Trevor Martin became interested in diagnostics when he was finishing his PhD at Stanford in 2016. He was looking for an opportunity to start a company around an idea that could potentially improve the healthcare system, and settled on diagnostics. He read an early paper by Doudna’s group that described using CRISPR to detect RNA, the molecular cousin of DNA. Many viruses that infect humans, like Ebola and measles, have RNA instead of DNA as their genetic material. Doudna and her team realized this ability could be used in disease detection, even as Zhang’s group at the Broad Institute was making similar discoveries.

Martin approached Doudna about starting a company based on her team’s technology, which they eventually dubbed DETECTR. “I originally just cold-emailed her. I had never talked to her before,” he says. Doudna introduced Martin to some of the doctoral students in her lab who were working on DETECTR, and a few months later, the teams joined up to start Mammoth Biosciences.

“I became really enamored with diagnostics because of how unsexy and overlooked the field was,” Martin says. “The diagnostics industry is using technologies that are many decades old.”

Martin is right. One of the chief techniques for infectious disease testing today has been around since the time of Alexander Fleming, the Scottish biologist who discovered the antibiotic penicillin in 1928. Bacterial or viral cells are taken from blood, urine, skin, or another part of the body, and grown in a dish to help identify infectious agents. Called a culture test, results can take anywhere from a few days up to a week or two, because some microbes grow more slowly than others.

With tuberculosis, it can take up to six or eight weeks to get a result. “That’s way too long if you need to get treatment,” says Emily Crawford, a scientist at the Chan-Zuckerberg Biohub who’s working on another CRISPR-based diagnostic tool, dubbed FLASH, that identifies drug-resistant microbes that may be present in body fluids.

Another conventional testing method — enzyme-linked immunosorbent assay, or ELISA — measures antibodies the body produces in response to certain infectious conditions and was developed in the 1970s. It requires a complex lab process and can take several days to get a result.

Then there’s polymerase chain reaction, or PCR, which was invented in the 1980s. It’s a way of making many copies of a specific DNA or RNA segment — say of a virus — essentially amplifying it until it can be detected. But the test needs to be processed on expensive machines that, on average, cost tens of thousands of dollars and require electricity and trained scientists to run. Many hospitals have the equipment and expertise necessary to do these tests, but smaller clinics often need to send patient samples away to companies like LabCorp and Quest Diagnostics.

“Right now it might take days to get an infectious disease result because of the centralization of testing… Moving that testing closer to the patient can turn that into a matter of minutes.”

So slow are most of the existing tests for infectious disease that, by one estimate, the underlying causes of up to a quarter of pneumonia cases and 30% of fever and sepsis cases are never fully identified. “Right now it might take days to get an infectious disease result because of the centralization of testing,” says Rahul Dhanda, president and CEO of Sherlock Biosciences. “Moving that testing closer to the patient can turn that into a matter of minutes.”

A good diagnostic tool needs to be both sensitive and specific. Sensitivity refers to a test’s ability to correctly identify those with the disease, while specificity is the ability to correctly identify those without the disease. A highly sensitive test means that there are few false negative results, and so fewer cases of disease are missed. A very specific test means that there are few false positives, thus minimizing the wasted treatment and anguish that can result from a misdiagnosis. Rapid nasal swab tests for influenza, which can provide results in 10 to 15 minutes, have been available for years, but they lack sensitivity, missing up to half of flu cases.

Mammoth and Sherlock say they’ve been able to achieve high rates of both sensitivity and specificity, but the companies’ platforms will need to be tested in clinical trials and compared with currently available tests. Neither company has said when they plan to do that.

Accuracy is only one hurdle. To be used widely in developing countries, a diagnostic would also have to be cheap, ideally between $1 to $3 per test, according to Ranga Sampath, chief scientific officer at the Foundation for Innovative New Diagnostics in Geneva, a global health nonprofit. (ELISA tests run about $15 to $20 each.)

Zhang has said that the materials to produce a SHERLOCK test cost less than $1. “When you scale up the production the cost will probably be even lower,” he adds. “That’s one thing that makes this attractive, especially if you want to use it in low-resource settings.” The challenge, he believes, will be manufacturing the materials on a wide scale and distributing tests around the world.

Sampath wonders about that, too. He notes that the majority of patients in low-resource countries are taken care of by healthcare workers in rural clinics, sometimes hundreds of miles away from the nearest city and hospital. “How do you get diagnostics into those settings?” he asks.

That’s a challenge researchers from the Broad Institute are already addressing. A team that’s collaborating with Zhang took the SHERLOCK system to Nigeria to see if it could be used in an active outbreak setting. Last year, a worrying spike in cases of Lassa fever swept across the West African country of Nigeria, which is home to more than 190 million people.

A viral, hemorrhagic fever, Lassa is part of the same family as the deadly Ebola and Marburg viruses, and kills several thousand people in West Africa each year. The diseases present similarly, at least at first, with hemorrhaging, fever, and diarrhea. “People come in and the first thing they have is a fever, which could be malaria, or flu, or something else,” says Kayla Barnes, a fellow at the Harvard School of Public Health and the Broad Institute. That makes it difficult for clinicians to diagnose Lassa off symptoms alone, so patients stand the risk of being misdiagnosed or missed completely, which in turn could further fuel an outbreak. It’s one reason why an accurate and fast diagnostic for Lassa is so desperately needed.

The sooner patients are diagnosed, the sooner they can get supportive care like rehydration, as well as treatment with the antiviral drug ribavirin, and the better chance they’ll have at recovering. So Barnes and her team, along with West African collaborators, are testing out the SHERLOCK system in Nigeria and Sierra Leone to see if they can identify cases as early as possible.

As a first step, they’re using the test in hospitals, but Barnes says the idea is to eventually move to villages and rural areas. (Up until recently, testing for Lassa fever was only available in one hospital in the entire country, though in response to last year’s outbreak the Nigeria Centre for Disease Control is opening up additional diagnostic clinics in other hospitals.) “Where it will make the most difference is in the community setting and getting patients to the hospital in time,” she says. So far, Barnes and her team have been able to identify a handful of patients with Lassa fever that were missed by current testing methods.

The current test for identifying Lassa requires a minimum of five hours under ideal conditions, but realistically, it can take labs in poor-resource areas around a day or two to get results. Using the SHERLOCK system, however, Barnes and her colleagues in Nigeria have been able to reduce that turnaround time to about three hours.

The current test also requires a cold chain — a temperature-controlled supply chain — as well as specialized expertise and an expensive machine powered by electricity. Both are often in short supply — less than 60% of Nigerians have regular access to electricity, a figure that falls even lower in rural areas. The SHERLOCK tests can be freeze-dried and use a small, electric-powered lab instrument to process samples, which Barnes says could be run off a car generator if electricity isn’t available.

While CRISPR-based tests may be simpler than the current alternatives, they will need to work outside a lab or hospital setting to make a difference in developing countries where infectious diseases like malaria and tuberculosis are still common. “CRISPR may be an enabling technology, but I’m not sure it’s going to fundamentally change the game of diagnostics unless we can get it into a format that people can use in their own hands,” says Dan Wattendorf, director of innovative technology solutions at the Bill & Melinda Gates Foundation.

Richer countries like the United States present a different challenge. Bryan Roberts, a partner at the New York-based venture capital firm Venrock who has invested in diagnostics companies, is skeptical about the idea of at-home testing. “Your performance is going to have to be exquisite,” he says. “If you tell a consumer without a healthcare provider around that they have something and they don’t, you’re in trouble. You’ll have to almost never be wrong.”

He’s also not sure there will be a huge market for individual consumers to buy these tests and keep them on hand. Patients are probably more likely to visit their local CVS or Walgreens to get a CRISPR-based test administered by pharmacy staff and obtain an instant readout instead of waiting to get a doctor’s appointment. That way, a healthcare professional could still explain the results to a patient. Roberts says there’s also potential for CRISPR-based tests to replace traditional ones in hospitals — but only if they’re truly faster and cheaper.