A common refrain from animal rights activists is that there are fundamental differences between humans and non-human animals that makes cross-species comparisons for medical research purposes pointless. It turns out, for example, that many mice models of cancer may have a fundamental flaw that makes it difficult, if not impossible, to compare them to human cancers.
But contrary to what animal rights activists seem to believe, such discoveries also help advance human understanding of disease and, ironically, do not mean that mouse models of cancer need to be abandoned.
In this case the debate is over telomeres. When human cells are placed in a culture in a laboratory, they will not divide indefinitely. Instead, after about 50 or so cell divisions, the cells will no stop dividing. This point at which cells stop dividing is called the Hayflick Limit.
It turns out that the Hayflick limit is determined by telomeres — these are long stretches of noncoded sequences at the end of DNA. In most cells, every time the cell divides, the length of the telomere sequences declines and the cell will stop dividing once the telomeres are exhausted. Only cells that divide a lot such as skin cells, germ cells and others maintain their telomere lengths intact.
What does this have to do with cancer? In some cases it is believed that mutations in a cell can cause it to keep dividing past the Hayflick Limit which eventually an become malignant growths. Researchers suspect that some cancers associated with aging are caused by this process.
But this is a major problem for mouse models, because mice have telomeres that are about twice as long as human beings. This means that, unlike human beings, mice cells keep dividing throughout the life of the mouse and they do not tend to experience the gradual fraying of the ends of the DNA strand that aged human cells do.
If this is true it means that existing mouse models of cancer are probably not appropriate for studying such cancers. In fact, mice do not tend to suffer from cancers which are associated with aging in humans, such as breast and colon cancer.
This is the point where animal rights activists would say, “aha, told you — there is no point in conducting cancer research in mice.”
But a much better response is to simply not study those particular forms of cancer in mice, or created genetically modified mice or use existing strains of mice that are more like human beings in this respect.
Both solutions are currently being investigated. Carol Greider, professor of molecular biology and genetics at the Johns Hopkins University School of Medicine, collaborated with another researcher to create a mouse that has telomeres that are similar in length to those in human beings. And wouldn’t you know it, such mice contract a range of cancers that is far closer to the human distribution of cancers than the traditional mice used in laboratories. That discovery in and of itself provided nice confirmation that telomeres indeed do play a role in cancers.
As an article in The Scientist summed it up,
DePhino and Greider’s diligence notwithstanding, Harrison says that, in general, researchers need to be more careful with their models. “We’re not looking at the whole mouse genome here; we tend to look at a very limited number of mouse strains, and that’s probably a mistake,” he says. Researchers must instead ask themselves, which kinds of mice are appropriate models for a given type of cancer? It may even be necessary to determine which mice make the best models for given groups of people, he adds.
Mucch genetic diversity has been captured by producing inbred mouse strains from previously unsampled, wild populations. These strains offer the genetic reproducibility that is so valuable in lab mice, but with a wider variety of genotypes and phenotypes. But Harrison stresses that using mice as models for cancer development has already been quite successful. For instance, every chemical that induces cancer in humans does so in mice as well, proving that the use of mice is an effective and powerful research tool. “If you lose the mouse as a tool, just because of some prejudice about telomeres,” he concludes, “you take away a lot of the opportunity for advancement.”
Source:
Telomeres as the key to cancer: could hundreds of mouse models be wrong? Jeffrey M. Perkel, The Scientist 16[11]:38, May 27, 2002.