Hop to it: Researchers evaluate rabbits’ evolved resistance to myxoma virus

February 14, 2019

It's common knowledge that rabbit populations are not easily controlled — they reproduce swiftly, and as a result, they have a severe impact on their environment, as when European settlers introduced the wild European rabbit to Australia in the late 19th century. In an attempt to reduce the population size that had grown to almost a billion rabbits by 1950, Australian scientists released the myxoma virus — a virus known to be deadly to rabbits at the time — to the rabbit population, and eventually did the same for populations in France and the U.K. However, after some time, fatality rates lessened in all three countries, and the rabbit populations rebounded but were now genetically more resistant to the virus.

Regarded as “one of the greatest natural experiments in evolution,” researchers naturally wanted to learn more, so they tackled the genetic basis of the newly resistant rabbit adaptation to this virus. Grant McFadden's lab belongs to the Center of for Immunotherapy, Vaccines and Virotherapy. Download Full Image

Partnering with the University of Cambridge and several other research institutes, researchers at the Biodesign Institute at Arizona State University, as part of Grant McFadden’s Center for Immunotherapy, Vaccines and Virotherapy, validated the role of specific rabbit genes in contributing to this acquired resistance in research published in Science magazine.

McFadden’s lab has many decades of expertise in the myxoma virus, studying subjects ranging from the virus’s replication in hosts to its potential use in treating cancer. For this project, they were tasked with determining whether certain rabbit genes that had changed in the 70 years of exposure to the virus were responsible for the rabbits’ acquired resistance to the virus.

“There are rabbits in each population that evolved at the same time but independently of each other,” said McFadden, a professor in the School of Life Sciences and director of the Center for Immunotherapy, Vaccines and Virotherapy. “The idea was to sequence examples of many rabbit genomes of all three places and see what they have in common, and that’s what led to this study. We came up with half a dozen gene variations in common — our job was to determine whether these variants of genes affected that virus in a lab setting.”

While the rabbits that were resistant to the virus survived and thus were selected for, the less pathogenic viruses were also selected for among the viral populations. This coupled with the fact that the same trend was seen in three geographically distinct regions of the world, serve as a concrete example of co-evolutionary forces that operate between viruses and their hosts, and being able to determine the genetic basis of this adaptation only furthers our knowledge of parallel adaptation.

“The host and the virus began to do a genetic dance with each other that was started over 70 years ago. For decades after that, no one knew what that genetic dance was, but now we have learned something new from the genomes of the surviving rabbits,” McFadden added.   

The researchers in the U.K. were largely responsible for utilizing modern sequencing technology to sequence the rabbit genomes in the populations now and compare them to genomes from past generations, while McFadden and his lab were responsible for determining whether the genes that emerged in all three rabbit populations were correlated to antiviral effects by testing the virus in cell culture. Ana Lemos de Matos and Masmudur Rahman, a postdoc and an associate research professor in McFadden’s lab, respectively, were responsible for testing the effect of these genes on the myxoma virus. 

By doing so, the researchers were able to validate the role of these genes in viral replication and indicated that selection for a more effective interferon response as part of the innate immune response to viral infection in rabbit populations was at play.

McFadden and his lab believe that one of the main takeaways from this study was to prove that co-evolution happens and can occur quickly after new virus-host interactions emerge.

“This is probably one of the best examples of co-evolution that we know of, where the virus is evolving, and the host is evolving, and they are evolving in concert with each other,” McFadden said. “This is a wonderful example of pure-curiosity research, and there may be implications down the line, but in terms of co-evolution, I can’t think of a better example on the planet.”

Gabrielle Hirneise

Assistant science writer , Biodesign Institute


Is your brain lying to you?

What magicians can teach scientists about observation

February 14, 2019

Observation is one of the most powerful tools that scientists use. They meticulously perform experiments, analyze data and interpret the results, then repeat that process hundreds of times.

But what if our brains are lying to us? Can scientists trust their observations? Parag Mallick is a computer scientist and researcher at Stanford Medicine and a world-renowned magician. Download Full Image

Parag Mallick, a computer scientist and researcher at Stanford Medicine and a world-renowned magician, explored these questions during a recent visit to Arizona State University. In “An Evening of Science and Magic,” sponsored by ASU’s Biodesign Institute, Mallick explained the concept of inattentional blindness to a full house at the Marston Exploration Theater.

What is inattentional blindness, and what can magicians teach us about science? Plenty, according to Mallick.

Inattentional blindness occurs when an individual fails to perceive objects or events because their attention is focused somewhere else. Magicians are experts at taking advantage of this gap in perception. Sometimes scientists may fall victim to this, researching the wrong thing at the wrong time because it made sense at the time to look at it.

“By being extremely cognizant of these gaps in perception, we might do a better job of avoiding them and interpreting our observations,” he said. “We then can do a better job of designing better experiments by becoming aware of these holes in our perceptions.”

Parag Mallick and Joshua LaBaer

Biodesign Institute Executive Director Joshua LaBaer (left) participates in a trick during Parag Mallick's "An Evening of Science and Magic" event. Photo by Andy DeLisle/ASU

Mallick became enamored with magic as a child when he was gifted a magic kit. His childhood hobby transformed into something more serious during college and graduate school when he formed a juggling group called Students Against Gravity. He also began taking classes at the Magic Castle in Hollywood, a clubhouse for the Academy of Magical Arts. He spent years perfecting his craft and started doing magic all over the city and eventually all over the world.

Mallick, now an associate professor who heads a cancer research lab at Stanford University, believes in tackling the impossible. He said magicians have long been willing to embrace the ludicrous in their performances, and this frees up their mind to explore more possibilities. Scientists should do the same.

“Scientists are in the habit of taking things that are impossible and making them possible,” Mallick said. He said a very good magician is meticulous. Just like a scientist will perform an experiment over and over again, a magician will repeatedly practice a trick until he or she perfects it. The extreme attention to detail for both professions results in the greatest successes of today.

“When you embrace the completely ludicrous to find inspiration, it frees your mind and you’re allowed to explore a much wider swath of possibilities,” Mallick said.

Joshua LaBaer, executive director of the Biodesign Institute, was excited to have the Science and Magic event come to ASU because it forces scientists and others to think outside of the box.

Parag Mallick and Joshua LaBaer

Joshua LaBaer volunteers for a trick during Parag Mallick's "An Evening of Science and Magic" lecture show. Mallick is a computer scientist and researcher at Stanford Medicine and a world-renowned magician. Photo by Andy DeLisle/ASU

“Research is all about discovering new things, including new patterns,” he said. “For scientists and researchers, we need to always remember that we cannot take the mental shortcut of assuming that what we see must be part of the previous pattern.”

LaBaer said science and magic are two places where we need to break the pattern-recognition process.

“We like to think of our brain as an open, unbiased instrument that collects data from our senses and then fully analyzes and interprets them. But, in fact, in order to reduce work and enhance response time, our brain cheats a little,” he said.

As a scientist, even if the data suggests the previous pattern, he said, it’s lazy to accept this without proving it.

“It is the magician’s job to trick us into believing the impossible explanation,” LaBaer said. “It is the scientist’s job to determine which explanation is correct.”

Throughout the evening, Mallick performed magic tracks that included holding a glass of water upside down without spilling any water, and solicited volunteers from the audience for a game of three-card monte and other card tricks. He closed his show by addressing some of the gaps in perception that the audience may have missed, which was met with wonder and applause by young and old alike.

Lastly, he reminded the audience that scientists are indeed making tremendous progress and saving many, many lives from cancer and other illnesses.

“I dare anyone to prove me wrong,” he said.

Jean Clare Sarmiento

Communications Specialist , Biodesign Institute