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Carlos Guerra Schrago: The theory and practice of evolution

The discipline that seeks to reconstruct the histories of species is itself evolving, according to UFRJ biologist

Personal archive In the company of Charles Darwin at the Natural History Museum in London in 2018Personal archive

Biologist Carlos Guerra Schrago, from the Department of Genetics at the Federal University of Rio de Janeiro (UFRJ), conducts extensive computer data analysis using statistics and gene sequences. Based on evolutionary theory, his work helps to understand certain aspects of the natural world, such as the ways in which a disease spreads (like the Zika epidemic that began in 2015), and the diversification of mammals, especially rodents and primates.

The variety of research subjects reveals how the same theory can be applied to all organisms, with one important difference: although their lives as individuals are ephemeral, microorganisms are able to perpetuate themselves through rapid multiplication. When reconstructed through the eyes of an evolutionist, the series of genetic modifications resulting from this replication is virtually transformed into a film telling the organism’s history.

After graduating in biology at UFRJ with a specialization in bioinformatics at the National Laboratory of Scientific Computing (LNCC) in Petrópolis, Guerra completed his doctorate at UFRJ in 2004 and, between 2018 and 2019, completed a postdoctoral internship at Harvard University, in the United States. In the following interview, given by videoconference, he talks about the changes that evolutionary theory is undergoing, and how he reacts when students contest the discipline. In his view, researchers fall into a trap when they react as if there is a clash between religion and science.

Your field of study is viral evolution. How do you view the novel coronavirus pandemic?
I haven’t yet analyzed the raw coronavirus material, but what caught my attention is that it may be the first time that evolutionary biology has dealt with a new practical problem, which is to assess if a sequence, either from a virus or a bacterial genome, has been manipulated in the laboratory. The study published in March in the journal Nature Medicine, which showed that the SARS-CoV-2 virus had not undergone genetic manipulation, was cosigned by a group of molecular virologists who work in evolution, and it’s had considerable repercussions. It’s actually a geopolitical problem, because knowing whether a sequence was of natural origin or not means assessing whether it was the object of bioterrorism.

This type of work also allows the virus’s molecular evolution to be analyzed to trace how it’s circulating and try to make predictions…
Certainly for epidemiological surveillance in any country it’s relevant to know the pace—the rate of growth and expansion of infections—and to try to trace where these viruses and sequences came from. But the work done so far lacks a large-scale sampling of gene sequences. It’s difficult to make inferences about the spatial and temporal dynamics of an epidemic when sampling is incomplete. In terms of the SARS-CoV-2 circulating in Brazil, it’s been shown that they are virus sequences originating from Europe and the USA, but the effort to obtain samples wasn’t homogeneous in every country.

Your lab works on Zika. What is the goal of your research?
Our questions are theoretical, and related to the Zika epidemic, and what applies to Zika is valid for any epidemic. The bioinformatics and molecular evolution methodologies are the same. We were interested in knowing how the relevant parameters behave for those working in public health, such as when the epidemic began, where it came from, and its growth rate. There are an enormous number of theoretical assumptions that we wanted to evaluate, and this requires very realistic computer simulations. Our job has been to design simulations for the epidemic’s growth and dynamics, trying to bring them closer to how the real virus is behaving in space and time. This allows us to assess the robustness of traditionally used methods, for example, for reconstructing the virus’s evolutionary history or calculating its spatial dynamics. We concluded that some of these methods have problems. We obtained more precise values when we used the silent mutations in the genome, in other words, mutations at the level of DNA that aren’t passed on to what’s apparent, the phenotype. Non-silent mutations, those that actually change a protein that affects a phenotype, are subjected to selection regimes and are more susceptible.

Perhaps natural selection is not the only explanation, but it’s still the best we have to understand the complexity of living beings

The work involves statistics and bioinformatics. Is it possible to explain how this works to the layperson?
In scientific publications—or even in science fiction films—DNA strings always appear with those little letters: A, T, C, and G. They are the nitrogenous bases that combine to form the DNA. One of the challenges for those working with molecular and genetic evolution is to look at these letters, with their diverse combinations and possibilities, and try to unravel the story behind them. It’s like coming home, looking around the rooms and trying to discover what happened while you were out. Sometimes it’s simple. If you have a dog and find everything in the living room torn up, you conclude it was the dog. But in many cases it requires the application of advanced models. It’s common for human thinking to make historical inferences. However, in evolutionary biology it needs to be supported by something more quantitative. In seeking to do an objective report, we draw on statistical inferences that allow us to quantify mutations in nature. In this history, we deal with everything—time, who is related to whom, where they came from, how they got here. These questions can be applied to viruses, plants, and animals.

How has this methodology evolved? How does it contribute to advancing knowledge?
The discipline of molecular and phylogenetic evolution emerged in the 1960s, although the concepts we work with are older—from a shared story of evolution about how genetic diversity responds to selection regimes. But they needed to be studied using algorithmic methods, and it was only possible to reach that level with the increasing use of computers in the natural sciences. It also depended on knowledge about nucleotide sequences, and the structure of DNA was only revealed in the 1950s. Until the appearance of this discipline, we had no idea how genomes evolved. With it, the issue became the subject of research and, using molecular data, it became possible to reconstruct evolutionary relationships between various species, and expand our knowledge about the tree of life in technical books on ecology, zoology, botany, or any area of biology. Today, the field of biology is quite unified by the evolutionary discourse.

When it comes to evolution and natural selection, people often think of animals or plants. You study the molecular evolution of viruses. Does the object of study make a difference?
It does make a difference, because in the case of viruses the rate of evolution is highly accelerated and it’s possible to observe the evolutionary process in more detail. In large mammals, it’s possible to look at photographs spread over millions of years and make inferences about what happened between one image and another. In the case of viruses, the time period is shorter, but there are also some complicating factors. The researcher needs to be attentive and choose the appropriate tools so as not to make a biased analysis, since there are methodologies for seeing pictures that are very distant in time and others for pictures that are very recent.

Viruses use host cells to multiply and leave parts of their genetic material inserted in the animals’ genome. How do viruses intertwine with our own evolutionary history?
What we have so far are case studies, some of them very interesting, showing that the role of these organisms is much more complex than we imagined. There’s no way of deciding whether—throughout the history of mammals or any other group—the contribution of viruses has been more positive or more negative. We tend to think it’s negative, as they are cellular parasites that use a cell’s machinery to replicate, and then the cell dies. But this isn’t always true, and they can bring about evolutionary innovation. That was unimaginable until a short time ago.

How short a time?
These ideas started to appear around the 1990s. Once the chemical nature of genetic material was understood, in 1953, a concept of the individual was created, closely associated with a single genome. It was understood that in a person’s cells, the genome could undergo minor mutations created during the process of cell division. Thus, the genome of a liver cell could be slightly different from the genome of a lung cell. But no one would have accepted that other genomes present in the body, originating from organisms as different as bacteria and viruses, could alter phenotypes to the point they influence a person’s behavior, with anxiety and depression. We arrive at a question: in the end, what is an individual? Is it just your genome or is it your genome plus this entire community of genomes that’s present in these microorganisms, including the viruses?

What will the answer be, in your assessment?
The development of sequencing techniques allows for a much more detailed analysis of the problem, and I think we’re in for some surprises in the coming years. It is a considerable challenge, even for bioinformatics. The complexity of the information is enormous, because variation exists not just between people, but also within the same person throughout their life. It’s impossible to make sense of this without the aid of computers. My impression is that, in the coming years, biology programs will of necessity have computer-programming content for their students.

Scientific discourse is limited by methodological naturalism to agents that must have a mechanistic, causal relationship

How do the contributions of microbiology influence knowledge about the theory of evolution?
The impact is still in progress. The complexity of the genome and its interaction with the genomes of all these microorganisms hasn’t been assimilated yet. There’s one group of researchers who consider natural selection the only explanation for the surprising organization that we see in living beings, while others think that phenomena beyond natural selection can contribute to evolution, and argue that evolutionary biology should be reformulated to incorporate these new developments, abandoning the classic conception, which dates back to the 1920s. Perhaps natural selection isn’t the only explanation, but it’s still the best we have for understanding the impressive complexity of living things.

Is there still a debate about whether viruses are alive or not?
The coronavirus pandemic has shown that an RNA molecule can stop the world. Within our cells, these molecules bring about a hierarchical network of chain reactions. It ends up being irrelevant to ask whether the virus is alive or not. This debate almost became like an argument over football teams.

We’re living at a time when we frequently hear people deny evolution. How do you deal with this as a teacher?
It’s a real problem. Students often ask questions with some religious content, but they’re rarely philosophical questions. What comes up in the classroom is this literal, simplistic interpretation, in which the student argues: “Ah, but that is not what it says in chapter so-and-so of the book of Genesis.” I think this is a good topic for analysis by sociologists. We must ask ourselves why this is appearing now, since it was something I didn’t see ten years ago. You have to put the problem into context. This isn’t a dispute between science and religion.

Why not?
Many researchers fall into a trap and turn something that is local and specific into a philosophical problem with no solution. In fact, we’re dealing with something much less sophisticated. The student never comes forward with an advanced theological discourse. I get the impression that some students enter evolution class thinking it’s a discipline for teaching atheism. So, it’s natural that they act with some hostility, because they grew up in a religious family environment and their understanding of morals is associated with religious principles.

How do you deal with it?
By fighting the perception that scientific discourse is atheistic preaching. The teacher needs to contextualize the limits and agents of scientific discourse. For the student, it must be clear that scientific discourse is limited by methodological naturalism to agents that must have a mechanistic, causal relationship. Any type of nonnatural agent is incompatible with the worldview of scientific discourse. I once had to explain: “This is an evolutionary biology class, not atheist apologetics. I am not an apologist for matters of the divine, I am a biologist.” After that, the student relaxed and understood that, from here on, making any kind of metaphysical leap would be complicated. And that includes accepting or rejecting metaphysical interpretations of naturalism. When someone says that pseudo-scientific hypotheses like “intelligent design” should be included in books on evolutionary biology, one must ask the following question: is what it proposes immersed in methodological naturalism? Do its agents of action have a mechanistic causal relationship? They don’t. So, great, you can do whatever you want with it, but it doesn’t go into a book on evolution. Creating this protection for scientific discourse avoids the problem, but it also has one consequence that some scientists dislike.

And what is that?
It’s the consequence of presenting scientific discourse as just one of the discourses possible for the human intellect. For scientists, dissociating the reciprocal relationship between science and knowledge is a difficult proposition. When it’s said that there are other forms of knowledge outside the safeguards of methodological naturalism, scientists have difficulty understanding this. For them, the world is only knowable through methodological naturalism.