Naked mole rats and cancer resistance

Cells have what is called contact inhibition. This means that once they come into contact with each other (or something else), they will cease to grow (or slow growth significantly). However, this is not true of cancer cells. Indeed, it is a hallmark of such cells; they grow and grow and even layer atop each other. Contact inhibition controls cell growth and cancer is, by one general definition, uncontrolled cellular replication.

A recent study led by Vera Gorbunova of the University of Rochester has focused on the naked mole rat and why it has never been observed to develop cancer.

The findings, presented in The Proceedings of the National Academy of Sciences, show that the mole rat’s cells express a gene called p16 that makes the cells “claustrophobic,” stopping the cells’ proliferation when too many of them crowd together, cutting off runaway growth before it can start. The effect of p16 is so pronounced that when researchers mutated the cells to induce a tumor, the cells’ growth barely changed, whereas regular mouse cells became fully cancerous.

This gene is on top of another gene which contributes to restricted growth. Humans (and other animals) only have one, p27, and it gets ‘worked around’ by cancer commonly enough. Cancer in the naked mole rat is theoretically possible, but since it has to breach two barriers to uncontrolled cellular growth, it is unlikely.

As always, there is an excitement with any discovery which could contribute significantly to curbing or stopping many of the major diseases afflicting humanity, but it must be met with temper.

It’s very early to speculate about the implications, but if the effect of p16 can be simulated in humans we might have a way to halt cancer before it starts,” [says Vera Gorbunova].

Might is the key word, and I think Gorbunova’s caution is appropriate. Cancer is a bit of a devil, to say the least, and every discovery seems to lead to a more complicated understanding of how it works. We’ll see what this research turns out to really mean.


HIV Evolution

Scientists have recently shown that the rate of evolution for HIV is not constant.

HIV is so deadly largely because it evolves so rapidly. With a single virus as the origin of an infection, most patients will quickly come to harbor thousands of different versions of HIV, all a little bit different and all competing with one another to most efficiently infect that person’s cells. Its rapid and unique evolution in every patient is what allows HIV to evade the body’s defenses and gives the virus great skill at developing resistance to a pantheon of antiviral drugs.

“A huge amount of HIV diversity accumulates in the body of a patient with HIV, and it’s a big reason why HIV is such a powerful virus,” said Ha Youn Lee, Ph.D., assistant professor of Biostatistics and Computational Biology at the University of Rochester and corresponding author of the study.

Lee and colleagues have settled a longstanding question about just how HIV morphs in the body. In a paper published Dec. 12 in PLoS Computational Biology , scientists show that HIV evolution in the body does not occur at a constant rate. Rather, the virus’s rate of change suddenly slows when the level of crucial immune cells known as CD4+ T-cells falls in a patient.

The team suggests several possible reasons for why HIV slows its evolution later in the disease process. One is that there are simply fewer immune cells left for the virus to infect. Another possibility is that since the immune system is no longer as effective targeting the virus, the virus no longer feels the “selective pressure” of the immune system, and the virus slows its evolution in response.

It’s no secret that HIV is a daunting virus. The fact that it has been shown now to have such a tremendous amount of variation should put no one at ease. There are literally thousands of different types of HIV in an infected individual’s body soon after the disease is contracted. Thousands.

Picture a criminal on the lam. When the police are out in force, the criminal must change his disguise more and more to survive, but when fewer police are present, the criminal can change his disguise less often. In the case of HIV, the virus actually eliminates the “police officers” – CD4+ T-cells patrolling the body. As time goes on and fewer immune cells are present to flag HIV, the virus no longer has the need to evolve as rapidly as it did when the cells were out in force.

This is a pretty apt analogy, if a bit 19th century/Sherlock Holmes-esq. As a secondary point, it’s nice to see such a blatant attempt at popularization within a science article.

As the virus mutates, giving birth to viral offspring called quasispecies, it presents an ever-changing face to the immune system, which is continually adapting itself to keep up with the onslaught. The immune system does a remarkable job fending off the assault, killing most of the viral particles every day. Even so, some of the virus is able to elude the body’s defenses and ultimately devastates the immune system in most patients.

Alas, not all evidence for evolution is pleasant. It’s roughly about as indifferent and pitiless as one might expect such a natural process to be.