Biomedical Research and Testing: What Are The Options?

“An integrated approach of clinical, whole animal and vitro studies is currently the best approach to advance science, develop new products and drugs, and treat, cure and prevent disease.”
Alan M. Goldberg, Ph.D., Director
Center for Alternatives to Animal Testing
Johns Hopkins University

What options are truly available to scientists today? What is meant by “alternatives”? The terminology used in referring to research and testing procedures can often be confusing. For example, it is a common misconception that “alternatives” implies complete replacements for animals. However, to scientists and to many other people concerned with animal welfare, the term also includes refinements in testing procedures to cause the animals less stress, or reductions in the number of animals required in a particular test, while maintaining the quality and validity of scientific information obtained.

Because in vitro and nonanimal procedures must generally be used in combination with live animal testing, many scientists view them as adjuncts that augment, supplement or complement animal research rather than totally replace it. In making decisions about what research and testing methods to use, the key questions are always: Does it produce the most reliable information, and does it help us predict how people will respond to a new drug, chemical or procedure? In practice, scientists use a combination of nonanimal, in vitro and animal methods to obtain the best information because all three contribute to the process in different, but equally significant ways.

Biomedical Research and Testing: Non-Animal Methods

Nonanimal methods generally prove most useful in the preliminary stages of research when scientists are still sorting out the fundamental problem. They often provide ideas about new research directions to pursue.

Testing methods that do not use animals directly include chemical, mechanical, mathematical and computerized models. It should be noted, however, that many of these methods depend on information previously obtained from animal tests.

In the field of medical education, computers and other forms of modeling and simulation have reduced the numbers of animals required for learning basic biology. Many educators, however, continue to make a strong case that hands-on examination of animals is necessary to provide science and medical students with important insights into anatomy and physiology. Who would choose a surgeon whose training had been limited to plastic models and computers?

Biomedical Research and Testing: In Vitro Methods

After developing ideas with nonanimal methods, in vitro models usually are most effective during early and intermediate stages of the biomedical research and development process. The term in vitro refers to experiments performed in laboratory containers, such as test tubes, with living tissues or biological materials often obtained from animals or people. Many people assume that in vitro methods are the opposite of in vivo-“in life.” While it’s true that these procedures can reduce the number of animals required, most in vitro methods still require enzymes, cells, tissues or organs drawn from animals.

The advantages of in vitro methods are that they allow research scientists to study a single effect of a substance or an action in isolation and offer high sensitivity without interference from other biological phenomena, such as hormones or immune responses. For many purposes they actually generate data faster and at far lower cost than methods using live animals.

In vitro models also serve as preliminary indicators of specific beneficial or harmful effects. These models enhance our understanding of how and why a material may affect a living system. One example is the Ames test for mutagenicity. A compound is tested first in bacteria for mutations, which signal the possibility that a compound could cause cancer.

Helpful as these methods are, they have many limitations. Information available from nonanimal models differs from what can be learned from laboratory animals primarily because results from nonanimal models tend to be theoretical rather than practical. But theoretical or hypothetical results of this kind can be confirmed only in living systems. In the Ames test, for example, not all cancer-causing substances cause mutations, and not all substances that cause mutations cause cancer. This means that further testing in animals is still necessary.

Despite their considerable predictive value, out of the thousands of nonanimal and in item models available, very few such models replace laboratory animals entirely. The diagnostic kit that replaced the rabbit in pregnancy testing is a rare example. And in safety testing, though the role of animals has been reduced in recent years, only a handful of scientifically satisfactory replacements have become available for the final phases.

Although research efforts continue, substitutes that eliminate the need for laboratory animals remain scarce for many educational, research and testing purposes. When the scientists must learn how a new substance or procedure will interact with living systems, there is no effective substitute for animals. No one can measure blood pressure in a test tube or learn to perform heart surgery using bacteria.

Biomedical Research and Testing: Animal Methods

Sophisticated as computer simulations and in vitro methods are today, they cannot generate sufficiently reliable data about how a substance affects a real living being-a complex, interactive system made up of dozens of organs, hundreds of biological messengers, thousands of enzymes and hundreds of thousands, if not millions, of different proteins, many of them not even identified. Animals remain the vital link.

Lower orders of animals-such as worms and salamanders-are useful, but they can model only a very limited number of human responses. It should come as no surprise that the best predictors of human responses are often higher-order animals, such as rats and mice, which account for about 90% of the animals used in research. Some critics of animal use contend that there is too much variability in diseases and drug reactions between different animal species to provide good information. Researchers are aware of and must understand those differences, but find they are far outweighed by the similarities.

Working with a clear understanding of how species differ, scientists continue to value animal models as the primary avenue to gaining useful insights into how people are likely to respond. Animals can give us a clear indication of how people may recover from a new surgical technique or respond to the long-term effects of a new medicine. They permit us to discover how a new substance interacts with different organs and systems, the different routes a substance may take when swallowed, inhaled, injected or absorbed, and whether a potential new medicine is likely to affect reproduction.

Biomedical Research and Testing: Human Studies

Taking what we learn about safety and effectiveness in the step-by-step approach from computer to test tube to animals, we can then progress to the next link in the chain-carefully staged clinical studies of new vaccines and medicines in human volunteers.

It would be unthinkable to test any medicine or procedure on people without first taking every reasonable step to ascertain its safety in animals to help assure that people will suffer no undue harm. No responsible group advocates testing a material first on people, nor would the public tolerate it from a social or ethical perspective.

Animals will remain indispensable to biomedical science for as long as anyone can predict because what they have to teach us about life itself and the effects of new medicines on life processes can be learned in no other way.
Biomedical Research and Testing: Safety at Work, at Home and in the Environment

By defining the safety and effectiveness of medicines, only the best and safest ones will be selected for use. Likewise, safety testing protects us from the dangers of new substances at work, at home or in the environment.

Although no complete replacement is as yet available for any level or phase of product safety testing or workplace safety research, recent advances in biotechnology and physiology hold promise for the replacement of animals for some routine toxicity and irritation testing. In In vitro and nonanimal models can help to screen for toxic effects, reducing the need for animals. When it comes to determining a substance’s possible harm to people, however, animals will continue to play an essential role.

People sometimes question whether the world really needs another cosmetic or household product or nonprescription drug. Only consumer demand can give that answer. But before new products are introduced, guardians of the public health and safety must do what they can to ensure that children who accidentally put makeup in their mouths or get household cleaner in their eyes would not die or lose their sight as a result. Imagine parents rushing a child to the emergency room and being told, “We don’t know if this product will make your child seriously ill, and we don’t know what treatment to use. The product has only been tested on the computer.”

It is important to recognize that most products advertised as “not tested on animals” contain ingredients that in fact have been tested on animals or a company could not ethically label a product as safe for human use. In most cases, safety studies on the active ingredients were completed in years past, often by the product supplier or by other companies.
Biomedical Research and Testing: Regulations Require Animal Testing

Federal regulations generally require information that can only be obtained from animals, to determine the safety and efficacy of a new medicine, medical procedure or consumer product and for good reason. It is the best way to protect the consumer.

The FDA and the Environmental Protection Agency (EPA) require comprehensive data about the efficacy and safety of new products and the hazards, if any, of new substances.

Other agencies, such as the Consumer Product Safety Commission (CPSC), Department of Transportation (DOT) and the Occupational Safety and Health Administration (OSHA), also require certain safety data that cannot be obtained without animals.

Regulators will accept data from supplementary and alternative models only after there is scientific proof of the validity of these models in a variety of settings. Consensus cannot be imposed on regulators or the scientific community. This process takes time and can be achieved only after extensive comparative scientific studies and experience demonstrate the accuracy and reliability of the new test.
Biomedical Research and Testing: The Search For New Models

Although the knowledge gained from animals is irreplaceable, the research community is committed to finding other ways to augment it. These new methods always grow out of what we learn from animal models and must be verified against them.

For decades, as part of their internal research activities, scientists in academic, government and industry laboratories have been seeking and developing nonanimal and in vitro tests. In methods that must involve animals, scientists work to refine techniques so as to minimize the animal’s stress. And they continue to do so. In this sense, scientists are developing and using alternatives all the time.

In addition, many organizations in both the public and private sector – including industry and research foundations and the National Institutes of Health, the nation’s premier biomedical research center fund research in the whole range of potential new methodologies. Companies that make pharmaceuticals, chemicals and cosmetics and fragrances lead the corporate effort through research, both in their own laboratories and in sponsoring research in others.

In the United States, the Johns Hopkins University Center for Alternatives to Animal Testing sponsors seminars to promote in vitro alternative technology and build consensus among scientists. In England, FRAME (Fund for the Replacement of Animals in Medical Experiments) engages in a similar enterprise.

Regulators have had an impact, too. Federal regulators from the FDA, Environmental Protection Agency and Consumer Product Safety Commission formed an organization known as IRAG – the Interagency Regulatory Alternatives Group-to gather data and exchange information about refined animal models and proposed nonanimal models.

Researchers in every sector recognize the importance of adopting new models, especially where their adoption will result in meaningful scientific information.
Biomedical Research and Testing: What Does the Future Hold?

Virtually no one associated with biomedical research, medical education or toxicity and safety testing has a vested interest in perpetuating animal models unnecessarily. On the contrary, it is in everyone’s interest to develop reliable, cost-effective in vitro and nonanimal models that give comprehensive, accurate information about living systems and speed the discovery of new medicines and technologies.

Research scientists have developed ways to grow or cultivate human tissues in the laboratory. They can also genetically engineer bacteria and yeasts to manufacture some enzymes and other proteins that might otherwise need to be isolated from animal tissues. Moreover, procedures involving animals are constantly re-evaluated with the aim of reducing the number of animals or refining the procedure to minimize the animal’s stress. The future lies in advances in these refinements and reductions, not in total replacement. The scientific community is committed to eradicating disease in both people and animals and keeping our home, work and recreation environments as safe as possible. Animals will continue to play an essential role in fulfilling that mission.

Are there alternatives to animal research? Alternatives, yes, but few true replacements. Animals are vitally necessary in the ongoing medical research that saves and enhances human and animal life.

The only other option is to halt virtually all progress, consigning ourselves, future generations and the animal world itself to a new dark age of hazard and disease.