Scientists Are Building an “AccuWeather” for Germs to Predict Your Risk of Getting the Flu
Applied mathematician Sara del Valle works at the U.S.'s foremost nuclear weapons lab: Los Alamos. Once colloquially called Atomic City, it's a hidden place 45 minutes into the mountains northwest of Santa Fe. Here, engineers developed the first atomic bomb.
Like AccuWeather, an app for disease prediction could help people alter their behavior to live better lives.
Today, Los Alamos still a small science town, though no longer a secret, nor in the business of building new bombs. Instead, it's tasked with, among other things, keeping the stockpile of nuclear weapons safe and stable: not exploding when they're not supposed to (yes, please) and exploding if someone presses that red button (please, no).
Del Valle, though, doesn't work on any of that. Los Alamos is also interested in other kinds of booms—like the explosion of a contagious disease that could take down a city. Predicting (and, ideally, preventing) such epidemics is del Valle's passion. She hopes to develop an app that's like AccuWeather for germs: It would tell you your chance of getting the flu, or dengue or Zika, in your city on a given day. And like AccuWeather, it could help people alter their behavior to live better lives, whether that means staying home on a snowy morning or washing their hands on a sickness-heavy commute.
Sara del Valle of Los Alamos is working to predict and prevent epidemics using data and machine learning.
Since the beginning of del Valle's career, she's been driven by one thing: using data and predictions to help people behave practically around pathogens. As a kid, she'd always been good at math, but when she found out she could use it to capture the tentacular spread of disease, and not just manipulate abstractions, she was hooked.
When she made her way to Los Alamos, she started looking at what people were doing during outbreaks. Using social media like Twitter, Google search data, and Wikipedia, the team started to sift for trends. Were people talking about hygiene, like hand-washing? Or about being sick? Were they Googling information about mosquitoes? Searching Wikipedia for symptoms? And how did those things correlate with the spread of disease?
It was a new, faster way to think about how pathogens propagate in the real world. Usually, there's a 10- to 14-day lag in the U.S. between when doctors tap numbers into spreadsheets and when that information becomes public. By then, the world has moved on, and so has the disease—to other villages, other victims.
"We found there was a correlation between actual flu incidents in a community and the number of searches online and the number of tweets online," says del Valle. That was when she first let herself dream about a real-time forecast, not a 10-days-later backcast. Del Valle's group—computer scientists, mathematicians, statisticians, economists, public health professionals, epidemiologists, satellite analysis experts—has continued to work on the problem ever since their first Twitter parsing, in 2011.
They've had their share of outbreaks to track. Looking back at the 2009 swine flu pandemic, they saw people buying face masks and paying attention to the cleanliness of their hands. "People were talking about whether or not they needed to cancel their vacation," she says, and also whether pork products—which have nothing to do with swine flu—were safe to buy.
At the latest meeting with all the prediction groups, del Valle's flu models took first and second place.
They watched internet conversations during the measles outbreak in California. "There's a lot of online discussion about anti-vax sentiment, and people trying to convince people to vaccinate children and vice versa," she says.
Today, they work on predicting the spread of Zika, Chikungunya, and dengue fever, as well as the plain old flu. And according to the CDC, that latter effort is going well.
Since 2015, the CDC has run the Epidemic Prediction Initiative, a competition in which teams like de Valle's submit weekly predictions of how raging the flu will be in particular locations, along with other ailments occasionally. Michael Johannson is co-founder and leader of the program, which began with the Dengue Forecasting Project. Its goal, he says, was to predict when dengue cases would blow up, when previously an area just had a low-level baseline of sick people. "You'll get this massive epidemic where all of a sudden, instead of 3,000 to 4,000 cases, you have 20,000 cases," he says. "They kind of come out of nowhere."
But the "kind of" is key: The outbreaks surely come out of somewhere and, if scientists applied research and data the right way, they could forecast the upswing and perhaps dodge a bomb before it hit big-time. Questions about how big, when, and where are also key to the flu.
A big part of these projects is the CDC giving the right researchers access to the right information, and the structure to both forecast useful public-health outcomes and to compare how well the models are doing. The extra information has been great for the Los Alamos effort. "We don't have to call departments and beg for data," says del Valle.
When data isn't available, "proxies"—things like symptom searches, tweets about empty offices, satellite images showing a green, wet, mosquito-friendly landscape—are helpful: You don't have to rely on anyone's health department.
At the latest meeting with all the prediction groups, del Valle's flu models took first and second place. But del Valle wants more than weekly numbers on a government website; she wants that weather-app-inspired fortune-teller, incorporating the many diseases you could get today, standing right where you are. "That's our dream," she says.
This plot shows the the correlations between the online data stream, from Wikipedia, and various infectious diseases in different countries. The results of del Valle's predictive models are shown in brown, while the actual number of cases or illness rates are shown in blue.
(Courtesy del Valle)
The goal isn't to turn you into a germophobic agoraphobe. It's to make you more aware when you do go out. "If you know it's going to rain today, you're more likely to bring an umbrella," del Valle says. "When you go on vacation, you always look at the weather and make sure you bring the appropriate clothing. If you do the same thing for diseases, you think, 'There's Zika spreading in Sao Paulo, so maybe I should bring even more mosquito repellent and bring more long sleeves and pants.'"
They're not there yet (don't hold your breath, but do stop touching your mouth). She estimates it's at least a decade away, but advances in machine learning could accelerate that hypothetical timeline. "We're doing baby steps," says del Valle, starting with the flu in the U.S., dengue in Brazil, and other efforts in Colombia, Ecuador, and Canada. "Going from there to forecasting all diseases around the globe is a long way," she says.
But even AccuWeather started small: One man began predicting weather for a utility company, then helping ski resorts optimize their snowmaking. His influence snowballed, and now private forecasting apps, including AccuWeather's, populate phones across the planet. The company's progression hasn't been without controversy—privacy incursions, inaccuracy of long-term forecasts, fights with the government—but it has continued, for better and for worse.
Disease apps, perhaps spun out of a small, unlikely team at a nuclear-weapons lab, could grow and breed in a similar way. And both the controversies and public-health benefits that may someday spin out of them lie in the future, impossible to predict with certainty.
Friday Five Podcast: New drug may slow the rate of Alzheimer's disease
The Friday Five covers important stories in health and science research that you may have missed - usually over the previous week, but today's episode is a lookback on important studies over the month of September.
Most recently, on September 27, pharmaceuticals Biogen and Eisai announced that a clinical trial showed their drug, lecanemab, can slow the rate of Alzheimer's disease. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend and the new month.
Listen on Apple | Listen on Spotify | Listen on Stitcher | Listen on Amazon | Listen on Google
This Friday Five episode covers the following studies published and announced over the past month:
- A new drug is shown to slow the rate of Alzheimer's disease
- The need for speed if you want to reduce your risk of dementia
- How to refreeze the north and south poles
- Ancient wisdom about Neti pots could pay off for Covid
- Two women, one man and a baby
Could epigenetic reprogramming reverse aging?
Ten thousand years ago, the average human spent a maximum of 30 years on Earth. Despite the glory of Ancient Greece and the Roman Empire, most of their inhabitants didn’t surpass the age of 35. Between the 1500s and 1800, life expectancy (at least in Europe) fluctuated between 30 and 40 years.
Public health advancements like control of infectious diseases, better diet and clean sanitation, as well as social improvements have made it possible for human lifespans to double since 1800. Although lifespan differs widely today from country to country according to socioeconomic health, the average has soared to 73.2 years.
But this may turn out to be on the low side if epigenetic rejuvenation fulfills its great promise: to reverse aging, perhaps even completely. Epigenetic rejuvenation, or partial reprogramming, is the process by which a set of therapies are trying to manipulate epigenetics – how various changes can affect our genes – and the Yamanaka factors. These Yamanaka factors are a group of proteins that can convert any cell of the body into pluripotent stem cells, a group of cells that can turn into brand new cells, such as those of the brain or skin. At least in theory, it could be a recipe for self-renewal.
“Partial reprogramming tries to knock a few years off of people’s biological age, while preserving their original cell identity and function,” says Yuri Deigin, cofounder and director of YouthBio Therapeutics, a longevity startup utilizing partial reprogramming to develop gene therapies aimed at the renewal of epigenetic profiles. YouthBio plans to experiment with injecting these gene therapies into target organs. Once the cargo is delivered, a specific small molecule will trigger gene expression and rejuvenate those organs.
“Our ultimate mission is to find the minimal number of tissues we would need to target to achieve significant systemic rejuvenation,” Deigin says. Initially, YouthBio will apply these therapies to treat age-related conditions. Down the road, though, their goal is for everyone to get younger. “We want to use them for prophylaxis, which is rejuvenation that would lower disease risk,” Deigin says.
Epigenetics has swept the realm of biology off its feet over the last decade. We now know that we can switch genes on and off by tweaking the chemical status quo of the DNA’s local environment. "Epigenetics is a fascinating and important phenomenon in biology,’’ says Henry Greely, a bioethicist at Stanford Law School. Greely is quick to stress that this kind of modulation (turning genes on and off and not the entire DNA) happens all the time. “When you eat and your blood sugar goes up, the gene in the beta cells of your pancreas that makes insulin is turned on or up. Almost all medications are going to have effects on epigenetics, but so will things like exercise, food, and sunshine.”
Can intentional control over epigenetic mechanisms lead to novel and useful therapies? “It is a very plausible scenario,” Greely says, though a great deal of basic research into epigenetics is required before it becomes a well-trodden way to stay healthy or treat disease. Whether these therapies could cause older cells to become younger in ways that have observable effects is “far from clear,” he says. “Historically, betting on someone’s new ‘fountain of youth’ has been a losing strategy.”
The road to de-differentiation, the process by which cells return to an earlier state, is not paved with roses; de-differentiate too much and you may cause pathology and even death.
In 2003 researchers finished sequencing the roughly 3 billion letters of DNA that make up the human genome. The human genome sequencing was hailed as a vast step ahead in our understanding of how genetics contribute to diseases like cancer or to developmental disorders. But for Josephine Johnston, director of research and research scholar at the Hastings Center, the hype has not lived up to its initial promise. “Other than some quite effective tests to diagnose certain genetic conditions, there isn't a radical intervention that reverses things yet,” Johnston says. For her, this is a testament to the complexity of biology or at least to our tendency to keep underestimating it. And when it comes to epigenetics specifically, Johnston believes there are some hard questions we need to answer before we can safely administer relevant therapies to the population.
“You'd need to do longitudinal studies. You can't do a study and look at someone and say they’re safe only six months later,” Johnston says. You can’t know long-term side effects this way, and how will companies position their therapies on the market? Are we talking about interventions that target health problems, or life enhancements? “If you describe something as a medical intervention, it is more likely to be socially acceptable, to attract funding from governments and ensure medical insurance, and to become a legitimate part of medicine,” she says.
Johnston’s greatest concerns are of the philosophical and ethical nature. If we’re able to use epigenetic reprogramming to double the human lifespan, how much of the planet’s resources will we take up during this long journey? She believes we have a moral obligation to make room for future generations. “We should also be honest about who's actually going to afford such interventions; they would be extraordinarily expensive and only available to certain people, and those are the people who would get to live longer, healthier lives, and the rest of us wouldn't.”
That said, Johnston agrees there is a place for epigenetic reprogramming. It could help people with diseases that are caused by epigenetic problems such as Fragile X syndrome, Prader-Willi syndrome and various cancers.
Zinaida Good, a postdoctoral fellow at Stanford Cancer Institute, says these problems are still far in the future. Any change will be incremental. “Thinking realistically, there’s not going to be a very large increase in lifespan anytime soon,” she says. “I would not expect something completely drastic to be invented in the next 5 to 10 years. ”
Good won’t get any such treatment for herself until it’s shown to be effective and safe. Nature has programmed our bodies to resist hacking, she says, in ways that could undermine any initial benefits to longevity. A preprint that is not yet peer-reviewed reports cellular reprogramming may lead to premature death due to liver and intestinal problems, and using the Yamanaka factors may have the potential to cause cancer, at least in animal studies.
“Side effects are an open research question that all partial reprogramming companies and labs are trying to address,” says Deigin. The road to de-differentiation, the process by which cells return to an earlier state, is not paved with roses; de-differentiate too much and you may cause pathology and even death. Deigin is exploring other, less risky approaches. “One way is to look for novel factors tailored toward rejuvenation rather than de-differentiation.” Unlike Yamanaka factors, such novel factors would never involve taking a given cell to a state in which it could turn cancerous, according to Deigin.
An example of a novel factor that could lower the risk of cancer is artificially introducing mRNA molecules, or molecules carrying the genetic information necessary to make proteins, by using electricity to penetrate the cell instead of a virus. There is also chemical-based reprogramming, in which chemicals are applied to convert regular cells into pluripotent cells. This approach is currently effective only for mice though.
“The search for novel factors tailored toward rejuvenation without de-differentiation is an ongoing research and development effort by several longevity companies, including ours,” says Deigin.
He isn't disclosing the details of his own company’s underlying approach to lowering the risk, but he’s hopeful that something will eventually end up working in humans. Yet another challenge is that, partly because of the uncertainties, the FDA hasn’t seen fit to approve a single longevity therapy. But with the longevity market projected to soar to $600 billion by 2025, Deigin says naysayers are clinging irrationally to the status quo. “Thankfully, scientific progress is moved forward by those who bet for something while disregarding the skeptics - who, in the end, are usually proven wrong.”