UNMC and Temple University researchers collaborate on first-time achievement
The day Howard Gendelman, M.D., announced that his University of Nebraska Medical Center team, in partnership with Temple University, had successfully eliminated HIV in a living animal was a long time coming after decades of research.
That moment seemed infinitely far off from when he was racing his station wagon on a Sunday morning to UNMC to transport a terminally ill patient. That was in the early 1990s, when HIV and AIDS were poorly understood and highly stigmatized. But when Gendelman, the Margaret R. Larson Professor of Infectious Diseases and Internal Medicine at UNMC, was called on to see her, the patient was in ICU with a high fever and showing signs of severe dementia. No one knew what was wrong with her. But after an examination, Gendelman quickly understood she was in the terminal stages of AIDS, an illness that would soon become a worldwide epidemic.
Gendelman knew the patient had only one chance: Promising new drugs had to be administered immediately. The medicine worked quickly. Within a week or two, the patient had regained consciousness and was almost back to her normal self — talking, walking and interacting with her family. It was one of the first complete reversals of AIDS dementia.
That patient’s recovery was likely one of the few moments when emotion proved contagious in Gendelman’s career as a physician-scientist at Albert Einstein College of Medicine, Johns Hopkins, the National Institutes of Health, the Walter Reed Army Medical Center and, for the past 27 years, UNMC.
As the patient later described in a book edited by Gendelman: He was “like a kid in a candy store.” He paraded his colleagues in to see me and called me “medical history in the making.” She recalled him saying, “It’s moments like these that make me so proud to be a doctor,” and then turning to his colleagues and saying, “It’s time to find a cure!”
That was more than 20 years ago. Since then, AIDS has ravaged communities and claimed an estimated 35 million lives. Today, it is somewhat contained by antiretroviral drugs that suppress the virus. New infections have fallen 39% from the epidemic’s peak in the late 1990s — a major win in the worldwide battle against the disease. Antiretroviral drugs allow AIDS victims to live seminormal lives — but not everyone can afford or access these lifesaving medicines. In 2016, the Joint United Nations Programme on HIV/AIDS announced that for the first time, more than half of the world’s population living with HIV was receiving antiretroviral drugs. But that still leaves roughly 16 million people living with the disease and not receiving treatment.
Then came the day that Gendelman announced a breakthrough in the painfully long search for a cure. On July 2, 2019, Gendelman, Prasanta Dash, Ph.D., Benson Edagwa, Ph.D., and other UNMC and Temple University researchers announced they had eliminated HIV, the cause of AIDS, for the first time in a live animal.
The team used a cutting-edge therapeutic strategy, known as long-acting, slow-effective release antiretroviral therapy (LASER ART) in combination with CRISPR, a revolutionary gene-editing therapy, to eliminate the virus in a mouse model of human disease. The model used mice with a human immune system developed, in large measure, by UNMC scientists Larisa Poluektova, M.D., Ph.D., and Santhi Gorantla, Ph.D
“Few thought that HIV could be eliminated,” Gendelman said. “But, today, things are no longer as they were.”
The announcement was a watershed moment in the history of HIV and AIDS. But, for Gendelman, it was not a moment of fulfillment. It was more like a step forward in a marathon still in progress. For him, the moment was about the slow-plodding work of scientific discovery. It was about the curiosity that first brought him into the world of scientific research. It was about the days and nights spent mulling over problems — because the workday of a scientist never really ends. It was about the behind-the-scenes legwork — writing grants, filing financial papers, setting up laboratories. It was about the slow, complicated work that — despite the magnitude of this breakthrough — is far from over.
“When you make a discovery, it’s about incremental steps,” Gendelman said. “It’s a process and far from a single destination. You must love the journey of science … the day-to-day operations, the good, the bad, the difficult obstacles. It is all about overcoming the odds and keeping focused on the quest.”
When that quest resulted in the elimination of a virus that has confounded doctors and scientists for years, Gendelman said the first thing he thought was, “Could this be a mistake?”
“Something happened. It may not be accurate. … We must be sure,” he said. “It must be reproduced, and we must search for all controls and all possibilities to any uncertainty.”
So the team tested it again. And again. And again — until they could say with near certainty that the virus had been, to the best of their abilities and knowledge, eliminated.
The discovery was published in the prestigious scientific journal Nature and picked up by media outlets around the world.
“This achievement could not have been possible without an extraordinary team effort that included virologists, immunologists, molecular biologists, pharmacologists and pharmaceutical experts,” Gendelman wrote in the press release. “Only by pooling our resources together were we able to make this groundbreaking discovery.”
It would also not have been possible without the infrastructure that UNMC has built over decades, supported by a community that believes in the medical center’s mission and believes that breakthroughs of worldwide significance can happen in a midsize, Midwestern city when it is empowered to think big.
But the breakthrough is really just the first step. Delivering it to the people who need it in the form of compliance-approved, effective, safe and lifesaving medicine is Gendelman’s next hurdle. It’s a complex and lengthy process that necessitates layers of testing, and highly specialized procedures and staff who can navigate the delicate process of human trials.
Typically, a powerful industry partner, such as a large drug company, steps in to help. But that can slow the process down significantly, and Gendelman hopes to move more quickly by producing the medicine in-house at the newly created Nebraska Nanomedicine Production Plant. Fully staffed, this facility will provide the specialized space required to produce FDA-compliant medicine — independently, rapidly and right here in Nebraska.
It will still be slow-plodding work, with highs and lows, hurdles and breakthroughs. But Gendelman doesn’t want to wait a moment longer than he has to, not when a cure is potentially within reach. The work is evolving rapidly and needs to be in the hands of those who need it. Gendelman can imagine the satisfaction in their recoveries — and looks forward to being able to take a breath, step back and appreciate what can be achieved, knowing Nebraska is at the center of all of it.
“We love what we did,” Sharon Holyoke said. “And we just hope we leave the world a better place than we started.”