The Obstacle is the Way

Posted by William Snyder on Monday, March 3, 2025 in Features, Homepage Highlights, Spring 2025 .

In late June 2024 James Crowe Jr., MD, began a grueling, seven-day, 155-mile ultramarathon through the Gobi Desert of Central Mongolia.

It was one of several physical challenges undertaken that year by Crowe, 63, whose lab at Vanderbilt University Medical Center has attracted international attention for developing monoclonal antibodies against a host of viral diseases, including COVID-19.

Six months earlier, and just 10 days after undergoing surgery to repair a torn meniscus in his left knee, he and his wife, Lisa Crowe, MD, a writer and retired Nashville physician, hiked an 85-mile circuit in Patagonia, Chile. In April he ran the Boston Marathon.

 For Crowe, these are more than physical tests of endurance and achievement. They’re about finding balance and living in the present. They also come at a time of big change for his lab, and for the Vanderbilt Center for Antibody Therapeutics (VCAT), which he directs.

In the summer of 2024, the center joined an extraordinary national effort to develop and stockpile new vaccines and antibody therapies that can be deployed rapidly to prevent another pandemic.

“We are launching a new, three- to five-year cycle of large-scale, rapid antibody discovery efforts,” Crowe said. “With over $100 million in new extramural support, we are committed to advancing our work in developing monoclonal antibodies for even more viruses.”

One of their targets is mpox, the virus formerly known as monkeypox, which is surging in parts of Africa. Crowe and his colleagues are working with the federal government and industry partners to advance mpox antibodies they isolated eight years ago into human trials.

“It feels good,” Crowe said. “We had been talking about a proactive program for a very long time. We have gotten large grants to make antibodies very rapidly, and we’re probably the fastest in the world.”

The Gobi March draws runners from all over the world. They come to Mongolia to test their mettle against the vast steppes, sand dunes, river crossings and great rock valleys of this sparsely populated country sandwiched between Russia and China.

On June 20, 2024, Crowe arrived in Ulaanbaatar, Mongolia’s capital, but without his luggage. “I spent two days walking around Ulaanbaatar trying to cobble together the things I needed, which was especially exciting because there was a snowstorm all day Thursday,” he posted to his blog on the sponsor’s website, www.racingtheplanet.com.

Among the 40 or so items required of every racer were hiking and running gear, a puffy jacket and a rain poncho to keep out the cold and wet, and seven days’ worth of food.

The ultramarathon began on Sunday, June 23, with a 21-mile jaunt through the rolling grasslands of the Orkhon Valley. “Wake at 2 a.m.,” Crowe wrote. “Stand outside the tent with a full moon shining silvery light on a quiet camp, pitched at the base of 1,000-year-old ruins of the palace of one of Genghis Khan’s generals.

“Ten miles in, we’d come upon a yurt (traditional tent home), with beautiful children in traditional dress waving kindly as we pass. A few minutes later, 50 horses would charge by on the ridge above, running wild and free … The steppes would be littered with the skeletons and skins of animals, … giving motivation to keep moving.”

Crowe is the Ann Scott Carell Professor and professor of Pediatrics and Pathology, Microbiology and Immunology in the Vanderbilt University School of Medicine.

He and his colleagues have developed cutting-edge technologies to identify and study clones of white blood cells producing specific, antiviral antibodies. They have identified human monoclonal antibodies against a host of pathogenic viruses, including Zika, Rift Valley fever, HIV, dengue, influenza and parainfluenza, Ebola, chikungunya, West Nile, norovirus, rotavirus and RSV.

Through their pioneering work in computational immunology, they have achieved major advances in the rational design of vaccines and antibody therapies, some of which have progressed to clinical trials and treatments.

In 2021 their groundbreaking work led to development of an injectable, long-acting antibody combination approved to prevent COVID-19 in high-risk patients. In June 2024, VUMC launched a clinical trial of another antibody they isolated targeting enterovirus D68, which is linked to a rare but devastating polio-like illness in children. And in October 2024, an antibody they’d isolated in 2012 that neutralizes the deadly hemorrhagic Marburg virus was sent for use in Rwanda, where at least 15 people had died during an outbreak.

A native Nashvillian whose grandfather was a Baptist minister and whose father, at 83, is still working as a radiologist, Crowe approaches his work and career with an intensity and sense of purpose that could easily become all-consuming. Yet there also is a joyful serenity about this youthful looking man with a boyish smile and sense of fun that belies the Olympian pace required to sustain his lab’s prodigious research output.

Sand. Rocks. Sky. That’s how Crowe began his summary of the third, 24-mile stage of the Gobi March on June 25.

“Amazingly we came upon a monastery, with various religious stone elements, and we each entered the temple there, which is active and replete with beautiful textiles, and skylight filtering from above. Incense was burning … Several of the adherents were on the grounds in traditional robes, smiling and blessing us along the way …

“I have been learning over the last few years that every moment can be holy … and every place can be holy … Still, to be in the Gobi Desert, in a verdant valley in the midst of vast dryness, at a monastery and temple, to be fully embodied and my mind turned off a bit, I just felt acutely aware of the transcendent nature of things … the way things really are through immanent beauty, peace, silence, Nature.”

Then came the sand dunes. “The high-mindedness of everything above gave way over time to the reality of slogging it in full exposure in the middle of the day in the desert … Dusty. Biting horseflies. Heat. Softer and softer sand.”

Crowe had to stop twice to clean and apply new tape to his feet, lance and treat new blisters, and change his socks.

“I had decided … I would under no circumstance expend any emotional energy in complaining or suffering or resisting it … I felt resistance at getting over that hot sand, but then remembered Marcus Aurelius proclaiming, ‘The obstacle is the way.’ And I immediately accommodated to it.”

Crowe grew up in Winston-Salem, North Carolina, and attended Davidson College, where for a time he juggled his love of playing college baseball with the demands of his premed curriculum.

Eventually medicine won out. It was a way, he perceived, that he could have a positive impact on the world. For a while, he wanted to be a medical missionary. During medical school breaks, he visited and worked in sites in Senegal, Kenya and Papua New Guinea.

There he witnessed the deaths of children from infectious diseases that could have been treated or prevented, if only the appropriate medication or vaccine had been available. Seared into his memory is the moment he delivered a child’s lifeless body to parents consumed by grief.

“If you have never personally experienced looking into someone’s eyes and saying that something could have been done about this, but wasn’t, and your child is dead,” he told writer Jessica Pasley for a profile published by VUMC in 2009. “You don’t get over that.”

Crowe met his wife during their first year of medical school at the University of North Carolina (UNC), Chapel Hill. They married in 1987, the week before they graduated. They have two children, Stephen and Catherine.

After completing their residency training together at UNC, Crowe took a turn toward science in 1990, when he accepted a fellowship and later served as senior research investigator in the Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

He returned to Vanderbilt in 1995 for a fellowship in pediatric infectious diseases and was appointed to the faculty a year later. Among many honors and recognitions, he was elected to the National Academy of Medicine in 2014.

The work of the VCAT, formerly known as the Vanderbilt Vaccine Center, has received significant support from the NIAID and the Defense Advanced Research Projects Agency of the U.S. Department of Defense, and from the German science and technology company Merck KGaA, which awarded Crowe a share of its Future Insight Prize in 2019.

Facilities also are important, and that’s where VUMC has provided fertile ground for research, most recently planning construction of a third, NIH-funded Biosafety Level 3 lab. “The institution has been very supportive of us over the last decade to get us situated (into) … a contiguous space where we can do the entire discovery program in one location,” Crowe said.

There is much left to do in combating viruses. “We’ve mastered the early discovery part,” Crowe said. “The next step is how to manufacture (antibody therapies) safely, quickly and cheaply.”

This process, called Chemistry Manufacturing and Control, is one of the most expensive parts of drug development. It’s one reason many promising therapies don’t make it through what is called “the valley of death” in the drug development pipeline.

With IDBiologics, a privately held biotechnology firm he founded in 2017 with support from VUMC to develop antibody drugs, “we’re talking to companies that have innovative technologies that would allow us to deploy these (manufacturing functions) in Nashville,” he said.

Another goal is achieving the vision of a large-scale development program he designed and termed AHEAD100.

Even before COVID-19, the world was confronted with recurring outbreaks of one emerging virus infection after another: chikungunya in 2013, Ebola in 2014, then Zika in 2015.

Crowe and his colleagues came up with a preemptory response: Advanced Human Epidemic Antibody Defenses 100 — a list of nearly 100 viruses with pandemic potential that need to be addressed now. “We’ve been doing these projects or at least pursuing them, whether or not we had funding, (because) we need to do all 100,” he explained.

To generate support for these projects, and to encourage greater collaboration among “pandemic prevention stakeholders,” including academic research institutions like VUMC, the government and industry, Crowe helped establish a Maryland-based nonprofit, the Global Pandemic Prevention and Biodefense Center, in 2021.

The Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness (ReVAMPP) program, announced in September 2024, is another step in that direction. The NIH has committed approximately $100 million a year to support research at VUMC and six other centers aimed at developing antibody therapies for nine groups of viruses that pose the greatest risk to human health.

Crowe estimated it would take $2.5 billion to develop, Phase 1 trial safety test, and stockpile antibodies for all the pathogens on the AHEAD100 list — $25 million per virus. Considering the trillions of dollars the COVID-19 pandemic cost the U.S. economy, not to mention the millions of lives lost worldwide, “it’s super cheap, and it’s super wise to do it,” he said.

On June 29, as he and his fellow runners rested at camp under Mongolian stars before attempting the last test of their ultra-exertions, Crowe posted this 15-word invocation of hope and acceptance: “Lord willing, I should finish now, given it’s only six miles. Though anything can happen.”

Finish he did. With a total running time over the seven-day course of 48 hours, 28 minutes, Crowe was squarely in the middle of the pack — 53rd of 107 runners who completed the ultramarathon. The fastest runner, a 40-year-old Japanese man, finished in 22 hours, 36 minutes. The youngest competitor was a 15-year-old Polish boy, and the oldest was a 71-year-old woman, a college professor from Arkansas.

But time and age weren’t important, Crowe decided. The real prize was wisdom. There is a lot in this world that humans can control. There is a lot they can’t. The wisdom is in knowing the difference … and in being good with that.

After he returned home, Crowe summarized his experience in a LinkedIn post: “I’m still in the middle of a practical year’s course in learning how to ‘accept things as they are’ … I find that fully embodied experiences in the elements, when it is viscerally obvious you really cannot control uncontrollable things, drive the point home in ways that coaching, reading books and deep thinking just can’t do.”

Crowe has returned to the lab but, deep inside, the desert will always be with him.

“I didn’t lose the North Star,” he said. “The desire to make a difference never goes away. I realize we can’t fix everything … but I do dream that after we’ve done our work, more people will live, … more children will survive to adulthood. If we contribute in small ways to that, I’ll be very happy.”