From Antivirus to Antibiotics, McAfee Searches for Last Cure

[herbsandhelpers]

From Antivirus to Antibiotics, McAfee Searches for a Last Cure

Allison Adonizio and John McAfee think they've discovered the next great antibiotic in the jungles of Belize. It's all natural. It's unpatentable. It's untested. And thanks to our business of medicine, it's not coming to America.

It grows wild along the shores of the New River, among the Mayan ruins of Lamanai, next to the lilies that are home to little yellow birds that skip across the pads. Inside Belizean plants used for generations by native healers, a suite of chemicals produce a natural "anti-quorum sensing" effect that interrupts bacteria's ability to communicate. And bacteria that can't communicate don't go pathogenically virulent.

At least that's the hope. If they're right, they've discovered the herbal equivalent of Neosporin.

Adonizio and McAfee, founders (along with technical chief Jim Zoromski) of Quorumex, have brought their "beta" production facility online next to the New River, complete with a production lab built by upriver Mennonites, who delivered the wooden building fully assembled by boat. A forty-foot loading dock has been cut into the riverbank, bulwarked by logwood poles that sprout new growth despite having been logged a couple months earlier. Things like to grow here.

We've traveled to the beta facility from McAfee's home in tony San Pedro on a chartered turboprop that lands on a gravel air strip among cane plantations. A gleaming white Ford F-150 and an unlicensed Jeep Wrangler wait with hired drivers. It's a tour for my benefit, in part—to disprove allegations, or at least implications—levied recently by Fast Company, that Quoremex is more hokum than hard science, a snow job financed by a man with a reputation for reveling in duplicity.

When McAfee pulls a bottle from "Topic-Qx" from his shirt and laments that I don't have a wound to test it on, I know how to remedy that. A minute later both of my arms are streaming blood, Topic-Qx is applied to the left incision, and the local workmen are shaking their heads and chuckling. [1]

Topic-Qx is Quorumex's first product, a topical solution of plant materials containing purported anti-quorum sensing properties. It's green, smells like mouthwash, and stings when applied. Dr. Adonizio later explains bashfully that the sting is from the alcohol in which the plant matter is suspended. Alcohol is the easiest spray-on solution for a fledgling company, but she worries that skeptics might chalk up Topic-Qx's antibacterial properties to the alcohol.

Minutes later we're motoring up the New River among the crocodiles towards—but not all the way to—Quorumex's forty-acre growing facility, where some of the plant reagents are being grown. On my left arm, a small rivulet of blood and the sticky green Topic-Qx, drying together in the sun.

To understand what makes Topic-Qx fight infection, you must first understand "quorum sensing", the method by which bacteria communicate.

In the 1960s, E.S. Kempner and F.E. Hanson discovered that Vibrio fischeri—a luciferin-producing bacterium that engenders bioluminescence in marine animals, like the Hawaiian bobtail squid—communicate using a bactera-to-bactera signaling system known as quorum sensing.

It takes a lot of energy to glow. It would be wasteful for a bacterium to glow alone, producing only a microscopic point of light. So Vibrio fischeri wait until there are lots of other Vibrio fischeri around before turning on their lights. And they know that there are lots of other Vibrio fischeri around by the amount of N-Acyl Homoserine Lactones (AHL) or autoinducers—little chemical postcards—present in their environment. The AHL or AL-2 autoinducers are produced by the bacteria themselves.

That's quorum sensing. The bacteria squirt chemicals into their environment as a way of saying "I'm here!" to other bacteria. And when enough of those chemicals are present, a quorum is reached, and something happens. Typically that something is cell division—virulence.

"Anti-quorum sensing" chemicals interrupt that communication. Many chemicals that exhibit anti-quorum sensing tendencies have been isolated from plants—plants have to fight off bacterial infection, too. One of the only commercial applications of anti-quorum sensing chemicals was derived from a Korean red algae that prevents biofilm build-up, making it useful as an anti-fouling agent in seawater pipes.

But even though anti-quorum sensing research has been going on for years, no one has ever commercialized a product as an antiseptic until Quoremex. Why not?

Toxicity, for one. That anti-fouling agent made from algae? Turns out the acylhomoserine lactone inhibitors used are toxic to humans. (Too bad. The plaque that forms on our teeth or the scum in our dog's water dish are also biofilms—ones we'd probably be happy to prevent forming.)

Stability has also been an issue. Making a shelf-stable anti-quorum sensing compound has proven difficult.

There's also the issue of which bacteria an anti-quorum sensing product affects. Different species of bacteria communicate using different quorum sensing signaling chemicals. What might interfere with one species' communication might not work on another.

Most practically, there's also the issue of necessity: Do we really need a replacement for topical antibiotics?

Allison Adonizio thinks we do. The thirty-year-old post-doc at Harvard wasn't ready to settle down in a Cambridge laboratory infecting nematodes with strains of pseudomonas bacteria to test plant compounds for anti-quorum sensing effects, despite having spent a decade in study of microbiology.

Adonizio had always been drawn to Belize, in large part because of the work of ethnobotanist Mike Balick, her "academic grandfather." Balick had traveled to Belize (and elsewhere) in the 1980s to study native healers and the plants used in herbal medicine. Adonizio used a free ticket she'd been saving and arranged for a two week retreat in Belize, bartering room and board from tourist hotels by offering to play folk songs on her guitar for guests. One of those guests was John McAfee, whose work with computer viruses—yes, he's that McAfee—had engendered an amateur's interest in biological pathogens. After many long discussions, Adonizio had found an unexpected benefactor. She returned to the U.S. to consider McAfee's offer of underwriting her research as a business partner in the company that would come to be known as Quorumex.

It wasn't an easy decision. She had a house to sell, a partner she'd have to leave behind, and the safe tedium of Harvard. And just to muddy the waters even more, Adonizio returned to discover that the National Institutes of Health had approved her grant proposal: she'd be funded to study quorum sensing disruption at home, too—if she wanted.

"I've always been a little more adventurous than most," says Adonizio. Two months later, she was headed to Belize, NIH grant ignored, lab equipment in tow.

Quorumex's charter is simple: Consult native healers about what plant medicines they use to treat certain afflictions; test those plants in the lab; if promising, harvest the plants for production.

The first suite of plants exhibit the same anti-quorum sensing properties around which Adonizio based her doctoral thesis, although there's hope that in time other treatments—anti-inflammatories, birth control, other solutions that have nothing to do with anti-quorum sensing at all—might be discovered. It's a simple story to understand, in part because since at least the '70s we've been inculcated by stories of miracle cures made from jungle plants. "We can't cut down the rain forest," goes the old saw, "What if we destroy the cure for cancer?"

In fact it's incredibly common for drugs to be developed from organic sources. [2] But Western pharmaceutical companies often isolate active compounds from the plant sources, both to make the mass synthesis of those compounds easier—and to make them easier to patent.

Quorumex's first product, the topical anti-quorum sensing agent Topic-Qx, is made from a proprietary blend of native plants, which makes it easier for the company to produce with relatively primitive facilities, but also creates a product that uses the fullness of chemicals inside its plant reagents. Since those plants evolved their own collection of chemicals which may be potentiating their antimicrobial effect in tandem, it might be better to mix them all together and let them work their magic as it has evolved inside the plant.

This has a curious side-effect: It makes Quorumex's products unpatentable —and they don't seem to care. Their manufacturing process is a trade secret. According to Quorumex, that's good enough.

Dozens of scientists around the world are researching anti-quorum sensing chemicals. I've spoken to several of them. Before my trip I asked them about the chances that Quorumex's products might have a practical use.

Most researchers gave a standard litany of cautions: shelf stability of compounds is difficult; toxicity is a factor; a broad spectrum of target bacterial species is unlikely.

I returned from Belize with six bottles of Topic-Qx—five in bottles with eyedroppers; one in an atomizer that I'd used on my own arm, all given to me by Quorumex to be distributed as I saw fit, with the special recommendation to find someone afflicted with a staph infection, on which Topic-Qx was said to be especially effective.

I offered three leading researchers in the field of anti-quorum sensing technique one of my samples for testing. They all refused.

The first chided me: "Isn't it your job as a journalist to be impartial?" he asked. "To take what they say at face value?" I didn't quite know what to say. I'd approached him expecting a reaction of overwhelming curiosity; instead I was being rebuked for my own incredulity.

By the time I tracked down Helen Blackwell, head of the Blackwell Lab at University of Wisconsin-Madison and referenced by many of her peers as one of two clear leaders in the field of anti-quorum sensing, I was girded for her refusal: "Test a competitor's product in my academic lab?" said Blackwell. "It would be a conflict of interest."

At this point my bafflement got the best of me. Why weren't any researchers the least bit curious about testing the efficacy of an over-the-counter, non-patented, plant-based product? I expressed this to Blackwell, who although apparently offended by my proposition, at least had the courtesy to clarify: She is also involved in a commercial endeavor to commercialize anti-quorum sensing treatments.

If she tested Quorumex's products in her lab it could jeopardize her ability to later patent and sell her own product.

John McAfee might be his own worst enemy—at least when it comes to the press. When I arrived in Belize, Quorumex staffers were still reeling from what they felt was a hit piece of McAfee in Fast Company, which painted McAfee as an arrogant huckster on the run from lawsuits in the United States, including one lawsuit that poses that McAfee's recklessness caused the death of two men in a flying accident.

McAfee had donated a boat valued at one million dollars to the Belizean Coast Guard. Fast Company implied this was to prevent the Coast Guard from harassing his fledgling water taxi service.

This accusation was one of the first things that McAfee brought up to me after my arrival in Belize. But first: John McAfee's wig.

Doug Maxwell, Quorumex's Vice President of Corporate Development—the business guy—picked me up from the airport in an electric golf cart, common land transportation in San Pedro, which is serviced primarily by boat. As we pulled away, Maxwell spoke of his experience in Belize—and San Pedro in particular. The town had its share of odd tropical characters, Maxwell explained, gesturing toward an old man shambling in the dusty street, stiff blonde hair obscuring his eyes.

"Like this old guy," said Maxwell. "I always stop and give him a ride." He slowed the cart. "Need a ride, old timer?"

The old man climbed onto the back of the golf cart, but even with sunglasses I could tell what the punchline was going to be.

"You're too easy to make," I said to McAfee. He laughed and took off the wig.

What would possess a person—the CEO of a fledgling biotech firm—to think this was the best way to introduce himself to an already skeptical reporter? Was he trying to put me on my heels, to suggest that it was prudent to question his truthfulness? Was he simply a playful person? Was he trying to enact some reverse-psychological gambit? Whatever his motivation, McAfee seemed genuinely perturbed that he'd been sniffed out so easily. When we arrived at a temporary laboratory in San Pedro, the gathered Quorumex employees gritted the same nervous smile: What has John gotten us into this time?

It's easy to understand why Fast Company and other publications have focused so frequently on McAfee rather than simply his endeavors—his pathos runs deep. McAfee's charming unabashedness to speak his mind about verboten subjects—sex, drugs, spirituality—is often tempered by how uncontroversial some of his positions actually are. McAfee has cultivated the air of a reluctant regent; the former devotee of Transcendental Meditation who just happened to become a millionaire; a man who left the United States not simply because of mistakes managing his fortune or to avoid lawsuits, but to retire to one of the most beautiful countries in the world; the man who can visit an island preserve and criticize the Audubon Society's unsightly blue signs for spoiling the pristine beach from the deck of his diesel-powered catamaran, the "My Freedom".

The boat that had gotten him so much negative attention after its donation? McAfee assured me as soon as I arrived that he had made the donation months before he had even considered operating a water taxi business, as if the timeline alone exonerated him.

Perhaps most galling is that both aspects of McAfee are concomitant—the grinning trickster who wants to give the impression of systemic mastery of both business and media exists alongside the compassionate, gentle man who thinks Crosby, Stills, Nash & Young were the pinnacle of pop music [3] and delights in discovering and sharing the weirdest anime and foreign cinema he can scrounge.

No matter how interesting McAfee may be, it's also clear that many of his business associates—from Quorumex employees to the faculty of the rural Galen University, where McAfee sits alongside several board members made nervous by his recent hyperbolic claims of persecution by Western pharmaceutical giants—would prefer that McAfee conduct his eccentrism a little less eccentrically.

"I'm 65-years-old. I'm not going to live forever." McAfee sat in the wind porch of his beachside home, a glass vase filled with sand serving as a cigarette ashtray—his only chemical vice. "And one of the largest tragedies of life as I see it is the use of power to collect wealth. I'm not talking about individuals, but collectives. Governments. America. Russia. The developed world."

"Belize has an army of about 300 men. No jets. No nukes. No bombs. AR-15s and a couple bazookas is about the extent of their arsenal. They are truly powerless. Belize is merely one example of nearly one hundred countries on this planet that are totally at the mercy of the developed world. I can't see any way that it's going to improve. The schism continues to widen with every passing year. To me, to do anything at all, to improve the stature of a country by using something unique [is positive]."

"But the paradigm is of a world that is in desperate need of new medicines, a world in which science has divorced itself from historical knowledge. In most cases, the chemicals constructed in a lab seem in the scientific eye to be superior in every way to some healer in the backwoods using a leaf from some unknown plant in an attempt to cure disease. There's no overlap. Or very little overlap."

It seems a bit haphazard—and despite McAfee's prostration, "bioprospecting" is hardly a new development in pharmaceutical research. But systematically interviewing native healers and then working with them for in-field testing—Quorumex's current plan for trials incorporate both native and formally trained healers, distributing Topic-Qx across Belize and Central America, using low-tech record keeping to track results—that could be a new direction.

"How long have the Mayans been here? Seven thousand years?," McAfee continued. "Some people say five thousand? Certainly a long time. And they have lived within this ecosystem and tested on their own bodies and the bodies of others many of these substances. You try to identify those that may have actually benefit. You bring them into the lab and say, do these have any anti-quorum sensing properties. If so, how potent are they? If you combine this plant with this plant and then put them in a petri dish, how potent is that? So you do all the science. You do it as best you can. And you do it within the context of the culture in which you are building your company."

That culture is Belize. And some of the locals are wary. My interview with the heads of Galen University, a tiny university near San Ignacio in Belize's Cayo District, underlined the danger of McAfee's chaotic approach to public relations. In early May, Belizean television news crews ambushed McAfee at the Belize City Airport as he returned from the United States and prompted him to allude to persecution from pharmaceutical companies, "...because if I succeed in what I am doing here in Belize then it will put many of these large international companies out of business."

Sitting in the warm office of university chairman Dr. Louis Zabaneh and (now) President Dr. Nancy Adamson, I posed the question: Had McAfee's behavior made them question their university's affiliation with Quorumex? (McAfee had made a donation to the school and served on its board; Dr. Adonizio has her lab in a small building at Galen in which she conducts most of her primary research, troubleshooting a finicky "Minus 80" freezer full of cell cultures while singing along to Jonathan Coulton songs.)

Dr. Zabaneh's response showed typical Belizean pragmatism: Certain "safeguards" would be put in place to protect the university.

"And perhaps," considered Dr. Zabaneh, "a small royalty."

Does Topic-Qx work? That's all that matters. In a marketplace of untested supplements that are more often than not completely ineffective but still wildly successful commercially, only time—and testing—will tell. Even an antibacterial treatment of modest efficacy could be an invaluable tool, especially manufactured inexpensively, renewably, and unencumbered by the patent system of the developed world. Unlike most pharmaceutical explorers, Quorumex is a Belizean company employing a large number of Belizean workers. (Although its principals are U.S. citizens—or in the case of McAfee, a former citizen.) It is free to pursue herbal cures the American pharmaceutical industry finds too unprofitable to test.

As I discussed these things with McAfee, staring at the beautiful beaches of San Pedro, now sparsely populated, the worldwide economic doldrums shuttering many resorts and keeping tourists away, I felt my arm itch. With an idle scratch, I inadvertently removed the scab from my left arm. After a week of daily applications of Topic-Qx, the cut on my left arm hadn't gotten infected at all.

But neither had the cut on the right.

[1] A second cut on my right arm was meant to serve as control, although I later discovered it wasn't cut as deeply. I'm a bad scientist.
[2] Paclitaxel (Taxol), a chemotherapy drug used to treat cancer, is derived from the bark of the Pacific Yew. So, hey.
[3] A fairly reasonable position, in this reporter's estimation.