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Butantan balances production and research

Funds from Infra give an incentive to laboratory work

The contribution that the Butantan Institute, a center of international excellence in the research and production of anti-poisonous serums, has already given to the country is unmeasurable. Created in 1901, by the physician Vital Brazil to combat an epidemic of the bubonic plague in the port of Santos, technology for the large scale production of vaccines and serums against poisonous animals and illnesses that threatened human beings was developed in its laboratories. Currently, there are presently 15 varieties of anti-poisonous serums being manufactured, along with six types of simple and combination vaccines against tetanus, diphtheria, whooping cough, tuberculosis and rabies, and as well the Anti CD3, used in the prevention of rejections in transplant surgeries. Every year, many millions of doses are produced to stock up health clinics throughout the country.

In spite of its recognition within the scientific community and its importance in public health, its researchers faced against difficulties. Until 1984 the production of serums was handmade. Without investments for the introduction of modern techniques, the production of vaccines would be seriously hurt. At that moment the Biotechnology Center was created: the production line became automated and a new generation of products destined towards the public health system was launched. The investment resulted in the expansion of the line of medicines: vaccines against meningitis C and hepatitis B, the botulinum toxin and biodrugs such as erythropoietin (for patients who are awaiting a kidney transplant) and lung surfactant (used to combat the syndrome of lung immaturity).

Nevertheless, the Butantan Institute needed to fill in a gap in the area of research. The reason for this was that the major part of its budget, a government grant and income from the sales of vaccines and serums, was pegged towards production. For this reason the laboratories were living with infrastructure problems that undermined the development of research. The buildings were from the days of the foundation of the institution and some had been constructed as the stables to keep animals and ended up being transformed into laboratories. Ivo Lebrun, of the Biochemistry and Biophysics Laboratory recalls that the installations had been inadequate for the research line being developed therein, that dealt with the isolation of toxins of snake poisons for the identification of the active principles with potential use in the area of medicine.

Totally modernized with funding from FAPESP’s Infrastructure Program, which invested around R$ 2.7 million in the institute, the laboratories began to operate at a higher standard of quality. For example, the renovation at Lebrum’s own laboratory permitted the fitting of spaces and in order to install the equipment necessary for the use of molecular biology techniques. These are fundamental techniques, since they permit that the toxins used in theresearch be produced within the laboratory itself. This way, the researchers no longer need to be dependent on some poison leftover. The technique also avoids the constant necessity of the extraction of poison from animals, some of them extremely rare.

“The quantity of poison was always a limiting factor, mainly with animals such as spiders and scorpions. Today we have the possibility of obtaining this material through cultures or bacteria in the quantity that we want and consequently we are able to study with more frequency and with less difficulty” explains Lebrun. The potential is huge. “These poisons produced by nature offer a series of biologically active compounds that have not yet passed through a thorough and intense study”, he states. A good example of this is the recent registration of a patent for an anti-hypertension drug originating from the venom of the jaracara snake. The study was developed at the Center of Applied Toxicology of the Butantan Institute, which is one of the ten Innovation and Development Research Centers (Cepids), created by FAPESP.

Another important line of research is being carried out in the Inflammation and Pain laboratory, a totally remodeled area and adequate for this particular type of study. There the animals, generally mice, spend their time in rooms with adequate temperature and lighting that are also soundproof to avoid any stress provoked by the movement of people and the smell of other animals that might interfere in the results of the tests. They are inoculated with various types of toxin and submitted to mechanical tests to evaluate the level of pain or of analgesia brought on by the poisoning.

Before the reforms, the laboratory used to work next to the Physiopathology laboratory, which brought with it serious drawbacks. “We were constantly losing results through external interferences. Now we don’t have to repeat the tests so many times, so the research advances much quicker”, says Yara Cury of the Pain Unit. The expectation here, too, is to improve the efficiency of the serums, by adding substances than can reduce the strong pain brought on by the venom of the majority of poisonous animals.

The main working environment in the Physiopathology laboratory, which had been made up of four rooms, was transformed into a spacious laboratory, well illuminated and with ample bench space. “We had been waiting for this since 1994” tells the researcher Ida Sano-Martins, who develops experiments with animals and poisoned patients in order to study the effects of the toxins and their biological activity. By identifying, in a more detailed manner, the action of the toxin on the organism, Ida believes that it will be possible to improve the efficiency of the anti-poisonous serums. For this she can count on the support of medical centers throughout the country.

In the Pharmacology laboratory difficulties were also overcome. “When it rained we had to cover the equipment with plastic covers”, comments Catarina Teixeira, chief of the sector. Another problem was to observe the changes in the behavior of the animals in tests with poison that acts on the central nervous system, one of the main lines of the laboratory’s research. Various factors collaborated in the improvements. An old bathroom gave way to a well mounted research animal breeding unit, with an air exhaust system and a video camera for observation. The culture room was built with an idle area according to international standards; the electrical circuitry also received special attention in order to guarantee the uninterrupted working of the greenhouse and the quality of the laminate flow so as not to harm the cultures.

Also in the Biotechnology Center, where the research is directed towards large scale production, various factory-laboratories were benefited. One of the results of these investments through the Infra-Structure Program was the setting up of the laboratory where is being created the production line for lung surfactant, a motive for commemoration by Dr. Isaías Raw, the director of the center. The researchers also commemorated. The exchange of information and collaboration work with colleagues in other regions of the country and abroad has grown. “Today the research is multi-disciplinary and multi-institutional. It is only possible to develop the work under adequate conditions” says Lebrun.