I direct a center for research on coronaviruses and other emerging pathogens. We’re part of a giant wave of research, at Penn and elsewhere, that’s addressing the crisis. In my own lab, I work with a colleague on SARS-CoV-2—the virus that causes COVID-19—and the lung microbiome. The bacteria that live in your lungs are generally sparse when you’re healthy but can proliferate when you’re sick. We’re using microbiome DNA-sequencing approaches to investigate that for SARS-CoV-2. We’re also sequencing genomes to determine the virus’s genetic code. This enables us to ask important questions: What seeded the epidemic here in Philadelphia? Is the virus evolving to infect people better? Is it evolving to evade drugs?
In comparison with other viruses, what really stands out about SARS-CoV-2 is just how infectious it is. People can spread it very early, when they have few or no symptoms. SARS-CoV-2 is much less lethal than HIV, for instance—but there are effective antiviral agents for HIV. The only drugs right now to treat SARS-CoV-2 are drugs made for other purposes.
There’s some hope for remdesivir, which was initially made to treat Ebola, but the real pharmaceutical development—the vaccine—is going to take much longer. A pharmaceutical company would take a million compounds and screen them against the assay of viral infection in cells. You get starting points, and you synthesize new compounds. You test to find ones that are nontoxic in people, then do larger tests to see if they’re effective in people. It’s a multiyear approach that’s just starting.
A new, high-tech approach to vaccine development looks promising.
A new, high-tech approach to vaccine development looks promising. In the old days you had to kill a virus and inject it into people, like the Salk polio virus vaccine. Or you’d grow virus in animal cells to create an attenuated virus vaccine, like the Sabin polio vaccine. But today you can make a genetic copy of a new virus’s proteins, either DNA or RNA, then inject it directly into a person. The proteins get expressed, and you develop an immune response. This can potentially be much faster than the old way of making vaccines.
At Penn we’re working on both RNA and DNA vaccines, and we’re actually starting to put DNA vaccines in people. One early target will be health care workers. In the absolutely rosiest scenario, there might be a vaccine in a year.
We’re also working on antibody tests that show if you’ve been exposed. We’re starting to see some evidence that if you’ve been infected once, you do get some degree of protective immunity. There’s also a therapeutic angle, in that people who have had effective antibody response can donate blood, and antibodies from that blood can be transferred directly to somebody who’s sick—passive immunization, it’s called.
Pandemics may become the new normal, and we’re learning a lot about how to prepare for the next one: Stockpile personal protective equipment. Have people trained and ready to work safely in our labs. Make medications that will hit many viruses, and stockpile them in advance. Be ready to test, and to get vaccines out really fast.
Personally, I’m locked down and socially distancing, like everyone else. I’ve been to my lab at Penn, but most of what I can do I do remotely. I’m staying home, and my two college-aged kids are home. There’ve been times when they were grumpy, I have to say, but I like seeing the family. I love seeing more of my kids.
Rick Bushman ’80, chair of the microbiology department, University of Pennsylvania