This man's potentially huge medical breakthrough can't get funding, so he's trying something desperate
Killing Sickness/Skye Gould for Tech Insider
Four years ago, Todd Rider was on top of the world. The MIT-trained bioengineer had developed a radical idea for killing viruses. Initial test results showed that his therapy, called DRACO, could kill every virus he threw it at: 15 viruses were killed in human cells, and two in mice.
It seemed like there was a chance it could be the biggest discovery in medicine since the invention of antibiotics. Enthusiastic headlines praised the potentially world-changing panacea. "Todd Rider Has a Kill Switch for Viruses," wrote Bloomberg Businessweek. The Verge: "Killing sickness: is DRACO a doomsday device for viruses?" Time magazine declared it one of the top 50 inventions of the year.
Yet over the next few years, things started going wrong. Rider moved from lab to lab and says he couldn't raise the money to continue testing DRACO, despite, he claims, the continued promise of the concept.
After working on his invention for 16 years, he's found himself in what he calls "the funding valley of death," too far along to get money from those who supported his preliminary studies and too far from market to get Big Pharma's backing.
With DRACO on the brink of becoming one of many potentially — potentially! — transformative breakthroughs that never pass the "good idea" phase, Rider has turned to the internet for help.
He launched an Indiegogo campaign on October 13 to raise $100,000, enough to restart his work, though just a fraction of what he truly needs. But after two months, he was only halfway there, so the campaign was recently extended.
It's impossible to know at this early stage if DRACO can do everything that Rider hopes it will — whether it will really be able to seek and destroy a wide variety of viruses inside a sick person.
And now we may never find out.
Here's the story of Todd Rider's journey to try to create a true cure-all for the often deadly viruses that pose an enormous, ongoing threat to millions of lives.
The rise of DRACO
About 16 years ago, Rider was struck by an idea — while in the shower — for a way not just to find viruses but also to eliminate the infection they caused.
Rider's journey to this moment began when he enrolled in MIT in 1986 at 17. He eventually finished his PhD in engineering in 1995, which he supplemented with biology and biomedicine courses at Harvard Medical School. After a brief stint at a startup, he joined MIT's Lincoln Laboratory, a research center focused on national defense.
At Lincoln, he'd been developing a new way to rapidly identify pathogens, the things that can make people sick. But just finding something that makes someone sick does nothing for them if there's no effective cure, as is the case for most viruses.
Viruses are among the oldest and fiercest threats to human life. Dengue, chikungunya, and polio wreak havoc and ruin lives in developing countries. The flu is associated with up to half a million deaths around the world every year, and viruses like Ebola can appear suddenly, killing thousands and destroying economies.
And no one knows what might emerge next: a flu like the 1918 pandemic that killed as many as 50 million people, some deadly form of MERS, or perhaps an engineered threat.
Rider's mid-shower flash of inspiration got him thinking about a bioengineered molecule that could find infectious agents and perhaps simultaneously eliminate the infection they caused.
If that worked against viruses, it would be one of the biggest medical breakthroughs in history.
It was the kind of big idea that drew Rider to science in the first place. If you watch his Indiegogo campaign video, you'll get it. (Is that four times we saw the Vulcan salute?)
While engineering his molecule, instead of looking for a single viral protein, Rider zeroed in on the structure of what makes a virus what it is in the first place.
RNA, a key building block of life, is found in healthy cells in single strands, unlike the famous double helix of its close cousin, DNA. But almost all viruses possess a long piece of double-stranded RNA. There are very short double-stranded pieces of RNA in some healthy cells, Rider says, but the length of the double-strands in viruses makes them distinct. This singular trait of RNA in viruses was the key to Rider's idea.
He realized that he could create a molecule to find infected cells that carry that viral signature. And he could make it do more than just identify them. All cells have the ability to self-destruct, so Rider programmed molecules to activate this kill switch after they attach to a virus, destroying the infected cells and the viral particles they were hosting.
Rider called these virus-assassinating molecules DRACOs, for Double-stranded RNA Activated Caspase Oligomerizers.
In the GIF below, a highly simplified and abstract model of what's happening inside a cell, the double-stranded RNA is on the left. The DRACO molecule attaches and then triggers the cell suicide.
With funding from the National Institutes of Health (NIH) and the Defense Advanced Research Projects Agency (DARPA), Rider was able to start building his virus-destroying molecule at Lincoln to test it out.
The first tests were conducted against a common cold.
Rider and a few collaborators infected human lung cells with a respiratory virus that causes colds and then injected DRACOs into the mix. The healthy cells survived, but the infected cells were destroyed.
When they did the same test with a flu virus, the infection cleared completely; only the healthy lung cells remained.
Rider tested the therapy against 15 different viruses in human cells and in mice infected with cold and flu viruses. In some cases, they injected cells first with DRACOs, and then tried to infect them with viruses. DRACOs showed a protective effect that lasted up to three weeks.
When used as a cure, DRACOs successfully stopped viruses in cells and mice as long as the molecules were delivered within the first three days of infection.
DRACOs wouldn't work on viruses that don't produce double-stranded RNA, but those are rare — a Verge story about Rider notes that one strain of Hantavirus doesn't have it, and many plant viruses don't, but most that infect humans do. There are also many families of viruses that DRACO hasn't been tested on yet, so we don't know whether or not it would work with them. That's exactly what Rider wants to do next — he's hoping to do his next experiments on herpes viruses.
It's worth remembering that only about one in 10 drugs that make it all the way to clinical trials turn out to be safe and effective enough to get FDA approval, and DRACO is still far from even being tested in humans. But those first findings were encouraging.
Rider published his initial results in the journal PLOS ONE in 2011.
And that's when those exuberant headlines about Rider's invention changing the world first appeared.
But almost immediately afterwards, support for DRACO seemed to falter, for reasons that are still murky.
The next year, Rider left MIT's Lincoln Laboratory to develop his work further at Draper Labs, a private company, due to what he describes as "changes in the management and their priorities at Lincoln Lab."
Lincoln declined to comment on Rider's departure, though a spokesperson noted that Rider's work was "out of the Lab's mainstream." Many of their projects focus on communications, electronics, space, and air and missile defense. Rider's project had spun out of the work he'd been doing for another initiative there, but it hadn't been his original mandate.
At Draper Labs, in 2014, Rider was able to secure a $2 million grant from the Templeton Foundation to further his research, so he could look into healing infected cells instead of killing them.
But Draper had also recently experienced a change in management, when the company's CEO stepped down.
Rider says Draper's new leadership seemed to pull away from certain areas of research, including DRACO and what the Templeton grant would have covered. (A representative from Draper told Tech Insider that it would be "inappropriate" for them to comment on DRACO, since it's not currently one of the company's projects.)
When Rider left Draper, the Templeton grant was "terminated," according to Earl Whipple, vice president of communications and public affairs at Templeton. Whipple said he could not get into specifics, but that the agreement "included the use of Draper's facilities." He did add that they "continue to believe the original scope and intent of the grant has merit."
In his view, Rider tells us, "institutions generally seem to be moving away from high-payoff but longer-term applied research."
Rider still had an idea that he thought had the potential to transform medicine. But he had no lab, no staff, and nowhere to work on it.
REUTERS/Frederick Murphy/CDC/HandoutWhen a new virus appears, like Ebola did in 1976, we have to scramble for a solution.
The funding valley of death
Rider describes the problem he's facing now as the "funding valley of death." He says that it's possible to get money for early research, but very hard to gather enough evidence to make a product seem like a lucrative bet for a pharmaceutical company, which won't come near new research like this until it's much further developed.
"It's a barbaric system," says Dr. Ben Barres, a professor of neurobiology at Stanford and the founder of a startup called Annexon Biosciences. "By the time any VC [venture capitalist] or pharma will fund you, you have to have made a drug, shown efficacy, and ... wrapped it up and tied it in a bow so they are sure they will make money."
Some of Rider's fans have posted comments worrying that pharmaceutical companies wouldn't want a cure like DRACO because it would prevent them from selling drugs over the long term. But it seems much more likely that these companies are just risk-averse in the first place, worried that a potential drug will be a failure, not that it will be too much of a success.
According to Dr. Michael Kurilla, director of the Office of Biodefense Research Resources and Translational Research at the NIH's National Institute of Allergy and Infectious Diseases (NIAID), the NIH is still interested in Rider's work and is willing to help fund it — they just want to hear from him again.
Rider, meanwhile, expressed frustration when we passed this message along. He says that he hasn't been able to get any NIH money from recent applications.
"I have now spent nearly 16 years pursuing every avenue to get funding for this work, with only limited success previously and none recently. It can take a month or more of working round the clock to write an NIH proposal, and most are summarily rejected without much comment," he says.
NIHThe NIH Clinical Center.
Kurilla did explain that they like to resolve difficult questions in the early stages of development. They want to figure out, for example, how a researcher will navigate the FDA approval process. They want to know if it will be possible to produce a new cure at a scale that would be helpful. These may seem less important than the initial question of "Does it work?" to an inventor, but they still need to be solved.
In the meantime, pharma companies want even more before funding new, unproven inventions. They want to see a long list of studies that show a new drug works in cells and animal models, and they want to see that these studies have been repeated many times.
Kurilla says that his office at the NIH tries to help people navigate all those steps, what they call the "translational" stage, but that it is complex.
Rider decided to set out on his own, launching the Indiegogo campaign with the backing of a futurist antiaging institute and a cadre of supporters on internet communities like Reddit, because he's frustrated working with many traditional institutions. He thinks there is no longer enough support for research that doesn't have a clear and immediate payoff.
Rider has struggled for funding ever since DRACO made its big splash in 2011. But he had some degree of support — and space to work — while still at Lincoln and Draper.
Ever since October 2015, when the Templeton grant was officially terminated, he's had none of that.
Could it work?
For now, it's hard to know how good Rider's idea really is, though it seems too soon to dismiss it.
His PLOS ONE study showed DRACOs successfully killing viruses, but most researchers want to see multiple studies showing something like that working safely and effectively before they're convinced.
And Rider is not the only one doing this type of work. A number of researchers are working on different kinds of what virologists refer to as "broad-spectrum antivirals," drugs that could fight off all kinds of viruses.
"If you have something like that, it doesn't matter what the virus is, we're going to be able to clear it and eradicate it," says Eleanor Fish, a professor in the Department of Immunology at the University of Toronto. "You've got a window of opportunity that's absolutely lost with pathogen-specific antivirals," drugs targeted toward just one virus.
DRACO is less proven and less far along than some other broad-spectrum antivirals. An interferon compound, for example, is based on something our body naturally produces and has already been used to treat hepatitis C. Fish has also tested it in humans against SARS, certain influenza viruses, and Ebola.
But no broad-spectrum antiviral is widely used yet. Some have failed when they've been tested in humans, something that might trip up DRACO as well. Others have painful and risky side effects. Fish says that many in the disease world tend to focus on preventing viruses using vaccines, rather than treating them using antivirals — but that a broad-spectrum antiviral would be incredibly useful for a virus for which a vaccine doesn't exist. Kurilla says that many people are scared to use new anti-infection drugs — like antivirals — because they don't want to encourage antiviral resistance, a problem that could eventually parallel the threat brought about by our over-reliance on antibiotics to treat bacterial infections.
Since viruses mutate quickly, they can easily develop resistance to typical antiviral drugs that target a specific protein found in the virus. Something like DRACO might in theory avoid this problem because it's not targeting one protein, but rather the genetic material that identifies something as a virus in the first place.
Killing Sickness/YouTubeRider plans to use funds to rent lab space at UMass Lowell.
The structural diversity of viral proteins has historically made it very difficult to design broad-spectrum antivirals that directly target many viruses, according to Dr. Shirit Einav, an assistant professor of medicine and of microbiology and immunology at the Stanford University School of Medicine, who also works in this area.
She says that while she doesn't know a lot about DRACO specifically, "it seems like there may be some potential." Still, she cautions, "we lose a lot of [antiviral] agents when we move from cells to mice and then from mice to humans."
Something that appears to work in cells might seem safe, but might not work or might have dangerous side effects in mice or other animals. Similar problems might not show up until human tests begin.
A number of virologists that we contacted weren't familiar with Rider's work. He doesn't come from the world of virus research, but rather is an engineer who has always tried to combine that expertise with his knowledge of biomedicine. In a world where people spend their lives specializing in and mastering one area of a discipline, Rider doesn't quite fit the mold.
Einav, of Stanford, joined many other specialists in saying that she would want to see more research — the research that Rider wants to do — before taking a position on how good DRACO really could be.
Several said there wasn't enough published work about DRACO to evaluate it, and that it was a bit confusing that the work hadn't been published in a journal that was more specifically about virology or medicine. PLOS ONE publishes scientific work from across all disciplines.
The lack of published data "does make me scratch my head," says Fish, of the University of Toronto. "If he'd been publishing really good data, if patents had been filed, we'd be able to scrutinize them."
While there is at least one patent related to Rider's DRACO work, there are still only a few published studies that mention the therapy.
One of the only other studies testing DRACOs against viruses was published in May by researchers from Sun Yat-sen University in China. They found that in cells, they could effectively use DRACO to kill a virus that frequently infects pigs.
A review of broad-spectrum antivirals that was also published this year referred to DRACO as "optimal ... for further development."
Dr. Xiaojia Wang, one of the authors of that review, told Tech Insider that he thinks DRACO is "very promising."
But most scientists haven't seen enough of Rider's work to offer a detailed opinion.
In response to a question posted on Quora that asked if DRACO was overrated, Dr. Ian York, a virologist, explained that it is "probably generally treated with mild interest and mild skepticism, for those researchers who have even heard about it or remember it. As far as I know, it's been described in one publication, in a mid-level journal, with no published followup and (critically) no replication outside the original lab, so few researchers are particularly excited by it yet."
While York told us that he couldn't comment without permission from the press office at the US Centers for Disease Control and Prevention, where he now works, the sentiment expressed in that thread summed up what the majority of virologists we consulted told us. It's too soon to say whether or not DRACO will work. Media hype shouldn't be a guide to how good it is.
But there are reasons to think that the excitement about DRACO's potential is not unwarranted.
Kurilla, of the NIH, had a particularly interesting response.
"The work we saw and the data [Rider] presented to us — there's no such thing as a slam dunk, but it looked promising enough with a very unique mechanism of action that we'd be very much interested in pushing this forward," he said.
NIAID/Flickr (CC BY 2.0)DRACOs worked against H1N1 influenza in cells and mice.
A world without viruses
While Rider's research has stalled, a therapy that could be used against all kinds of viruses, even ones we've never seen, would propel medicine into a future that's much safer than the present.
As journalist David Quammen explains in his book "Spillover: Animal Infections and the Next Human Pandemic," a deadly new virus will inevitably appear: "If you're a thriving population, living at high density but exposed to new bugs, it's just a matter of time until the [Next Big One] arrives."
There's also the possibility of the accidental release of a deadly flu or the intentional release of some kind of contagious agent.
Making a drug for each virus that appears could cost billions of dollars, according to Fish. "If you're going to make an antiviral for every emerging virus, that's a whole lot of money," she says.
Something that could automatically interfere with some part of the virus life cycle just by recognizing that it's a virus or another pathogen would circumvent that problem, according to Kurilla.
As the recent Ebola epidemic showed, he explains, it's hard to come up with a treatment for something in the middle of an epidemic. The NIH had been trying to work on Ebola for years, but there had been so few cases before the 2014-15 outbreak that they hadn't seen it enough to come up with a specific treatment.
That's why having something on hand beforehand that could potentially treat any virus — even a rare, mysterious, or mutated one — is so appealing.
Reuters/Brian Snyder
So how should something be supported and funded from the idea stage to the point of clinical reality?
As we can see with DRACO, a good idea alone is not enough.
All the potential in the world does not mean a promising drug will be safe enough to use in humans, effective enough to warrant FDA approval, or scalable enough to be produced and delivered sustainably. Many good ideas don't even end up being fully tested. Someone could theoretically develop a cure for a certain kind of cancer, but if they can't figure out how to use it — and if they can never get it into human trials, which cost millions of dollars — that cure goes nowhere.
Should Rider find a way to make the NIH finally give him more money, even if he thinks the process is impossible? Should pharma companies be less risk-averse and more willing to bet on DRACO and other things like it? Should individuals be counted on to crowdfund complex scientific research?
There are no easy answers.
"People seem to think that the approach and the experimental results to date are great," says Rider. But they also think "that someone else should pay for the next steps."
In the last email Rider sent us, he lamented the fact that there wasn't more general funding for the sort of research he wants to do:
I grew up on stories of what had happened in the Manhattan Project in the 1940s, Bell Labs in the 1950s, NASA in the 1960s, and the new biotech industry in the 1970s, when government and corporate sponsors were willing to invest large amounts of money, lots of personnel, and many years of effort in developing completely revolutionary technologies.
In contrast, nowadays it feels as if everyone is so focused on what they will sell next year, or what their stock price will be tomorrow, that they seem entirely focused on just developing the next smart phone app or a slightly improved version of Viagra. Sometimes I feel as if I had been born in the wrong time.
Rider's Indiegogo campaign for DRACO is now scheduled to end on December 22. When this story went live, he had raised just $51,354 out of his $100,000 goal. He thinks he'll need at least $2 million to get to the next phase of research, where pharmaceutical companies and venture capitalists might be interested if things continue to look promising.
But even that will be only the beginning.
