NOTE: The following article appears in the May 2020 issue of Texas Monthly.
Story By Peter Holley
More than three months had passed since the pathogen appeared on the map in Central China, tearing through Wuhan, an industrial city of 11 million, with alarming speed. Nearly two months had passed since the disease crossed the Pacific Ocean and landed in Washington State, where it quickly began spreading among residents. And a little over a week had passed since the potentially deadly, SARS-like respiratory virus that causes COVID-19 officially touched down outside the nation’s fourth-largest city, promising to unleash upon Texas the same chaos that was still rippling across Asia and much of Europe.
The Coronavirus Pandemic
If there was ever a time to consider every possible solution to the rapidly encroaching pandemic, it was now. But as they sat in a cozy office on the fifth floor of a glassy, twenty story office building inside Houston’s Texas Medical Center on a Friday in mid-March, Peter Hotez and Maria Elena Bottazzi—two of the world’s most prominent infectious disease experts—instead found themselves desperately, and mostly unsuccessfully, trying to get the world’s attention. They claimed to have a possible vaccine for COVID-19—at least 20,000 doses of which sat untouched in a lab freezer in a strip mall three miles down the road from their office. It was a stockpile of a four-year-old SARS (severe acute respiratory syndrome) vaccine they had manufactured that, because of the similarities between that disease and this new one (both are coronaviruses), had the potential for cross protection. Nobody could say for certain whether the vaccine was capable of saving lives, but at the very least, the researchers maintained, they should be given an opportunity to find out.
“We have the experts in Texas, we have the facilities in Texas, we have the virus here, and we have the clinical people who can do the studies,” said Bottazzi, her voice rising in frustration. She is the co-director of Texas Children’s Hospital’s Center for Vaccine Development and associate dean of the National School of Tropical Medicine at the Baylor College of Medicine. “We have the largest medical center in the world, and with all this combined, we should already have had this vaccine in the human population.”
Hotez, her co-director and dean of the NSTM, agreed. A normally affable scientist, he’d begun to appear angrier than might be expected for a man who favors polka-dot bow ties. That’s because, despite all of his and Bottazzi’s credentials and the urgency of the moment; despite their appeals to health officials, Congress, and the public; despite their needing only $3 million to pull the vaccine out of the freezer and start testing on people, they were stuck. Rather than leading the fight against COVID-19 from their lab, they were waging a daily battle, in emails and phone calls, against bureaucracy.
In 2016, the researchers said, half a decade after their research began, their team was ready to begin testing their SARS vaccine. Unfortunately, as the researchers soon discovered, the interest in SARS vaccines had dried up—and with it any available funding from investors and grants to advance testing to a clinical phase. With the virus no longer circulating (the SARS outbreak occurred in 2003), the interest in that disease had been displaced by morepressing epidemics like Middle East Respiratory Syndrome (MERS), Ebola, and the Zika virus. But in December of last year, when news of a new SARS-like virus began circulating among health officials in China, neither Hotez nor Bottazzi were totally surprised. “We’ve always thought if there was a SARS and then there was a MERS, maybe there’s going to be something else,” Bottazzi said.
“I haven’t been getting much sleep,” said Hotez, his eyes bleary. Though his own efforts to revive his lab’s vaccine had so far been frustrating, he maintained optimism about the wider efforts underway to tackle COVID-19 in Texas and beyond. Indeed, his fatigue was typical of that felt by scientists across the state in several other labs at the forefront of the worldwide struggle to contain the disease. Hastened by the virus’s genome being published online by Chinese scientists in January, their work has moved at a never-before-seen pace. By the time the first COVID-19 cases were identified in Texas, in February, the combined efforts of the state’s scientists were already having an unmistakable impact on the race for a breakthrough.
There may be no other institution in the world throwing as much brainpower at COVID19 as the University of Texas Medical Branch at Galveston (UTMB). Over several decades, the Galveston National Laboratory at UTMB, a high-security biocontainment facility, was instrumental in developing the first Ebola vaccine, which was approved by the FDA late last year, as well as testing a Zika vaccine, after the 2015 U.S. outbreak of that virus. The lab also partnered with Hotez and Bottazzi in developing their SARS vaccine.
In February, UTMB’s researchers were among the first in the world to receive live coronavirus samples from the Centers for Disease Control and Prevention. Scott C. Weaver, director of the Institute for Human Infections and Immunity and scientific director of the Galveston National Lab, estimated that ten UTMB scientists were actively working with the virus in their labs while several others were studying the virus using data.
Among their most intriguing campaigns is a project using genetically modified mice to trace how coronaviruses replicate and spread through cells.
“These mice may be key to a lot of research that seeks to understand the disease process and for efforts to create new antiviral drugs,” said Weaver.
UTMB has also notched an agreement with Moleculin, a Houston biotech firm that has developed a cancer-fighting drug that may be able to interfere with coronaviruses by slowing down or stopping the replication of virus-infected cells, giving the body’s immune system more time to fight back. UTMB also has an expert exploring which bat viruses require mutation in order to jump to human hosts, offering possible clues about the origins of the latest outbreak.
The research circulated by UTMB, which has allowed its researchers to assist and influence labs all over the world, partly explains why there are already 44 possible COVID-19 vaccine candidates in development, according to the World Health Organization. Back during the Zika crisis, UTMB’S research spread across the global medical community rapidly, helping establish new digital trade routes for research. Such collaboration and early dissemination of findings has only increased with the latest outbreak. “Coronavirus has created an unprecedented sharing of data,” Weaver said. “Scientific communication has had some underlying improvements because of these global emergencies.”
Two hundred miles northwest of Galveston, the Sauer Laboratory for Structural Biology at UT-Austin, which opened in 2017 and has become a global leader in the use of an imaging technology known as cryo-electronic microscopy, has underscored the importance of investments in advanced research facilities. There, associate professor Jason McLellan made news in February by leading a team that created the first 3D map of the coronavirus spike proteins, the portion of the virus that gains access to human cells, passing along the infection. In recent weeks, McLellan’s team, which has been researching coronaviruses like SARS and MERS for years, has shared the map with researchers across the world.
With the atomic scale model in place, a scientist at the National Institutes of Health, working with Massachusetts-based biotech firm Moderna Inc., has created an early vaccine that is in the first stage of a clinical trial, which will determine the vaccine’s safety on several dozen healthy volunteers.
“As soon as we knew this was a coronavirus, we felt we had to jump at it,” McLellan told UT News, “because we could be one of the first ones to get this structure. We knew exactly what mutations to put into this, because we’ve already shown these mutations work for a bunch of other coronaviruses.”
His comments parallel those of Hotez and Bottazzi. As COVID-19 was racing through China in January, a research contact in that country confirmed to the team in Houston that the virus was more closely related to SARS than to MERS. As soon as scientists were able to identify the new coronavirus’s genetic code, Bottazzi and Hotez began to explore the similarities between it and the SARS virus in closer detail. What they’ve discovered, they said, is promising.
Not only do the two viruses exhibit similar genetic codes and bind to the same receptors on human cells, new lab experiments appear to show that the blood of patients infected by SARS in 2003 can neutralize the virus that causes COVID-19, meaning some people may have an inherent immunity.
“That’s when the little light bulb turned on,” Bottazzi said. “We realized that they’re so similar that maybe our vaccine is something that can be repurposed for this new outbreak. Even though it may not be the perfect vaccine, it’s certainly sufficiently similar that it will provide some added value in reducing the severity of the disease.
For all the good work being done, researchers like Bottazzi and Weaver caution that there is no quick fix for the new coronavirus. Even the most sanguine forecasts—those that assume unpredictable human trials will proceed without a hitch—do not predict a widely used vaccine for the public until well into 2021, at the earliest.
That’s simply how long it takes to develop and test a vaccine, to ensure that it’s not only effective but safe, in the general population and for groups of patients with specific characteristics. But it’s also a reminder of the importance of funding research with uncertain tangible results in times when there’s no imminent crisis. The neglect of Hotez and Bottazzi’s SARS vaccine is an example of what can happen when research funding freezes up. When funding continues, so can progress. Three years ago, using a technology developed by microbiologist John Schoggins, of UT–Southwestern Medical Center, in Dallas, researchers began a study that identified a protein produced by the human immune system that can inhibit coronaviruses, including SARS and MERS. With the benefit of multiple grants, Schoggins and his international partners continued their work and determined this February that the same protein inhibits the COVID-19 virus. Any potential for developing this knowledge into a treatment remains years off—but it’s years closer than it would have been without continued funding.
Hotez and Bottazzi are hopeful that their vaccine will be tested in clinical trials soon. Once they get funding in place, they said, they could begin testing their vaccine in clinical trials on Texans infected with COVID-19 in as little as six weeks, possibly sooner. The idea that just $3 million—a sum of money amounting to a modest NBA contract—is all that stands in the way is simply too absurd for them to consider it insurmountable. “I’m upbeat because, you know, if I focused on my frustration, I could just sit down and cry,” said Bottazzi, forcing a smile twelve hours into a day that began, like so many recently, with buzzing text messages from researchers around the world at 3 a.m. “I mean, the frustration is invigorating us to do a hundred thousand things at the same time.”
As we spoke, Hotez’s iPhone began buzzing. On the line: a reporter from 60 Minutes. Normally a great opportunity, as far as interviews spotlighting academic work are concerned, but not the audience the researchers were truly seeking. Who they really wanted to talk to, they said, was somebody in the federal government with the power to fast-track the testing of their vaccine.
Even now, when everything is going crazy and we should have all the resources at our command to move this forward, we’re still getting these emails that say, ‘Here’s a request for applications,’” Hotez said, referring to government agencies that have asked his team to apply for grant money, a process that would take months at best.
Navigating America’s sprawling, regulation-clogged public health infrastructure is a familiar challenge to researchers, of course. Hotez has recently become more strident in his public remarks. When he testified before the House Committee on Science, Space, and Technology on March 5, he said that by failing to fund vaccine development when the private sector wouldn’t, the government had missed a major opportunity to avoid a health crisis. “It’s tragic that we won’t have a vaccine ready for this epidemic,” Hotez said then. “Practically speaking, we’ll be fighting these outbreaks with one hand tied behind our backs.”
In the meantime, he and Bottazzi have pivoted to soliciting the investment they need from regional philanthropists. Bottazzi, who was born in Italy but has spent thirty years in Texas, has shaped her appeal around a theme that Texans are uniquely receptive to: bragging rights. “It would be fantastic to say that Houston has one of the first vaccines [for COVID19] being evaluated,” she said. “How could that not resonate?”
Additional reporting by Jason Heid.