Lab at Hershey Medical Center identifies a virus that could kill cancer

Nick Malawskey | By Nick Malawskey | The Patriot-News
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on November 27, 2011 at 12:00 AM, updated October 19, 2015 at 2:16 PM

NOTE: To new readers that discovered this story on Facebook, please note this article was originally published on Nov. 26, 2011. 

This is not the kind of lab we picture when we think of world-changing science. It's not the clean, spotless modern laboratories of television or movies.
It's a cluttered, workaday environment, where plastic test tubes rub shoulders with petri dishes and tubs of chemicals on busy shelves.

The white board isn't covered with the scrawl of complex mathematical formulas, but reminders of whose turn it is to buy the doughnuts.
But it is here, on the fifth floor of the Penn State Milton S. Hershey Medical Center, where Dr. Craig Meyers and his team might have conducted a miracle.
A common virus, omnipresent in the world.
When it infects humans, it does no harm.
It's the type of discovery that could change the world.
And like all great stories of scientific discovery, it begins with a moment of sublime serendipity, not unlike Isaac Newton nodding off beneath an apple tree.

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 and attack living cells, inserting viral genes inside healthy cells. The viral genes then hijack the cell, using it to reproduce and create more viruses.
AAV2 doesn't work that way.
"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 — and alter the chances of someone developing cervical cancer.
Which is exactly what Meyers' lab at Penn State was studying when the lab had its Newton-under-the-apple-tree moment five years ago.

Lab at Hershey Medical Center identifies a virus that could kill cancer On the fifth floor of the Penn State Milton S. Hershey Medical Center, Dr. Craig Meyers and his team might have conducted a miracle. VIDEO BY: CHRISTINE BAKER, The Patriot-News

Meyers has spent the last 18 years at Penn State, most of it studying HPV.
He was one of the first scientists to grow the virus in a laboratory setting, and today his lab is one of the major suppliers of HPV for scientific studies.
A few years ago, he was continuing his research into HPV, cervical cancer and the relationship with AAV2.
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.
On a whim, Meyers told one of his research assistants to infect a cancer cell culture and let it sit for awhile — say, a week.
They were all dead.
"We thought something had gone wrong," Meyers said. "My first reaction was: 'The incubator. I'll have to get the incubator fixed.'"
The lab repeated the process five, 10, a dozen times. Each time, it had the same result.
A week after being infected with AAV2, the cervical cancer cells were dead.
"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."

The Penn State lab isn't the first to announce what could be a major breakthrough using viruses to combat cancer.
Twenty years-ago, researchers at the University of California thought they found the silver bullet — a modified cold virus that killed about 60 percent of human tumors grown in laboratory mice.
News of the research caused The New York Times to ask: "Can the common cold cure cancer?"
Headlines in The Los Angles Times and The Pittsburgh Post-Gazette proclaimed the research to be "a cancer-killer."
It didn't turn out that way.
During clinical testing in humans, the modified virus fizzled. But the research, which centered around a gene named P53 did rejuvenate an entire field of study — oncolytic virology.
The link between viruses and cancer isn't anything new. For close to a century, scientists have believed there is some connection between the two.
In 1904, doctors first noticed that leukemia patients occasionally went through periods where they appeared to get better — and those periods corresponded with outbreaks of the flu.
The 1950s saw a flurry of activity, when several viruses — including hepatitis B and West Nile — were used in human trials in an attempt to treat cancer. While both viruses caused some tumor regression, the side effects, namely contracting hepatitis and West Nile, outweighed the benefits.
The study of viruses as anti-cancer agents petered out under the weight of a basic catch-22: Researchers needed something tough enough to survive the human immune system, but also a virus that wouldn't adversely affect normal human cells.
When then-President Richard Nixon went before the nation in 1971 to declare a crusade against cancer, it was widely believed that cancer was caused by viruses altering the DNA of healthy cells.
While that's true in some cases, in others cases, cancer's runaway growth of cells is caused by faulty genetics or cell mutation due to environmental conditions.
It wasn't until decades later that technology and basic scientific understanding — of cancer and virology — caught up to the idea of using viruses or "oncolytic viruses" to deliver anti-cancer treatments.
Since the first studies in the mid-1990s with the mutated cold virus, there have been a number of advances in the field, and numerous modified viruses are currently being tested around the world.
Five years ago in China, the first oncolytic virus, H101, was approved for clinical use, ironically a variant of the modified cold virus studied in the mid-'90s in California.
The Chinese — their testing standards are a bit more lax than ours — use H101 in conjunction with chemotherapy to reduce or eliminate tumor growth in patients with head and neck cancers.
In the U.S., a Massachusetts-based biotechnology firm named BioVex is testing a modified version of herpes in patients with stages III and IV of melanoma.
An earlier study by BioVex showed eight of the 50 patients treated with the virus recovered completely and a majority of the patients showed improvement.
The treatment holds enough promise that Amgen, one of the world's largest biotechnology companies offered $1 billion to acquire BioVex earlier this year.


The common cold viral study two decades ago highlights some of the major hurdles in moving a virus-based treatment from the laboratory to the bedside.
There's a world of biological complexity between mice and humans, and the vast majority of drugs, somewhere around 90 percent, never bridge that gap.
In the case of the modified cold virus, researchers didn't account for the fact that most people, at one time or another, suffer from the cold and build biological defenses against it.
So when they introduced the engineered virus, the body attacked and killed it, reducing its effectiveness in treating patients.
Then they ran into their second major hurdle — discouraged, their industry partner, Pfizer, pulled its funding from the project.
The American Cancer Society, which funds cancer research, estimates it takes about 10 to 12 years to fully develop a drug or therapy from the laboratory to bedside use.
"There's just tremendous challenges," cancer society spokeswoman Lynne Ayres said.
Drugs have to go through a series of tests prior to their use on humans, then at least three levels of human testing.
All of which requires time and money — roughly $2 billion annually. The American Cancer Society and the National Institute of Health are only able to pay for about 10 percent of the grant requests they receive.
That means a lot of research could be stalled in the pipeline. Even Meyers' research wasn't able to secure national funding for his preliminary testing of the AAV2 virus.
His most recent research was funded through a roughly $35,000 grant from the Pennsylvania Breast Cancer Coalition.
Even once a drug or therapy passes through the FDA approval process, there's one final step before it makes it to the general public — production and distribution.
"You've got to get funding to bring it to the market, which involves getting [pharmaceutical industry] support," Ayres said.
"Something they can make money on," she said. "These are the realities."


Meyers' research — and the resulting publicity — have made him something of a public figure overnight.
It's a request he simply cannot fulfill yet.
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.
Remember Muzyczka at the University of Florida?
He's among the 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.
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."
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."

Steps to FDA approval
It's a long, long road from the laboratory to the bedside, governed by the Food and Drug Administration. The vast majority of all drugs and therapies developed don't make it. The American Cancer Society estimates it takes about 10 to 12 years to fully develop a drug or therapy from the laboratory to bedside use.
Source: Federal Food and Drug Administration

Dr. Craig Meyers

  • Age: 53
  • Professor of microbiology and immunology at Penn State College of Medicine
  • Received his doctorate from the University of California, Los Angeles in 1990. Did his postdoctoral training at the Howard Hughes Medical Institute, University of Chicago.
  • Meyers' lab focuses on the human papillomavirus, HPV, which is believed to be one of the major causes of cervical cancer. Meyers' lab was one of the first to grow HPV in a laboratory setting. He has recently been researching the relationship between HPV and a common virus, adeno-associated virus type 2.
  • Lives in Derry Township with his wife of 31 years. They have four sons and two granddaughters.