At the In Defense of Animals web site, IDA reprints a list of “Animal Rights Victories in 1999” that was compiled by Michael Markarian of The Fund for Animals. Not surprisingly, one of the “victories” on the list never actually happened. Midway through the list is this item,
The NIH banned the use of mice in monoclonal antibody production, saving the lives of up to one million mice per year, and admitting that animals feel “pain, distress, or discomfort.”
The only problem is that the NIH did not ban the use of mice to produce monoclonal antibodies and the reason it decided against a ban goes to the heart of the debate over animal research.
What’s a monoclonal antibody? It is a method of mass producing specific antibodies. Researchers take tumor cells that will reproduce forever if given the proper nutrients and fuse those with cells that produce specific antibodies. The result is called a hybridoma which is then cloned to produce large numbers of cells that will produce specific antibodies.
The ability to produce monoclonal antibodies is a direct result of years of animal research and animals are essential for the first phase of the process, the creation of a hybridoma. Typically, a hybridoma is created by immunizing an animal (almost always a mouse), and then obtaining immune cells from the animal’s spleen. These cells then get fused with the tumorous cancer cell so that they can reproduce indefinitely.
Nobody suggests that there is an animal alternative to this process. Regardless of how they are later cultivated, monoclonal antibodies require the use of an animal during the initial phase.
But cultivation of these cells is another story. Researchers are able to growth monoclonal antibodies either in vivo or in vitro.
The in vivo model involves injecting animals (again, almost always mice) with hybridomas. The hybridomas reproduce and produce a fluid called ascites on the animal’s abdomen. The fluid contains a large number of monoclonal antibodies that can then be harvested for further study.
The in vitro model involves culturing the hybridomas in one or another culturing medium. Note that this also involves the use of animals (though not whole animals), with the most popular method of culturing being using fetal bovine serum.
In 1997, the American Anti-Vivisection Society petitioned the National Institutes of Health to prohibit researchers receiving NIH grants from using the whole mouse method to produce monoclonal antibodies. Since in vitro methods were available to produce the antibodies, AAVS argued, animals were suffering needlessly.
Contrary to what IDA apparently believes, the NIH rejected an outright ban. Instead, after commissioning a study of the issue from the National Research Council, it issued a policy that for NIH grants in vitro methods of monoclonal antibody production should be the preferred method of production.
Using whole mice to produce monoclonal antibodies is still allowable under NIH, however, it in vitro methods are not suitable for one reason or another.
The National Research Council that looked into the issue found that there is a continued scientific need to produce monoclonal antibodies in mice. According to its 1999 report (which is available here),
There are several reasons why the mouse method of producing mAb cannot be abandoned: some cell lines do not adapt well to tissue-culture conditions; in applications where several different mouse mAb at high concentrations are required for injection into mice, the in vitro method can be inefficient; rat cell lines usually do not efficiently generate mAb in rats and adapt poorly to tissue-culture conditions but do produce mAb in immunocompromised mice; downstream purification or concentration from in vitro systems can lead to protein denaturation and decreased antibody activity; tissue-culture methods can yield mAb that do not reflect the normal modification of proteins with sugars, and this abnormality might influence binding capacity and other critical biologic functions of mAb; contamination of valuable cell lines with fungi or bacteria requires prompt passage through a mouse to save the cell line; and inability of some cell lines that do adapt to tissue-culture conditions to maintain adequate production of mAb poses a serious problem. For these reasons, the committee concludes that there is a scientific necessity to permit the continuation of the mouse ascites method of producing mAb. However, note that over time, as in vitro methods improve, the need for the mouse ascites method will decrease.
Maybe someday there will be no need to use mice to mass produce monoclonal antibodies, but that day is not yet upon us.
At the time the NIH changed its policy, the American Anti-Vivisection Society estimated that about 90 percent of monoclonal antibody production done as part of NIH grants would move to in vitro models, with the other 10 percent still being performed in vivo. So far, this writer is unaware of any research on just how much the new policy affected the landscape of monoclonal antibody production.
But, one thing that did not happen was an outright ban of antibody production in mice as In Defense of Animals and The Fund for Animals claimed.
Animal Rights Victories in 1999, Compiled by Michael Markarian of The Fund for Animals For the 2000 Summit for Animals. In Defense of Animals, 2000.
Animal protection group precipitates historic policy change at NIH. Press Release, American Anti-Vivisection Society, December 22, 1999.
Monoclonal Antibody Production. National Research Council, 1999.