News Report / Profile
Professor Miguel Castanho - Interview
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Miguel Castanho, born in Santarém, graduated in Biochemistry at the Faculty of Sciences of the University of Lisbon (FCUL) in 1990. He got a PhD in Molecular Biophysics from the Higher Technical Institute in 1993, at the age of 26.
He holds a vast curriculum in the fields of Teaching and Research and was the Assistant Director of the FMUL (2011-2016) and the Vice-President of the Foundation for Science and Technology (FCT) (February 2016 - September 2017). He accepted these positions because he believes that "it is necessary to accept challenges when one is called upon to take on greater responsibilities".
He is currently working as a Full Professor at the Biochemistry Institute of the Faculty of Medicine of the University of Lisbon and is responsible for leading a Research Team at the iMM - the MCastanho Lab. – member of the FMUL's School Board and of the Editorial Board of News@FMUL.
He has been awarded several prizes and honours, however, he confided in us that the awards he treasures the most are the ones he received from his students (the Golden Harrys for Best Professor of the Year at the FMUL).
Currently, we continue to be constantly warned by the specialists against the excessive use of antibiotics: and this was the motto for our interview with Professor Miguel Castanho, however, what began as an interview with a very objective purpose, soon became a pleasant conversation about his work and the development of his career over the last few years.
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Professor, we know that the first antibiotic was discovered in the 1930's and that, during World War II, it helped save many lives. However, is its constant presence in our daily lives turning it into our number one enemy?
That is not linear! The discovery of antibiotics brought about a first stage of euphoria. The excitement increased with vaccination and the world went through a stage in which everyone believed it would be possible to defeat microbes, by being vaccinated or taking antibiotics. This stage of euphoria was followed by a phase of concern, which culminated in the anticipation of relatively dark scenarios. And why? Because, during the excitement stage, many pharmaceutical companies were no longer focused on the creation of new antibiotics. Infectious diseases were no longer that appealing from the market perspective. The presumed regression of infectious and contagious diseases was not paying off the investment and the pharmaceutical agencies began to consider chronic and oncological diseases more appealing, as these would provide a higher and more lasting return.
What were the consequences in the long term? Bacteria adapt. The first antibiotic kills the ones that are sensitive to that agent, but there is one fraction that multiplies, creating a bacterial population that becomes resistant to that antibiotic. This is a continuous cycle. In the event of a second antibiotic, there is a new selection of the population. So, successively, the microbe populations become more and more resistant and, if there is no renewal of antibiotics from generation to generation, this balance ceases to exist. That's where we are right now, due to the underinvestment witnessed over the last few years as a consequence of the euphoria that was experienced, together with the widespread prescription and access to antimicrobial agents.
We find ourselves at a very critical point, because, in fact, there has been an increase in the number of deaths caused by bacterial infections and we need to go back a little and rethink antibiotics, the actions to be taken and create new molecules. Above all, they need to be developed considering the resistance of bacteria, that is, it is not only important to assess the degree of efficiency of a given antibiotic, but also to consider the bacteria's capacity to develop some kind of resistance against its action.
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And what if that renewal of the antibacterial strategies does not happen?
Some of the future projections are rather concerning as they show an increase in the resistance of some of these bacterial strains and that these may reach a level of harmfulness that may result in more deaths than in the case of oncological diseases.
A report from the economist Jim O'Neil, presented in May 2016, indicates that by 2050 more than ten million people, that is one person every three seconds, may die as a result of resistance to antibiotics compared to what happens nowadays.
According to Eurobarometer data on knowledge of antibiotics, Portugal is one of the European countries with a greater lack of knowledge when it comes to the effects of antibiotics: 60% of the Portuguese population believes that antibiotics kill viruses and 50% believes they should be used to cure cases of cold and influenza. Only 20% of the respondents said that they have received information on this matter over the last 12 months. That is why it is important to educate the society on how to make a suitable, informed and conscious use of the available resources.
To make matters worse, there has been an increase in the number of people that are against vaccination.
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These anti-vaccination movements are becoming more widely accepted.
Yes, I would say that it happens for non-scientific, or even anti-scientific reasons. There is a perpetuation of some beliefs that go against the greatest scientific evidence and that have been leading to the reappearance of some diseases that had been practically eradicated in some parts of the globe, namely in countries with more organized and more advanced health systems. Measles, for example, had already been declared under control and now it is seen as an increasingly important public health problem, as a consequence of the non-compliance with the vaccination plans, which has been affecting individual and group immunity.
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You were saying that there is the need to develop new antibiotics with the "capacity to anticipate" the resistance created by bacteria. We know that you are leading a project that deals precisely with research on this new generation of drugs. Is there already any new data that can get us in the right direction?
We can say that we are on the right path, that much is true, but there is still a long way to go!
In this case, the main idea is to focus on the structures that the bacteria cannot "conceal". Because, nowadays, the mechanism of action underlying most of the antibiotics is based on the connection to proteins; however, bacteria have the capacity to change those proteins, by providing them with a new structure, which hampers the interaction with the antimicrobial molecules. And that is how bacteria gain resistance.
It is easy for bacteria to change protein structures. There are, however, other structures that are common to many cells since, during the course of evolution, no alternatives were found for that component. There is no great difference between a bacteria, one of the simplest cells in the world, and a neuron, a highly differentiated cell unit; after all we are talking about an evolution of millions of years. But, for example, the structure of the membrane that separates them from the outside world is common to both and based on a lipid bilayer. This fact leads us to believe that, if we attack that structure - the membrane - in the bacteria, it will not be able to find an alternative and will hardly be able to adapt. In fact, they can even counter the effect of the antibiotics we are using a little bit, but this is the concept. So, we are able to say that we are on the right path, as the bacteria will hardly be able to find a quick and effective resistance mechanism, but this a "cat-and-mouse game" that we keep on "playing".
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Is there currently any kinds of bacteria that we should really worry about?
Yes, yes, there are and they are well identified. We are especially focused on Staphylococcus aureus and Pseudomonas aeruginosa. Multi-drug resistant infections associated with healthcare are a very serious problem. And, unfortunately, they often result in death.
There is a recently published study that shows that infectious and contagious diseases caused by bacteria and viruses are the 7th cause of death in Portugal, and this is something we did not anticipate a few decades ago.
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If asked to run an awareness campaign focused on the massive use of antibiotics, which message would you choose to convey?
That is a hard question, but I would surely use a wordplay that would reflect the idea that, sometimes, the real protection consists of not using antibiotics, contrary to what people think. It could be something like, "Protect yourself! Do not use antibiotics!". But it would also be, like all slogans, a little ungrateful and risky. We mustn't be neither absolute nor fundamentalist. In fact, the excessive prescription and use of antibiotics for therapeutic purposes is not the biggest problem, but rather the excessive presence of antimicrobial agents in our daily lives (for example, in floor cleaning detergents, in the cloth we clean tables with, in the toothpaste).
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What do you mean, Professor?
Everywhere, the widespread use of antibiotic compounds selects, in its course, the bacteria populations that are resistant to those agents. The problem is that we are killing the bacteria that do not harm us and allowing the ones that are resistant to antibiotics to survive, some of which can be harmful.
People, in general, seek for a clean and sterile environment, because, for us, sterility is a synonym for cleanliness. And that is why antibiotics are so widely used, not only through medical prescription.
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Professor, at the iMM you are leading a research team that works in rather distinct fields, including antibiotics; what is the connection between these diseases?
It may look strange for those who are not involved, because the diseases are very different, but at the molecular level - and we, as Biochemists, work at the molecular - there are mechanisms that are common to all of them and that are similar to each other.
The object of our study is, mainly, the interaction between peptides (which are a kind of microproteins) and lipid bilayers, that is, cell membranes. This interaction is relevant, for example, when a virus enters a cell. In a first phase, we try to characterize that event and, then, manipulate it to inhibit the virus from entering the cell.
When we develop antibiotics, what we really want is to create a peptide (one of those microproteins) that will interfere with the lipids from the bacterial membrane, thus causing an injury. Consequently, from the molecular perspective, these are relatively identical phenomena. And this is the same mechanism that is applied to tumours: we have come to the conclusion that we can use the same concept if the goal is to attack the surface of the tumour cells.
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Can we say that your team is declaring war not only on bacteria, but also on viruses?
Yes, and on tumour cells as well. That's what keeps us moving forward. The Brazilians have a very good comparison to say that a certain task is hard, but at the same time beneficial - they say: "It's just like panela: sweet but hard". Panela is a sweet that looks like sugar blocks.
Our job is sweet, but it is not soft (easy); it's just like panela!
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You were the Deputy Director of our Faculty; is there any special moment that you still remember? Tell us a bit about that time...
I got into the FMUL in 2007 and became a member of the Board a few years later.
I was really surprised by Professor Fernandes e Fernandes' invitation. Following the retirement of Professor Joaquim Alexandre Ribeiro, who was the Deputy Director, Professor Fernandes e Fernandes invited me to integrate the Board and I accepted his invitation because I like challenges that I feel are worthwhile, even though I expected a lot of hard work, as I had already been the Chairman of the Scientific Board of the Faculty of Science and I was aware of how demanding it is to perform duties in Governing Bodies.
The first thing I realized when I took on the position of Deputy Director was that the FMUL is more homogeneous and better organized than most faculties and that it has a more consolidated organic administrative structure. It also provides a greater support to research, when compared with other faculties. It is a Higher Education Institute that makes a decisive contribution to the research that is developed within its premises: whereas, in most cases, faculties receive funding for research to pay for general expenses related to their facilities and infrastructure, the FMUL, on the contrary, makes a significant investment in scientific research developed in research centres and institutes connected to it, by bearing a great share of the general expenses related to the facilities and infrastructure.
In addition, I was also quite impressed by the students' capacity to promote extracurricular events and activities, which show their cultural, social and humanitarian commitment, and that is unusual. Contrary to what most people think, medical students are different not only because they are academically successful, but also, to a great extent, because they are more methodical and more culturally and socially committed. That's what distinguishes them the most. These were the good surprises.
On the other hand, I believe that the FMUL is a system that is closed in on itself and, in my opinion, it would benefit from taking into consideration the good practices adopted by other faculties and from having a culture of greater openness.
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What particular moments do you remember?
I remember... Look [NR: he says, while pointing to a picture] there's the photo of Professor Fernandes e Fernandes' farewell, on his last day. I think it was a moment of great awareness and mobilization, because it was a surprise farewell party with a massive and spontaneous participation of all of us. Almost all the administrative staff of the Faculty were there.
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I remember many debates with the Course Committees on the improvement of education and the Integrated Master's Degree in Medicine. The first years of the Curricular Reform required a lot of commitment to recognize and fill many gaps. The students from the successive Course Committees were great: critical but constructive. An example for all of us!
The 2007/2008 academic year and the following years marked a period of consolidation of the curricular restructuring and, obviously, the whole process was led by Professor Fernandes e Fernandes. When I joined the Board, we were still implementing and putting the process into practice and it was clearly the right moment to provide the FMUL with a modern education system; it was kind of a quantum leap towards modernity, which was extremely important and required a lot of courage, and I am really proud to have been involved in the process together with Professor Fernandes e Fernandes, who was, indeed, the great mentor of this paradigm shift.
I was still the Deputy Director when the current Director, Professor Fausto Pinho, took office. He brought his personal mark to the Board and is still following the path towards modernization and successfully consolidating it.
I remember it perfectly that the education restructuring at the FMUL was, at a first stage, really undervalued by other faculties, but, later on, it has been adopted by many institutions, one by one. It was extraordinary to follow the trajectory of the other faculties, which eventually followed the same path as the FMUL, albeit later on. Among the older and more experienced faculties, the Faculty of Medicine was the first to embrace an integrated and modern education.
I also had the pleasure of following up the pioneering spirit of the establishment of the Lisbon Academic Medical Centre, which was established at the initiative of Professor Fernandes e Fernandes, and relied on a lot of personal and institutional support. Once again, this concept was undervalued by the other Schools at first; however, all the faculties are now integrating, one by one, the so-called Academic Clinical Centres. The FMUL started many years ahead and this whole process has been implemented in a particularly methodical and intentional way, by following a plan that went through many stages and that has been taking its course. I admit that it might have taken longer than we would have expected, but we are definitely blazing the trail.
From an administrative perspective, we have implemented many measures aimed at space management and at clarifying a series of procedures that I believe to have greatly contributed to the faculty's transparency and visibility. Nowadays, the FMUL has a more clearly identifiable link to research than before.
In short, I am very pleased and confident, but I have also got a lot of grey hair during my time as a member of the Board; it is not easy, it is an extremely difficult position that requires your full attention.
At a later stage, I became the Vice-President of the Foundation for Science and Technology, the FCT, a position that was also highly demanding.
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Do you also have good memories from the FCT?
Yes, I do! Actually, working for FCT is easier than I thought, particularly thanks to the skills of the people who work there. The main difficulties are not related to the Foundation itself, but to the interface between the FCT and the various institutions, some of which are really difficult to deal with. Currently, it is even worse, since the FCT has lost its centrality and autonomy. This issue is related to the way the flow of funds is managed, to the dissemination of tasks and the dilution of responsibilities in the management of Science in Portugal, which cause FCT to lose its importance and independence. But this is a subject for another interview. [NR. Laughs and a final smile]
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Cristina Bastos
Equipa Editorial