Accessed 4th
September 2013
The Revolutionary New
Birth Control Method for Men
By Bill
Gifford
April 26, 2011 |
12:00 pm |
The promising procedure, developed by scientist Sujoy Guha, is in
late Phase III clinical trials in India, which means approval in that country
could come in as little as two years.
Photo: Anay Mann
One Saturday in
January 2010, Devendra Deshpande left his home in
the Delhi
suburbs and drove into the city to get a vasectomy. He was 36 years old,
married with two young kids, and he thought it was time.
He arrived at the hospital around
midday and met Hem Das, then the hospital’s chief vasectomy surgeon. Das had an
interesting question for Deshpande. Rather than receive a traditional
vasectomy, would Deshpande like to be part of a clinical trial for a new
contraceptive procedure?
Das explained that the new method did
not have some of the drawbacks associated with a regular vasectomy. First,
sperm would still be able to escape Deshpande’s body normally, which meant he
would be free of the pressure and granulomas that sometimes accompany a
vasectomy. More important, it could be reversed easily, with a simple follow-up
injection.
“I am normally not adventurous when it
comes to getting myself operated on,” Deshpande deadpans. But the new method
sounded good to him, and according to the published studies he read on his
smartphone in the waiting room, it seemed safe. He gave his wife, Vinu, a call,
and although she sounded nervous on the phone, she said she was fine with it.
Deshpande decided to try the experimental method.
When his turn came, he lay down on the
table, and an orderly draped his lower body with a green surgical cloth that
covered everything but his scrotum. Then Das moved in with a needle containing
a local anesthetic. Once the drug had taken effect, Das gathered a fold of
skin, made a puncture, and reached into the scrotum with a fine pair of
forceps. He extracted a white tube: the vas deferens, which sperm travel
through from the testes to the penis. In a normal vasectomy, Das would have
severed the vas, cauterized and tied up the ends, and tucked it all back
inside. But rather than snipping, Das took another syringe, delicately slid the
needle lengthwise into the vas, and slowly depressed the plunger, injecting a
clear, viscous liquid. He then repeated the steps on the other side of the
scrotum.
The procedure is known by the clunky
acronym RISUG (for reversible inhibition of sperm under guidance), but it is in
fact quite elegant: The substance that Das injected was a nontoxic polymer that
forms a coating on the inside of the vas. As sperm flow past, they are
chemically incapacitated, rendering them unable to fertilize an egg.
If the research pans out, RISUG would
represent the biggest advance in male birth control since a clever Polish
entrepreneur dipped a phallic mold into liquid rubber and invented the modern
condom. “It holds tremendous promise,” says Ronald Weiss, a leading Canadian
vasectomy surgeon and a member of a World Health Organization team that visited
India
to look into RISUG. “If we can prove that RISUG is safe and effective and
reversible, there is no reason why anybody would have a vasectomy.”
But here’s the thing: RISUG is not the
product of some global pharmaceutical company or state-of-the-art
government-funded research lab. It’s the brainchild of a maverick Indian
scientist named Sujoy Guha, who has spent more than 30 years refining the idea
while battling bureaucrats in his own country and skeptics worldwide. He has
prevailed because, in study after study, RISUG has been proven to work 100
percent of the time. Among the hundreds of men who have been successfully
injected with the compound so far in clinical trials, there has not been a
single failure or serious adverse reaction. The procedure is now in late Phase
III clinical trials in India, which means approval in that country could come
in as little as two years.
But RISUG is garnering interest beyond India. Every
week, Guha’s inbox fills with entreaties from Western men. They’ve heard about
RISUG on Internet forums or from occasional mentions in newspaper and magazine
articles. Some of them even volunteer to travel to India, offering themselves as lab
rats. Guha puts them off gently but politely; for now, the trials are open only
to Indian men. Everyone else has to wait. “Our options suck,” fumes one
frustrated correspondent, a Florida
real estate manager who emailed Guha a few years ago. “I’d gladly put my balls
on the chopping block for the benefit of mankind.”
He may yet have that opportunity.
Thanks to a novel collaboration between Guha and a San
Francisco reproductive health activist, RISUG could soon be on the
road to FDA approval in the US.
In both the East and the West, the need
for better contraceptives couldn’t be clearer. India
will soon surpass China
as the world’s most populous nation; in the poorest Indian state, women bear an
average of nearly four children. Cheap to produce and relatively easy to
administer, RISUG could help poor couples limit their families—increasing their
chances of escaping poverty. In the developed countries, it would help relieve
women of the risks of long-term birth-control-pill use and give men a more
reliable, less annoying option than condoms. About half of all pregnancies in
the US
are unplanned. Come up with a better contraceptive and the likely results are
all good: fewer unwanted kids, fewer single parents, and fewer abortions.
Marooned in the
marshes of West Bengal, 20 hours by rail from New Delhi, the small city of Kharagpur is a likelier spot for a prison
than for one of the world’s most elite technological institutions. In fact,
under the British, it was the site of the notorious Hijli detention camp, where
rebel intellectuals were imprisoned. After India’s independence in 1947, Prime
Minister Nehru pointedly established the first Indian Institute of Technology
on the site; today, a steady stream of recruiters from Microsoft, Sun, and
Facebook make pilgrimages to the campus in search of the brightest Indian talent.
Guha was a member of IIT’s fifth
entering class, in 1957—attending school where his uncle, a radical writer, had
been imprisoned years earlier. After Guha reached retirement age in 2002, he
returned to Kharagpur from Delhi. Driving around campus today in his 1967 Fiat
sedan, Guha points out buildings that he has reclaimed from the jungle and
retrofit with labs and workshops—a kind of rogue operation within the
university walls. A former mining department building now serves as a RISUG
production facility, where his staff mixes up batches of the polymer used in
the procedure.
Besides RISUG, Guha is also developing
an artificial heart based not on a human heart but on that of a cockroach,
which has 13 chambers. His artificial version has five chambers in its left
ventricle, which allows it to step up pressure more gradually, inflicting less
stress on the mechanism and materials than a conventional design. In another
building on campus, he is raising goats that will eventually receive the
experimental hearts.
A birdlike man with clear, olive-toned skin and an elegant manner,
Guha seems to have been transported from another century. In a sense, he was:
Born in 1940, before independence, he still uses Britishisms like see
here and good
man. He doesn’t waste oxygen on small talk, so when he does speak
you know to listen. Nevertheless, he has a lively sense of humor, and when
something amuses him he’ll burst into a delighted, high-pitched laugh. At age
70, he still does not need glasses, which he attributes to his daily eye
exercises. Every night, he jogs 2 miles around the IIT campus carrying a
rolled-up belt to ward off stray dogs. “Every part of the body must be
exercised,” he says.
Guha has a penchant for simple yet profound inventions. As a young
graduate student at St. Louis University during the mid-1960s, he devised an
electromagnetic pump that had no moving parts; instead, it used the ionic
charge of seawater to create force. As he explained to a visiting reporter from Popular
Science, his pump could also serve as a silent engine for
ships—or nuclear submarines. A version of that electromagnetic “caterpillar
drive” is, of course, at the center of the film The
Hunt for Red October. As has happened with medical discoveries
from penicillin to Viagra, Guha was searching for something entirely different
when he stumbled across the idea that became RISUG. In the early 1970s, at the
behest of the government, Guha was looking for a way to purify water in rural
pumps. Treating the water chemically could be too expensive and
infrastructure-dependent; he needed a method that was permanent, safe, and
cheap. Then a hotshot young professor at the IIT campus in Delhi, Guha figured
out a way to line the pumps with a substance that would kill bacteria without
depleting itself.
But the project was never completed. In
the mid-1970s, India awoke to its urgent population crisis, and the
government’s priorities changed. Guha refocused his work on the field of
contraception. He soon realized that the same basic concept could work inside
the pumping mechanism of the male anatomy—the vas deferens.
In 1979, when Guha was 39, he published
a simple four-page paper that outlined the basic concept of RISUG. He had begun
experimenting with a common polymer, called styrene maleic anhydride. The SMA
was mixed with a solvent called dimethyl sulfoxide, or DMSO, and injected into
the vas deferens of 25 male rats. Each male was placed in a cage with three
breeding females. After six months, none of the female rats had become
pregnant. (In the control groups, all of the females became pregnant.) Guha and
his team also showed that the substance could be flushed out with a simple
injection of DMSO. Normal fertility soon returned.
They refined the method and tried it
successfully in monkeys, whose reproductive physiology is close to that of
humans. As a high-molecular-weight polymer, the mixture was not absorbed by the
body, nor was it flushed out by the flow of seminal fluid. It anchored to the
inner wall of the vas, and in laboratory tests it appeared to be nontoxic.
Plus, it seemed to retain its effectiveness indefinitely, like a magnet. In
1989, it was injected into a human subject for the first time. It worked.
HOW IT WORKS
1.
A reversible vasectomy begins like a regular vasectomy: The surgeon
makes a small puncture in the scrotum and extracts the vas deferens, a slender
white tube. But rather than severing the vas, the doctor injects the vessel
lengthwise with a nontoxic, stable polymer mixture. The process is repeated on
the other side.
2.
The polymer, a compound of styrene maleic anhydride
(or SMA, an ingredient in floor polish) and dimethyl sulfoxide (or DMSO, a
common solvent) anchors itself to the tiny folds in the vas, clinging to the
tissue. Sperm and other fluids can still get through, avoiding the backup
pressure sometimes associated with a vasectomy.
3.
As sperm pass through the vas, the positively
charged polymer interacts with the negatively charged sperm, rupturing cell
membranes and damaging sperm tails. The sperm are thus incapable of fertilizing
an egg. Sperm production and male hormone levels are not affected.
—Bill Gifford
Illustrations: Teagan
White
Ever since the birth
control pill was approved by the FDA in 1960, scientists
in the West have been looking for a male equivalent. It’s been a rocky road, in
part for biological reasons: Hormonally, it’s much easier to control a single
monthly event like ovulation than to try to stop the endless onslaught of
sperm.
An equivalent “pill” for men would
somehow have to stop sperm production without neutralizing their libido or
erectile function. Pharmaceutical companies and government agencies have sunk
millions into hormone-based contraceptive research that has yielded few viable
products.
And then there’s RISUG. Rather than
shutting down sperm production, with the potential side effects that entails,
it acts more like a tollbooth on the sperm superhighway. As the negatively
charged sperm pass by, they are essentially zapped by the positive charge of
the SMA polymer. So a RISUG-injected man will still ejaculate millions of
sperm, but most will be dead: tails snapped off, cell membranes ruptured.
As a contraceptive, RISUG faces a far
more difficult road to approval and commercial acceptance than, say, a new
antidepressant medication. While an antidepressant would be considered a
success if it worked in 75 percent of patients, a contraceptive like RISUG will
be compared to a conventional vasectomy, which works more than 99 percent of
the time. Furthermore, it has to be free from the serious side effects that
were common with early experimental hormone-based male contraceptives. And it
cannot cause birth defects down the line—ever. “Nobody wants another thalidomide,”
says Ron Weiss, the Canadian vasectomy doctor.
In human tests, RISUG performed
extremely well. In the first clinical trial of 17 men, published in 1993, all
the subjects who received above a certain dosage became azoospermic—that is,
they produced no viable sperm. By 2000, it was in Phase III clinical trials in
India, the final stage before approval. The compound was injected into 139 men,
and the early results looked promising. In May 2002, it was announced that
RISUG was on track for approval in India and would be rolled out on a limited
basis within six months.
At around the same time, a World Health
Organization team came to visit Guha’s lab in Delhi and examine his data. This
itself was a triumph: It meant RISUG was finally on the international radar.
Weiss, a long-time advocate of the process, was with the group and performed
the operation. But the five-person team came away skeptical.
In its report, the WHO team agreed that
the concept of RISUG was intriguing. But they found fault with the homegrown
production methods: Guha and his staff made the concoction themselves in his
lab, and the WHO delegation found his facilities wanting by modern
pharmaceutical manufacturing standards. Furthermore, they found that Guha’s
studies did not meet “international regulatory requirements” for new drug
approval—certain data was missing. The final recommendation: WHO should pass on
RISUG.
But within India, at least, RISUG still
seemed to be headed for approval. Then, in mid-2002, after Guha and his team
had spent years cultivating allies in India’s infamous bureaucracy, a new
health minister took over, and the Indian Council for Medical Research
(equivalent to the US National Institutes of Health) put the brakes on the
trials. Before new patients could be injected, the NIH asked that some of the
subjects be analyzed further and that basic toxicology studies be redone.
Of particular concern was the
possibility that SMA—a resin found in floor polishes and automobile body
panels—is toxic. Styrene and maleic anhydride are indeed toxic separately. But
Guha points out that while sodium and chlorine are also toxic individually, “we
take sodium chloride all the time.”
The analogy holds for RISUG: Lab tests
show that SMA is nontoxic. Guha had convinced the Indian government of the
compound’s safety back in the ’80s; now he had to do it all over again, and he
was exasperated. Mysterious press reports appeared, stating that some patients
had experienced “complications”—which turned out to be nothing more than
transient scrotal swelling. In the press, Guha suggested that his doubters had
deliberately slowed RISUG to make way for competing hormonal injections
developed by foreign companies. True or not, it didn’t make him any friends.
“It was not a problem of science,” says
A. R. Nanda, an early supporter of RISUG and former secretary of the department
of family welfare. “It was a problem of politics and ego.”
In the middle of it all, Guha reached
mandatory retirement age, leading him to leave his post at IIT Delhi, close to
the levers of power. He retreated to Kharagpur, in the jungle. But instead of
giving up, he dug in, remembering what an old mentor had told him early in his
career: that any new scientific idea had to experience four stages of reaction,
which correspond to the name of the Hindu god Rama.
“In the first instance, there will be
rejection—R,” Guha says, sitting in a folding chair in his fluorescent-lit lab.
“If you pursue it, there will be anger. You have to persist. Then, a phase of
mellowing will come: ‘Ah, yes,’ people will say. ‘Maybe there’s something to
it!’ Then, if you still have patience and courage, will come a stage of
acceptance.”
From his home base in
Ottawa, Ronald Weiss marvels at the possibilities of RISUG.
“If you’re looking for the better mousetrap, this is it,” he says. “I have
received emails from men all over the world kind of champing at the bit to get
RISUG.”
Weiss had been trying to bring the
process to Canada starting in the late ’90s. But when he presented his notes
and Guha’s published studies to the regulators at Health Canada, they shot him
down. Guha’s studies did not meet their standards, they said. All of them would
need to be redone. “Essentially, we were in a situation where we would have to
start from zero,” Weiss says. “We would have to redo every single study to get
approval. And I didn’t have millions of dollars at my disposal.”
He looked around for a corporate
partner but found no takers. Unlike birth control pills, which must be used
daily, sometimes for years, RISUG is a long-lasting, low-cost treatment (the
syringe could end up costing more than the material it injects).
“Pharmaceutical companies are not interested in one-offs,” Weiss says. “They’re
interested in things they can sell repeatedly, like the birth control pill or
Viagra.”
Reluctantly, Weiss gave up on his plans
to commercialize the procedure in North America. But a woman named Elaine
Lissner picked up where he left off. Lissner’s interest in male contraception
started in the late 1980s, when she was an undergraduate at Stanford. She took
a seminar there from Carl Djerassi, one of the inventors of the female birth
control pill, who once famously declared that no woman then alive would see a
male contraceptive in use during her reproductive lifetime.
Lissner found herself asking the same
question that millions of men and women have asked: Why not? Why should there
be plenty of options for women and none for men? In college, she’d seen the
reproductive havoc wreaked on her friends by a world that places most of the contraceptive
burden on women. She wrote a paper outlining what was being done about
nonhormonal methods of male contraception, which could be summed up in two
words: not much. There were actually, she discovered, men who soaked their
testicles in scalding hot water, thinking (correctly but painfully) that it
would reduce their fertility. There had to be a better answer.
She founded a small nonprofit advocacy
group called the Male Contraception Information Project to push for better male
options. By 2001, she had concluded that RISUG was the most promising new
development out there and began tracking its ups and downs closely.
By 2009, though, she had grown
frustrated with the lack of progress on RISUG in India. Luckily, she was in a
position to do something about it. At the beginning of the real estate boom,
she’d invested a small amount of money in her father’s construction company,
which had become wildly successful building houses around Reno, Nevada. She
parked the profits in a small private foundation called Parsemus and set about
putting money behind RISUG.
In February 2010, Parsemus bought the
international rights to the RISUG technology from Guha and IIT Kharagpur for
$100,000. They had worked closely together for years, and she had earned his
trust. She also hired Gary Gamerman, a consultant who specializes in
shepherding products through the complex FDA approval process. The plan was to
get RISUG OK’d in the US, perhaps even before it hit the market in India.
“What’s the alternative?” Lissner asks. “Just keep complaining?”
Gamerman told her what she already
knew: She would have to begin at the beginning—by making a batch of SMA/DMSO
compound in a certified pharmaceutical plant in the US. Later this year,
Lissner and her team will begin basic toxicology testing, and if the material
passes muster—as it always has in the past—then they will test it in rabbits,
hoping to repeat Guha’s results on rats from 1979. Oh, and it won’t be called
RISUG anymore. One of Lissner’s first acts was to name the compound Vasalgel.
But to get human clinical trials going will take more funding than the $500,000
that Lissner has budgeted; Gamerman estimates that the whole approval process
could cost $4 million to $5 million. “There should be tons of interested
potential partners,” she says, reeling off a list that includes Planned
Parenthood, USAID, organizations like the Bill & Melinda Gates Foundation
and the Susan Thompson Buffett Foundation (which have invested in population
control and women’s health), and a group called WomanCare Global, run by a
former pharmaceutical exec.
“If it’s no longer a crazy Indian idea
and it’s something that’s working in India and in rabbits in Ohio and in the
first 20 men in the US,” Lissner says, “then there’s got to be a point where
there’s just no excuse for a Gates or a Buffett not to get on board.”
Just this past year, in fact, Guha
received a $100,000 Gates Foundation grant to pursue a variation of RISUG in
the fallopian tubes as a female contraceptive. More important, the Gates grant
marked an important milestone for Guha, an international validation of his
work. It’s been a long time coming—and an important step toward the final stage
of Rama: acceptance.
Meanwhile, after a repeat of some of
the basic toxicology tests (and another shift in the political wind), Phase III
trials have resumed in India with full government support. Five hundred
subjects are expected to be enrolled at 10 study centers around the country.
One of those patients was Devendra Deshpande, the man who read about the safety
of RISUG on his cell phone before undergoing the procedure.
A software engineer for an American
company, Deshpande is slim and sharp-featured, dressed in the global nerd
uniform of neat burgundy sweater and faded jeans. He and his wife, Vinu, a
broad, cheerful woman, are part of the burgeoning new Indian middle class. They
live in Noida, a Delhi suburb, in a complex of new two-story town houses. They
have a car and a tidy, comfortable home that resounds with the cries of two
energetic young children, a boy and a girl.
An hour after the procedure started,
Deshpande was on his way home. He had two band-aids on his shaved scrotum, plus
a handful of painkillers and a course of ciprofloxacin—Indian doctors do not
mess around when it comes to prescribing strong antibiotics. He used the pain
pills for a couple of days and felt some tenderness and swelling for a week but
no other side effects. There was no recurring scrotal pain, as sometimes
happens with a vasectomy; on most days, he forgot that the stuff was in there.
Which, if you think about it, is the
goal of any contraceptive (not to mention the theme of endless Trojan condom
advertisements): You forget about it. No one had to take a pill every day.
Nobody had to have bloating or other side effects. No “accidents.”
And regarding what Indians
euphemistically term “the family life,” he says, there was one big plus: He
didn’t have to continue using condoms for three months, as is recommended after
standard vasectomies.
“It was business as usual,” Deshpande
says. Vinu giggles. “Probably better!”
