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INTERVIEW

Dimas Covas: The trajectory of Butantan

The hematologist from USP readies the São Paulo institute to fight the pandemic and has plans to transform it into one of the world’s top producers of vaccines and serums

Léo Ramos Chaves

Originally from Batatais in the state of São Paulo, physician Dimas Tadeu Covas in 2017 temporarily left his professorship at the University of São Paulo’s (USP) Ribeirão Preto School of Medicine to run the Butantan Institute in the state capital. In early 2020, when the pandemic had just begun, he stopped his reorganizational plans and began to receive publicity for the São Paulo institute, which in February completed 120 years, as one of the centers for Covid-19 combat in Brazil.

Covas is 64 years of age, Catholic, married, has two children (17 and 23), does not have registered parents in the municipality of São Paulo, and admires Italian Dominican friar Thomas Aquinas (1225–1274). He is at the forefront of CoronaVac, the Covid-19 vaccine produced by the Chinese company Sinovac and approved on January 17th for emergency use in Brazil, after phase 3 clinical trials coordinated by Butantan. At the beginning of January, he granted the following interview by videoconference.

Age 64
Field of expertise
Hematology, biotechnology, Stem cells
Institution
University of São Paulo (USP)
Educational background
Bachelor’s degree in Medicine (1981) Master’s (1986) and PhD (1993) from the University of São Paulo’s Ribeirão Preto School of Medicine (FMRP)
Published works
305 scientific articles, author, and coauthor of 15 books, with the most recent being the Manual of Transfusional Medicine, 2014

How did Butantan participate in the development of CoronaVac?
The relationship with Sinovac was established to facilitate the development of a Covid-19 vaccine. The first reason that justified this agreement was that CoronaVac was ready in April 2020. It was an adaptation to a prior vaccine against another coronavirus—SARS-CoV-1—which causes SARS (Severe Acute Respiratory Syndrome). It was made using a production technology that we know well, that of inactivated virus, very similar to that used to make the dengue vaccine. The second reason was the possibility of bringing the vaccine to Brazil quickly. The agreement involves Sinovac supplying the raw material. By December 2020, Butantan had already brought 10 million doses to Brazil with additional quantities available by the end of 2021. Today, we only take care of filling and a change in formulation. In China, the vials have a single dose. At Butantan, we routinely produce 10 doses per vial. To incorporate the production technology, we are building a multi-purpose facility. We will produce the Covid-19 vaccine there, as well as others made from vero cell cultures (commonly used strain for microbiological cultures, made from isolated cells from the kidneys of monkeys). The transfer that interests us is that of the vero cell bank as we are familiar with the production technology. We use the coronavirus culture to produce an anti-coronavirus serum (vaccines trigger the production of antibodies, while serums are the actual antibodies). The cells used by Sinovac to produce the vaccine are the best for virus growth. The agreement allows for transfer if this is what we are interested in.

What does your interest depend on?
What we need to assess is our suitability to produce the vaccine in Brazil. This depends on the speed of the pandemic and the development of other vaccines. Sinovac has significant capacity for production. Beginning in October 2021, when the facility becomes operational, we will decide about how to incorporate the banks and the possibility of producing the vaccine at the institute.

The Covid-19 vaccines were developed very fast, in less than one year, rather than the usual 10. How was this possible?
The production process for CoronaVac already existed, so what is new is the virus. The virus itself can mutate at any moment. The most important issue for us is having a strain defined for vaccine production. The mutations are expected as the virus lives in the human body. To this point, no mutation has threatened the production of neutralizing antibodies. The world is prepared to follow this viral evolution and perfect the vaccines as needed. The initial formulations have been made quickly to meet urgent needs, which happen with this pandemic. With time, we will have the conditions to perfect and produce better vaccines. Inactivated virus vaccines are traditional and safe. On the other hand, those made through other technologies, such as RNA and adenovirus, still have to prove their long-term safety.

How is the institute progressing with the dengue vaccine?
The phase 3 trials with volunteers have just finished, and now we are in the monitoring phase used to assess cases and possible vaccine side effects. After two years, there has been an increase in dengue cases. This growth allows us to study the performance of the vaccine on four subtypes of the dengue virus. I imagine that, before the end of 2021, we will have conclusions and will be able to register with ANVISA (Brazilian Health Regulatory Agency) use of the vaccine with the general population.

Today, the only vaccine Butantan fully produces is that for influenza, while importing and packaging another six…
In reality, we fully produce two vaccines, in phases. One against the flu and the other, in the piloting phase, against dengue. Butantan’s longest standing vaccine, DTP (for diptheria, tetanus, and pertussis or whooping cough), is in fact no longer produced here. The vaccine for hepatitis B is produced through a partnership with Korea. There has been a change in how we view the functioning of the global chain of vaccines. Often production is contracted in other countries, known as CMO (contract manufacturing organization). In fact, we are in the process of organizing so that one of our facilities can be used as a CMO as another vaccine producer. The agreements for supporting a production chain are evidence of a new future in this area. You do not have to participate in every phase of the vaccine production process, but you do need the capacity to partner with other entities to carry out these support functions. The partnership with Sinovac is our first experience in this area.

Is it not risky to depend on imports for almost everything?
We do not depend on imports and we are not importing. What we have are commercial production agreements with companies, which is routine for Butantan. One example of this is contracting with a Chinese company to make its iPhone. What is important is developing biotechnology. Today, we are only independent in three biotechnological processes: those for the vaccines for rabies, dengue, and the flu. In terms of serums, we have complete independence. Butantan has not lost its tradition in this area, but rather, is increasing its production capacity. We are supplying to other countries and soon will begin operations of yet another serum production unit. We plan to distribute serums worldwide.

The pandemic came when we were preparing to take a big leap. This leap happened last year

How are you managing the continual loss of researchers at the institute due to retirement and no replacement as there are no public competitions at present?
For many years, Butantan has not contracted researchers for their entire career. However, the Butantan Foundation has more autonomy, contracting researchers and providing opportunities to more professionals. A growing roster. In recent years, the rate of contracting has been very high. When a researcher leaves, for example, it does not mean that there will be a replacement in that area as we are restructuring the institution in the direction of its true purpose, which is to invest in people to help us fight problems that we can actually address. We had a sector here that studied ornithology. This is interesting work, but it is not part of the institute’s mission. This also applies to the sector that studied insects. The activities that are not proprietary to the institute tend to disappear, which is absolutely normal during a phase of restructuring.

How was Butantan before the pandemic and how is it doing now?
When I arrived here and took on this role, almost four years ago, I found Butantan rather lethargic, with management problems, lack of focus, scattered activities, and lack of clarity about its primary mission. This is normal for a 100-year-old institution. I was living in another reality and I thought differently, focused on medical and biotechnology areas. I wanted to bring enthusiasm to Butantan to see the institute’s great potential. The pandemic arrived at a significant moment—when we were preparing to take a big leap. This leap took place last year. We opened a new facility for the flu vaccine—one of the largest in the world—with the capacity to produce close to 160 million doses per year. This completely changed the face of Butantan. I think I was able to infuse the enthusiasm and the will to get things right. Today, Butantan is an institution with a clearly defined purpose. Yes, it is a research institution, but doing research is not its primary purpose. We are also an educational and cultural institution. However, our focus is on the production of serums, vaccines, and technological solutions that support public health care. We were rammed by this pandemic and we have acted on various levels. We built a network of coronavirus tests and laboratories throughout the state of São Paulo. We have undertaken epidemiological modeling projects and done field testing. Our team went into communities, doing drive-thru testing and many other uncommon activities.

What are the plans after the pandemic?
Butantan will be one of the top producers of vaccines and serums in the world. We were interrupted by the pandemic, but there was already a strong force moving us in this direction, including a project for seven new facilities that we will revisit as soon as possible. We are also planning to build a monoclonal antibody facility, which will begin operation soon. The area of serums is being completely redeveloped.

What did you learn during the pandemic?
First, I learned that human effort is unlimited. Whenever you think you have reached the limit, you discover it was not your limit and that you have much more to give. The pandemic has been a challenge that no one was prepared for but that has created a huge window of opportunity. On the other hand, it has shown us very clearly our weaknesses. Brazilian scientists have never been so clear about the weaknesses we need to overcome and the issues to resolve.

What weaknesses?
We have deep weaknesses, such as training, education, country goals, industrial policy, and other topics everyone has heard us talk about. A crisis like this shows that we still have much to plan and build, as a country. We have little training in philosophy and logic, which help us to understand reality. I believe that one of my tasks, as a university professor, is to help others look at their own environment as they develop structured thought—the profound thought of logic—and consistently ask themselves if they are actually seeing reality or if they are lost in a false reality. I also really like to read about the philosophy of science. I have not given up on the work of Thomas Aquinas. He walks with me and is my refuge, helping me to question what I need in these moments of crisis. I am not interested in the theological thought of Thomas Aquinas, but rather the thought of the realist philosopher who talks about what the world is.

Do you still do research?
I am the coordinator of the Center for Cell Therapy (one of the Centers for Research, Innovation, and Distribution, supported by FAPESP) and of the National Institute of Science and Technology of Stem Cells and Cell Therapy, both at USP in Ribeirao Preto. My area of research was always biotechnology and stem cells, continuously seeking to solve practical problems (see Pesquisa FAPESP issue no. 286). I have significantly reduced the number of students I teach and advise, but I maintain contact with my research group, which works well with little conversation and a lot of work.

For many months you have been consistently sought after for interviews. How are you managing the media?
You mean, how am I learning to manage it? I have survived the media since the beginning of the pandemic because I am completely honest and I have sound opinions. In the interviews, I like to be transparent and truthful about what I think. I have been invited often to the panel at the Jornal da Cultura and it has been a great learning experience. At the beginning, I saw myself as absolutely incomprehensible. I talked about RT—progression rates—but this language was the same as what I used with colleagues at the university, and I saw that it did not reach the broader public. Over time, I discovered that, instead of talking about RT, I should say that the epidemic is exploding, or the number of cases is rising at a speed we have not seen before. Then people start to pay attention. I am still learning the language of communication with the general public. Sometimes it is difficult.

Do you do any media training?
My media training is my daughter Giulia (17), who says: “Dad, today went well.” Or: “Today you were not that great, ok?” Today you talked about things over here…”. For some time, she thought about a career in medicine, but I advised: “Don’t follow my example, ok? I will be angry if you choose to be a doctor because I am one. You will need to convince me that you have a vocation and you will do well.” Today I think she is not thinking of this anymore.

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