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(Written
for Minnesota Technology Magazine, Fall, 2001)
MINNESOTA TECHNOLOGY 2001 TEKNE AWARD WINNER
PROFILE
INNOVATION: LIFE SCIENCES
3M
Pharmaceuticals, 3M Company
In 1981, two colleagues at 3M Pharmaceuticals-chemist John
Gerster and biologist Richard Miller-started working to find
a more effective way to treat herpes. In July 1997, that
collaboration bore marketplace fruit with 3M's introduction
of Aldara™, a topical cream proving effective in treating
genital and perianal warts.
Yet, more important than its potential to improve the lives
of the countless people worldwide who endure recurring
genital and perianal warts is the science behind the family
of immune-response modifiers (IRMs) discovered and developed
by Gerster, Miller and 3M Pharmaceuticals. Some are calling
the work a medical breakthrough, thoroughly innovative in
how it helps a body to stave off certain viral maladies by
helping cells enhance their own immunities. Indeed, these
new-to-the world therapeutic agents show promise as
treatments for a wide spectrum of ailments, from genital
warts and herpes to skin cancer and other cancerous and
pre-cancerous conditions.
Just as notable are the economic implications. Some
estimates place Aldara's sales potential well in excess of
$100 million, which could be just a precursor to what some
anticipate to be a $1 billion-plus family of products. All
this resulted from an effort that at one time faced
cancellation.
In the early 1980s Gerster created compounds designed to
treat herpes. Standard procedure first tests such compounds
using in vitro cell cultures; if they show promise, the
compounds advance to in vivo animal testing. The problem:
Gerster's compounds showed little in vitro promise.
The story might have ended here, but Miller decided to take
another look at Gerster's compounds and advanced them into
animal testing despite their poor in vitro showing. To
everyone's astonishment, the animal tests showed a level of
activity as striking as it was unexpected. However, in a
stunning setback, 3M canceled the project in January 1983 to
concentrate resources on another pharmaceutical that
appeared more immediately promising and closer to market.
Miller convinced management to let him and Gerster keep
working on IRMs. Their results continued to reinforce
earlier promise-so much, that 3M reinstated the IRM program
in July 1983, with a significant increase in resources.
Gerster and Miller shifted their focus from herpes to
genital and perianal warts because the IRM compound proved a
potent inducer of interferon-a cytokine protein used by
cells of the immune system to communicate with each other,
and shown to have some effect on genital and perianal warts
caused by the human papillomavirus. Traditional treatments
attempt to provide antibodies by injecting human gamma
globulin from blood, or attempt to trigger an immune-system
response by injecting vaccines. Extreme cases involve
surgical or chemical removal, which is oftentimes painful,
resulting in destroyed tissue and scarring
In contrast, IRMs such as 3M's -which are applied
topically-cause the body to generate its own protection by
producing interferon and other cytokines. These proteins
actually help the immune system control and/or eliminate the
virus-infected cells, while producing a level of immunity
from the infecting virus. Applied topically, Aldara™ cream
induces the production of interferon and other cytokines in
the body, causing the warts to disappear, and, in most
cases, stay away.
Anecdotal evidence abounds concerning other potential uses
for immune-response modifiers. A clinician in Germany used
Aldara™ cream to treat a genetic disorder, epidermodysplasia
verruciformis, which caused warts to break out over more
than half of a patient's body. Photographs of the patient's
hands showed 100 percent remission of the warts after Aldara™
cream had been applied for 12 weeks.
Dr. Stephen K. Tyring, professor at the University of Texas
Medical Branch at Galveston, said that Gerster and Miller's
compounds "are beginning to show promise in a spectrum of
other viral diseases such as herpes simplex viruses as well
as non-viral diseases such as basal cell carcinoma (the most
prevalent cancer in the world)." Dr. Kenneth F. Trofatter,
Jr., professor, Department of Obstetrics, Gynecology and
Women's Health at the University of Minnesota Medical
School, wrote: "Programs have recently begun to explore the
activity of these drugs against cervical dysphasia, another
human papillomavirus-related condition that is the precursor
for more than 500,000 cases of cervical cancer seen annually
around the world."
What had begun as collaboration between a
chemist and a biologist has given the world a unique medical
technology of demonstrated benefit today, and suggesting
exceptional promise for tomorrow. Its impact on treating
viral infections could be as profound as when sulfa drugs
gave way to penicillin and opened the door to antibiotic
therapy for bacterial infections. According to Trofatter,
the work of Drs. Gerster and Miller has the potential to
change the very basis of medical practice over the next
half-century.
-Greg Irsfeld
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