Tuesday 25th February 2020

Carcinogenicity studies on animals

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Bruce Ames

Laboratory rats

Laboratory Rats

Dr. Bruce Ames is a Professor of Molecular Biology and Biochemistry at the University of California, Berkeley, and a Senior Scientist at Children's Hospital Oakland Research Institute.

Ames is a member of the National Academy of Sciences and was on its Commission on Life Sciences. He was a member of the board of directors of the National Cancer Institute, the National Cancer Advisory Board, from 1976 to 1982.

A highly prolific scientific author with over 450 publications, he is one of the few hundred most-cited scientists in all areas of science.

He invented the test that carries his name, the Ames Test, one of the most used tests for carcinogenicity (cancer-inducing quality) of substances, a method for testing the mutagenicity of substances cheaply and easily that does not use animals.

Ames helped to secure bans on many dangerous synthetic substances in the 1970s. He is also a leading researcher in the field of cancer prevention and other diseases prevention.

Professor Ames is one of the most highly respected cancer researchers and microbiologists in the world, and his opinions have been supported by the US National Research Council.

Professor Ames’ opinion is that cancer tests using animals give a misleading picture. Feeding animals extremely high doses of substances, which is the normal procedure, can cause chronic cell death simply because of a localized overload, for example of the stomach. Cancer develops only because of the high dosages administered, which means that the studies say nothing about the substance’s actual capability of causing cancer in human subjects at the exceedingly lower levels to which humans are exposed.

An enormously high proportion of all the substances in the world would probably prove cancer-inducing with animal studies, which clearly indicates that these tests are measuring not carcinogenicity, but something completely different, localized overloading.

The founder of pharmacology, the 16th century scientist Paracelsus, said that every substance under the sun is toxic, it just depends on the dose:

All substances are poisons; there is none which is not a poison. The right does differentiates a poison and a remedy. [Emphasis added]

Every chemical substance is harmless or harmful at various levels of ingestion. Orange juice can be described as one the healthiest possible of all the foods and drinks you could have, but if you drink 50 or 60 cartons a day it will probably harm you. Sometimes doctors report that they had to treat a patient who had drunk so much water to require medical attention. The goal is to find that threshold, the point at which a substance ceases to be good for you or at least innocuous and becomes damaging. That point obviously varies for each substance. But animal tests are designed in such a way that confuses the problem, rather than clarifying it.


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Examples of exaggerated cancer risk estimates: chrysotile & pesticides

Animal studies of substances are usually performed at near-toxic doses of the compound. These results have been misinterpreted as meaning that low doses of them can potentially induce human cancer. About half of all the chemicals tested, natural or synthetic, cause cancer in rats or mice at these exceedingly high doses.

A plausible explanation for this high proportion of positive results is that administering substances at near-toxic levels often causes chronic cell killing and consequent cell replacement, which is a risk factor for cancer but only limited to these hugely high doses.

Simple extrapolations, transferring test results of chemicals from the near-toxic dose in rodents to the low-level exposure in humans, thus committing several fallacies at the same time, i.e. ignoring species differences as well as dose discrepancies, has led to exaggerated cancer risk estimates, an imbalance in the perception of hazard, and finally a wrong allocation of resources.

A classic example of this is that of chrysotile, a mineral substance which, just because it is also known as white asbestos, has been erroneously associated with real killers causing asbestosis, mesothelioma and lung cancer, the amphiboles, also known as blue and brown asbestos, which are entirely distinct and chemically different from chrysotile. There is evidence that the latter poses very low risk to human health, as is today recognized by the vast majority of scientists.

For years there had been confusion among scientists themselves about what form of asbestos caused what and how. But in the early 21st century this was clarified by a number of studies, including some using electron microscopy.

A strong element of confusion on the entire issue was brought by animal experiments.

A milestone study report is "The health effects of chrysotile: Current perspective based upon recent data" by David Bernstein and John Hoskins, published in Regulatory Toxicology and Pharmacology in 2006, which shows that chrysotile fibres rapidly break apart in human lungs into fibrils so small that they pose no more risk than dust particles; so only heavy and prolonged exposure to crhyrotile can cause lung cancer. It says:

"The chronic inhalation toxicity studies that have been performed on chrysotile in animals have unfortunately been performed at very high exposure concentrations and so under conditions of lung overload. In consequence their relevance to human exposures is extremely limited."

It also says:

"Recent quantitative reviews of epidemiological studies of mineral fibers have determined the potency of chrysotile and amphibole asbestos for causing lung cancer and mesothelioma in relation to fiber type and have also differentiated between these two minerals... The value of the present and other similar studies is that they show that low exposures to pure chrysotile do not present a detectable risk to health."

Another example of problems created by carcinogenicity tests on animals with their misleading results is that relating to pesticides, the risk posed by which has been greatly overestimated by giving lab rats and mice extremely high, close to harmful doses, in order to get a cancer frequency high enough to have statistical significance. Bjorn Lomborg, in The Skeptical Environmentalist, writes:

"On evaluation, the question then arises as to what the cancer risk to mice on a high dose means to human beings at low intake levels. The question is whether one can transfer conclusions drawn from mice to humans, and from high doses to low ones. The short answer is: we do not know."

To conclude, non-animal, in vitro biomedical research using cell cultures will throw light on how living cells become cancerous. It is this kind of research, rather than maximum-tolerated-dosage tests on rodents, that will generate breakthroughs in the war against cancer.


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