Barbara Peters Smith, Herald-Tribune
June 16, 2012
At first glance, the gleaming white building on a quiet Sarasota side street looks like any doctor’s office. But inside, scientists in a ground-floor laboratory conduct research that could one day transform the human race’s long-running battle against infection — from annoying sinus irritations to deadly flesh-eating bacteria.
Their work may seem straight out of a science-fiction movie: manipulating the human microbiome — the trillions of microbacterial cells on and in the body.
These cells, which can adhere to almost any human surface — mouth to skin to gut — can glom together to form biofilm, a fortress that helps them resist the current antibiotic arsenal.
The Quorum Biofilm Research Laboratory, part of the five-physician Hawthorne Clinic in Sarasota, is challenging the conventional wisdom about antibiotics, in a way not seen since 19th-century physicians began to question the value of draining patients’ blood to rid them of disease.
Instead of sending one antibiotic to fight a single type of bacteria, the battle would involve attacking the multitude of bacteria types found in a certain biofilm.
Scientists are just beginning to figure out how much these biofilms can protect or harm us. Less than four years ago, the National Institutes of Health launched its Human Microbiome Project as a foray into this unexplored territory.
Just last week, the project’s team of 200 scientists published their first results: a sequencing of thousands of bacterial strains from 250 healthy individuals.
“This whole concept that the human body is really an ecosystem, that you are actually walking around with all these cells that are not human — that’s a hard concept to wrap your head around,” says Robert Deschenes, who chairs the department of molecular medicine at the University of South Florida’s College of Medicine.
But Quorum Biofilm’s married team of Nicholas Monsul, a plastic surgeon, and Eva Berkes, an immunologist, have wrapped not only their heads, but their lives, around this newly emerging approach to health care.
Their home-grown research lab, staffed with five full-time scientists, is creating and testing original antimicrobial products, the first of which may reach the market within a year. So far the two have poured their own money into the project, but they are now quietly talking to investors who might help the work expand.
The biofilm venture offers Monsul and Berkes a novel business model for diversifying the traditional — and rapidly disappearing — independent medical practice.
But they expect it to do much more.
“It’s just a small dream,” says Berkes, half-smiling, “that can absolutely be made real: individualized microbiomial medicine.”
It could even catapult Sarasota to prominence in the biomedical field — as so many had hoped Maine’s Jackson Laboratory might do when it tried and failed last year to establish a personalized medicine institute here.
‘Inflammation is key’
While countless well-funded institutes and drug companies are chasing the dream of personalized medicine based on the human genome, Monsul and Berkes are after bigger game. The human microbiome is a teeming and warring collection of microbes, mostly bacteria, that colonize the body from birth. Your unique microbiome makes up more of what travels along with you each day than the genes you inherited from your mother and father.
“There are roughly a hundred trillion cells on your person,” Monsul explains. “About 10 percent have your particular DNA and the other 90 trillion — that’s like deficit numbers — are bacterial cells. That’s a huge population.”
This is not the kind of thing most physicians learn about in medical school. But one measly hint dropped in the course of his studies, Monsul says, “snapped my head up.”
“Someone said there are 3 billion bacteria in your mouth at any given moment,” he remembers. “That’s a lot.”
Berkes notes that “a classic example of biofilm and the human microbiome imbalance is gingival disease — plaque on your teeth.
“Go ask any dentist,” she says. “They know more about biofilm than most doctors do.”
By the time the couple met, they each had concluded that modern medicine was missing the point when it came to fighting infections, using outmoded 19th century tactics. If your eyes itch, or your hip implant is rejected, the infected site is tested, a bacterium identified and a medication prescribed.
“The problem is that antibiotics are geared to kill bacteria in isolated, individual states,” Berkes explains. “Antibiotics have never been tested to kill bacteria in biofilm states — never.”
Yet, according to the Centers for Disease Control, bacteria populate our bodies in a biofilm state about 80 to 90 percent of the time.
Monsul and Berkes will not say how much of their own savings have gone into the lab. They anticipate that their first product to be marketed will be a nasal spray to target rhinosinusitis — an inflammation of the nasal passages that makes life miserable and can invite complications like asthma.
“Inflammation is key,” says Monsul. “The microbiome that lives on us in a biofilm state has an interaction within our immune systems. An imbalance can lead to inflammatory bowel disease, skin issues, eye disorders. But this is a mass, an organ that you can manipulate. I think we found one little, tiny piece of that puzzle.”
A patent application they have filed covers a complex process of manipulation, to change the very makeup of a biofilm and render it less harmful. But because that process uses naturally derived compounds, the products they create can be sold over the counter.
“If we shoot initially for FDA approval” by the federal Food and Drug Administration, says Berkes, “it might be many years before my patients can take advantage of these. I would really like for them to be able to go to the store and say ‘Ah, here’s something I can take to feel better.’”
But she knows the value of patience, and the potential for failure.
“It’s hard to be the first,” she admits. “You make just as many mistakes as you can potentially make innovations. In fact, you innovate by making mistakes.”
Local connection If these products reach the market, Sarasota patients and doctors will have played a key role in their development. The small-town pipeline that provides Quorum Biofilm with interesting specimens is part of what lured lab director Greg Hebert from his job at a large biotech firm in the Northeast.
“What’s strange in the really large biotech companies is the bureaucracy of what people can and can’t do,” Hebert says. “The researchers in a school of medicine can’t obtain samples from their own colleagues in the clinics. But I have M.D.s from different fields feeding me these super clinically relevant samples. I’m taking these bacteria from people who have an infection they’ve had for years.”
Most microbiologists isolate different bacteria, says Hebert, but he and his staff mix them and watch the interaction. This kind of play can be distracting: Hebert and Berkes say the specimens in their lab are so rich with possibility that sticking to the research plan has been a challenge.
“We try to stay as focused as possible on the product pathway,” Hebert says. “But we’re regularly pulling up interesting things that we’re going to go back to. We’re currently sitting on an active ingredient that we isolated from a patient, exceedingly different from other bacteria. That one has to sit aside, because it’s not on our immediate route.”
Berkes and Monsul feel certain they are in the right place to pursue their outsized dream; they say Sarasota offers them a community sophisticated enough to nurture and value biomedical breakthroughs.
‘Let’s build a lab’
It was music, not molecules, that brought Berkes and Monsul together in 2003. They met at a rehearsal for the Sarasota Music Festival.
“The rehearsals are the best,” says Berkes, a former member of the Sarasota Youth Orchestra.
Her parents moved to Bradenton in 1976, and she grew up in Southwest Florida before going on to Williams College and the University of Florida’s medical school. A fellowship in allergy and immunology at the Scripps Institute in La Jolla, Calif., instilled a passion for research. But family drew her back to Sarasota and private practice — a choice between the lab bench and the bedside that seemed inescapable.
“At Scripps, I told the head of my division, ‘But I like seeing patients,’ and he said, ‘You’ll just have to get over that,’” she recalls.
Monsul came of age as a pianist in the Philadelphia area. He went to Drexel University, Hahneman Medical College and Yale University, followed by research fellowships at Johns Hopkins. When he decided to practice reconstructive surgery, specializing in the face and eyes, he chose Sarasota as “a perfect place to live.”
What began as small talk over Max Bruch’s symphonies quickly escalated to the common ground of microbiomial research. They started a family — Phinneas is now 4 and Julian almost 3 — and decided to open a medical clinic together, but with a twist. Monsul likens their lives to those of medical pioneers in earlier days, who invented new drugs and procedures in their home labs after hours.
They worked on the brutal patent application process, using Berkes’ ideas from her immunology studies. The goal was to create products that would combat the chronic, stubborn types of infection and inflammation that she saw her patients living with, and suffering from, for years.
The point of no return, says Berkes, came about two years ago, when they had already broken ground on what would be the Hawthorne Clinic.
“We were standing over in the old house next door that was my original allergy office,” she recalls. “Construction had started on this building, and Nic says, ‘Let’s build a lab over there.’ I went, ‘Really?’”
Now, when patients come to the clinic — also home to another allergist and two dermatologists — they can see through a glass wall the lab where researchers are studying biofilm specimens from Sarasotans like them.
“Now my patients are saying, ‘When is your stuff coming? When is it going to be in a bottle? When can I use your spray? When can I use the rinse? When is your skin cream going to be ready? We’re going as fast as we can,” Berkes says.
Says Duchenes, the USF biologist, “This science is at an early stage, and they’re probably out ahead of it.
“I actually don’t know of any other case where a private physician has put an emphasis on research to the extent they have done.”
Original article in the Herald-Tribune.