The Laboratory of Molecular and Integrative Urology at the Albert Einstein College of Medicine is a startling, almost radical study in the aesthetics of the unsexy. Its six dim-lit labs are drab and boxy, and filled with the kind of whirring, buzzing equipment that might make a man fear for his gonads. There are scalpels for slicing and incubators for heating and large Cryostar freezers for extreme, minus-70-degree freezing. In one lab, rats get snipped down the middle so teeny-tiny catheters can be inserted into their bladders—not the most arousing sight.
And yet, the small Bronx laboratory is on track to make erectile history, to go down in the urology books—if not girlie mags and geezer journals—as one of the sacred shrines of male potency. Thanks to the promise of an experimental new gene therapy, it could become birthplace of the world’s first genetically engineered erection.
“We think that we’ve hit on something,” said Dr. Arnold Melman, the eminent urologist whose serves as director of the lab and chair of the Albert Einstein department of urology, as he sat in his office on a recent Wednesday morning. “[Gene therapy] has been a disappointment … so if this works, it has a chance of being one of the success stories. It would be a gigantic step forward.”
Leave it to the hard-on to revolutionize medicine.
Erectile dysfunction is an unlikely candidate for gene therapy, the brave, super-hyped practice of inserting genes into a patient’s cells to treat a disease. To begin, it has proved largely disappointing—impotent, one might say—as a near-term solution to the body’s most devastating diseases. And because of its potential risks, scientists have embraced it almost exclusively as a treatment for serious, pulse-stopping ailments like cancer—not as a treatment for lifestyle conditions.
But for some six years now, Dr. Melman and his small hive of scientists have been plugging away to bring the promise of gene therapy to the war on impotence. With the help of funding from a few wealthy patients, they tried and erred. And eventually stumbled on hMaxi-K, a treatment that uses what is known as the Slo gene to restore vim and vitality to the vertically challenged penis. Each injectable treatment is expected to last as much as six months.
The gene therapy is still in its early, test-and-tweak phase. But just last month, the scientists celebrated the completion of the first hMaxi-K clinical trial, a two-and-a-half-year process that demonstrated that the treatment did not turn its 11 human guinea pigs into two-headed, hyper-virile monsters—or, at least, that it didn’t seep into sperm, spark an allergic reaction or inspire any other “adverse events.” And within the next few months they plan to embark on a 100-patient, phase-two trial to show that the drug actually works. If all goes according to plan, they hope to begin marketing the world’s first genetically modified erection treatment within five to six years.
“The concept is fascinating. And if it works, it’s great,” said Dr. Andrew McCullough, director of male sexual health at New York University Medical Center and one of the two principle investigators in the hMaxi-K clinical trial. “It would be huge; it would be as big as Viagra was when it hit.”
Eight years after Pfizer’s little blue pill galvanized the impotence industry, the quest for a more perfect erection continues—in part out of scientific fervor, in part out of the promise of profit, and in part because the extant drugs (including Levitra and Cialis) are not quite the wonder pills they were hailed to be.
For all the hype, today’s holy trinity of erection drugs work in only 60 percent of patients, and even then the side effects—like headaches, indigestion and blue-tinted vision—can dull the enthusiasm of the most eager user. More recently, reports of blindness in as many as 50 Viagra-takers have sparked an F.D.A. investigation into the billion-dollar love drug. And then there’s the minor problem of timing: The awkward, unromantic fact that after the naughty urge arises, it can take as long as 35 thumb-twiddling minutes for old pokey to rise and shine.
Such design flaws have created an opening for scientists like Dr. Melman and a handful of his fellow erectile-dysfunction pioneers. At present, at least two other labs are working on their own gene-therapy elixirs—the labs of Drs. Jacob Rajfer and Nestor Gonzalez-Cadavid at U.C.L.A., and of Dr. Wayne Hellstrom at Tulane University (though Dr. Hellstrom’s work has been largely stalled since Hurricane Katrina). Only Dr. Melman, however, has succeeded in taking the next experimental step: reproducing the gene-therapy tests in the human male.
(In the wake of his early success with E.D., Dr. Melman is also preparing to launch an hMaxi-K trial for overactive bladder, one of several so-called smooth-muscle-cell conditions that include asthma, hypertension and diabetes as well as impotence. Dr. Melman believes they could all conceivably benefit from hMaxi-K someday.)
“As in everything in science, every group is competing with the other,” said Dr. Gonzalez-Cadavid when asked whether the news of Dr. Melman’s early research success concerned him. But, he added, he was also glad for his competitor’s progress, since it demonstrated that other erectile-dysfunction warriors were on the right path.
“This,” he said, “will be [an] incentive for our groups and other groups to go to the clinical area.”
THE SCIENCE OF THE GENETICALLY ENGINEERED erection—a science that is at once rigorous, elegant and mind-scramblingly involved—begins with a paradox: In order to make a penis hard, the smooth muscle cells of the shaft need to be soft, or relaxed.
In the case of many impotence sufferers, however, these smooth muscle cells have a hard time relaxing. They remain tense, rigid, unable to respond to the stimuli that set their sex machinery in motion. And that is where gene therapy comes in. With the injection of the Slo gene, the smooth muscle cells produce a protein that, in turn, sets off a chain of reactions that cause the cells to relax.
Or, as Dr. McCullough explained, “Basically, the guy comes in, he has a tourniquet put around his penis, you give him the injection, you leave it on for 30 minutes, you take it off, end of story.” For the next three to six months, his penis should be able rise and fall on command.
This, at least, is the operating theory.
Thus far, only 11 brave men with moderate to severe erectile dysfunction have dared clamp on the tourniquet and try out the treatment. These men were volunteers in the phase-one clinical trial that began in January 2004 and ran, in six-month increments, until this past June 6. Because the trial was meant to test safety rather than efficacy, the drug was administered at cautious, lower-than-treatment-level doses, which didn’t generally produce Johnny Wadd erections—or, in some cases, any erections at all. But in the two men who received the higher doses, the medicine seems to have waved its magic, cell-relaxing wand, because, well, they got their hard-ons.
“They said it was like they were young men again. They were having spontaneous, normal erections,” said Dr. Melman in his precise, Bronx-inflected accent—though he also warned that these results could not be read as proof of success. “It’s only a phase-one trial with a limited number of people, so you have to have very limited claims,” he said.
But even if later trials should prove wildly successful, will men really submit to having their penises pricked and injected every six months? Will the injections actually work in the diverse, flaccid masses? And is it really safe?
Ever since an 18-year-old boy with a rare metabolic disorder died in a gene-therapy trial in 1999, the bold new biotechnology has been tainted with the risk of deadly, unintended consequences. These tend to be rare, but in several trials, patients have come down with everything from serious immune-system reactions to cancer—hardly the kind of risks one wants to take for a hard-on.
Dr. Melman and his peers brushed off these concerns, insisting that hMaxi-K was safe, in large part because it is designed somewhat differently than most gene therapies. While many treatments rely on weakened viruses to guide genes into cells, hMaxi-K uses something called, appropriately, naked DNA to do its maneuvering. And this slinky, simple, naked DNA hasn’t (thus far) been linked to dire diseases.
“I would say [there are] no issues about safety,” said Dr. McCullough, the phase-one investigator.
Even so, at least one doctor wondered whether the public would be willing to overlook all the ghoulish what-if scenarios, to stake their health on the promise of an erection.
“I think the issue of an injection that works for six months—that’s going to require some fairly heavy-duty safety data, long-term safety data,” said Leonore Tiefer, a veteran sexologist and clinical-psychiatry professor at N.Y.U., launching into a monologue about potential side effects and the unpleasantness of injections—particularly the unpleasantness of injections.
“It’s not a trivial thing,” she said. “The penis looks a little delicate, so to be shooting things into it just raises worries.”
And yet, for all the sexologist’s skepticism, men might prove all too willing to brave a few pricks and prodding.
“I put in a manuscript once that it [was] the fountain of youth,” said Dr. Melman of his hMaxi-K therapy. “We’re talking about modifying the aging process.”