edge medicine, which is inseparable from research. The hospital’s management recently announced the decision of refusing to attend to simple cases, to invest in the institution’s original vocation, which are the complex cases. Strictly speaking, the measure was already a reality. The HC has a telephone line for making appointments, created to avoid waiting in line. In practice, it works like a filter.  It gets 20,000 calls a day and books 200 appointments.  “Without dispersing efforts with cases that are not serious, we will be capable of doing research of a better quality and of improving the teaching”, explains Giovanni Cerri, the FMUSP current director.  “The school is doing very well, when compared with schools in Brazil, but in the light of the performance of schools in other countries, we can see that it is possible to improve”, he says.

It is difficult to quantify the impact that the excessive movement at the HC has on the training of its students.  Our students are so good that they overcome any of the institution’s deficiencies”, says Professor Paulo Saldiva, the coordinator of the FMUSP’s Atmospheric Pollution Laboratory, one of the institution’s most productive, with over 20 researches published a year in international magazines. The FMUSP’s entrance examination is hotly contested and selects the elite from amongst the candidate – the passing mark for the medicine course is the highest of all the careers. Afterwards comes the battle for vacancies in medical residency, which attracts the best talent in the country.  Joining the postgraduate programs is equally contended for.  “We can enjoy the luxury of not absorbing the researchers we train, because the next year’s intake will be just as good as this year’s”, says Saldiva.

The FMUSP’s researchers would like the institution to invest more in medical investigation laboratories. They recall that the public system pays the Hospital and Clinics according to a special table, which pays up to 46% more for each procedure, for being an institution that is dedicated to research.  “The hospital gets 46% more from the public system for doing research, but it gives back to research only 2%. You can say that it is not much”, says Professor Eduardo Massad.  But even granting the current incentive to research met some opposition from the teaching staff who cultivate the institution’s professionalizing tradition. This tension is healthy.  Nobody doubts that the FMUSP’s great vocation will continue to be that of a great medical school, and the HC’s, of being an important center of assistance to the population.  But the prestige of the quadrilateral bounded by Dr. Arnaldo and Dr. Enéas Avenues has a lot to do with the research produced there, with the capacity that the institution maintains for pushing back the frontiers of medicine.