What Does A Mouse Virus Have To Do With You?
Scaling the walls of the orthodox scientific community has not been easy.
Viruses, which are simply small packages of genetic material, are the most abundant infectious agents on earth. They can infect plants and animals, including humans. Viruses tend to be species-specific; that is, they tend to target one single species and, typically, only one tissue in that species. For instance, the polio virus specifically targets humans and specifically infects only nerve cells, not liver cells. On the other hand, the hepatitis virus targets liver cells, not nerve cells.
Viruses can be transmitted horizontally, from person to person, as is the case with influenza. Or they can be transmitted vertically, from parent to child, as is the case when an HIV-positive mother gives birth to an HIV-positive child. Viruses can pass not only from mother to child, but from father to child by way of genes hidden in sperm cells.
A virus that causes cancer is called a tumor virus or oncovirus. Worldwide, the most common of these is the hepatitis B virus. It causes acute, immediate liver infection but also causes liver cancer in some individuals long after the first illness has passed. Another common tumor virus is human papilloma virus, HPV. It causes cervical cancer and, fortunately, an effective preventive vaccine is beginning to reduce the number of new cases in the United States. Professor Zur Hausen, the scientist who labored for years trying to prove that HPV caused cervical cancer, an ordeal for which he was ridiculed and belittled by the academic community for more than ten years, won the Nobel Prize in medicine last year. Small comfort for the heroic fight he waged outside the walls of a seemingly impenetrable scientific fortress.
The proof that a virus was capable of causing cancer was obtained in 1910 when Dr. Peyton Rous demonstrated that a virus unquestionably caused solid tumors in chickens. By the 1950’s, scientists were wondering whether viruses might cause cancer in humans, too. Now we know they certainly do. So far we’ve discovered seven human cancer viruses, and more discoveries appear to be near at hand. Indeed, the prevailing wisdom now suggests that, after tobacco, viruses are the most likely cause of all human cancers.
The problem with nailing down the causal relationship between a virus and a particular cancer is this: tumor viruses have the baffling tendency to infect a cell and then disappear, leaving no trace of themselves behind, but rendering the infected cell sufficiently transformed that, over time, it eventually becomes cancerous. In fact, scientists working at Memorial Sloan-Kettering Cancer Center in the 1960s came to the conclusion that the more active the virus was in causing cancer, the less evidence there was of it in the cancer cells that eventually formed. This observation was in contradistinction to the normal pattern of viral infections in which the virus is commonly found in very high levels in infected tissue, making the link between the virus and the disease more definitive and demonstrable.
Tumor viruses cause cancer by inserting their genes into the genetic material of the cells they infect. Sometimes viral genes are, themselves, capable of producing cancer. These genes are called oncogenes. But other viral genes, which are completely benign in and of themselves, manage to insert themselves near an oncogene, causing the oncogene to be activated and leading to eventual cancer formation. This latter mechanism is referred to as “insertional mutagenesis” and it is one of the means by which the mouse mammary tumor virus (MMTV) causes breast cancer in mice.
It should come as no surprise that viruses that infect animals can be very similar to viruses that infect humans. After all, plants and animals and, more recently, humans have been sharing the same environment with the most common infectious agents, viruses, for millions of years. It only makes sense that an animal virus might, over the course of years, change just enough to be able to “jump species” and infect humans. This is precisely what scientists believe happened in 1918 with the jump of H1N1 influenza from pigs to soldiers as they made their way to in Europe at the beginning of World War I.
The most common case of this transition from animal to man relates to HIV and its animal (chimpanzee) equivalent SIV. Although the hypothesis that SIV was a precursor to HIV was extremely controversial – even dismissed outright – at first, it is now fully acknowledged that SIV, found in chimpanzees, gave rise to HIV, now the scourge of the planet. (One comes to the conclusion that initial, emotional condemnation of a scientific hypothesis is a rather good sign of its validity.) The final proof that SIV was the precursor to HIV came in 1999, when researchers at the University of Alabama found a type of SIV that was nearly identical to a particular variant of HIV. With irrefutable data in hand, the scientists concluded that the SIV they had isolated was the ancestor of HIV-1. They hypothesized that a chimpanzee must have been infected with two similar viruses, and that the two viruses swapped genetic information, called recombination, to form the new HIV strain that triggered the global AIDS pandemic.
When John Bittner first discovered the mouse mammary tumor virus (MMTV) in 1936 he must have wondered whether such a virus might also exist in humans. And when he discovered that the mouse virus was able to pass from mother to pup via breast milk, he must have worried that a similar transfer could occur in humans. Years later, other researchers looking for the human equivalent of MMTV began to find evidence of a virus that was at least 95% similar to the mouse virus in 40-75% of human breast cancer specimens. Other researchers found evidence of a virus very similar to MMTV in human breast milk and in the blood of women whose breast cancers carried evidence of the virus. The idea of a human mammary tumor virus, HMTV, was born.
The presence in mice of a virus, MMTV, that causes breast cancer in 95% of the mice it infects, and the presence of a virus in human breast cancers that is 95% similar to the mouse virus, HMTV, raised strong suspicion that a virus was at play in a large portion of human breast cancer. Now scientists have found evidence of MMTV in cats and in dogs. One researcher believes that these companion animals may be the agents of transfer, along with mice themselves, of the breast cancer virus to humans.
Other viruses are also on the list of breast cancer suspects: human papilloma virus (!) and bovine (pig) leukemia virus. The data continue to converge on the hypothesis that viruses, like HMTV, cause breast cancer. We are long over due bringing this subject to the forefront of modern medical research. In the past two years, I have been fortunate to have had the opportunity to do my part to raise this issue nationally and, last month, internationally. And just yesterday I was invited to speak about this subject again this coming Spring. This latest invitation is in addition to the presentation I will be making to another international community April, 2011 in Munich, Germany.
Now, wouldn’t it be wonderful to find the money to support not only the conversation but the research?
So, what does a mouse virus have to do with you? I think a lot. I will let you know more as soon as I know more. Stay tuned. And, please, tell a friend.
References:
Bittner, Science, Vol. 84, No. 2172, 1936
Ford, Clinical Cancer Research, 1118, Vol. 9, March 2003, 1118-1120
McLaughlin-Durbin, Biochimica et Biophysica Acta, 1782, 2008, 127-150
Lawson, Breast Cancer Research, 3, 2001, 81-85
Pogo, Cancer, June 1, 2010
Pogo, Breast Cancer Research Treatment, 26 September 2010
Wang, Cancer Research, 61, feb 15, 2001, 1754-1759
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Right on the ball!