|Animal Testing: The Beginning of the End?|
A scientific revolution is underway that promises to spare millions of animals from suffering and death.
|Skin and eye irritancy testing is frequently |
conducted on rabbits.
At issue is how best to assess the potential health hazards of the tens of thousands of chemicals to which humans are exposed.
Crude animal tests have been the mainstay of toxicity testing for decades, notwithstanding incredible advances in understanding human biology over the years.
Incremental gains have been made in developing non-animal methods of testing, especially in Europe over the last 10-15 years. However, recent developments suggest that the quiet evolution of alternative methods will turn into a fast-paced revolution in testing methods. And the driving force is coming from an unlikely source—the U.S., which to date has largely been simply reacting to developments in Europe.
In June, the prestigious U.S. National Research Council (NRC) issued a report calling for a paradigm shift in toxicity testing, away from animal tests which, in some cases, were decades old, towards cell-based methods that model the early stages of toxicity in the human body.
In February of this year, three agencies within the federal government announced that they would cooperate with each other to begin conducting the research and development necessary to implement the NRC vision.
This revolution is especially welcome to proponents of non-animal methods within the U.S., who have long lamented the slow pace of progress here. Our frustration was recently highlighted in a front page story in the Washington Post, which was critical of U.S. government's past efforts and pointed to the NRC vision as the way forward.
|An estimated 20 million rats and mice are |
used in the U.S. in research and testing each year
Outdated, Time-Consuming and Costly
Millions of animals are used every year in the U.S. and abroad to assess the potential health hazards of cosmetics, soaps, household cleaners, pesticides, drugs, and other chemicals and products to which people might be exposed.
In these assessments, chemicals are applied to the animals' eyes and skin or injected into their bodies, or the animals are forced to ingest or inhale them.
The animal protection community has long criticized animal testing methods as inhumane and scientifically flawed. Instead of the traditional animal methods, we have advocated that industry and government establish active programs to develop alternative methods.
These new methods follow the "Three Rs" approach, which entails replacing animals in specific tests (the ideal solution) or, in the meantime, reducing animal numbers in specific tests, or refining tests to lessen animal suffering.
Both industry and government have begun to make strides in advancing alternative methods, but progress has still seemed frustratingly slow in light of the magnitude of the problem. Over the past decade the pace has quickened, particularly in Europe.
But the recent developments in the U.S. have offered the hope that sophisticated, non-animal methods could be developed that could replace virtually all animal-based toxicity testing in as little as ten years.
The NRC's report, Toxicity Testing in the 21st Century: A Vision and a Strategy, calls for a bold new approach that would limit animal testing to specific challenging situations for which the emerging paradigm was not yet suited. But over time, the role for such "targeted" animal testing would diminish as the new approach is progressively developed and implemented.
The NRC report builds on its earlier analysis, issued in 2006, that characterized the current testing paradigm as slow, expensive, technologically dated, and not up to challenges of the modern era, as well as costly in terms of animal use and suffering. The HSUS was proud to have its vice president for animal research issues, Dr. Martin Stephens, serve on the NRC committee that produced these two reports.
Experts Weigh In
Of course, reports alone have no hope of changing conditions for animals unless they are implemented. The HSUS had been meeting with representatives of key federal agencies to see if they were interested in implementing the NRC vision.
The agencies included the National Institutes of Health Chemical Genomics Center, the National Toxicology Program, and the Environmental Protection Agency. Indeed, in February, these three agencies announced that their "Memorandum of Understanding" to begin conducting the research and development necessary to implement the NRC vision.
The announcement was by made by high-profile government scientists in prestigious venues, which signaled its importance. Two key players included Elias Zerhouni, director of the NIH, and Francis Collins, director of the NIH's National Human Genome Research Institute and the prime mover behind the NIH's historic Human Genome Project.
|Guinea pigs have been widely used|
in laboratories for skin allergy tests.
Zerhouni, Collins, and others made the announcement during the annual meeting of the American Association for the Advancement of Science.
The announcement coincided with an article on the collaboration by some of the same scientists published in the prestigious AAAS journal Science.
Coverage of the announcement was extensive and provided further encouragement to animal protectionists hungry for a big breakthrough in the animal testing field. USA Today's Elizabeth Weise was one of the first reporters to cover the story.
According to Weise, NIH's Collins characterized the current paradigm as "… expensive and time-consuming." It also, "used animals in large numbers, and it didn't always work."
Weise also gives a flavor of the modern "high-throughput" testing already in place at the NIH's Chemical Genomics Center. Citing Christopher Austin, the Center's director, she notes that "thousands of chemicals can be tested at one time under a method that uses a 3-by-5-inch glass tray with 1,536 tiny wells, each a fraction of a millimeter across.
A few hundred human cells grown in a test tube go into each well. Then, guided by a computer, the testing machine drips a different chemical into each well. After a while, the machine shines a laser through each well to see how many cells remain. A computer analyzes the toxicity of each compound based on how the cells react."
Weise then contrasts the new paradigm with the old by citing the director of the NIH. She writes: "By comparison, it's taken the EPA 30 years to rigorously test 2,500 potentially toxic compounds, says Elias Zerhouni...Animal testing won't disappear overnight, but the agencies' work signals the beginning of the end, Zerhouni says," echoing a quote by The HSUS's Stephens earlier in the article.
The announced collaboration will surely be a milestone in the development of non-animal methods.
By itself, it has the potential to be a core element of progress. However, its impact can be greatly magnified by strategic alliances with other key players, including the European Centre for the Validation of Alternative Methods and interested corporations such as Procter & Gamble and Unilever.
The HSUS estimates that to fully realize the NRC vision within 10 years would take an overall commitment between industry and government of $200 million per year ($2 billion total).
The NRC vision and the government's collaborative effort to implement that vision offer the promise of a revolution in a field that otherwise clings to tradition.
|Botox and The LD50 Test|
The Washington Post's recent front page story on animal testing, Testing May Kill Animals Needlessly, opens with a profile of an HSUS priority target. The infamous LD50 test, developed in the 1920s, has been all but abandoned as a safety test.
However, it continues to be used to assess the potency of Botox Cosmetic and similar products that are based on the powerful botulinum toxin.
In this application of the test, mice are injected with samples from each new batch of the toxin, in order to determine the dose that kills 50% of the animals. The "Lethal Dose 50%" or LD50 is then taken as a measure of a batch's strength. The animals experience a wave of paralysis that culminates in asphyxiation, no doubt after considerable distress.
The HSUS has been pressing this issue with Botox manufacturer, Allergan Corporation. Allergan claims to be making progress but has been reluctant to share the details of its testing and its alternatives program.
In our latest move to spur progress on the issue, The HSUS, along with the Calvert Funds (a socially responsible investment firm), has filed a shareholder resolution urging the company to regularly update shareholders and the public on its progress in phasing out the LD50 test.
Europe Leads the Way
The bright spot in the alternative testing field has been Europe, where legislation such as the Cosmetics Directive is seen as a powerful driver of progress on alternative methods.
The directive calls for a phase-in ban on the marketing of animal-tested cosmetics in Europe by 2013. And the government's European Centre for the Validation of Alternative Methods has been actively funding and coordinating the development and validation of alternative methods.
The greater focus on alternative methods has surely been one reason for the dramatic decline in animal use in toxicity testing seen in the United Kingdom (see figure).
Unfortunately, it is not clear whether this trend is mirrored in other countries, given inadequacies in their reporting systems.
Even developments in Europe that threaten to dramatically increase the scale of animal testing can have a silver lining. A new law known as "REACH" will launch a massive round of toxicity testing of existing and new chemicals, yet animal protectionists have worked hard to ensure that testing takes account of alternative methods and testing strategies that limit animal use.
U.S. Moving Toward Alternative Testing Methods
The situation in the U.S. has been frustratingly slow by comparison, as the Washington Post chronicled. The ECVAM's U.S. counterpart, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and its Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), have been chronically underfunded.
Even still, "ICCVAM/NICEATM have made limited progress and have not exerted strong leadership on alternative issues," according to Sara Amundson, executive director of the Humane Society Legislative Fund and a leading lobbyist for alternative methods.
"Their recently released five-year plan, mandated by Congress to bring some strategic focus to their efforts, has not inspired much enthusiasm."
Moreover, no legislative counterpart with the force of the EU's Cosmetics Directive has been driving positive change in the U.S. To the contrary, legislative mandates such as the EPA's Endocrine Disruptor Testing Program have not been seized upon as opportunities to significantly ramp up efforts on alternatives.
According to Andrew Rowan, HSUS executive vice president and long-time advocate for alternative testing methods, "Out of all current efforts, the federal government's new collaboration offers the best hope of energizing the United States's contribution to animal testing alternatives and realizing the NRC vision. It provides a unifying framework for finishing the job that ECVAM has so ably begun."
The government's collaboration is an enormous opportunity but many questions and challenges remain. Will it be adequately funded? How can this effort be better coordinated with other efforts internationally? What is the best strategy to validate the emerging high-throughput systems?
For its part, The HSUS will be working actively to ensure that the government's collaboration is adequately funded and lives up to its promise.
The HSUS has worked for decades to advance the concept of the Three Rs, formulated in 1959 by British scientists William Russell and Rex Burch. And we have worked tirelessly to see that it is adopted not only in theory, but in practice.
Some of our myriad efforts include:
- Early 1960s - The HSUS established a specialist committee on Alternatives to Animal Research and began to urge the scientific community to develop and implement such methods.
- 1962 - an HSUS-commissioned study of the statistical design of published scientific studies concluded that at least 25 percent fewer animals could have been used without compromising the results.
- 1979 - The HSUS published a report, Alternatives to laboratory animals: Definition and discussion.
- 1980 - The HSUS launched, with animal activist Henry Spira, the Coalition against the Draize Test to highlight the practice of toxicity testing on animals and to call for a switch to non-animal methods.
- Early 1980s - an HSUS scientist served on an advisory panel that helped shape the Congressional Office of Technology Assessment's 1986 report, Alternatives to Animal Use in Research Testing and Education.
- 1986 - The HSUS issued an 86-page report, Alternatives Current Uses of Animals in Research, Safety Testing, and Education: A Layman's Guide.
- 1987 - The HSUS published an analysis of the historical importance of alternative methods in biomedical research that had been awarded Nobel Prizes.
- 1991 - The HSUS established the Russell & Burch Award to encourage scientists to pursue the Three Rs approach,
- 1993 and 2000 - The HSUS was part of a consortium that successfully lobbied for the language that led to the establishment and strengthening of the Interagency Coordinating Committee on the Validation of Alternative Methods.
- 2000 and 2007 - laws were passed in California and New Jersey to require the use of alternative test methods, strengthening government and industry's investment in their implementation and use.
- 2001 - The HSUS supported the establishment of the Alternatives Congress Trust, the organization that now plans and supports the international congresses on alternatives.
- 2007 - the NRC issued its landmark report, "Toxicity Testing in the 21st Century, A Vision and Strategy." An HSUS staff member was a key member of the NRC panel.
- Late 2007 - The HSUS co-launched a website, AltTox, devoted to promoting and implementing non-animal methods of toxicity testing.
- 2008 - The HSUS estimates that, worldwide, funding into non-animal alternatives for safety testing is now greater than $50 million a year (compared to around $100,000 a year 25 years ago).
- By 2008, The HSUS's activities on pain and distress have caused a major rethinking of how the research community addresses and alleviates pain and distress in animals in the laboratory.