When a new biotech company leapt into public consciousness with the bold promise of a product that could run hundreds of medical tests in a doctor’s office on a single drop of blood, it sounded too good to be true. David Grenache says he was skeptical from the very beginning.
“That was a fantastical claim,” says Grenache, former president of the American Association for Clinical Chemistry. “I think myself and all of my colleagues just looked at each other and said, ‘No way. That’s not possible. The technology doesn’t exist.’”
The technology didn’t exist. Theranos, despite all its flashy promises, wasn’t actually able to run tests accurately in its device on a single drop of blood. Two years after the company closed its labs, its charismatic founder Elizabeth Holmes and former company president Sunny Balwani were indicted for fraud.
With the end of Holmes’ trial approaching and Balwani’s trial set to kick off in January, the Theranos chapter in the blood testing tech story is coming to a close. But the dream of eliminating trips to the lab by doing diagnostics on small, portable machines and on smaller amounts of blood isn’t over. Other companies have pressed forward over the past decade. The COVID-19 pandemic has increased interest and investment in at-home testing that may benefit easier blood testing, as well.
the dream of eliminating trips to the lab by doing diagnostics on small, portable machines and on smaller amounts of blood isn’t over
But will any of them be able to carry out Theranos’ promise? Grenache says he doesn’t think so — and that many of the hurdles that made experts so skeptical of Theranos’ pie-in-the-sky claims still exist today.
“Any claim like that, that sounds too good to be true, should be approached with a healthy dose of skepticism,” he says.
A single drop
Blood tests do a lot: assess how well organs are working, diagnose immune disorders, and flag changes that could hint someone has cancer. Typically, they require a trip to a doctor’s office or a lab to siphon off around a shot glass’s worth of blood. That blood is then analyzed by specialized machines that can be anywhere from desktop computer to refrigerator sized — machines that might only be found at a separate, off-site lab.
Theranos promised to change that process by only taking a few drops of blood, which it said it could use to run lots of tests at once on a scaled-down, small machine that could fit on a desktop. “We’re able to do all the testing using just a single microsample, rather than having to draw a dedicated tube for each type of test,” Holmes told Wired in 2014.
Reasonable research teams are pursuing versions of those goals, says Mike White, a genetics professor at Washington University in St. Louis. Multiple groups are working on developing ways to miniaturize tests and put them onto a small chip so that they could be used at a bedside or in an office, he says. It’s a painstaking, resource-intensive process — groups have to validate each test they’re shrinking down, one by one. “It’s quite challenging to do that, but there are a lot of possibilities, and a lot of technological developments,” White says.
And devices that can run multiple tests also aren’t that unusual. Dozens of tests can be run on a machine called the Siemens Advia 1800, which is around the size of a minifridge. The pressures of the COVID-19 pandemic also pushed forward new efforts to develop tests that can check for multiple diseases at once, says Catherine Klapperich, director of the Laboratory for Diagnostics and Global Healthcare Technologies at Boston University. It became important to test for flu and COVID-19 simultaneously, for example.
“There’s no magic bullet, and that was the weird thing about Theranos’ claims”
But combining those two features — devices the size of a desktop that can run hundreds of tests — is harder to pull off. And it becomes even less so when you add in the idea that they could work off of a few drops of blood. “There’s no magic bullet, and that was the weird thing about Theranos’ claims,” White says. “They seemed to claim that they had one key trick that made a whole bunch of different things easy, and that turned out not to be true.”
Sometimes, a single drop makes sense. People can accurately check their blood sugar levels on a finger stick, and finger sticks can also measure how well someone’s blood clots. But other tests might need more blood to get a clear picture of someone’s health. A tiny drop of blood might not have high enough concentrations of a particular protein, for example, that a testing device would need to detect it accurately. Drops of blood are also so small that each one tends to have different amounts of various cells and platelets, research from 2015 found. The study took six drops of blood in sequence from 11 people and found that the levels of things like hemoglobin (a protein that carries oxygen) and white blood cells varied widely between each drop.
That could mean a difference between flagging a potential problem and missing it. Some illnesses cause low hemoglobin counts, for example. A single drop tested might not pick up that signal or could show lower levels just because of the makeup of that specific drop. “For certain things, you can take a million drops of blood, but a bunch of them — or most of them — are not gonna have what you need,” Klapperich says.
“A test that could test a whole bunch of things like that would still be progress, even if it’s not from one drop of blood”
Still, there are efforts to up the number of tests that can accurately run on smaller amounts of blood at the same time. “A test that could test a whole bunch of things like that would still be progress, even if it’s not from one drop of blood,” White says.
But there’s still a limit on how many tests can be run on each bit of blood, Grenache says. Some require chemical reactions that change the blood enough that it can’t be used for other things, while others extract individual components of the blood, similarly rendering it useless for subsequent tests. “You’re not going to do 100 tests,” he says. “I don’t see that happening.”
A chilling effect
The Theranos saga, though, stalled efforts to make progress toward the blood testing improvements that experts think are possible. While the company was still out in public making grand, sweeping claims about how many tests it could run on drops of blood, academic researchers working on similar blood testing problems struggled to get funding for their own work. “People told me it had a chilling effect on funding,” White says. “Why should the NIH fund something if Theranos has already solved the problem?”
“it had a chilling effect on funding”
And then, when a Wall Street Journal investigation first revealed that Theranos couldn’t actually accomplish what it had promised, investors still didn’t want to fund the projects. “There was this phase of well, you know, that’s a scam, so we’re not going to invest in these types of companies at all,” Klapperich says.
Even scientists are a bit more likely to knee-jerk assume new blood testing projects, especially those that say they can run multiple tests at once or can run tests on small amounts of blood, aren’t realistic. It was always important to approach those claims with a healthy degree of skepticism, Grenache says. But before Theranos, people might not have dismissed them outright as impossible. Now, people are more likely to, he says.
The past two years of the COVID-19 pandemic, though, likely helped counteract Theranos’ chilling effect on investment into new types of testing. The overwhelming need for fast, easy-to-use diagnostics supercharged the development of at-home tests and opened up billions of dollars in funding. Even though COVID-19 testing uses nasal swabs or saliva, the realizations about how important rapid, bedside tests could be — and that they didn’t exist — could translate to blood as well.
Theranos may have been the worst-case scenario for the testing industry, but the big-picture idea — that testing should be faster and more convenient — is still true, Klapperich says. “Now, people are trying to sort out the question of what was real about what Theranos was saying. Because we still need this stuff.”