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.
Earlier this year, California-based Ambry Genetics announced that it was discontinuing a test meant to estimate a person's risk of developing prostate or breast cancer. The test looks for variations in a person's DNA that are known to be associated with these cancers.
Known as a polygenic risk score, this type of test adds up the effects of variants in many genes — often in the dozens or hundreds — and calculates a person's risk of developing a particular health condition compared to other people. In this way, polygenic risk scores are different from traditional genetic tests that look for mutations in single genes, such as BRCA1 and BRCA2, which raise the risk of breast cancer.
Traditional genetic tests look for mutations that are relatively rare in the general population but have a large impact on a person's disease risk, like BRCA1 and BRCA2. By contrast, polygenic risk scores scan for more common genetic variants that, on their own, have a small effect on risk. Added together, however, they can raise a person's risk for developing disease.
These scores could become a part of routine healthcare in the next few years. Researchers are developing polygenic risk scores for cancer, heart, disease, diabetes and even depression. Before they can be rolled out widely, they'll have to overcome a key limitation: racial bias.
"The issue with these polygenic risk scores is that the scientific studies which they're based on have primarily been done in individuals of European ancestry," says Sara Riordan, president of the National Society of Genetics Counselors. These scores are calculated by comparing the genetic data of people with and without a particular disease. To make these scores accurate, researchers need genetic data from tens or hundreds of thousands of people.
Myriad's old test would have shown that a Black woman had twice as high of a risk for breast cancer compared to the average woman even if she was at low or average risk.
A 2018 analysis found that 78% of participants included in such large genetic studies, known as genome-wide association studies, were of European descent. That's a problem, because certain disease-associated genetic variants don't appear equally across different racial and ethnic groups. For example, a particular variant in the TTR gene, known as V1221, occurs more frequently in people of African descent. In recent years, the variant has been found in 3 to 4 percent of individuals of African ancestry in the United States. Mutations in this gene can cause protein to build up in the heart, leading to a higher risk of heart failure. A polygenic risk score for heart disease based on genetic data from mostly white people likely wouldn't give accurate risk information to African Americans.
Accuracy in genetic testing matters because such polygenic risk scores could help patients and their doctors make better decisions about their healthcare.
For instance, if a polygenic risk score determines that a woman is at higher-than-average risk of breast cancer, her doctor might recommend more frequent mammograms — X-rays that take a picture of the breast. Or, if a risk score reveals that a patient is more predisposed to heart attack, a doctor might prescribe preventive statins, a type of cholesterol-lowering drug.
"Let's be clear, these are not diagnostic tools," says Alicia Martin, a population and statistical geneticist at the Broad Institute of MIT and Harvard. "We can't use a polygenic score to say you will or will not get breast cancer or have a heart attack."
But combining a patient's polygenic risk score with other factors that affect disease risk — like age, weight, medication use or smoking status — may provide a better sense of how likely they are to develop a specific health condition than considering any one risk factor one its own. The accuracy of polygenic risk scores becomes even more important when considering that these scores may be used to guide medication prescription or help patients make decisions about preventive surgery, such as a mastectomy.
In a study published in September, researchers used results from large genetics studies of people with European ancestry and data from the UK Biobank to calculate polygenic risk scores for breast and prostate cancer for people with African, East Asian, European and South Asian ancestry. They found that they could identify individuals at higher risk of breast and prostate cancer when they scaled the risk scores within each group, but the authors say this is only a temporary solution. Recruiting more diverse participants for genetics studies will lead to better cancer detection and prevent, they conclude.
Recent efforts to do just that are expected to make these scores more accurate in the future. Until then, some genetics companies are struggling to overcome the European bias in their tests.
Acknowledging the limitations of its polygenic risk score, Ambry Genetics said in April that it would stop offering the test until it could be recalibrated. The company launched the test, known as AmbryScore, in 2018.
"After careful consideration, we have decided to discontinue AmbryScore to help reduce disparities in access to genetic testing and to stay aligned with current guidelines," the company said in an email to customers. "Due to limited data across ethnic populations, most polygenic risk scores, including AmbryScore, have not been validated for use in patients of diverse backgrounds." (The company did not make a spokesperson available for an interview for this story.)
In September 2020, the National Comprehensive Cancer Network updated its guidelines to advise against the use of polygenic risk scores in routine patient care because of "significant limitations in interpretation." The nonprofit, which represents 31 major cancer cancers across the United States, said such scores could continue to be used experimentally in clinical trials, however.
Holly Pederson, director of Medical Breast Services at the Cleveland Clinic, says the realization that polygenic risk scores may not be accurate for all races and ethnicities is relatively recent. Pederson worked with Salt Lake City-based Myriad Genetics, a leading provider of genetic tests, to improve the accuracy of its polygenic risk score for breast cancer.
The company announced in August that it had recalibrated the test, called RiskScore, for women of all ancestries. Previously, Myriad did not offer its polygenic risk score to women who self-reported any ancestry other than sole European or Ashkenazi ancestry.
"Black women, while they have a similar rate of breast cancer to white women, if not lower, had twice as high of a polygenic risk score because the development and validation of the model was done in white populations," Pederson said of the old test. In other words, Myriad's old test would have shown that a Black woman had twice as high of a risk for breast cancer compared to the average woman even if she was at low or average risk.
To develop and validate the new score, Pederson and other researchers assessed data from more than 275,000 women, including more than 31,000 African American women and nearly 50,000 women of East Asian descent. They looked at 56 different genetic variants associated with ancestry and 93 associated with breast cancer. Interestingly, they found that at least 95% of the breast cancer variants were similar amongst the different ancestries.
The company says the resulting test is now more accurate for all women across the board, but Pederson cautions that it's still slightly less accurate for Black women.
"It's not only the lack of data from Black women that leads to inaccuracies and a lack of validation in these types of risk models, it's also the pure genomic diversity of Africa," she says, noting that Africa is the most genetically diverse continent on the planet. "We just need more data, not only in American Black women but in African women to really further characterize that continent."
Martin says it's problematic that such scores are most accurate for white people because they could further exacerbate health disparities in traditionally underserved groups, such as Black Americans. "If we were to set up really representative massive genetic studies, we would do a much better job at predicting genetic risk for everybody," she says.
Earlier this year, the National Institutes of Health awarded $38 million to researchers to improve the accuracy of polygenic risk scores in diverse populations. Researchers will create new genome datasets and pool information from existing ones in an effort to diversify the data that polygenic scores rely on. They plan to make these datasets available to other scientists to use.
"By having adequate representation, we can ensure that the results of a genetic test are widely applicable," Riordan says.
New Podcast: George Church on Woolly Mammoths, Organ Transplants, and Covid Vaccines
The "Making Sense of Science" podcast features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This monthly podcast is hosted by journalist Kira Peikoff, founding editor of the award-winning science outlet Leaps.org.
This month, our guest is notable genetics pioneer Dr. George Church of Harvard Medical School. Dr. Church has remarkably bold visions for how innovation in science can fundamentally transform the future of humanity and our planet. His current moonshot projects include: de-extincting some of the woolly mammoth's genes to create a hybrid Asian elephant with the cold-tolerance traits of the woolly mammoth, so that this animal can re-populate the Arctic and help stave off climate change; reversing chronic diseases of aging through gene therapy, which he and colleagues are now testing in dogs; and transplanting genetically engineered pig organs to humans to eliminate the tragically long waiting lists for organs. Hear Dr. Church discuss all this and more on our latest episode.
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Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.