There were three critical events that led John Rodakis (MBA 1997) to form the nonprofit N of One in 2014 and ultimately dedicate his life to surfacing breakthrough autism research.

The first occurred on Thanksgiving of 2012. He had driven about four hours with his wife and two children from his home in Dallas to his parents’ place in Ruston, Louisiana, the small town of about 22,000 where he grew up. While there, the kids, then two and three years old, started running a fever, which would eventually register around 104 degrees. After finding a quick care clinic to treat the children, both tested positive for strep throat, were prescribed the antibiotic amoxicillin, and gradually started to improve.

“And then,” Rodakis says, “my life changed.”

His son had been diagnosed with autism spectrum disorder (ASD) earlier that year, and he had subsequently tracked the child’s daily behaviors. It was a meticulous system, with Rodakis entering notes on more than 20 parameters—including mood, gross motor, and energy—and then downloading the data into Excel for deeper analysis.

On the fourth day of amoxicillin treatment, Rodakis noted that his son seemed less rigid and more agreeable than earlier in the week. The father initially wondered if this was just the “fever effect,” a phenomenon of behavioral improvements noted by some parents of children with ASD when their kids have fevers, which he had previously observed in his son; but the fever had already broken by then. His son seemed happier, calmer, more easygoing, and talkative. The next day, his son was even more compliant and agreeable. “Good speech and eye contact,” Rodakis wrote. Despite months of struggle to simply push the pedals on a tricycle Rodakis had bought to help him with motor development, now his son was riding it around the living room. As the days progressed, there were similarly positive reports from his occupational therapist. Rodakis began to suspect the antibiotic was creating the improvements, and, after some outreach and research, discovered many other parents had made similar observations during antibiotic treatment—with one clinical trial from 1999 documenting such effects.

The incident came at an inflection point for Rodakis. His son’s diagnosis had left him at a loss. “I had the same experience of virtually every other parent who’s been through this journey,” he says. “The doctors call you into the little room and they say, ‘I’m sorry to tell you, your child has autism. It’s genetic. There’s nothing that can be done about it.’ ” The only thing that’s been shown to be of any value, Rodakis was told, was a therapy called applied behavior analysis. “Then they handed us a list of ABA providers and said, ‘good luck.’ And that was all the medical system had for us.”

At first, he accepted that answer at face value, but nonetheless began to dig deeply into the existing autism research in the hopes he might find some early stage treatments that might prove helpful for his son. Rodakis had a bachelor’s degree in molecular biology and had spent the early part of his career as a medical venture capitalist. His week would often start with a partner dropping off a pitch deck for a biotech startup that was developing a treatment for some rare condition, with the directive to “get smart” on it before a Friday meeting. He knew how and where to look for answers.

As he started to read more of the research, he did indeed find that most of it focused on genetics. There was, however, the occasional research paper that implicated other areas such as the immune system or the microbiome—which seemed to better align with what he had observed with his son. He chased those ideas with intense interest, often cold-calling the paper’s authors to learn more about their theories.

“The more I dug, the more convinced I was that there was more going on than just genetics,” says Rodakis. “I had watched my son’s symptoms melt away on occasion, first with a fever and later with an antibiotic, and there were many such stories from other parents and clinicians. And I thought, ‘If we can find a way to understand and harness that, maybe we can find a way to help him and others like him.’ ”

But that would require a paradigm shift in the field. What he saw in the research landscape was too few people chasing limited ideas, little appetite for new approaches, and no promising treatments on the horizon. Somebody’s got to do something about this, he thought.

But he wasn’t positive it should be him.

Sure, he could start a nonprofit and try to raise money to advance some of the underfunded and unheralded research he was starting to find. But he was a professional investor—what did he know about starting a nonprofit? Or philanthropy in general?

This internal struggle led to the second pivotal event, when he took these concerns to his mentor, Marshall Payne (MBA 1983), founding partner of the Dallas private equity firm CIC Partners, with whom Rodakis had worked over a summer break at HBS. At Payne’s downtown office, Rodakis laid out the rationale for a nonprofit. He also shared the concern that he might not have the right skill set to run it and wondered whether he should try to hire someone.

“You’re the perfect person for the job,” Payne suggested. “You have a scientific background, the ability to spot promising investments that could help advance therapies, a personal passion that will drive the work, and a very useful penchant for perfectionism. It’s clear as day,” Payne told him. “It has to be you.”

It was not what Rodakis expected to hear, but he trusted Payne’s judgment. As he began to move forward, though, doubts still lingered. Would this effort take away from his ability to find his son the best medical care? Would he still be able to pursue his investment career?

This ambivalence ended with a third, violent incident.

Rodakis had met a friend in downtown Houston on a Friday night and they were on their way home. The streets were packed. As he drove, he watched a car approach in the distance, swerving and traveling at a very high speed. The car ultimately hit a telephone pole across from Rodakis, narrowly avoiding a busy food truck, and then shot across the street at his car, completely shearing off its front. The sudden fury of the events had him expecting death or at the very least severe pain; only a few inches separated him from both.

In the split second of stillness that followed the impact, he wondered how he could still be alive. “Why was I spared?” It came to him immediately: The nonprofit. There was no more doubt. He knew what he needed to do.

The prevalence of ASD continues to rise: The Centers for Disease Control reported earlier this year that 1 in 36 children in the United States has been identified with the condition, up from the 1 in 88 reported in 2008, and more than quadruple the 1 in 150 reported in 2000. Yet after launching N of One in 2014 and starting to get a feel for the landscape, Rodakis discovered that most medical research around ASD was concentrated on examining genetic causalities. Very little attention was being paid to other emerging areas of research, like the microbiome or the immune system. Part of the issue, he realized, was that the field was dominated by just a few big funders who focused most of their resources on genetic research.

“That’s not how innovation and venture capital work,” noted Rodakis. “In the startup world you have 50,000 entrepreneurs and hundreds of VCs, funding a wide variety of ideas, and out of that chaos come genuine breakthroughs. We really didn’t have that in the ASD field.” Plus, he figured, with so much time and money already being spent on genetic research, was he really going to be able to contribute anything new?

There was also the issue of how to fund this new venture. None of the existing medical nonprofit strategies seemed right for him. There was the nonprofit model, which raises smaller donations from lots of donors. “They may spend, say, $10 million to raise $15 million,” says Rodakis. That takes a lot of staff, and one thing Rodakis learned about himself during his time at HBS was that he preferred working in small groups. He wasn’t the one to build and lead a massive organization. And while he had done well for himself, the foundation model—typically led by a very wealthy philanthropist—wasn’t an option.

His research did uncover an interesting approach employed by the Cystic Fibrosis Foundation, which required a small royalty in exchange for early stage research funding—which led, in one case, to a $3.3 billion windfall when that research became a promising treatment. “In theory they never have to ask another donor for a dollar. And I said, ‘I know what that looks like. Investing in promising early stage projects and having a small financial stake in the outcome: That’s venture capital,’ ” says Rodakis. While that approach might pay off in the long term, what was he going to do in the meantime?

As he was mulling how to create change without a fortune, he recalled an interview for a hedge fund job early in his career. It was a long and tortuous interview that started at 1 a.m. because the trader worked overnight in Asian markets. At one point, the interviewer listed a series of very successful people and celebrities like George Soros, Michael Jordan, and Madonna, and asked Rodakis what they all had in common. After 20 misses, Rodakis surrendered. “Leverage!” the interviewer screamed. “They all control lots of money—whether or not they have it.”

“I thought, you know what? I don’t have to build a war chest; I just have to convince the people who have the war chest to start allocating it differently,” says Rodakis. If he could convince the National Institutes of Health, for instance, to dedicate some portion of their massive funding to some of these new directions, it would likely be much more than he could ever raise on his own. “There’s my leverage,” he concluded.

But how to do that? Rodakis settled on a two-pronged strategy to redirect funding to his growing list of emerging areas. One arm of the strategy was to attempt to persuade researchers and funders by meeting with them directly or publishing articles in the media. “But that only gets you so far. Serious funders and their researcher advisors are convinced by high quality, published research.” So the other strategy arm was for N of One to use small amounts of capital to fund small-pilot studies at top institutions that would shine a light on new promising theories. “The idea was to de-risk speculative-but-potentially-breakthrough ideas to a point where larger funders would take a chance.”

In September 2017, Rodakis published an op-ed piece in the Wall Street Journal with the headline “Autism Research Should Be Financed Like Venture Capital,” arguing that the concentration of capital in autism research was stifling innovation. “Researchers should be rewarded for stretching beyond conventional views in search of breakthroughs,” he wrote.

The goal was not to drive donations to N of One; it was to change the direction of the ocean liner. He wanted to shake things up. “It’s guerrilla-warfare advocacy,” he concedes. “I don’t wake up every day and say, ‘How do I build the biggest nonprofit?’ I wake up and say, ‘What can I do today to maximize the flow of funds and maximize the research in these emerging areas?’ Because I’m convinced if we focus on these areas, we will increase our chances of finding that major breakthrough that we’re looking for.”

Rodakis knew that changing perceptions in the research community would take groundwork. Within 45 days of founding N of One in 2014, he helped convene the first-ever conference on autism and the microbiome at Arkansas Children’s Hospital, in Little Rock. “The field was so nascent that, despite flying researchers in from as far away as Sweden, we couldn’t find eight researchers to fill the day—so we actually had some people go twice,” he recalls with a smile.

He continued to push on all available levers. Realizing that promising research often does not reach patients because it cannot be successfully commercialized, Rodakis has focused on helping early stage companies. N of One provided seed funding, for instance, to BioROSA, a startup led by his inaugural conference cosponsor and longtime collaborator, John Slattery, that is developing a blood test for autism. He also spent months chasing down the IP rights for suramin, a century-old drug historically used to treat African sleeping sickness, a parasitic disease, and later tested as a treatment for metastatic cancer. N of One had supported a trial by researchers at the University of California San Diego that showed the drug addressing the core symptoms of ASD, with some non-verbal children speaking, according to their parents, the first sentences of their lives. After unsuccessfully trying to negotiate use of the drug from Bayer, he continued to pull at the thread. He leaned on his HBS connections and personal conviction to get the attention of the CEO of Pfizer (which had unsuccessfully tried to develop suramin for cancer in the 1980s) to help him locate 14 boxes of relevant research data in a warehouse in Kalamazoo, Michigan. While the plan was to build a company to commercialize suramin, Rodakis shelved the effort once he saw two bigger players begin to invest in the drug for ASD.

He wasn’t frustrated by the competition; he was relieved. Getting new ideas to market is a positive outcome, no matter who takes it there. “I want to focus on generating as many new, promising ideas as possible. I don’t need to run them.”

Most days, that requires hustle, influence, and networking. “I get in touch with people I think can help and say, ‘I think there are answers in some of these underfunded, emerging areas. I need your help,’ ” Rodakis notes. He and Slattery consult regularly to review emerging ideas. “We strategize where the organization can get the largest impact for the smallest amount of dollars,” Slattery explains.

Judy Van de Water, a prominent researcher on the immune system in ASD at UC Davis, is another regular checkpoint for Rodakis. “A lot of times you’ll get funding from an entity that is just looking for a progress report,” says Van de Water, whose lab has also received financial support from N of One. “But John’s very active in the discussions, in the planning, and in the execution.” He’ll also bring his potential connections and highlight new findings he’s tracking. “He’s constantly surveying what’s going on out there in the literature and research and asking how we take advantage of this. How do we do this?”

Nonetheless, the currents Rodakis is fighting are strong. “Autism research is still dominated by geneticists and genetic research,” observes Sarkis Mazmanian, a Caltech researcher who studies the relationship between the gut microbiome and ASD, and whose work N of One also supports. “That’s constricted funding and therefore growth in this field.” This microbiome research has led to a therapeutic (currently in Phase II trials) designed to manage some of the irritability and anxiety that can be associated with ASD. “Autism is a very complex condition,” says Mazmanian. “But at the end of the day, I think the microbiome is going to be a part of the puzzle. And that’s why we need intrepid people like John—not just thought leaders, but people who are going to really fund alternative ideas.”

There has been notable movement on that front. In July, the Simons Foundation—whose influential Simons Foundation Autism Research Initiative (SFARI) commits about $90 million per year to autism research—released a reanalysis of existing research on connections between the gut microbiome and ASD and found a “definitive association” between the two—though, notably no causality. “One of the reasons that SFARI has moved into this field is that the microbiome might offer a significant way to improve the quality of life of kids,” says John Spiro, senior vice president and senior scientist at SFARI. “It’s also deeply fascinating from a scientific standpoint. It’s absolutely clear that our understanding of how the bugs in the gut affect the brain and behavior and the immune system is still in a very primitive state. And that’s exciting.”

Rodakis has started to collaborate more regularly with the team at SFARI. In 2022, Harvard Medical School immunology professor Jun Huh, a researcher at that school’s Blavatnik Institute supported by both SFARI and N of One, was looking to further his studies of autism’s fever effect. Rodakis asked SFARI for help in making connections to test the hypothesis using blood from children with ASD, and SFARI obliged. He had gone from challenging the existing powers in the field to working with them to solve common problems.

Rodakis is recounting this experience in late February from the 42nd floor of a Midtown Manhattan conference room lent to him by classmate Sarat Sethi (MBA 1997). He was in town to speak at a conference, Workshop on the Microbiome in Autism, hosted by SFARI. Unlike Rodakis’s conference nine years earlier, there was no shortage of ideas on the agenda, with some 30 researchers on hand for a day-and-a-half packed with panels, presentations, and working sessions.

At the conference, Rodakis felt like he was watching a sea change. Here was one of the most powerful autism organizations in the world signaling that they might just be starting to see things a different way. It validated so many of his early hunches and the chances he took on them.

He can do without the plaudits, though. “Look, I’m just a dad who saw some things that didn’t seem to fit the view at the time and said, ‘Maybe we can make more headway if we diversify our approach.’ And now I’m seeing that happen, and we have potential treatments in clinical trials based on these new areas. That’s exciting for me.”

Rodakis acknowledges that there are some who do not agree with the idea of treatments for autism. “Our focus is on finding answers for those who are more severely affected, but the pushback tends to come from adults who are able to advocate for themselves. I dream of my child being able to do that someday,” he says. “Acceptance and support for people with differences is unarguable, but right now I’m trying to create more options for those who have significant struggles—those who are profoundly affected—to have the best possible chance at an independent life.”

In the ASD research community, parental advocacy has been a crucial force. Van de Water, the UC Davis researcher, notes that her school’s MIND Institute, a center for autism research where she serves as associate director, was not only partially funded by but also literally built by supportive parents. “It’s a movement of people who are not accepting the answer that their children are born that way,” she says.

Spiro at the Simons Foundation says that parental involvement will be critical as ASD research advances. “If you have a young child with cancer, when they’re treated at a hospital, they’re involved in some kind of study protocol. And if things don’t work or if they work really well, that’s all flowing back in a way that’s incorporated into future treatment.” Comparatively, the ASD field is like the Wild West, he notes: fractured and siloed, with parents involved in disconnected efforts. “Trying to engage families in high-quality research—like we are trying to do at the Simons Foundation and like the efforts John has been involved with—is going to be absolutely critical. Autism is enormously heterogeneous and trying to break down that heterogeneity is going to involve getting a lot of people involved in research—all shapes, sizes, backgrounds, and ages.”

Rodakis’s ability to focus on making inroads in the research community has been aided by a more stabilized family life. “When you have a child with severe autism, it can be a tough home life. For the first five or six years, my wife and I were just hanging on.” There were daily tantrums and screaming meltdowns that went on for hours as Rodakis was trying to launch N of One and his wife was working full-time. “My rule of thumb is that severe autism takes one parent out of the workforce, at least for a while. I’m always looking for help from like-minded parents, and along the way I have met many parents who have wanted to help our effort, but their home life was such that they just didn’t have the time. My son is in such a better place now, and I think a lot of it’s because of things I learned and people I met through N of One. And I’ve got some bandwidth back.”

He is using that bandwidth to start an investment management firm, Metris Capital Research, which utilizes quantitative strategies he developed while running N of One. It was partly borne of necessity: Rodakis takes no compensation from N of One, but managing it didn’t leave him enough time to continue to be an active investor, either. His solution was to develop a systematic investment strategy to free up some of his time and help support his family. He also sees the new firm, if successful, as one way to eventually drive more funding to autism medical research, with plans to allocate a portion of the profits to N of One. “I’m inspired by what Jim Simons has been able to do,” notes Rodakis. Simons founded a wildly successful hedge fund, Renaissance Technologies, which has allowed him to fund his sprawling scientific philanthropy operation. Rodakis hopes his firm can replicate even some small portion of that.

The work is never done, though. “The time frames are long, and at times you don’t even know if you’re making progress,” he acknowledges. “There’s no quarterly profits; there’s no ‘sell the company and count your money.’ ”

“But there are some promising leads,” Rodakis says. Back when he started N of One, there was little in the ASD drug development space that offered much optimism. Now there are more than a dozen therapies in various stages of clinical trials, he says—and some of them arose from either research N of One has helped support or the overlooked research areas that it has long championed. “And that’s a much more hopeful future than existed when I started.”

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