On the fifth floor of the Penn State Milton S. Hershey Medical Center, Dr. Craig Meyers and his team might have conducted a miracle.
What he and his lab claim discovery of is breathtaking in its simplicity.
A common virus, omnipresent in the world, which when it infects humans, does no harm. What it does when introduced into certain kinds of tumors, however, is cause the virus to go wild, liquefying every cancer cell it comes into contact with.
It’s one of the smallest, simplest viruses, and yet, adeno-associated virus type 2, or AAV2, could be among the most important agents in modern medicine. That’s because it’s almost perfectly imperfect.
For whatever reason, through its evolution, AAV2 developed what would, in most cases, be a dead end. It cannot easily reproduce.
Viruses live and reproduce through asexual replication. In the simplest terms, they infect an organism, attacking living cells, inserting viral genes inside healthy cells which then hijack the cell, using it to reproduce and create more viruses.
The new viruses are released into the environment, where they begin infecting other healthy cells.
AAV2 doesn’t work that way.
At the University of Florida in Gainsville, Nicholas Muzyczka has made a career studying AAV2 and he knows the virus about as well as anyone.
“And the deal with [AAV2] is that it will go into the cells in your body — and do nothing,” Muzyczka said. “It’ll just sit there.”
By itself, the virus is harmless and, in some cases, won’t even replicate.
Instead, it relies on a “helper” virus to poke it along. One of its helper viruses is believed to be the human papillomavirus, or HPV, which is widely believed to be one of the major causes of cervical cancer.
There has also been evidence that not only does HPV impact AAV2, but AAV2 might have some form of impact on HPV, possibly altering the chances of someone developing cervical cancer.
Which is exactly what Meyers’ lab at Penn State was studying when the lab had its break-through moment five years ago.
What happened involves a cervical cancer sample, some AAV2 and a few extra days in an incubator.
Other studies indicated that women with cervical cancer don’t have AAV2 and women with AAV2 don’t have cervical cancer.
Meyers and his lab were trying to figure out why.
Their method was simple: Infect groups of cervical cancer cells with AAV2 and harvest the cells after 24, 48 or 72 hours to note any changes taking place.
On a whim, Meyers told one of his research assistants to infect a cancer cell culture and let it sit for awhile a week.
A week later, she walked into his office and said something strange had happened. That culture of cancer cells they had infected a week ago were all dead.
“We thought something had gone wrong,” Meyers said. “My first reaction was: ‘I’ll have to get the incubator fixed.’”
The lab repeated the process a dozen times. Each time, it had the same result.
In every trial, a week after being infected with AAV2, the cervical cancer cells were dead.
The lab began to spread out its research, collecting other types of cancer samples from other labs to infect with AAV2, including breast cancer.
Each time, they had the same results: Infect the cancer cells, wait a week and the cells died. By replicating the experiment, the laboratory was able to gain some understanding of the mechanics of what was happening.
“What the virus seems to be doing is turning on [a gene in] all these cancer cells that causes them to die, to turn on themselves and commit suicide,” Meyers said.
Even more encouraging, when his lab infected mice that had human breast cancer tumors with AAV2 earlier this year, they found the tumors had liquefied, a reassuring result because that isn’t always true.
“A lot of times in science, you tend to plan out your experiments and you have a goal, your hypothesis of what you’re trying to prove,” Meyers said. “But sometimes you see bits of data or someone else’s work and you get an idea … a lot of times some of the best things come from those little ideas.”
Every day, he gets emails from people congratulating him on his findings. And every day, he receives just as many from people begging for a cure.
It’s a request he simply cannot fulfill yet.
Yes, the virus appears to work in a laboratory setting and has destroyed tumors in mice. But his research still has a long road ahead of it before it makes its way to hospitals.
His next step will be to push toward clinical trials in people. But first he has to complete pre-clinical testing before he can apply to the Food and Drug Administration for human testing.
Bottom line: Even with unlimited funding, it could be another two to four years before Meyers injects AAV2 into the first patients.
Until then, he’ll continue to receive the emails from desperate people, begging him for a cure.
“It’s a very emotional topic. Everyone has somebody they know who has one type of cancer or another,” Meyers said. “And cancer’s not like one day you’re alive and the next day you’re dead. It’s a long, debilitating, chronic problem.
“You need to be reminded sometimes that the research you’re doing could have an affect on people out there.”
In the meantime, Meyers isn’t the only one looking at AAV2.
Nicholas Muzyczka at the University of Florida, mentioned earlier, is one among many researchers looking at AAV2 for its use as a transportation device for genes.
Because the virus is so simple, it’s relatively easy for scientists to remove its small amount of genes and replace them with human ones.
The idea is to introduce the carrier virus into the body of a person who might be suffering from a genetic disorder due to a problem in their own body’s DNA structure.
AAV2 virus, carrying the human genes, enters the patient’s cells and inserts its DNA fragment into our genes, repairing or replacing the broken sequence.
Because the virus is small, simple and doesn’t easily replicate, it reduces the chances of something going wrong.
“In a lot of different ways, it’s proving to be the safest way to deliver genes,” Muzyczka said. “And a lot of people are getting kind of excited about this because it does seem innocuous.”
It’s already being tested to treat hemophilia in England, where researchers used it to introduce healthy genes into people with the condition.
AAV2 then could be the key to one of the medical holy of holies. Real, systemic gene therapy.
Not only could it kill cancer cells, but it could be the vehicle to treat other genetic conditions, such as Alzheimer’s disease, Parkinson’s disease and cystic fibrosis.
“No one’s at the point where the Food and Drug Administration has approved it,” Muzyczka said. “But it is getting to the point where people think it’s going to work.”