Animal Cancer Tests

The chemical causation of cancer is not a simple process. Many, perhaps most, chemical carcinogens do not have the potency to cause cancer in their usual condition. The non-cancer causing form of the chemical is called a procarcinogen. Procarcinogens are frequently complex organic compounds that the human body attempts to dispose of when ingested. Hepatic enzymes chemically change the procarcinogen in several steps to yield a chemical that is more easily excreted. These chemical changes result in modification of the procarcinogen (with no cancer forming ability) to the ultimate carcinogen (with cancer causing competence). Ultimate carcinogens have been shown to have a great affinity for DNA, RNA, and cellular proteins, and it is the interaction of the ultimate carcinogen with the cell macromolecules that causes cancer. It is unfortunate indeed that one cannot look at the chemical structure of a potential carcinogen and predict whether or not it will cause cancer. There is no computer program that can predict what hepatic enzymes will do to procarcinogens and how the metabolized end product(s) will interact with cells.

Great strides have been made in the development of chemotherapeutic agents designed to cure cancer. The drugs have significant efficacy with certain cancers (these include, but are not limited to, pediatric acute lymphocytic leukemia, choriocarcinoma, Hodgkin's disease, and testicular cancer) and some treated patients attain a normal life span. While this development is heartening, the cancers listed are, for the most part, relatively infrequent. More common cancers such as colorectal carcinoma, lung cancer, breast cancer, and ovarian cancer remain intractable with regard to treatment.

These several reasons are why animal testing is used in cancer research. The majority of Americans support the effort of the biomedical community to use animals to identify potential carcinogens with the hope that such knowledge will lead to a reduction of cancer prevalence. Similarly, they support efforts to develop more effective chemotherapy. Animals are used under terms of the Animal Welfare Act of 1966 and its several amendments. The act designates that the U. S. Department of Agriculture is responsible for the humane care and handling of warm-blooded and other animals used for biomedical research. The act also calls for inspection of research facilities to insure that adequate food, housing, and care are provided. It is the belief of many that the constraints of the current law have enhanced the quality of biomedical research. Poorly maintained animals do not provide quality research.

In trying to evaluate whether mouse cancer research will apply to humans, the first question that crops up is why use mice when one is interested in curing human cancer? There are several reasons. Mice share many common features with humans and develop all the types of cancer that humans develop. They also have the same genes involved in a lot of these cancers.

Mice are readily available. Candidate drugs cannot only be tested on people. It would be unethical, immoral, and probably illegal. However, before a new drug can be tested on humans, there have to be some guidelines about what it can do. These guidelines come from mice and other animal models.

Mice can develop human cancers. Furthermore, human tumors can be implanted in mice. In addition, mice have simpler genetics. Genetically identical mice simplify experiments by minimizing the confusion that arises when testing drugs on mixed populations. In theory, genetically identical mice should all respond the same to a given form of treatment. By adding or deleting genes from mice, scientists learn how that gene's products influence a treatment and thus, obtain valuable clues to the biochemistry of cancer.

The "nude" mouse lacks a thymus gland, needed for the development of the immune system. Since its immune systems is so defective, this mouse does not reject transplanted human cancers and is widely used to test cancer drugs.

Despite the numerous advantages in using mice as models for studying human cancers, it has to be emphasized that mice are not men and mouse results may not apply to people. No generalizations can be made about the individual drugs. Each new drug is new—and one has to go through the process of testing its toxicity and effectiveness. There are many reasons to be cautious when interpreting animal tests. Many mouse experiments have been proven wrong in the past and scientists have been disappointed going from mice to people. There are several cancer cures—interferon, interleukins, and cytokines—that worked much better in mice than in people.

Although much of the rationale for testing drugs on animals rests on the similarities among organisms—similar does not mean identical. Basic cellular enzymes—and the DNA code that governs life's chemistry and structure—are similar in widely divergent organisms. Genes with the same function in mice and men contain, on average, 85% similarity in the actual sequence of DNA subunits. But, it is possible that even a single change in the order of DNA bases can make a huge difference. Sickle cell anemia is a painful disease caused by one erroneous atom in the hemoglobin molecule that carries oxygen in red blood cells. This mistake, results from a single erroneous subunit among the thousands that comprise the hemoglobin gene.

And then there is the toxicity issue. Interleukin-2 is a blood-borne signaling molecule that produced remarkable results against cancer in animals a decade ago. But in people, it caused leaks in blood vessels, and could never be used at the dosages that worked so well in animals. Instead of becoming the magic bullet some had predicted, IL-2 is now a small member of the overall anti-cancer tool kit.

Beyond these issues is another more serious concern—the nature of the experimental tumors. The mouse experiments use tumors that grow well in laboratories, but human tumors arise spontaneously and could have quite different genetics and properties. The biology of the tumor may be different, not because it is a human tumor growing on a mouse, but because it is spontaneous and not grown in a lab.