COVID Brings Evolutionary Virologists Out of Shadows, Into the Fight

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It has been a strange, exhausting year for many evolutionary virologists.

“Scientists are not used to having attention and are not used to being in the press and are not used to being attacked on Twitter,” Martha Nelson, PhD, staff scientist who studies viral evolution at the National Institutes of Health (NIH), told Medscape Medical News.

Over the past year and a half, the theory of evolution has been thrust into the spotlight ― more now than ever, perhaps, as the world is stalked by the Delta variant and fears arise of a mutation that’s even worse.

We’ve also debated the origins of SARS-CoV-2 and the rise of the Delta variant, and have speculated about vaccine efficacy and the possible need for booster shots. In all these instances, consciously or not, we’re engaging with the field of evolutionary virology.

It has been central to deepening our understanding of the ongoing pandemic, even as SARS-CoV-2 has exposed gaps in what we understand about how viruses behave and evolve.

Evolutionary virology experts believe that after the pandemic, their expertise and tools could be applied to and integrated with clinical medicine to improve outcomes and our understanding of disease.

“From our perspective, evolutionary biology has been a side dish and something that hasn’t been integrated into the core practice of medicine,” said Nelson. “I’m really curious to see how that changes over time.”

Pandemic Evolution

Novel pathogens, antibiotic-resistant bacteria, and cancer cells are all products of ongoing evolution. “Just like cellular organisms, viruses have genomes, and all genomes evolve,” Eugene Koonin, PhD, evolutionary genomics group leader at the NIH, told Medscape Medical News.

Compared to cellular organisms, viruses evolve quite fast, he said.

A study recently published in the Proceedings of the National Academy of Sciences (PNAS) exemplifies evolutionary virology in action. In the study, Koonin and fellow researchers analyzed more than 300,000 genome sequences of SARS-CoV-2 variants that were publicly available as of January 2021 and mapped all the mutations in each sequence.

The researchers identified a small subset of mutations that arose independently more than once and that likely aided viral adaptation, said Nash Rochman, PhD, a research fellow at the NIH and co-author of the PNAS study.

Many of these mutations were concentrated in two areas of the genome ― the receptor binding domain of the spike protein, and a region of the nucleocapsid protein ― and were often grouped together, possibly creating greater advantages for the virus than would have occurred individually, he said.

The researchers also found that from the beginning of the pandemic, the SARS-CoV-2 genome has been evolving and diversifying in different regions around the world, allowing for the rise of new lineages and, possibly, even new species, Koonin said.

During the pandemic, researchers have used evolutionary virology tools to tackle many other questions. For example, Nelson tracked the spread of SARS-CoV-2 across Europe and North America. In a study by Rochman and Koonin that is currently undergoing peer review, the investigators found recently vaccinated individuals, who are only partially immune, are at the highest risk for incubating antibody-resistant variants.

C. Brandon Ogbunu, PhD, an evolutionary geneticist at Yale University whose work is focused on disease evolution, studied whether SARS-CoV-2 would evolve to become more transmissible, and if so, would it also become more or less virulent. His lab also investigated the transmission and spread of the virus.

“I think the last year, on one end, has been this opportunity to apply concepts and perspectives that we’ve been developing for the last several decades,” Ogbunu told Medscape Medical News. “At the same time, this pandemic has also been this wake-up call for many of us with regards to revealing the things we do not understand about the ways viruses infect, spread, and how evolution works within viruses.”

He emphasizes the need for evolutionary biology to partner with other fields — including information theory and biophysics — to help unlock viral mysteries: “We need to think very, very carefully about the way those fields intersect.”

Nelson also points to the need for better, more centralized data gathering in the United States. The sheer volume of information scientists have collected about SARS-CoV-2 will aid in the study of virus evolution for years to come, said Koonin.

Evolution in Medicine

Evolutionary virology and related research can be applied to medicine outside of the context of a global pandemic. “The principles and technical portions of evolutionary virology are very applicable to other diseases, including cancer,” Koonin said.

Viruses, bacteria, and cancer cells are all evolving systems. Viruses and bacteria are constantly evolving to thwart drugs and vaccines. How physicians and healthcare professionals practice medicine shapes the selection pressures driving how these pathogens evolve, Nelson said.

The rise of antibiotic-resistant bacteria is a particularly relevant example of how evolution affects the way physicians treat patients. Having an evolutionary perspective can help inform how to treat patients most effectively, both for individual patients as well as for broader public health, she said.

“For a long time, there’s been a lot of interest in pathogen evolution that hasn’t translated so much into clinical practice,” said Nelson. “There’s been kind of a gulf between the research side of evolutionary virology and pathogen emergence and actual practice of medicine.”

As genomic sequencing has become faster and cheaper, that gulf has started to narrow, she said. As this technology continues to prove itself by, for example, tracking the evolution of one virus in real time, Nelson hopes there will be a positive snowball effect, leading to more attention, investment, and improvements in genomic data and that its use in epidemiology and medicine will expand going forward.

Bringing viral evolution studies more into medicine will require a mindset shift, Ogbunu said. Clinical practice is, by design, very focused on the individual patient. Evolutionary biology, on the other hand, deals with populations and probabilities.

Being able to engage with evolutionary biology would help physicians better understand disease and explain it to their patients, he said.

To start, Nelson recommends requiring at least one course in evolutionary biology or evolutionary medicine in medical school and crafting continuing education in this area for physicians (presentations at conferences could be one way to do this, she notes).

Nelson also recommends deeper engagement and collaboration between physicians who collect samples from patients and evolutionary biologists who analyze genetic data. This would improve the quality of the data, the analysis, and the eventual findings that could be relevant to patients and clinical practice.

Still, “my first and inevitable reaction is I would so much rather prefer to exist in relative obscurity,” said Koonin, noting that the tragedy of the pandemic outweighs the advancements in the field.

Although there’s no going back to prepandemic times, there is an enormous opportunity in the aftermath of COVID to increase dialogue between physicians and evolutionary virologists to improve medical practice as well as public health.

Nelson summed it up: “Everything we uncover about these pathogens may help us prevent something like this again.”

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