Though neither
is imminent, both are on the drawing board, as are vaccines to combat other
addictions. While scientists have historically focused their vaccination
efforts on diseases like polio, smallpox and diphtheria — with great success — they are now
at work on shots that could one day release people from the grip of substance abuse.
“We view this as
an alternative or better way for some people,” said Dr. Kim D. Janda, a
professor at the Scripps Research Institute who has made this his life’s work.
“Just like with nicotine patches and the gum, all those things
are just systems to get people off the drugs.”
Dr. Janda, a
gruff-talking chemist, has been trying for more than 25 years to create such a
vaccine. Like shots against disease, these vaccines would work by spurring the
immune system to produce antibodies that would shut down the narcotic
before it could take root in the body, or in the brain.
Unlike
preventive vaccines — like the familiar ones for mumps, measles and so on — this type of injection
would be administered after someone had already succumbed to an addictive drug.
For instance, cocaine addicts who had been vaccinated with one of Dr. Janda’s
formulations before they snorted cocaine reported feeling like they’d used
“dirty coke,” he said. “They felt like they were wasting their money.”
It’s a novel use
for vaccines that has placed Dr. Janda, who is 54, in the vanguard of addiction
treatment. Because addiction is now thought to cause physical changes in the
brain, doctors increasingly advocate medical solutions to America’s drug problem,
leading to renewed interest in his work.
“It’s very
fashionable now,” said Dr. Janda, seated in a black leather chair in his
office. “When we started doing this 27 years ago, it wasn’t.”
In July, Dr.
Janda’s lab — 25 researchers, most of graduate-school age — made headlines when
it announced that it had produced a vaccine that blunted the effects of heroin
in rats. Rodents given the vaccine didn’t experience the pain-deadening effects
of heroin and stopped helping themselves to the drug, presumably because it
ceased to have any effect.
But as has often
been the case in Dr. Janda’s career, the breakthrough came on the heels of a
setback: A Phase 2 clinical trial for a nicotine vaccine that was based largely
on his work was declared a failure this summer when people receiving the drug quit smoking at the same rate as people receiving
a placebo.
To this day,
despite many promising breakthroughs, not one of Dr. Janda’s vaccines has won
approval from the Food and Drug Administration. For despite many successes in
the lab — including promising animal tests — the vaccines have yet to produce
consistent results in humans during clinical trials.
“It’s like
having the carrot right in front of the horse,” he said. “The big problem
plaguing these vaccines right now is difficulty predicting in humans how well
it’s going to work.”
Or, he added,
“maybe I’m just unlucky.”
The scientific
principle behind Dr. Janda’s vaccines is, as he put it, “simplistically
stupid.” Much like vaccines against disease, they introduce a small amount of
the foreign substance into the blood, causing the immune system to create
antibodies that will attack that substance the next time it appears.
The difficulty
is that molecules like cocaine, nicotine and methamphetamine are tiny — much
smaller than disease molecules — so the immune system tends to ignore them. To
overcome that, Dr. Janda attaches a hapten — which is either a bit of the drug
itself, or a synthetic version of it — to a larger protein that acts as a
platform. The last part of the vaccine is an adjuvant, a chemical cocktail that
attracts the immune system’s notice, effectively tricking it into making
antibodies against a substance it usually wouldn’t see.
“It’s not like
some magical premise,” Dr. Janda said. “And the beauty of it is you’re not
messing with brain chemistry.”
The contrast, he
said, is to medications like Suboxone or methadone that are currently used
to treat heroin addiction. In addition to blocking heroin’s effects, the
medications induce a mild high in many patients.
Dr. Janda says
he has tried and failed to make vaccines against alcohol and marijuana abuse.
In the case of alcohol, he said, ethanol molecules proved just too small to
attach to the protein that would deliver the immunity. And in the case of marijuana, the main ingredient that produces the high — tetrahydrocannabinol, or
THC — hides too well inside the body.
He has also
tried formulating a vaccine against obesity. Rather than block a foreign
substance, that vaccine would block the effects of a peptide hormone produced
by the stomach called ghrelin that signals hunger in the brain. So far, a
version of the vaccine has been shown to lower food intake in animals, though —
again — it’s unclear whether it will work in humans.
Even so, addicts
and their families are clamoring to get into Dr. Janda’s clinical trials. He
says he gets e-mails every week from addicts asking to be included. He has had
to turn away parents who showed up at his office with their drug-addicted
children after reading about his work.
“What am I supposed to do, go in the
lab and pull it out of the refrigerator and inject you?” he said. “I guess it’s
been so devastating in their families that they’re looking for anything, and
there’s just nothing out there. It’s really sad when you see these types of
things.”
Despite the
disappointments, some scientists predict that Dr. Janda will succeed. No less
an addiction expert than Dr. Nora Volkow, director of the National Institute on
Drug Abuse, calls him a “visionary” who saw the opportunity to treat addiction
with medicine decades before most. Indeed, one reason that her institute is a
chief source of Dr. Janda’s financing is Dr. Volkow’s belief that his work will
eventually produce a marketable vaccine.
“Now many people
say, ‘Yes, of course’ ” to the idea of treating drugs through vaccines, Dr.
Volkow said. “But that took many years, and he traveled the road when there was
a lot of skepticism.”
Today, the
scientists who are working to create vaccines against narcotics include Thomas
Kosten at the Baylor College of Medicine and S. Michael Owens at the University
of Arkansas. Dr. Kosten has had limited success with a cocaine vaccine, while
Dr. Owens is focused on vaccines for methamphetamines.
All three
researchers say they are hobbled by a lack of interest — read: financing — from
pharmaceutical companies in vaccines for any drug other than nicotine,
presumably because there is little money to be made in a shot given once every
six months, and because such companies aren’t eager to associate their brands
with drug addicts.
And yet Dr.
Janda’s lifelong pursuit of vaccines against narcotics began not with some
painful family struggle with addiction, but in a simple request in the 1980s
from one of the Scripps Institute’s former corporate partners.
“They were
interested in the whole antibody area,” he said. “They kind of approached me
and said, ‘Could you make antibodies to a drug of abuse?’ So we embarked on
this.”
Dr. Janda spent
many years trying to bring his own vaccines to market. In the ’80s and ’90s, he
helped start some small pharmaceutical companies that patented and tested his
work, with varying degrees of success. One burned through $60 million of venture capital with nothing to show for it; another sold for $95 million in 1999, but
“due to bad management and bad splits, I ended up with about enough money for a
case of beer,” he said — even more disappointing, perhaps, for a man with a
taste for expensive bourbon.
These days, Dr.
Janda prefers to publish his results in scientific journals and let others try
to bring the vaccines to market.
He is quick to
caution that taking away someone’s ability to get high off of one drug hardly
cures them of their addiction problems. There’s nothing to stop a vaccinated
cocaine addict, for example, from turning to methamphetamines.
Like any
anti-addiction treatment, his vaccines are simply meant as “a crutch for people
wanting to go into abstinence,” Dr. Janda said. “The whole thing with addicts
is you have to want to get off the drug, or it’s not going to happen.”
He is also wary
of ethical issues posed by his work. Today, a recovering cocaine addict will
pass a drug test just days after getting clean. But once vaccinated, that
person could be tested for antibodies for up to six months, alerting employers
to his struggles with addiction.
“Before a parent
takes a kid into college, can she take him in for a round of vaccines against
all drugs?” asked Jenny Treweek, a researcher at Janda Laboratories who is
working on a vaccine for Rohypnol, otherwise known as the date-rape drug. “Some teenagers might have a
real problem with that.”
It’s questions
like that — and the desire to solve the molecular puzzle he’s set up for
himself — that motivate Dr. Janda to spend seven days a week in his lab, he
said. He spends much of that time tweaking the components of his vaccines —
trying different proteins or haptens, adjusting the adjuvants — hoping to hit
precisely the right formula.
“If I vaccinated
three people and they all got the same” immune response, he said, “then you
would have a really straightforward shot how to move things forward.”
But with nearly
30 years of tweaking already under his belt, he seems increasingly resigned to
the idea that it might not be he who eventually moves it across the finish
line.
“I figure I have
eight or 10 years left,” he said. “If something doesn’t go in eight or 10 more
years, then it’s someone else’s turn.”
Por DOUGLAS QUENQUA – The New York
Times
