The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Commemorative Booklet for CAAT 20th Anniversary Symposium

Henry Was Right

By Lisa Libowitz and Carol J. Howard

"...audacity must be fused with attention to detail, with an awareness of social attitudes, power relations and scientific possibilities."

Henry Spira, 1980

If any single quote could capture CAAT's first 20 years, this is the one.

It took audacity to think a new center, staffed initially by two people, could change the way the scientific world does business.

It took audacity to insist that scientists and activists must work together as partners.

And it took audacity to be the "bad guys," telling activists that laboratory animals remain necessary in research and telling scientists that inhumane science is lousy science, no matter what knowledge it yields.

Audacity alone, however, wouldn't have gotten much accomplished, if the time hadn't been right for change. Twenty years ago, the phrase "not tested on animals" was unknown. There was no "alternatives field." And yet Europe, ahead of the United States as usual on social issues, had begun to think about issues of animal rights and animal welfare. In this country, Henry Spira put the suffering of laboratory animals in the headlines and made everyone take notice.

Henry taught an entire generation about power relations. He taught some of you, as well, in his gentle, polite, but persistent way. And Henry was a master of detail. He did his homework. He realized which companies would be vulnerable, and how.

He targeted the cosmetics industry. And so through the CTFA, some of you established CAAT.

Yet even Henry didn't fully grasp the scientific possibilities for the fledgling center he helped create. It took a little-known book by two British scientists, two men who had come together briefly for just one project, to give CAAT a vision for the future and a scientific philosophy that would shape the next 20 years.

That philosophy was simple but radical: humane science is the best science. According to Bill Russell and Rex Burch, humane science is achieved through adherence to a process known as the "3Rs": Replace animals with other methods when possible. If animals are necessary, reduce their numbers to the absolute minimum. And refine methods to eliminate, or at least minimize, any pain or distress. We call these approaches "alternatives." CAAT wasn't the first to discover this philosophy, nor were we the only organization to embrace it. We've had our share of "audacious" company: FRAME, ZEBET, NCA, CCAC, ANZCAART, UCCAA -- Could Russell and Burch have imagined the "children" their brief union would produce? Or the scientific revolution their collaboration inspire?

For there has been a revolution, led by organizations devoted to scientific excellence and animal welfare. Today we have in vitro methods in use (or in development) that, as part of a testing strategy, allow us to predict which chemicals will cause irritation or an allergic response when they come into contact with your skin or your eyes, which chemicals will cross the blood-brain barrier, and which may harm your nervous system or your unborn child.

We have new models for the cornea that may soon help us understand which eye injuries will heal, and how quickly.

We even have an in vitro test to tell us whether the shellfish we harvest from the sea will make us sick.

And this handful of examples represents only the methods CAAT has helped develop. Every day, around the world, companies and academic research labs devote millions of dollars to new in vitro methods.

For those who work in the personal care products industry, this is all old news. Today, almost no one uses animals for cosmetics tests anymore. Avon, Mary Kay, L'Oreal, Gillette, Procter & Gamble -- the list of those who have stopped testing their products on animals in the last 20 years (or so) is long.

Did they simply bow to political pressure? Bad press? Hardly -- although animal rights' groups served as a catalyst for change. No, in case after case, it took a transformation of scientific possibilities into in-house research programs, extramural grant programs, or some combination of both to develop the new approaches that allowed them to change.

Progress has been driven by money as well as science: in Europe, most of the funds came from government, in the United States, from industry. But these distinctions blur as companies and regulatory agencies on both sides of the Atlantic realize that funding alternatives is critically important to the future.

The In Vitro Testing Industrial Platform, a consortium of European companies with an active interest in alternative methods, lists 124 in vitro protocols on its web site. Many of these have yet to be universally accepted as "validated," but they are already in use, in companies eager to reduce or eliminate animal testing.

In vitro studies aren't exactly new -- they date back to Anton von Leeuwenhoek's observations of protozoa, sperm, and bacteria under his self-made microscope in the 17th century. In our lifetimes, many advances in human health -- the discovery of penicillin, the development of the polio vaccine -- were made possible by research in vitro.

On the other hand, in vitro science and, in particular, the development of in vitro methods to predict and measure toxicity, has come into its own in the last 20 years. Far more than half of the presentations at major meetings of the Federation of American Societies for Experimental Biology and the Society of Toxicology, for example, now focus on in vitro studies.

Think about this: Just a few years ago, the National Cancer Institute used as many as 4.5 million rodents a year to screen chemicals for anti-tumor activity. The animal model, however, was far from ideal, and NCI sought an alternative for scientific reasons. After much internal review and debate, NCI scientists switched to the use of a cell culture screening system incorporating human cancer cell lines. The program now uses between 500,000 and 1 million mice per year -- reducing animal use by more than 80 percent.

In vitro methods have served as alternatives in more arenas than product safety tests, too. Consider the production of monoclonal antibodies: for years the standard approach was to harvest these antibodies from painful tumors artificially stimulated in mice. Today, we have in vitro production methods capable of providing almost any MAB in any amount.

The alternatives field today is more than in vitro methods, however. Much more.

We have statistics programs to help scientists choose the right number of animals, companies and organizations devoted to the efficient production of animal and human cell lines for in vitro tests, and animal-sharing programs that reduce the use of animals within an institution. We have high throughput screening programs that allow us to test massive numbers of potential new drugs.

We have databases devoted to the identification and alleviation of pain. We have whole scientific meetings devoted to the definition of distress. We have new technologies that allow us to predict the course of an infection in a mouse, treat the infection at an early stage, and study the treatment in a living, whole animal -- without pain.

Can you remember when it was still acceptable to use curare without anesthesia to immobilize a research animal during surgery? Forty years ago it was common; today it would be unimaginable. Twenty years ago, the LD-50 was widely used; today, it is history.

We have manikins and models, videos, virtual reality, and computer simulations that allow schools to train future doctors and veterinarians, dramatically reducing the number of animals sacrificed in these efforts. There is no scientific reason a child ever need cut open a frog again.

We have journals and symposia and too many newsletters to read. Our burgeoning field even has produced sub-specialties, in database development, information dissemination, literature searches. In environmental enrichment, statistical analysis, and humane endpoints. In pain identification and management.

We have a triennial World Congress.

We also, finally, have established centers for validation of alternative methods in both Europe and the United States. While our approaches to validation vary, our underlying goal is the same: to provide tests that are reproducible and valid for use as alternatives. Validation, of course, continues to be our "Sisyphus," as Horst Spielmann pointed out at the Third World Congress -- our seemingly eternal challenge of finding ways to gain universal acceptance for alternative methods.

And we have the steady march of science coupled with technology: molecular biology and in vitro toxicology. Without this march, this partnership between science and technology, these advances would not exist.

We have had our failures, too. Perhaps the greatest one, as Frank Baker pointed out at the last CAAT Advisory Board retreat, has been our failure to replace the Draize eye test. Despite millions of dollars devoted to research, a score of new methods, endless meetings and validation efforts, and the collaboration of companies and organizations around the world, we still haven't gotten rid of Draize. We failed, he said, because we forgot to put the science first -- to understand the mechanisms underlying our endpoints.

Perhaps, with so many recent advances in our understanding of the eye, we will celebrate the end of Draize at the next CAAT anniversary banquet.

Another failure, perhaps, has been our inability to sell the concept of alternatives to many in academic research. Scientists who are perfectly comfortable using phrases like "best practice" and "good experimental design" object to the terms "refinement" or "reduction." Many of them strenuously insist that alternatives do not exist.

Yet these scientists are our partners for the future. Genomics and proteomics are both the hottest areas in biology and the key to many new alternative methods. New technologies, and the application of older technologies to animal research in new ways, will allow us to collect data with far fewer animals and may truly allow us to design painless protocols. Who would have believed, 20 years ago, that the same chemical that allows a firefly to light up the night one day would allow us to trace the course of disease in an animal? Who knows which discovery today will change how -- or whether -- we use animals 20 years from now.

Scientific possibilities, Henry said. And social attitudes.

We need to find better ways to talk to each other, to use language that will communicate without alienating, that will allow us to achieve common goals. We need to do a better job educating our scientists, because they ultimately are responsible for the use of animals in their laboratories.

In the Netherlands, anyone about to touch a research animal must spend eight hours a day, five days a week, for three weeks first learning about animal care and alternatives. In the United States, many organizations barely pay lip service to educating their scientists and staff, even within some of the most renowned institutions of higher learning. We need to find a way to make the Netherlands model work here.

We have many challenges ahead. The pharmaceutical industry is eager for more predictive, more humane tests that will allow them to evaluate both toxicity and effectiveness at earlier points. We still do too little to address pain in research animals, and almost nothing for distress. Although a range of alternatives exists in education, we haven't done the job of putting them into enough classrooms.

We still use primates.

Many scientists and even leaders in the alternatives field believe transgenic animals hold the key to eliminating the use of higher mammals. If this is the case, they will be a powerful alternative. Yet many animal welfare questions exist in the use of these animals. If, as Nobel Laureate Peter Medawar said, "...the appropriate use of animals is our best hope to eliminate their need in experimentation," then concern about animal welfare issues in the use of transgenic animals seems not only wise but also essential.

Twenty years later, Henry is still right. "If people are going to develop alternatives, it's the people in the research community who will be developing alternatives," he said. "If you're going to get the regulatory agencies to change their requirements, it's going to be animal researchers who are the ones who are going to do it...

"These are the folks that you need to be serious about change."