Science's Next Top Supermodel?

The naked mole-rat may save us from brain damage, pain, cancer, and even aging
 

 

Sure these dirt-dwellers look like a part of the male anatomy with buck-teeth, but their attributes only go up from there (pun?). They survive long periods without oxygen, show insensitivity to pain, and unlike related mice that live 2-4 years, the naked mole-rat lives into its 30s. For humans, that would be a lifespan extension of ~ 400 years. Not impressed? Well they also don't get cancer....ever.

Oxygen Smoxygen

Our brains are damaged after just 3 minutes of oxygen deprivation. This is a concern for heart attacks and strokes, where blood supply to the brain is interrupted. Brain tissue of the naked mole-rat remains functional three times as long as brain tissue of mice, and when oxygen is restored, the brain recovers. With their claustrophobic environment of underground tunnels they've evolved to contend with low oxygen and high carbon dioxide levels. Naked mole-rats protect their brains using the same strategy as infants. Infant humans are more tolerant to oxygen deprivation than adults, and calcium is the culprit. Normally, calcium in our brain helps memories form. But the balance is delicate: too much calcium is damaging. When our brains are oxygen starved, they no longer regulate calcium entry, resulting in too much calcium and brain damage. Researchers discovered that calcium channels in infants close during oxygen deprivation, protecting the brain from calcium overdose in the womb, where the baby gets much less oxygen. After birth, however, oxygen is plentiful, and these channels are replaced by ones that open in response to oxygen deprivation, often leading to cell death. Naked mole-rats retain "infant-style" calcium channels even as adults, which explains their resiliency. These findings provide a new strategy to help victims of heart attack and stroke: design a drug that quickly increases the number of infant-style calcium channels in the brain. This could provide valuable protection during a time when the supply of oxygen-rich blood is stunted.

Are you a man or a mole-rat?

I recently went on a whiskey distillery tour and the guide asked me to stick my nose in the fermenter and take a whiff (Fermentation: Sugar = CO2 + Delicious Alcohol). I jolted up with my nostrils being pricked by a thousand horseradish-tipped needles. High levels of CO₂ can be painful to the eyes and nose due to the formation of acid on the surface of those tissues. A less sadistic experience is the feeling of burping through one’s nose after drinking a coke. Mole-rats are completely insensitive to this and other irritants. The nerve fibers that respond to irritants are less sensitive in naked mole-rats. Importantly, these fibers are responsible for the pain people experience after an injury. Surprisingly, naked mole-rats have these fibers everywhere, but they do not make the neuropeptides usually released because of a gene defect associated with relaying the message of pain. A greater understanding of how this type of pain processing is altered in naked mole-rats has significant implications for the treatment of chronic pain in humans.

Is Joan Rivers a Mole-Rat?

With a recorded lifespan of 32 years, they are the longest-lived rodents known, and remarkably, they are in good health for most of their lives. At an age equivalent to a human age of 92 years, naked mole-rats show unchanged levels of activity and metabolic rate, sustained muscle mass, fat mass, bone density, cardiac health, and brain function. They delay the onset of aging and compress the period of decline into a small fraction of their overall lifespan. These findings of sustained good health are turning current theories of aging on their head. For example, the widely accepted "oxidative stress theory of aging" attributes our decline in function to damage caused by reactive oxygen species. In much the same way that oxygen causes your car to rust, cell membranes, proteins, and DNA are also damaged. Over time, we "rust", which causes our bodies to slowly malfunction. Surprisingly, naked mole-rats also show high levels of rust at an early age, yet cellular function is not impaired. Another aging theory is that the length of an organism’s DNA ends (telomeres), is a marker of aging. As our cells divide, the ends of our chromosomes get shorter and shorter, eventually chewing into genes required for cellular function. But the naked mole-rat has short telomeres, similar to those of humans. Thus, the telomere theory is unlikely to explain their longevity. Where's the fountain of youth?!

Rat for the cure

The naked mole-rat doesn't get cancer. Scientists have blasted these critters with cancer causing radiation and no tumors develop. Some real jerks even altered their DNA to produce aggressive tumors. Again; nothing! But the jerks did notice something intriguing. The cancerous cells didn't die, they just stopped dividing. It seems as though the naked mole-rat is very good at recognizing abnormal cells, neutralizing cell overgrowth, and repairing DNA. The genome of the naked mole-rat has unveiled novel insights into why they are impervious to cancer. Given that cancer is one of the largest contributors to mortality in elderly humans, these cancer prevention pathways may contribute substantially to the longevity of naked mole-rats.

They sure are ugly, but we are slowly recognizing the beauty from within. Research on this fascinating animal will do so much. If I'm ever saved from brain damage, pain, cancer, or even aging because of these critters, I'll be the guy in the naked mole-rat mobile with the naked mole-rat tattoo on the way to PetSmart to buy a dozen naked mole-rats....to be my pets!!!

Your Genome for the low price of $999!

For $1,000 bucks, you can get your entire genetic code and its secrets. And it's only getting cheaper!

The machine itself takes up as much space as a printer, it does an entire genome in a single day, and costs only $100,000; making it affordable for medical practices.

For now, research labs will be the main customers, to obtain the complete genome sequence of people with cancer or autism, for instance, to seek out a disease's underlying genetic causes and ways to treat it.  In the very near future the door will open to people who are not ill.

The Data Deludge Revolution?

One problem is that the costs only start with the actual sequencing. The cost of understanding the sequence will be much, much higher. For example, in one study the sequencing cost $48,000, but because it found 2.6 million DNA misspellings and 752 other genetic glitches, it took a few hundred thousand dollars worth of labor to understand what the sequence meant. My wife is currently working to improve data quality when sequencing cancerous tumors.

It would take a genetic counselor roughly 5 hours to explain what a typical genome means, further adding to the true cost. If you want me to recommend a job for your kids?

GENETIC COUNSELLING!! We do not have nearly enough to meet the need if sequencing becomes widespread. Will doctors pick up the slack? 90% of patients trust their physician to explain genomic data to them, and 90% of physicians say they don't feel comfortable explaining genomic data...MDs, go figure.

The genomic revolution has arrived! And herein lies the crux of the matter.

Will you want to know?

You'll know if your baby will have a genetic disease, such as autism. In some instances the disease will be curable. In others, you'll know the dreadful future of this baby. Will you want to know?

Babies will certainly be first in line for sequencing. The US and Canada already screen newborns for at least 29 genetic diseases. But we need to be careful how we utilize this information. Do you tell a newborn's parents his apoE status? That is, whether he has the form of a gene that raises the risk of Alzheimer's disease? Will you want to know?

You'll know your chances of getting a variety of different diseases, such as alzheimer's or cancer. Will you drastically change your quality of life to prevent these diseases?  Will you live an entire lifetime worried, but well? Will you get the disease anyways!? Will you want to know?

Insurance companies and businesses may one day get a hold of your code. Can you get a discount on insurance with an impecable genetic code? Can you get insurance at all with a code plagued with error? Will Tobacco, drug and even food companies focus their marketing to those that show a susceptibility to addiction?

What if the information becomes public? Will a first date involve a comparison of eachothers genetic makeup? If you're incompatible for producing healthy offspring, do you stop from getting to know someone that could have been your, for the lack of a better term, soul mate? Will you want to know?

EVERYONE carries genes that predispose them to more than one serious or lethal disease. Bioethicists are only beginning to study how that knowledge might affect someone's decisions, from marrying or having children to saving for retirement.

The cost of sequencing will continue to plummet. A "zero-dollar genome" is already forseable, making it likely that it will be a part of routine clinical care.

And here is my microbe spin. There are more bacterial cells in you and on you then there are human cells. What about their DNA? Welcome to your METAgenome! Soon you will know the sequence of your human cells and all the bacterial cells that make you, you! There are many mysterious and still unnamed genetic diseases that are linked to the genetic makeup of your bacteria, and this information will soon be available for solving these riddles.