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Illustration by Daniel Hertzberg

Feature

The Future of Pandemics is Proactive

Instead of playing catch-up with the next new virus, precision medicine aims to let us find it early and deal with it swiftly

By Bruce Grierson, ’86 BA(Spec)

Illustration by Daniel Hertzberg
July 08, 2020 •

On March 17, David Wishart, ’83 BSc(Hons), fielded a call from Medellin, Colombia. A company called Quantrack had a job for him.

The novel COVID‑19 coronavirus had its hooks in the country. The Quantrack team figured that if Wishart, a professor of both biology and computing science, could make one of his famous heat-maps showing the virus galloping across the landscape, it would help Colombians understand the crisis in a way that raw numbers couldn’t. It seemed a perfect application of the mapping technology. Wishart said yes, and his computing staff of four at The Metabolomics Innovation Centre got to work creating a data map, without charge.

By then infection and mortality data were pouring out of governments, health systems and universities all over the world. It appeared COVID‑19 might be the disease the World Health Organization was preparing for when it put out a call in 2015 to the world’s top virologists to propose methodologies for developing vaccines. Even the dreaded one that it dubbed “Disease X.”

So, Wishart decided to scale up and expand the scope of the mapping project to the whole Earth. He called the interactive web tool Covidmapper.

By crunching data from multiple sources — government, universities, the WHO — he and his team created a kind of real-time snapshot of the ever-morphing moments that added up to the virus’s global impact. With a degree of granularity normally available only to epidemiologists, the average citizen could see how fast this thing was spreading. And where.

A kind of magic ratio of 50-to-1 began to emerge from the data. Fifty negative tests for every positive test seemed to be a kind of tipping point: countries that exceeded that ratio were in good shape. Indeed, by mid-April the death rates in those countries that hit the ratio were one-one hundredth of those countries that didn’t.

But the true value of the Covidmapper technology was only just becoming apparent.

Wishart’s team had tracked backward, retroactively filling in the picture right back to Jan. 1. That long runway made it possible to then track forward into the future. This thing, they realized, was a kind of crystal ball.

“It’s predicting what’s going to happen,” Wishart says. To the great, unGoogleable question that was on everybody’s mind in that moment — when can we resume our lives? — Covidmapper seemed to point toward answers. These are invaluable data, the kind that allow people not just to react, but to plan.

And planning is what this story is all about.

*****

In this pandemic, we’ve all now seen what “we weren’t ready” looks like: full lockdown, with an almost incalculable economic and psychological fallout. International borders slammed shut. Businesses shuttered. Civil liberties suspended. “This is a totally unprecedented situation,” we’ve heard over and again. There was no playbook.

But the public-health response actually was adhering to the playbook — the only one it knows: admit the sick, identify the disease, make a drug to treat it. Or at least try to keep people alive until the cavalry arrives in the form of a vaccine. “Medicine has always been reactive, just like our response to pandemics is always reactive,” Wishart says.

The problem is, the cavalry may never show up. So few viruses have ever been quashed by safe and effective vaccines that some names come readily to mind. Polio. Smallpox. Mumps. Measles. Every research team working on COVID‑19 knows it’s bucking serious odds to come up with a vaccine in the 12- to 18-month window repeatedly stated as the goal. No one has ever done it.

John Lewis is one of the people hopeful that an unprecedented collective global effort will pull off the heretofore impossible. Lewis is a professor of oncology, a prostate cancer researcher, and is helming a group working furiously on a COVID‑19 vaccine. “Fear of our loved ones getting this thing,” as Lewis puts it, provides another level of motivation for researchers. He knows this more intimately than most. Lewis lost his father-in-law to kidney cancer in 2002 and it was the inadequacy of available tools for the job at the time that prompted him to pursue a career in genetic medicine. “I thought, ‘We can do better than that,’ ” he says.

Lewis, who also holds the Alberta Cancer Foundation Frank and Carla Sojonky Chair in Prostate Cancer Research, has since staked his career on the promise of precision health care; his focus is personalized cancer medicines and vaccines. It’s part of an anticipated shift from generalized health care, based on population averages, to specific care aimed at the individual on the other end of the stethoscope. For Lewis, the future medical ideal will involve sequencing the genomes of every cancer patient and then very quickly designing medicines uniquely tailored to that person.

It’s that approach that the health-care biotechnology company headed by Lewis, Entos Pharmaceuticals, is applying to the COVID‑19 challenge. As of late March, the lab had begun manufacturing vaccine candidates against the novel coronavirus and is in the process of testing in animal models before moving to human trials.

If Lewis is betting on the power of genetic science to help us eventually get the better of disease, Wishart is doubling down on a lesser-known human bio-map — one for which the U of A has become the world leader.

*****

Coursing through the bloodstream of you and me and all living organisms are small molecules called metabolites — smoke from the metabolic fire. Like the genome, each person’s metabolome, thousands of circulating compounds, is unique. Taken together, they amount to a kind of report card of your health right now, except that it’s in code. The patterns need to be algorithmically crunched to make sense and Wishart, who has invented several processes that make the metabolome easier to sequence, has effectively shepherded the metabolome into the scientific mainstream. He oversees The Metabolomic Innovation Centre, located at the U of A. The centre houses the Human Metabolome Database — an open-source archive of all known metabolites and their structures.

“We can tell more from the chemicals or the proteins in your body than we can tell from the genes,” Wishart says. “The genome tells you what might happen to you. The metabolome tells you what is happening to you.” Say, for example, you’re a 40-year-old woman who feels healthy; your metabolome might tell a different story. “It might say, ‘You’re trending toward diabetes in about 15 years.’ ” The metabolome could even help detect colon cancer from a urine test. To be clear, it’s not the cancer itself that the test picks up, but rather biomarkers of the disease. It zeroes in on a few key metabolites, measures their concentrations, runs them through an algorithm and determines whether you have cancer. 

“My view of precision medicine is proactive medicine,” Wishart says. “It’s trying to say, ‘You’re predisposed to this,’ or ‘This is happening but it’s early stage so we can do something about it.’ That kind of information gives us agency.” These are proactive public health measures, he says. 

The three “omics” — genomics, metabolomics and proteomics (the study of proteins in the body) — are the large-scale studies of very small building blocks of our bodies. In the future, all three will likely be marshalled in a kind of synchrony to help avert pandemics. How?

Well, think of what might happen if everyone had access to their own biodata. A device installed in the plumbing system of every home could analyze body waste for pathogens and send the results — zoop! — to your smartphone.

“That’s possible and even happening,” Wishart says. Indeed, the U of A is developing technology that is leading the world in metabolite analysis, and “smart toilets” are being developed in Japan, Europe and elsewhere. They’re not yet ready for prime time, but here’s how they could work.

“If you had something that could perform a quick chemical analysis before you flushed the toilet, you might see if you’re, say, developing pneumonia,” Wishart says. “And then see if it’s bacterial or viral pneumonia — which is very close to what COVID causes in people.” In a pandemic scenario, you might know early on when to self-isolate.

Knowing your risk factors can also help people make healthy decisions. “Who is dying from COVID?” Wishart asks rhetorically. “It’s generally people who have underlying conditions. In some cases, they don’t know that. ... But if you could do metabolomic tests on people, you might be able to detect those silent risk factors,” he says. “That is precision medicine. That’s identifying the risks and then deciding how you treat people in a proactive way.

“If we had those smart toilets, then everyone would probably have a risk profile. They’d know, oh, I’ve got these issues, and COVID’s hitting now, so I’d better stay in.”

This year, COVID‑19 testing ramped up all over the world, resulting in unprecedented amounts of biodata. Paired with the kind of geodata now instantly available from smartphones, it amounts to a powerful tool to contain this pandemic — and possibly avert the next one. It’s easy to imagine the day not so far in the future when border agents can dial up an instantaneous risk profile of every individual before admitting them into the country. They could see an electronic bread-crumb trail of someone’s recent travels, or call up a traveller’s health status, medical history, proof that their vaccinations are up to date, how sleep-deprived they are, their vitamin D levels, alcohol consumption, even how they’re managing stress.

Of course, all that shared data comes at a cost.

“There are obviously ethical issues around data ownership, data collection, data sharing and, quite frankly, privacy,” says Michael Van Manen, ’04 BMedSc, ’05 MD, ’13 PhD, who holds the Endowed Chair in Health Ethics and is director of the John Dossetor Health Ethics Centre.

“Who owns personal health data? Does ownership reside with the individual from whom the data was taken, or with the organizations that collect and store the data? Who decides on the appropriate use of such data? What happens if data is used in a way departing from the purpose in which it was collected?”

Clearly, there are a lot of important questions, and we are only just beginning to tackle them. But Van Manen offers some considerations. For example, what’s the trade-off between privacy and the greater good?

“We will need to ask how do these technologies change the nature of our relationships with one another, our responsibilities to one another, and of course, our existence within society.”

After all, Van Manen says, at its core, ethics is about how we live our own lives while being part of a community of others. Which is why even the discussion of basic human rights over the past few months — the right to open your business versus the rights of others to avoid the risk of increased community transmission — has been complex.

“We are entitled to many rights, and sometimes rights come in conflict with each other.”

*****

It’s what humans do that so often produces what looks, down the line, like awful bad luck. This pandemic is not really about the unique terribleness of COVID‑19. SARS was 25 times as deadly. Ebola was 70 times as deadly. What makes COVID‑19 so dangerous is that it doesn’t sicken its host right away. It lurks in them undetected as they unwittingly pass it on. And in a globalized age, the “passing it on” is savagely efficient.

“It’s planes that made COVID‑19 spread so quickly,” Wishart says. “Planes are basically missiles launching viruses around the world. If we’d had planes that flew that fast 100 years ago, it wouldn’t have been 50 million that died of the Spanish flu, it would have been 400 million. You could have been talking about an extinction event.”

In 2020, it was shared information, the advance notice, that made a difference, he says. “If we hadn’t understood where this disease was coming from and just lived our lives normally, if we hadn’t done anything — no social distancing at all — our numbers said by April 1 COVID‑19 would have killed 40 million people. That’s how many people died of the Spanish flu over the course of a year. To take 40 million people off the planet in a month and a half: society collapses. Everything collapses.”

Now that we know first-hand the damage a pandemic can do, one would assume all world governments will make it Job 1 to ensure that something like this never happens again by rallying up a robust and nimble response protocol. Maybe you install walk-through fever scanners at every international nodal point — seaport, airport, international train station — and perhaps also in sports arenas, concerts halls, even shopping malls, Wishart suggests. You keep teams of epidemiologists on permanent standby, as Bill Gates famously envisioned, so the moment a disease outbreak is reported anywhere in the world, they’re parachuted in to test and contact-trace and nip the contagion in the bud. In effect, you create a kind of pandemic defence system. Meanwhile, you also work on improving the host: us. You leverage cutting-edge science to enhance the human immune system.

Perhaps the COVID‑19 crisis is an opportunity. It’s the occasion for the pivot the world needs, from reactive to proactive medicine.

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