America’s opioid crisis has reached epidemic proportions, claiming the lives of 130 people each day and 400,000 since 1999.
BY ALEX SAKARIASSEN
To passing eyes, the town of Puyallup where Tomi Cook spent her high school years looks the perfect picture of Seattle suburbia. Quiet cookie-cutter houses, rows of shopping centers, happy upper-middle-class families going about their happy lives. She doubts anyone would have suspected that pills were tearing through her community.
For Cook it started with “baby blues,” those 30-milligram Percocets she and her classmates would grind up and snort. Then she learned how to rub the time-release coating off OxyContin pills and, as her tolerance grew, how to boil the pills down and put them in a needle. It felt to Cook as though her entire graduating class was using and abusing prescription pills, an epidemic parents seemed to keep hush-hush. Before long, she turned to heroin.
“I felt at that point I was already so deep into it and I hated myself so much for what I was doing to myself,” Cook says. “I was accepted into the University of Washington, which was my dream school, and ended up drop- ping out because of my drug use.”
Cook sits cross-legged on a floral print ottoman inside her office at Missoula’s Open Aid Alliance, a nonprofit dedicated to fighting the stigmas swirling around drug use and HIV. As she tells her story, her hand gestures—index and middle fingers outstretched as one— invoke the deep spirituality that’s been central to her recovery. Her office is soft and soothing, a painting of a hummingbird mounted below a string of Christmas lights on the wall behind her. Nothing about the 30 year old shows that she used to be, as she puts it, “that girl that was strung out, shooting up behind your dumpster.”
Heroin ushered Cook into a darkness she describes as warm and seductive. When rehab proved unsuccessful, she thought a move to Tokyo would provide the fresh start she needed. Instead she wound up worse off than before, struggling to finance her addiction and switching from heroin to crystal meth. Suicide became the only out she could see, and she slid kimono-clad into her bathtub one day intent on taking her life. After that, her friends got her a plane ticket to Seattle to be with her mother. But during a layover in Honolulu, Cook simply walked off the plane and spent the next year homeless and high on the streets of Hawaii, where she says she became a ghost. She didn’t sleep, didn’t brush her teeth, didn’t change her contacts, and rarely ate more than a candy bar.
Cook may have hated herself at times.Yet there’s a side to drug use that’s rarely acknowledged, one that might be difficult to grasp for those who have never wrestled with an addiction.
“There’s something about drugs that gives you an instant sense of connection and belonging and peace and contentment,” Cook says. “As soon as you shoot up, it’s just like, ‘ahhh.’ And that’s what kept me using for a long time. I had this belief of, ‘All of these normal people going around their day-to-day lives, they don’t get to experience that incredible blissful euphoria that I get to feel … They’re just going through the motions and I feel sorry for them, and I would never want to be them living their boring fucking lives.’”
Cook’s point helps to explain why people continue to use substances that, according to the National Institute on Drug Abuse, claim more than 130 lives a day nationwide. The Centers for Disease Control and Prevention reports that, between 1999 and 2017, more than 700,000 people have died from drug overdoses. In Montana with a population just topping 1 million, first responders this year alone have administered more than 500 units of Naloxone, a nasal spray that reverses opioid overdoses. And those are just the numbers recorded by the Montana Department of Health and Human Services; the 2017 Legislature made Naloxone available over the counter, meaning any member of the public can get it and use it without a prescription.
Major crises like this have a tendency to attract novel solutions, and that’s where western Montana comes into play. Backed by a windfall in research funding and rising interest among private investors, two separate biotech projects in Missoula and Bozeman are attempting to tackle a national crisis from very different angles. For people facing the challenge of overcoming an opioid addiction — a challenge Cook equates to scaling a mountain — the outcome of that research could mean the difference between life and death.
When you think of a vaccine, what usually springs to mind are those nasty germs lurking on every public doorknob and in every sneeze echoing through the line at the coffee shop. Influenza, tuberculosis, whooping cough—these are the sorts of diseases that prompt us to be pricked with needles every season in the hope of keeping fever and sniffles at bay. Jay Evans, director of the Center for Translational Medicine at the University of Montana, has spent nearly 20 years endeavoring to help our bodies better fight back against microscopic invaders. Even with the knowledge that comes from those years of research, Evans would be among the first to admit that the idea of a vaccine against drugs like fentanyl or heroin sounds, well, rather strange.
Yet in fall 2018, that’s exactly the idea Evans found himself kicking around. As part of its ongoing effort to marshal soldiers to the opioid conflict, the National Institutes of Health had rallied experts in drug abuse and vaccine research from across the country for a workshop in Bethesda, Maryland. Evans was on the organization’s list in part thanks to the decades of work his team has performed in the field of adjuvants, immunological agents that enhance the body’s antibody response.
“NIH calls us and asks us to help them; wants us to give them a project so they can send some money to the University of Montana. We’re going to apply for that every time,” he says.
Evans looks every part the quintessential scientist. With inquisitive eyes set behind a pair of frameless glasses, a wry, knowing smile creeps across his face anytime he rattles off complex biomedical terms. That he wound up on the frontlines of the opioid crisis comes as no surprise. The Center for Translational Medicine has a deep, rich history both in the research community and in western Montana. The group got its start when Edgar Ribi, a researcher at Rocky Mountain Labs, founded Ribi Immunochem Research in 1981 to focus on improving the efficacy of vaccines through use of a compound called monophosphoryl lipid. What started as a small outfit in Ribi’s garage has since blossomed into a full-scale biotech facility owned by multinational pharmaceutical giant GlaxoSmithKline.
Evans joined the company’s adjuvant team in 2000, fresh from a lab gig where he’d worked on HIV and gene therapy. In early 2016, the research group left the GSK facility to establish the Center for Translational Medicine and Inimmune, a Missoula- headquartered corporation designed to carry the center’s biotech breakthroughs to market.
“That’s why NIH contacted us, because that’s right in our wheelhouse,” Evans says. “And because of that, we’re in a position to move something from an early discovery research phase into people quickly…We just plug that into our current portfolio of vaccines we’re working on.”
After the meeting in Bethesda, work moved quickly. Evans’ team dove into the early research phase, and in July 2019 secured a $3.3 million NIH grant to fund its efforts. Evans submitted a grant request last September for an additional $10 million, which he says is enough to carry the opioid vaccine project through to phase 1 trials in humans.
The science behind how Evans hopes to vaccinate people against fentanyl and heroin is, in a word, cool. And it all starts with a synthetic molecule known as a hapten. Due to the strictures of Federal Drug Administration regulations, not to mention the potential hazards for lab personnel, Evans’ team doesn’t actually work with fentanyl or heroin. Instead the center’s chemists create a hapten that looks like the drug, just without all the nasty effects. On its own the hapten won’t trigger the immune system, so the team attaches an adjuvant to it called CRM 197, a bacteria toxin that tells the body to get down to business. The antibodies created as a result will react not only to the CRM 197 but to the hapten riding on its surface, blocking the fentanyl- or heroin-lookalike from crossing the blood-brain barrier. If actual fentanyl or heroin enters the bloodstream, those same antibodies will attack it just like the hapten.
“They can actually take their hand and put it on a pot of boiling water and they wouldn’t sense pain …”
Lost yet? Well, think of your immune system like a search and rescue team, and hapten as a small child in dark clothes lost in the woods. Odds are, search and rescue won’t have much luck spotting the child. But stick a big pink backpack on the kid and he or she will stick out from a long ways off. CRM 197 is the big pink backpack.
None of this is new to Evans or his crew. It’s exactly what they’ve been doing with influenza and other infectious diseases for more than 20 years. There is a unique challenge to the opioid vaccine, however. The Center for Translational Medicine has to ensure that the vaccine only acts against the intended target. In some ways, that challenge is the inverse of what Evans is attempting to tackle with the flu: making a nonseasonal vaccine that applies more broadly across strains.
“You don’t want to give someone a vaccine and then have pain meds not available to that person if they got injured and needed it,” Evans says. “It’s a regulatory component to make sure we are successful in targeting the drug we want to target but the antibody response doesn’t spill over and stop that patient from being able to take any kind of opioid-based medicine to control pain.”
Evans also notes that the opioid vaccine isn’t a permanent fix. Over time, a recipient’s antibody response will decline and, without CRM 197 to kick things into high gear, they’ll be just as susceptible to the negative effects of fentanyl and heroin as before. If a recovering addict relapses, Evans says, they’d need a booster shot.
The Center for Translational Medicine isn’t forging ahead alone. During the workshop in Bethesda, Evans had a chance meeting with Marco Pravetoni, associate professor of pharmacology at the University of Minnesota. Pravetoni hails from a research team that specializes in vaccines against addictive substances. In fact, he’s currently preparing for phase 1 clinical trials of an oxycodone vaccine he first began developing in 2008. The two immediately recognized the combined strength their teams would bring to the opioid crisis—a true peanut-butter-and- jelly moment, with Evans’ adjuvants promising to enhance the effectiveness of Pravetoni’s vaccines.
“Vaccines such as the ones against opioids have a weakness, which is that these vaccines may not be very immunogenic,” Pravetoni says. “That means they may not work necessarily in everybody that receives [them]. One way to get around this particular problem is to combine the vaccine with adjuvants so that adjuvants will increase the immunogenicity of these vaccines. In simple terms, you are more likely to generate an effective and protective response in more people after immunization.”
Six months into the project, Pravetoni has already recorded decreased respiratory distress and decreased toxicity levels in mice treated with the adjuvant-enhanced vaccine from Evans’ team. He expects the research to move from rats to mice this winter, and eventually, pending FDA approval, into phase 1 trials. Once complete, the vaccine could prove an invaluable resource not only for those fighting opioid addiction but for those in high-risk occupations who may accidentally come into contact with fentanyl, including law enforcement personnel and airport security.
“If you had a custom official vaccinated against carfentanyl, that’s an added protection so those people are less likely to be suffering from the toxicity if there is even the remote possibility that they’re exposed to this material,” Pravetoni says.
When it comes to solving a public health crisis as severe as opioid addiction, no stone is being left unturned. And in Bozeman, Montana, one biopharmaceutical company has opted to tackle the long-game. SiteOne Therapeutics was founded in late 2014 with a singular mission: to reduce, or eliminate for good, the nation’s need for opioids by giving people in pain a non-opioid alternative.
SiteOne’s research is rooted in a rare disorder, first described in the early 1930s, known as congenital insensitivity to pain, or CIP. The human body contains a number of sodium channels, pathways that support essential functions like breathing and circulation. One of these channels, Nav 1.7, is specifically involved with pain response, and patients with CIP have a genetic mutation that blocks this channel.
“They can actually take their hand and put it in a pot of boiling water and they wouldn’t sense pain,” says SiteOne President and CEO Stan Abel. “They might be able to feel warmth, they might be able to feel the concept of the water, etcetera, but they wouldn’t feel pain. And it extends beyond thermal pain. They can break a bone and not feel it.”
That a condition like CIP attracted the attention of pain therapy researchers doesn’t exactly stretch the imagination. It’s exactly what set SiteOne founders Justin Du Bois and John Mulcahy down the path of identifying a compound that could act in a similar manner to the genetic mutation, and they eventually settled on marine guanidinium, a toxin present in, among other things, red tide. By reverse engineering the compound, they were able to block the Nav 1.7 channel effectively preventing pain response from reaching the brain.
Again, the science can be a bit befuddling so think of the pain as an oil leak running into the side-channel of a river. You could catch the oil by dropping one of those absorbent booms in the main channel downstream of the leak, the same way opioids block pain in the central nervous system. Or you could, as SiteOne hopes to do, drop that boom into the side channel itself, keeping the oil and the boom safely in the river’s periphery.
“We would have none of the addiction potential and presumably none of the other important concerning side effects that opioid-based or narcotic-based pain therapeutics would have,” Abel says. “If we’re successful with this, we could potentially change the world and how pain is managed, not only post-operative pain or pain from injury but also things like chronic neuropathic pain.”
So far, SiteOne is primarily focused on intravenous application of its non-opioid pain therapies, with the intent of supplementing or replacing opioid use in hospitals. Because blocking Nav 1.7 doesn’t involve a drug binding to opioid receptors in the brain, SiteOne’s approach carries none of the respiratory depression risk or addiction potential of Vicodin or fentanyl.
But blocking Nav 1.7 is tricky business. All those sodium channels in the body look similar and hitting the wrong one could have dangerous if not lethal consequences. Accidentally block, say, Nav 1.5 and you could stop a patient’s heart. It’s a promising enough avenue, however, that SiteOne isn’t the only company exploring how Nav 1.7 could help solve the opioid crisis. Pfizer, Merck, Amgen—many of the major pharmaceutical companies also have active Nav 1.7 programs.
SiteOne’s work has proven promising enough that the NIH awarded the company a $1.4 million grant in September 2018. The high-profile nature of the fight against opioid abuse and dependence has also helped attract private investors and venture capital dollars, Abel says. And while he hopes SiteOne team’s work will reach the phase 1 trial phase in 2020, Abel adds they’re still a lot of work and hundreds of millions of dollars in capital away from making good on their mission.
“Unfortunately science is science, development is development, and the regulatory process is what it is. And it’s for good reason. We’re trying to understand whether our drug candidates are safe to bring into people and [if] they work the way that we hope they do. That takes time to understand.”
“The people who are dying from overdose and becoming addicted are not the homeless people you see on the street, the gangs and all the violence associated with that. It’s people on university campuses and people in the workforce. It can impact anybody.”
Time is a luxury some don’t have. Montana’s opioid death rate in 2017 was 2.3 people per 100,000, or roughly 23 people in a population of one million. Nationwide, more than 47,000 people died from opioid overdoses that same year. Each of those deaths spirals outward, altering forever the lives of family and friends. Evans feels fortunate that no one in his immediate family has been hit by the epidemic. “But also,” he says, “it’s only a matter of time because opioids are so easy to get addicted to.”
Tomi Cook feels fortunate too, for how her story played out. While in Hawaii, she received a Facebook message from a childhood babysitter noting her potential and the profound impact she’d had on those around her. Days later, Cook awoke on a beach with a bent needle in her arm, wondering why the universe refused to let her go. That was when her dealer handed her a brown baggie containing iboga, a West African psychedelic known for producing intense hallucinations and, at least anecdotally, for reducing opiate withdrawal symptoms. What Cook experienced upon taking it was a spiritual awakening, one that forced her to acknowledge that her drug use was a symptom of deeper childhood trauma she’d never truly grappled with before.
“We’re not taught how to face our traumas, how to emotionally regulate, how to stop perpetuating these generational patterns that get passed down to us, like ‘shut up and buck up,’” Cook says. “I think the opiate epidemic is a result of a cultural epidemic. We’re so fucking isolated and lonely and lack meaning in our lives.”
That Facebook message and the iboga trip were enough to convince Cook to detox in the rural Montana basement belonging to her dealer’s parents. From there she struck a new path, earning a master’s degree in clinical mental health from the University of Montana, landing a job at the Open Aid Alliance and reconnecting with the natural world she’d grown up loving.
A vaccine like the one Evans and his team are developing would have made the struggle easier, Cook says. One of the most daunting obstacles to getting clean is the withdrawal process, which lasts anywhere from a week to 12 days. The picture Cook paints is pure hell: melting into a pool of her own sweat, throwing up into a bucket, defecating for what seems like the first time in a year. Then there’s the thought of facing your emotions again, and the desire to return to that familiar numbing agent. “[A vaccine] would have allowed more space to focus on healing and alternative, healthier coping skills and behaviors,” she says. “It would have created more space.”
Cook did relapse once, an experience that reinforces the need for non-opioid painkillers like the one SiteOne is developing. She had her wisdom teeth pulled and got a prescription for hydrocodone. Then she went back for a second prescription. She was on the tail-end of a breakup, and the emotional pain gave her an excuse to embrace an old habit. Cook laid in bed for a week, high and terrified and wondering who she might know that would have heroin. A friend pulled her back by reminding her how hard she’d worked, how much she’d gained, how far she’d come.
It’s an overwhelming temptation to hit what Cook calls the “fuck it button.” The world’s ending, we’re destroying the planet, why not just pop a pill to numb it all? It felt good, she says, to surrender to the darkness once more. However, she’s brutally honest with herself about what would happen if she ever started using again.
“What’s helped me stay clean is I just know, in the deepest part of myself, that if I were to relapse I would die this time,” Cook says. “I just know that would be the end of me.”
In many ways, Cook’s story represents the extremes that addiction can drive people to: homelessness, desperation, suicidal ideation. The research being conducted at the University of Montana and SiteOne could certainly benefit those who have found themselves in similar straights. However, opioids have been nicknamed a “silent killer” for a reason. They afflict a broad range of citizens and not just those who are, as Cook described herself, shooting up behind your dumpster.
“The people who are dying from overdose and becoming addicted are not the homeless people you see on the street, the gangs and all the violence associated with that,” Evans says. “It’s people on university campuses and people in the workforce. It can impact anybody.”
As the nation grapples with questions surrounding the worst drug crisis in American history, western Montana is working toward its own solutions. For many, the answers can’t come soon enough.
Freelance writer Alex Sakariassen has spent the past decade penning long-form narrative stories that spotlight the people, the politics and the wilds of Montana. A North Dakota native, he splits his time between Missoula’s ski slopes and the quiet trout waters of the Rocky Mountain Front.