When Eddie Holmes was at school in the UK, his biology teacher refused to discuss evolution.
“He was a creationist … he just refused to teach the entire evolution section of the textbook.”
Yet decades later, Professor Holmes, now at the University of Sydney, is being honoured as a world-leading authority on evolution — specifically, the evolution of viruses, including SARS-CoV-2.
At an online ceremony Professor Holmes has been awarded the top Prime Minister’s Prize for Science, worth $250,000.
Reflecting on his school teacher’s silence on evolution, Professor Holmes figures it “completely backfired”.
“It certainly made me more interested in finding out what evolution was all about.”
At university, Professor Holmes straddled arts and science by doing anthropology, which he was excited to discover was essentially about evolution.
“There it was,” he says. “The forbidden fruit.”
For his PhD at the University of Cambridge in the 1980s, Professor Holmes used gene sequencing to track subtle changes in DNA to map the evolution of humans and other primates.
“I became more interested in genetics — the mechanisms of evolution.”
But in the 1990s, things slowed down a bit when he found himself in northern California studying genetic variation by counting the bristles on the back of fruit flies.
“I felt life was passing me by.”
Meanwhile, a hundred or so kilometres south, the city of San Francisco was in the grip of the deadly AIDS epidemic.
And after hearing a talk on how the culprit pathogen, HIV, was mutating quickly, Professor Holmes saw how he could use his skills to more practical benefit.
Life in the fast lane
Viruses evolve on such a different time scale to what he’d studied before.
This rapid evolution meant genetics could be used to help track a virus through a population in closer to “real time”, and help save lives.
“If we know how a virus is spreading through the population, then we know what the most likely mechanisms of spread are, and the most likely risk factors. Then you can act to stop those.”
Back in the UK, Professor Holmes used genetics to trace the spread of HIV in Edinburgh.
“I looked at how the virus spread through different risk groups, particularly injecting drug users and haemophiliacs.”
Work like this helped reveal that people with haemophilia had been infected with HIV when they were treated with contaminated clotting factors.
Years on, the same techniques are at the heart of “genomic tracing” used to track the spread of SARS-CoV-2 and identify hotspots of transmission.
Professor Holmes also uses evolutionary genetics to determine the origin of viruses.
“Virtually every human virus comes from an animal reservoir somewhere,” says Professor Holmes, who has worked on everything from influenza, HIV and hepatitis C to dengue, Zika and Ebola.
Feeling the weight of responsibility
When COVID-19 arrived on the scene, Professor Holmes found himself at the centre of high drama.
It was on New Years’ Eve of 2019 that he first noticed in his Twitter feed reports of pneumonia of an unknown cause at Wuhan Central Hospital in China.
Professor Holmes had recently studied patients with similar symptoms at the very same hospital.
So he wasted no time in reaching out to his Chinese colleague, Professor Yong-Zhen Zhang of Fudan University, Shanghai, offering to help pin down the unknown pathogen.
But the emergence of SARS-CoV-2 at a hospital he’d worked at was not the only coincidence that put Professor Holmes at the centre of the COVID-19 story.
It turns out the disease was linked to the Huanan Seafood Market, which he had visited in the past.
On Sunday, January 5, 2020, Professor Holmes was in a car headed for a Sunday brunch on Sydney’s northern beaches when his phone pinged.
Professor Zhang had received the virus sequence back from the lab and it looked a lot like SARS, the virus responsible for the 2003 outbreak in China.
“I sort of swore down the phone — we thought it was like SARS back again.”
Others had also sequenced the new virus’s genome, but Chinese authorities were being strict on what information could be released, Professor Holmes says.
But as the week wore on, social media and press reports clamoured with speculation, and Professor Holmes grew increasingly frustrated.
He didn’t like being “a gatekeeper” of such crucial information — making the viral sequence public was essential for the development of diagnostic tests and vaccines that could save many lives.
“I felt a huge weight of responsibility,” he says.
So after talking to Professor Zhang, he carried out what University of Sydney colleague Professor Stephen Simpson calls “one the most important acts of data-sharing ever undertaken”.
On January 10, 2020, he uploaded the genome to a “virus chat” website, and became the first person to release the sequence of SARS-CoV-2 to the world.
Professor Holmes tweeted his post and then sat back with a huge sigh of relief.
“At that point I went, ‘thank God’. The pressure was lifted.”
The inevitable pandemic, but with surprises
The outbreak of COVID-19 came as little surprise to Professor Holmes, who knows just how common it is for coronaviruses to jump species.
“It was actually bleedingly obvious, quite frankly, that it was going to happen. And it will happen again,” he says.
But like many others, he assumed SARS-CoV-2 would be a localised and containable outbreak, like the first SARS.
While the first SARS was only passed on when people had symptoms, SARS-CoV-2 turned out to be more “insidious”, because people can spread it when they don’t know they’re infected.
Evolution of the SARS-CoV-2
Professor Holmes says he was also surprised at the emergence of the more infectious Delta strain, which also appeared to cause more severe disease.
“I didn’t think the virus had that capacity to evolve.”
But while Delta evolved at a time people had little immunity, he says widespread vaccination will change the selection pressure on the virus going forward.
This is likely to push the virus towards better evading our immune system and re-infecting people who are already infected, Professor Holmes says.
But, he says, the results of this will be unpredictable, likening viruses to a Swiss Army knife.
“They’re very compact. In that Swiss Army knife, you’ve got a whole bunch of blades … if you wanted to make a thicker pair of scissors, you’d need to remove one of the other blades.
Evolution aside, Professor Holmes emphasises that getting vaccinated will reduce the number of people dying from the virus.
The future of pandemics
Viruses are everywhere and most of them don’t actually cause disease, but modern life encourages the emergence of new pathogenic viruses, Professor Holmes says.
“There’s no doubt in my mind we’ll get more pandemics.”
He’s called for countries to learn from the experience of SARS-CoV-2, and be more prepared for a broader range of pathogens.
This includes developing universal vaccines, designed to recognise a diversity of strains. And he thinks we need to boost local vaccine production.
Professor Holmes also thinks there should be better regulation of the wildlife trade, which increases the exposure of humans to new viruses.
“In my own mind, the wildlife trade is what underpins COVID-19,” he says.
Back in 2014, Professor Holmes snapped caged raccoon dogs being sold at the Wuhan market he visited and studies have since confirmed these animals were also at the market in 2019.
While SARS-CoV-2 has not yet been linked to raccoon dogs, these animals were involved in the first SARS outbreak.
Professor Holmes has also called for better surveillance of emerging pathogens as humans face increased contact with wildlife.
Beyond factors like the wildlife trade, deforestation, and international travel, global warming is triggering more movement of animals, increasing human exposure to them.
“Climate change and pandemics go hand in hand,” Professor Holmes warns.