Grande Entrevista: Professor António Coutinho sobre “A importância da Biologia Evolutiva na Medicina.”

<h3 style="text- Burberry Cashmere Scarf Sale a lign: justify”> As of 2010 António Coutinho was the only Portuguese ISI highly cited researcher.
“I believe, profoundly that we must understand evolutionary biology of diseases to understand evolutionary biology. Because diseases have always been there, in all living creatures. So it is an important component of evolutionary biology, in itself.”

António Manuel Pinto Amaral Coutinho é um imunologista português que recebeu inúmeros prémios pelo seu trabalho científico e pelo seu sucesso em impulsionar a ciência em Portugal.

Dirigiu o Instituto Gulbenkian de Ciência de 1998 a 2012. Actualmente é membro da sua Comissão de Gestão. Em 2012 foi nomeado membro coordenador do Conselho Nacional de Ciência e Tecnologia, e é professor catedrático convidado de Imunologia da Faculdade de Medicina da Universidade de Lisboa.

It is a sunny Friday morning and I am sitting in António Coutinho’s new office at the IGC, sipping a bica, comfortably nestled in a chair. He has meanwhile jumped out of his, now sitting in a crouched position next to the coffee table as if he is about to hop away. He is making a point, of course: a point for the study of evolution.

“Birds live like this all the time, you know. Their hind legs are just this part,” he points at his shins. “You can see it when you eat a chicken. I never realized this until a few weeks ago, but all birds crouch!”

This peculiar posture of our feathered friends was the topic of a conversation he recently had with an orthopedic surgeon. You would think that this should be low on the list of subjects to discuss between an immunologist and an orthopedist— but you would be wrong. Coutinho had just seen a video describing the evolutionary history of birds, and how their dinosaur ancestors are the ultimate explanation for their permanently stooped state. His friend the orthopedic surgeon, however, had known this for years. Coutinho was not surprised: for a doctor whose specialization deals with deformities of human bones, knowing how their evolutionary history had a hand in their weaknesses, is only natural. Indeed, he told me, from all medical specializations it is orthopedics that most closely deals with evolution.

“When a specialist deals with posture problems, they then go and read that our ancestors walked on four legs, and then half on four, half on two, and so forth. They have to understand that their knowledge of the evolutionary process is important structurally, because the weak points are determined there.”

But it is not just orthopedic surgeons who benefit from understanding evolution: during his own career in immunology, António Coutinho witnessed how considering evolutionary principles fueled a breakthrough period in his field.

“For many years, essentially until the 1950s, principles of variation and selection were not considered, and progress in understanding the biology of the system was practically zero.  But then these seminal papers appeared that changed everything. The next twenty years held fantastic progress, because now there was a correct framework to think about immunology—a framework based on evolution. Few biological disciplines have grown as much and as explosively as immunology grew in that time.”

But while this explosion happened during the 1960s and 1970s, the use of evolutionary hypotheses for the progress of immunology is far from  over.  For  example,  current  research  on immune regulation can make use of comparisons with invertebrates:

“At some point, some of our colleagues at the IGC—Élio Sucena and Alexandre Leitão—had an idea to look in invertebrates, to see whether some cells were already more regulatory than others: this, then, must have happened well before there was adaptive immune system with lymphocytes. These things are not known at all! What we’re missing here is proper evolutionary biology, because we need to understand the process of evolution in the self-amplification of information, in the regulation of self-amplification, et cetera. However, and more broadly, there is very little evolutionary biology of diseases in general—of any disease. There are a few things here and there, but evolutionary biologists don’t get into diseases, for some reason.”

This is where António Coutinho gets to his ultimate message, appealing to me directly:

“If I were a young and ambitious evolutionary biologist—like you—I would study the evolution of diseases! I’m serious! You study all sorts of strange things in your flies, but you’re not studying diseases. Of course, you study infection, and the evolution of infectious agents; in flies and other animals. You look at the genes that are involved, and discover all sorts of interesting things. But all the other diseases—degenerative diseases, aging disease—nothing of this is studied from an evolutionary point of view.”

It is a passionate message, and a clear call upon the evolutionary biology community—not just myself—to apply their skills and knowledge to the very practical science of medicine. But, I wonder, aren’t there reasons for the lack of evolutionary biologists working on human illnesses? After all, most diseases only start playing a role late in life, after reproduction. Coutinho, however, disagrees with me.

“Not all of them, not at all. There are many of diseases that affect a person late in life, but the initiation of the  process is much before. An example of this, which is seen epidemiologically, is obesity. Increasingly, people are starting to see that obesity is essentially determined by conditions during pregnancy. So if during pregnancy the fetus is submitted to caloric restriction, then homeostatic metabolic rates are set to a given level. When the child grows up, and it is exposed to overfeeding, it may become obese. We all know that many people overeat, but not all of them become obese; conversely, sometimes the poor obese people don’t really eat extraordinarilymuch. It may have to do with genes, for sure, but also with something else. To me, obesity is a typical example of a disease that is amenable to an evolutionary approach, because it has a lot to do with life style. With ecology.”

He chuckles. Indeed, looking at life style as the ecology of humanity is an interesting way to include evolutionary and ecological   principles into medicine. But the influence of ecology on our health goes beyond our current environment.

“If we look at things like population expansion, for example. Here we can find the reason for many of the problems with genetics of human  diseases, and correlations between diseases and genes—or markers of genes. Because there were these very biased population expansions in the past, you know. Tremendous expansions. Humankind expanded I don’t know how many fold in the last thousand years! If you then look at populations and try to correlate things, you are bound to find enormous founder effects and things like that. Here, especially, it is absolutely necessary that serious evolutionary biologists are involved.”

This is not all that is wrong with the era of genomics. Coutinho rewordpress:

“There was a lot of hope some years ago—ten, fifteen years ago—that genetics and genomics would contribute a lot. This has not been the case; there was an enormous investment for very little result.”

He explains that correlation studies do not only encounter the effects of population expansions, but also are very limited in the understanding that they provide:

“We simply don’t know enough physiology to understand the associations. What is missing here, essentially, is knowledge about the underlying mechanisms of disease, the molecular physiology. And of course the ultimate understanding of  that will come from evolutionary biology; that is clear.”

In Coutinho’s vision, however, it would not just be the evolutionists making a mass-transition to the medical sciences. No—populating the scientific void between medicine and evolution needs to come from those two fields in concert. Coutinho himself has actively contributed to the curriculum of the MD-PhD program at the Gulbenkian Institute, ensuring that evolution was part of their study. Not to everyone’s delight, however. I asked him if he had any idea why he encountered resistance.

“Oh yes. I think it is based on ignorance, to start with. It is also based on the fact that science, for many doctors, is—you know, it’s interesting probably, but it’s not down to earth. It’s not relevant!”

He slaps his hand on the table, emphasizing the ferocity of this viewpoint.

“We have to understand that doctors have this incredible and immediate need to deal with someone who is suffering. So if you come with theories on how this suffering has evolved—they can’t care less! They want to solve it! And it is less apparent that to be able to solve that, you must understand what has happened 100 million years ago. The presence of the patient is so strong, and helping those people—helping people—was the major motivation for why they wanted to be doctors.”

While he understands their motivation, Coutinho is critical of the scientific literacy of many doctors, and views this as a major hurdle in the collaborations he so desires to see. Science, he has noticed, is not part of the average MD education.

“The teaching of medicine is not science-based. So far. We see this problem in the MDs that used to come to our PhD program: they are absolutely scandalized that somebody can stand up and say ‘This article that came out in Cell or JM or something is wrong!’ They cannot understand this. After a few months they are reformatted, as they themselves  say”— he chuckles—“and start having the ability to criticize science. They are extremely critical about medical operations— medical attitudes, and medical acts. They criticize each other harshly, saying: ‘You should have operated sooner,’ or ‘You shouldn’t have operated at all.’ But they are not trained to have serious scientific criticism. Therefore, I think this can only be corrected in school.”

Fortunately, he thinks, this development is happening already. And he has an explanation for it:

 “More and more doctors indeed start having a comprehension of scientific language. In the US things went faster because they have graduate entry into medical school, so people get  in, already holding a degree in science. In Europe we have some graduate entry; in Portugal we have one school that does it, so I think this will improve. The MD-PhD programs also help the situation a lot, and those are present in most European countries.”

It’s an ongoing evolution of the  field,  which started out as a deeply empirical one:

“Medicine used to be empiricism only. There was no science, just technology. As late as the 1980s, the main movement in medicine was to be completely evidence-based; it was the ultimate empiricism. Only include things that have been proven to work, with no concern for why or how. I do understand the wish to do this: it is very practical. But it has nothing to do with science.”

With medical education undergoing this drastic revision, Coutinho comes back to his earlier point: medicine for evolutionary biologists. Here, too, he sees a solution in education:

 “We need to have some kind of courses, maybe a month or two, for biologists on diseases. On human diseases. To give condensed information on medicines to biologists in general, so that the same type of cross talk becomes possible. That is: the doctors understand the scientific language, but the scientists must somehow understand some of their jargon as well. Otherwise it will be very difficult to communicate. It is easy when you get into a collaboration, and you have the time to explain to each other what you mean—but to attract people to get together, you need to understand what they say.

Because in the end, it is collaboration that harbors the real potential. Not just doctors and evolutionary biologists: interdisciplinary science that connects proximate and ultimate causes, mechanisms and history, to a complete understanding of diseases.

Coutinho stresses:

“We need, in my very personal opinion – we need more physiologists, and I am not talking about physiology like dissecting frogs and stimulating muscles, or physiology like doing only electrocardiograms. No, it is time now to study physiology with a genetic and molecular basis. This is not an area that attracts many people in medical research: physiology as such is an old discipline, and the evolution of the field was therefore not favored. Biochemistry was substituted by molecular biology, so most of these people don’t know any chemistry these days. But we need to correct that. We need to have more physiology – mechanisms of disease – and evolutionary biology, to create the understanding of all of that together.”

It is a tempting future: with funding being cut left and right, tapping into the  money available for biomedical research is an enticing thought. As Coutinho phrased it,

“For the concerns of this society in which we live, the contributions for medicine will be more valued. They may not necessarily be more valuable, but they will be more valued. For sure.”

And just in case we haven’t been sold on his idea, Coutinho emphasizes what’s in it for evolutionary biology. After all, diseases are a part of biology. They have evolved.

“I believe, profoundly that we must understand evolutionary biology of diseases to understand evolutionary biology. Because diseases have always been there, in all living creatures. So it is an important component of evolutionary biology, in itself.”

 As happened in the field of immunology,  there may be many principles to discover in—and apply to—other branches of medicine. Principles that could be, as happened in immunology, at the base of a paradigm shift in the field. A paradigm shift, but not the end:

“Twelve years later after publishing his original paper on natural selection in antibody formation, Niels Jerne wrote another paper called ‘Waiting for the End’, as he himself thought that during those 12 years everything had been solved. Of course, the principles were all solved—well, almost all. There were things to be done still. But in that sense that people say, ‘Magalhães has solved geography’, because he proved that the earth was round. Of course there was still a lot of geography to be done, and there are still a lot of geographical societies all over the world—I don’t know what for, but they are there. So it goes for areas of  science that solve the main principles: there is a lot of gardening to do afterwards. For many of these things we were talking about, diseases et cetera, we need these principles—we need to solve the principles.”

 For both solving the principles and the gardening afterwards, António Coutinho sees a key role cut out for evolution:

 “You cannot understand function and the significance of anything – be it a molecule, an organ, or whatever  – you cannot understand that unless you study evolutionary biology.”

Barbara Vreede e Patrícia Beldade