From ANIMAL PEOPLE, October 1997:
JENKINTOWN, Pa.––Monoclonal
antibodies, the American Anti-Vivisection
Society has long quietly gambled, will some
day become as notorious as the LD-50 and
Draize chemical safety tests.
Then, AAVS believes, outcry may
force regulatory and procedural changes in
monoclonal antibody production that could
save a million mouse lives a year, largely
through adoption of an alternate production
method that AAVS funding has helped perfect.
Last April, after years of preparation,
AAVS took the first big step toward
making monoclonal antibodies a public issue,
introducing a campaign titled “Antibodies
Without Animals.” It drew favorable note
from the trade magazine Lab Animal, and
from a variety of scientific, technological,
and legal journals, but none from mainstream
media––and none at the time from A N I M A L
PEOPLE, because we knew we’d need more
space to explain what it was all about than was
immediately available.
“Monoclonal antibodies are used in
essentially every field of human and veterinary
research, and in diagnosing and treating many
cancers, bacterial and viral infections, and
other ailments,” AAVS eventually explained
in a succinct campaign summary. “They are
especially useful because they attack specific
antigens within the body, where they are used
to identify and/or destroy foreign materials.
Unfortunately, many laboratories still use the
outdated and painful ascites method of producing
monoclonal antibodies. When animals
are used,” tumor cells are injected into their
abdominal fluid. This, AAVS continued,
“causes ascites––a painful swelling of the
abdominal peritoneal cavity. It is estimated
that more than one million animals,” most or
all of them mice, “undergo this torment each
year in the U.S.
“Since 1975,” AAVS added, “scientists
have known that monoclonal antibodies
could be produced without the use of animals,
but animal use proliferated in small-scale production.
In the 1990s, the AAVS Alternatives
Research & Development Foundation provided
funds for experienced scientists to develop
an efficient, humane laboratory method of
monoclonal antibody production: gas-permeable
tissue culture bags. These specially
designed plastic bags grow a desired antibody
when the correct cells and culture medium are
placed in them. The bags make more monoclonal
antibodies in less time for less money,
and eliminate the contamination which results
from the use of ascites. Many other alternatives
are available.
“The alternatives are so simple, reliable,
and economical,” the AAVS campaign
summary emphasized, “that the Netherlands,
Germany, and Switzerland have banned the
use of animals. In April 1997, the European
Centre for the Validation of Alternative
Methods published its recommendation that
the entire European Union prohibit animal
monoclonal antibody production. The EU,”
AAVS declared, “is expected to follow the
ECVAM recommendation.”
The U.S. lags behind, AAVS indicated,
in part because Animal Welfare Act
enforcement regulations exclude mice (as well
as rats and birds) from the definition of “animal,”
a bit of bureaucratic gerrymandering
maintained by the USDA Animal and Plant
Health Inspection Service to avoid having to
attempt broader enforcement. The exclusion
of mice means, essentially, that ascites monoclonal
antibody production involves animals
who are for the most part not protected by law.
Further, the AAVS campaign summary
said, the AWA “requires all animal laboratories’
Institutional Animal Care and Use
Committees to ask experimenters whether they
considered alternatives before proposing to
experiment on animals. Unfortunately, experimenters
in the U.S. are not required to use
alternatives whenever possible. European law,
in contrast, mandates the use of alternatives
whenever they are valid and obtainable.”
PETITIONS
Trying to expedite progress toward
the universal use of non-animal monoclonal
antibody production, AAVS on April 23 filed
legal petitions with both the USDA and
National Institutes of Health.
The USDA was asked to “Modify
the current definition of animal that excludes
mice, rats, and birds from coverage under the
AWA,” and to issue a new regulation prohibiting
“the use of animals in the production
and use of monoclonal antibodies.”
The NIH was asked to issue a similar
prohibition, to formally confirm the validity
and reliability of alternative monoclonal antibody
methods, to encourage acceptance of the
alternative methods by “proposing a regulation
requiring all NIH scientists and grantees to utilize
the alternatives,” and to “initiate a
training program at NIH to train scientists
in the use of the alternatives.”
Ron DeHaven, USDA Animal
and Plant Health Inspection Service acting
deputy administrator for animal care,
responded first, on August 6.
“In 1990,” DeHaven recited,
“the USDA analyzed the impact of bringing
rats, mice, and birds under regulation.
The USDA concluded that there
were 1,735 facilities registered under the
AWA that use rats, mice, and other
species, and estimated that there were an
additional 2,324 unregistered research
facilities that use only rats and mice.If
these facilities were regulated, they
would represent a 96% increase in the number
of animal research sites under USDA inspection
authority.”
This, DeHaven continued, would
have cost an additional $3.4 million a year,
out of the total 1990 APHIS budget of about
$9 million. APHIS funding in the years since
has not kept pace with inflation. “We are now
inspecting 9.3% more facilities than in 1992
with 15 fewer inspectors,” DeHaven said.
“We believe that the additional workload associated
with the regulation of rats, mice, and
birds would severely compromise our ability
to protect the species we currently cover.”
DeHaven reminded AAVS that, “In
enacting the AWA, Congress specified that
the USDA is not to interfere with the design or
performance of research or experimentation.
To prohibit an often used, proven research
procedure such as monoclonal antibody production
in animals is an action that the USDA
does not have the legal authority to take.”
DeHaven did “concur that in vitro
monoclonal antibody production is fast becoming
the state of the art.”
NIH RESPONDS
NIH director Harold Varmus replied
to AAVS on September 18. “Many in vitro
methods are scientifically acceptable, reasonable
and practically available for the production
of monoclonal antibodies,” he agreed.
“In the U.S.,” Varmus asserted further,
“the NIH has been and will continue to
be a major supporter of the studies that
have led to the development of acceptable
alternative methods for producing
monoclonal antibodies. The NIH has
strongly encouraged the use of alternative
methods for producing monoclonal
antibodies among the investigators it
supports through the world.”
However, Varmus continued,
“Despite many advances in understanding
the process of antibody formation and cell
culture technologies, the state of the science
has not yet reached the point where a total ban
on the use of the mouse ascites method can be
justified, whether or not NIH has the regulatory
authority to issue such a ban.”
Varmus further argued that the existing
AWA and Public Health Service Act regulations
are sufficient to “ensure that in vivo
monoclonal antibody production in mice is not
performed unnecessarily.”
Thus, Varmus concluded, “The
NIH has determined that it is not appropriate
to prohibit the use of mice in monoclonal antibody
production.”
Varmus rejected the AAVS petition
one week before the start of a two-day conference
on “Alternatives in Monoclonal Antibody
Production,” which AAVS executive director
Tina Nelson said “was organized by NIH after
the AAVS petition was filed, and is in direct
response to the actions requested.”
Nelson personally took over public
communications concerning the monoclonal
antibody campaign after former AAVS director
of special projects David Cantor, only
recently recruited from PETA, was laid off in
June. Cantor predicted in the autumn edition
of The Civil Abolitionist, a leading independent
antivivisection newsletter, that the AAVS
“Antibodies Without Animals” campaign “will
do well,” eventually.
First, though, activists must understand
it.
