Kevin A. Roberts
Alex Ramsey, an assistant professor of psychiatry at Washington University
You have a gene. It’s called “cholinergic receptor nicotinic alpha 5 subunit,” or CHRNA5 for short. It does important things inside your body. Certain sections of it, for example, dictate how your brain processes nicotine. That’s true for everybody. You may, however, have variants in and near this gene that put you at risk: They make you more likely to become a heavy smoker; to develop lung cancer and develop it earlier; and to struggle more than other people to quit. This is all backed up by solid published scientific research. Most of it has circulated for a decade or more.
A few years ago, Alex Ramsey, an assistant professor of psychiatry at Washington University, began trying to translate this research into action. He wondered: What would happen if smokers learned whether they had the CHRNA5 variants—that is, whether the genetic cards were stacked against them? There was a chance they’d turn into defeatists and keep puffing away. On the other hand, Ramsey hypothesized, they might react by making a special effort to cut back or quit.
Ramsey and his team recruited 108 smokers for a study. Each smoker sent a saliva sample to 23andMe, the ancestry-focused genetic-testing service. When the raw data came back from 23andMe, the team combined it with other factors to place each participant in a risk category, the highest being “Very High Risk.” As it turned out, 54 smokers were considered Very High Risk; nearly all had CHRNA5 variants. Each participant then met in-person, one-on-one with Ramsey or a teammate who revealed his or her risk category, the presence or absence of CHRNA5 variants, and guidance for obtaining prescription and over-the-counter therapies such as lozenges or patches. Over the next two months, the smokers answered questionnaires over the phone. The results were published in February in the journal Cancer Prevention Research.
The team learned that across the board, smoking had dipped, but “the benefits appeared to be greatest” in the Very High Risk group. Sixty-one percent of this group had cut back, a quarter had tried to quit, more than a fifth had begun to take cessation medication, and 7 percent said they’d kicked the habit altogether. (Some reported more than one outcome.) That may seem like a tiny impact, but it could be significant at scale. Smoking is the leading preventable cause of death in the U.S. The Centers for Disease Control and Prevention estimate that it causes 480,000 deaths each year. Even a 7 percent reduction in that figure would mean 33,600 fewer lives lost.
“I don’t want to overstate the importance of this study,” Ramsey says, “but there seemed to be a signal that we need to investigate this further.”
Ramsey is a scholar of dissemination and implementation science, commonly abbreviated as D&I. It’s the study of how to take solid research—be it recent or the kind that has collected dust for years—and put it into practice so that it improves health in tangible, real-world ways. Such an endeavor may seem obvious, but D&I is a relatively new field; it’s only been around since the 1990s. It’s also necessary. Consider the chaos that ensued after the discovery of the COVID-19 vaccines.
“We’ve too long assumed that once we have a breakthrough, people will start using it—If you build it, they will come,” says Enola K. Proctor, a professor at Wash. U.’s Brown School and one of the field’s pioneers. “We knew the vaccine was coming, but we didn’t invest as a country in vaccine rollout, and therefore we’re seeing delays and too little uptake.”
The vaccine ordeal dominated the national news, yet many of the systemic failures that D&I targets are more commonplace—for example, the fact that millions of Americans have high blood pressure but fail to take medications that could reduce their risk of heart disease. And beyond encouraging sound practices, D&I scientists also seek to discourage ineffective ones—for instance, the overprescription of antibiotics or the tendency of county health departments in Missouri and elsewhere to put on health fairs, despite scant evidence that they actually improve health. (In D&I jargon, these are examples of “misimplementation.”)
One drag on scientific progress in the United States is that D&I, like the adjacent and overlapping field of public health, is not swimming in cash, relatively speaking. Overall, only about 0.1 percent of the nation’s health expenditures is spent on health-services research, which includes D&I, according to a 2018 textbook co-edited by Proctor and her Wash. U. colleagues Ross C. Brownson and Graham A. Colditz. While the National Institutes of Health invests about $41.7 billion in medical research each year, the “overwhelming majority” of that money, Proctor observes, goes to “discovery research” and only a small fraction to D&I.
Some scientists fail to grasp D&I’s utility, Proctor says. The division head of a hospital once asked her why he needed a scientific approach to change his staff’s behavior—all he had to do, he claimed, was email everyone a new guideline, then they’d follow it. “Well, there’s no methodology behind that,” Proctor says, “and that failed. So I think part of the growth of the discipline is to help people outside D&I understand how complex it is.” Indeed, that complexity can be intimidating: “Sometimes people [in science] look at it and realize the scale of the variables and think, ‘I’ll go back to lab.’”
Mark McGovern, a professor in Stanford University’s Department of Psychiatry & Behavioral Sciences who focuses on D&I, agrees that it entails “more mess and noise” than lab work does. “I think early on, there was a lot of work to be done on the terminology and models and theory-building and consensus about how to understand the phenomena,” recalls McGovern. “Only in the past five years or so has D&I science become better at measurement. That’s the crucible of science. Without that, you can’t replicate it.”
Ramsey is aware of the limitations of the smoking-cessation research that he and his colleagues published in February. It was a single-arm study, so he considers it a proof of concept. Now he’s recruiting another 128 smokers to do a randomized controlled trial. All smokers will have their DNA analyzed by 23andMe, and all will log on to one-on-one Zoom calls with a team member and receive general guidance on how to quit. Half of the smokers, however, will see a screen showing their CHRNA5 results and their overall risk category. The idea is to isolate and measure the effect of that approach.
Even if the effect looks small, there appears to be no obvious harm in Ramsey’s experiment: Nearly every participant in the previous study felt no regrets about learning details of his or her CHRNA5 gene cluster and ultimately found it useful. And the results could have implications for treating other high-risk behaviors such as drinking and overeating.
“The risk of trying this is low,” concludes Ramsey, “but the risk of not trying is high.”
Kevin A. Roberts
Dr. Rupa Patel, in Wash. U.’s Division of Infectious Diseases
While Ramsey’s basic inquiry was Does this intervention improve health?, Dr. Rupa Patel in Wash. U.’s Division of Infectious Diseases is working on a different but related problem: Once you know that an intervention works, what’s the best way to encourage its use?
In 2012, the FDA approved a game-changing drug in HIV prevention: pre-exposure prophylaxis, or PrEP. It was a pill that, if taken daily, would reduce the risk of contracting HIV from sex by more than 90 percent.
Then as now, CDC statistics showed that the majority of new infections came from male-to-male sexual contact. This problem had a personal resonance for Patel: Her brother had come out as gay as a teenager, and she had completed part of her medical training at an HIV outpatient clinic in Dallas. She was looking for a way to keep working with the LGBTQIA+ community and others at risk of contracting HIV.
She found it at Wash. U., where in 2014 she launched a PrEP program and specialty clinic. The goal, she says, was not to drive up the number of prescriptions. Rather, it was to make sure that folks who could benefit from PrEP had enough accurate information to make a well-informed decision. “I was concerned there were too many people who didn’t know about it,” Patel recalls.
Patel conducted a survey. She recruited participants by posting flyers at clubs, bars, coffee shops, restaurants, and a bathhouse; in all, 49 people answered written questions. The data showed that 86 percent of respondents had heard of PrEP but only 13 percent were taking it. This suggested that people knew about the pill but maybe they didn’t know all the details.
The survey then pointed to where an educational campaign might be focused. Condomless sex tended to result from meetings in certain venues, both virtual and physical; according to the data, Facebook and Grindr were the most popular virtual venues, with Grindr having the highest “centrality.” After Patel discovered this and placed ads on that app, traffic at the clinic picked up. This proved to be a more efficient use of resources, too, Patel argues: One ad on a single app, she learned, could cost anywhere from $2,000 to $5,000 per month.
As for the “physical venues,” there were a handful of nightlife spots that Patel did not name specifically in her published research, but she did point out that these spots varied by race—that is, white and Black members of the gay community tended to visit different locales at different frequencies. That was important because the need for outreach to Black gay men was clear: The CDC was projecting that half of them would get an HIV diagnosis in their lifetime. She wanted to ensure they received sound information about PrEP.
As more patients came to the clinic, Patel learned about them by giving a questionnaire to those who consented. About two-thirds of the 100 respondents reported that they had a primary care physician. Of those, half had asked their doctor for PrEP and weren’t prescribed it—mostly because the doctor didn’t know it existed or mistakenly thought it required a specialist visit. “I didn’t want people to get excited about it and go to their doctor but then feel deflated,” Patel says.
So Patel and her collaborators turned to the supply side: They conducted provider education sessions, created a PrEP implementation toolkit, and mapped out a network of providers who were available via public transit and vetted as safe spaces where people could feel comfortable talking about their sexual health. They gathered all of this into a directory and had it nested on the website of the Missouri Department of Health and Senior Services.
Another issue was cost. There was an array of programs that defrayed the expense of PrEP for those who needed help, but Patel found that many people didn’t know about them. To complicate matters, Missouri was a non-Medicaid expansion state, and many of her patients were underinsured or uninsured. So in her outreach, she has emphasized that there are low-cost and no-cost ways of getting PrEP—for example, at her clinic. Plus, it’s now easier than ever to get a PrEP prescription because telehealth has become so normalized.
“One of my greatest achievements right now is how many scheduled calls are coming from a patient’s parked car,” she says. “They’re taking a break at work and seeing me on their phone. They didn’t have to drive in or take a sick day or get someone to cover for them. It’s just integrated into their daily lives.”
According to government stats, the number of PrEP users in Missouri has risen more than sevenfold since Patel launched her clinic. Her efforts contributed to that figure, but, for her, a better metric of success is the rising number of people who see PrEP as an option. “I want everyone to hear about PrEP from multiple angles so they can have all the info to make the best choice for them,” she says.
The government has supported both Patel and Ramsey in their D&I projects: Patel was awarded a grant from the CDC to build PrEP capacity in multiple states, and Ramsey’s work has been funded by the NIH.
David Chambers, deputy director for implementation science at the National Cancer Institute, was among the first doctors at NIH to advocate for D&I in the early 2000s. He says he feels “heartened” about the field’s prospects in a way he didn’t decades ago. “There have certainly been more articles and more conversations at different conferences about the impact of our science on the pandemic and vice versa,” Chambers says. “I think it’s a bit too early to see if some lessons we’ve been learning will persist, but I’m encouraged.”'
