Carl Zimmer's Blog, page 26

Cancer-Proof Rodents: My New “Matter” Column for the New York Times

Source: http://commons.wikimedia.org/wiki/Fil...

At this weekend’s Cancer and Evolution meeting, one of the highlights was a talk from a husband-and-wife team of biologists at Rochester University about naked mole rats. As far as scientists can tell, naked mole rats don’t get cancer, despite living up to 30 years. That’s pretty remarkable when you consider that another rodent–the lab mouse–has a 47% cancer rate during its brief, two-year life.

So a number of researchers have been searching the biology of naked mole rats for their secret. The Rochester scientists may have found a crucial ingredient in their cancer defense. And, by happy coincidence, Nature is publishing their report today. That’s the subject of my “Matter” column this week. Check it out.

Dracula’s Children

Millions of years ago, some bats gave up their old habits of hunting for insects and tried something new: drinking blood. These creatures evolved into today’s vampire bats, and it’s mind-boggling to explore all the ways that they evolved to make the most of their sanguine meal.

A lot of the adaptations are easy enough to see with the naked eye. Vampire bats have Dracula-style teeth, for example, which they use to puncture the tough hide of cows. When they open up a crater-shaped wound, they dip in their long tongue, which contains two straw-shaped ducts that take up the blood.

Finding these prey has led to another remarkable adaptation that you can see–at least if you’re a scientist who studies how vampire bats move. Like other bats, they can fly, but on top of that, they can also walk and, yes, even gallop. Here is a video of a running vampire bat made by Dan Riskin (see this Loom post for details). Of the 1200 or so species of bats, vampire bats are among the very few that can move quickly on the ground.

Vampire running! from Carl Zimmer on Vimeo.

But vampire bats have many other adaptations for drinking blood that are invisible. They use their combined senses–long-range vision, a sharp sense of smell, acute hearing, and echolocation–to find their victims. In their noses, they even have heat-sensitive pits that detect the heat of warm-blooded animals. Once they land on an animal, they apply those pits to the skin to locate capillaries full of hot blood close to the surface.

Photo by Bruce Dale/National Geographic

When vampire bats dip their tongue into a wound, they don’t just draw out blood. They also put their saliva into their victim. And in this liquid are still more invisible adaptations for a blood-feeding life. Vampire bats, you see, are venomous.

This may sound odd. That’s because we usually think of venom as a chemical an animal sticks in your body to cause you pain or death. But biologists define venom more broadly than that: it’s a secretion produced in a specialized gland in an animal, which is delivered to another animal by inflicting a wound, where it can disrupt its victim’s physiology.

Snake venom, the sort we’re all most familiar with, can disrupt physiology to the point of death. And it does so in several ways–jamming neurons, for example, or causing tissue to rot. But other animals that don’t set out to kill their victims also produce venom. Vampire bats, for example, don’t want eat a whole cow. They just want to take a sip.

Unfortunately, drinking blood has some drawbacks. Vertebrates come equipped with lots of molecules and cells that plug up wounds. As soon as they sense even a tiny tear in a blood vessel, they start making clots to staunch the flow.

Vampire bats use venom to keep the blood flowing. In a new paper with a title worth quoting in full–“Dracula’s Children: Molecular Evolution of Vampire Bat Venom”–an international team of scientists explore the molecules that vampire bats use to subvert blood’s defenses.

What’s most striking about vampire bat venom is how it goes after its victim from so many directions. Blood clots develop through a series of reactions that involve a chain of enzymes. Vampire bats produce different proteins to go after different enzymes in that chain. Platelets, which are cell fragments, also clump around wounds to help heal wounds. Vampire bats make separate compounds that attacks platelets.

To make their venom cocktail, vampire bats have repurposed old molecules for new jobs. When any vertebrate formed a blood clot to stop a wound, it needs to break that clot down once the wound is healed. An enzyme called plasminogen activator creates a supply of molecules called plasminogen, which chops up the clots. Vampire bats produce plasminogen activators in their blood for this job. But they also produce an extra supply in their mouth glands. When the plasminogen activators get into a wound, they use the victim’s own plasminogen to keep the blood flowing.

Once bats borrowed plasminogen activators to use in their venom, the molecules became better adapted to that new job. Normal plasminogen activators get cleared from the blood stream by other enzymes. That’s important for our survival, because otherwise they would hang around and make it hard to form new clots. Vampire bat plasminogen activators have a slightly different shape that shields them from their victim’s enzymes.

Together, these molecules are so effective that a cow will keep bleeding long after a vampire has flown away. While scientists have been studying vampire bat venom for decades, they’re still finding new molecules in the cocktail. The authors of “Dracula’s Children” applied a new method to the search. They caught two vampire bats and cataloged all the genes that were highly active in their mouth glands. The scientists then identified the genes and studied the properties of the proteins they encoded. They discovered dozens of new proteins. Some of them kill microbes, keeping the bat’s food supply clean. Some expand blood vessels, increasing the flow into the wound.

When a cow gets attacked by a vampire bat, it’s not entirely helpless. Ranchers have noticed that when bats feed over and over again on their herds, the cows bleed for a shorter period of time. Scientists have found that this happens because the immune systems of the animals learn to recognize some of the venom molecules and attack them. In the new study, the researchers found venom molecules that can ward off the immune system. But the venom itself is evolving to escape the immune system’s recognition, taking on new shapes that may allow them to go unnoticed.

Reading “Dracula’s Children” gives me a potent sense of deja vu. I recently wrote a feature about ticks for Outside, and in the research for the piece I learned all about how ticks produce saliva loaded with proteins that, among other things, open blood vessels, use our own molecules to break up clots, and do many of the things that vampire bat venom does.

Vampire bats are what you get if you turn a mammal into a tick. And I mean that as the highest compliment.

(For more on the convergences of parasites, see my book, Parasite Rex.)

Permanent Present Tense: My Review of a Remarkable Book On Memory

Say the letters “H M” to a neuroscientist, and chances are he or she will nod knowingly. H.M. was a man who died in 2008. His full name was Henry Molaison, and a surgical procedure in the 1950s left him without much of his memory. Studies on his mind laid the groundwork for our understanding of memory today. In tomorrow’s issue of the Wall Street Journal, I review a remarkable biography of Molaison, written by MIT neuroscientist Suzanne Corkin, who studied him from their first meeting in 1962 till his death–and beyond. While it’s not a perfect, it is–pardon the pun–a memorable one.

Putting the Brakes On Cancer’s Evolution

I arrived this afternoon in San Francisco, so that I can participate in an exceptional sort of meeting: the 2nd International Biannual Evolution and Cancer Conference. Friday night I’ll be giving a talk about some of the lessons we can learn about cancer from other animals (details at the end of this post), but for the most part, I’ll be on the receiving end, learning about the latest research at this fascinating crossroads.

Cancer is fundamentally an evolutionary disease, as I explained in a 2007 article for Scientific American. By which I mean that cancer is an inevitable menace to any multicellular organism, which has led the evolution of lots of anti-cancer defenses in our biology. But each time cancer emerges, it plays out in an evolutionary process, a natural selection happening within our own bodies. As new mutations arise, certain cancer cells fare better than others. Tumors evolve, as their cells gaining all sorts of abilities–such as attracting new blood vessels to feed their voracious appetites–that their ancestors didn’t have.

A number of scientists have been exploring ways to approach the battle against cancer, informed by an understanding of how evolution works. It’s a promising idea, but it demands answering a lot of basic questions before too many patients start getting treatments influenced by Darwin. Today, by happy coincidence, one of the organizers of the meeting I’ll be at, Carlo Maley of UCSF, and his colleagues have published a paper on just this sort of work. Their research suggests that one way to fight cancer is to put the brakes on its evolution.

For a decade, evidence has been emerging that a daily dose of aspirin can lower the death rate of several kinds of cancer. Yet the reason why it does so has been locked in a black box. Maley and his colleagues set out to understand that reason. They focused on one particular kind of cancer aspirin can help, which strikes the esophagus. People sometimes develop a pre-cancerous condition called Barrett’s esophagus, in which fast-growing, irregularly shaped cells start to grow on the esophagus lining. Those cells sometimes give rise to full-blown cancer cells, causing esophageal adenocarcinoma.

For years, Maley and his colleagues have been studying a large group of patients with Barrett’s esophagus. For this particular research, they wanted to see how the cancer progressed in people both while they were taking aspirin and while they weren’t. They selected thirteen people from the study and examined biopsies from their esophagus taken over the course of as long as 20 years.

The scientists then looked at a sample of cells from each biopsy and scanned their DNA. This information allowed them to draw evolutionary trees for the cancer cells, so that they could see how the cells had evolved from a common ancestor. By following the branches of the tree, the scientists could identify the new mutations, broken chromosomes, and other abnormalities that arose along the way. They could then calculate the rate at which those abnormalities appeared.

The results were pretty clear. Aspirin cut the rate of new abnormalities in the cancer cells–by a factor of ten. Natural selection only works if there is variation to select from. The more variation there is, the faster it transform a population–whether that population is army ants, marigolds, or cancer cells. Maley’s study suggests that aspirin somehow preserves the integrity of cancer cell DNA and thereby blocks their evolution.

One intriguing finding of the new study is that in many cases, the cells didn’t accumulate their mutations gradually, but in bursts. Could this be an inner punctuated equilibrium? A study on only 13 people can only be preliminary–a dip of the toe into a lake of new ideas. But it also shows just how rich those ideas can be.

[I will be speaking at 7 pm Friday June 14 at Robertson Auditorium on the UCSF Mission Bay Campus at 1675 Owens Street. More details are here. The rapper Baba Brinkman will be performing after my talk. The whole shebang is free.]

Letting Gems Speak: My New “Matter” Column For The New York Times

We typically look at rubies and other gems as treasure, bling, or signs of matrimony. But they are also historians, telling us about what the Earth was like hundreds of millions of years ago. In today’s Matter column in the New York Times, I talk to geologists who treat jewels as archives of planetary history. Check it out.

Poison, Camouflage, and the Rainbow of Evolution

We have a habit of seeing nature in snapshots. We marvel at the adaptation of a species–see Ed Yong today on the maneuverability of cheetahs, for example–and don’t give much though about how it came to be. These snapshots can become downright confusing when we survey the diversity of many different species. Each species may have a radically different solution to the same problem. If one solution is so impressive, how could another one evolve, too?

The cure for this puzzlement is to get away from the snapshots. A species is a blurry, speckled thing. It’s made up of populations spread across a range, and each population is made up of many individuals, each with its own somewhat distinct set of genes. Those genes flow around the range, from individual to individual, mixed into new combinations, some spreading far and wide, some vanishing after a generation.

The picture I’ve reproduced above is a wonderful epitome of that blurriness. It shows frogs that live in Costa Rica at various spots along the Pacific Coast. Some frogs, like the green one at the northern end of the coast, develop colors that help them fade into surrounding vegetation. It’s an impressive way to hide from predators, matching one’s skin to the color of plants.

Other frogs, like the bright red one at the southern end of this picture, are not shy at all. They use brilliant colors, rather than masking ones, in order to ward of predators. These frogs produce poisons in their skin, which can sicken or kill an attacker. By developing a bright color that pops out from the surroundings, frogs can make it easy for birds and other predators to learn to link their appearance to a nasty experience. As a result, the predators stay away.

Same problem–two solutions. Which brings up the question, why would some frogs hide from predators while others tried to get their attention?

And here’s what’s so fascinating about this picture. Those frogs you see are all part of the same species, the granular poison frog, Oophaga granulifera.

In the journal Evolution, Beatriz Willink of the University of Costa Rica and her colleagues take a look at this species’s spectrum from camo green to strawberry red. The frogs don’t just vary in color. They also vary in the way they behave. The green frogs are shy compared to the red ones. Willink and her colleagues found that the green males sang less than half the time that the red male frogs did, for example. The green frogs also spent less time looking for food. In skin and brain alike, the green frogs survive by hiding, while the red frogs fend off death by showing off.

The frogs freely mate with their neighbors, which means that genes from one end of the species range can flow towards the other. And yet those flowing genes have not smeared the species into a single kind of frog. Across just 25 miles or so, they can span the distance from camouflage to conspicuousness.

As effective as those two strategies may be, Willink and her colleagues found that in between the extremes, the frogs were intermediate. Some were yellowish-green, while others were orange. But the intermediates didn’t smoothly grade from one end of the spectrum to the other. They had fascinating jumbles of traits.

There are two ways for frogs to contrast with their surroundings, for example: in brightness and in color. The intermediate frogs had a low brightness contrast, like the green frogs, but a high color contrast, like the red frogs. And instead of having an intermediate level of boldness, they were almost as bold as the red frogs, too.

All the frogs in this species have to cope with predators, and they’re evolving different ways to do so–not just through camouflage or conspicuousness, but in combinations of the two. Willink and her colleagues argue that the low brightness contrast of intermediate frogs is a good way to avoid notice from birds, because their brains seize on changing brightness contrast to notice prey. If that fails, and a bird comes closer to investigate, a frog can still boost its odds of surviving with high color contrast, which is how birds learn to stay away from poisonous prey.

For some reason scientists have yet to work out, the balance of strategies that works best is different at the northern and southern ends of the frog’s range. Ian Wang of the University of California, Davis, has found that the yellow and green populations of frogs evolved from the red one. In other words, they abandoned the showy colors of their ancestors. It’s possible that geography explains why they did so. Northern frogs may face a bigger threat from snakes, for example, which rely on smell instead of vision to recognize dangerous prey.

Wang also found that the green frogs are actually more toxic than the red ones. Rather than waste effort on showy red pigments, perhaps the northern frogs evolved to put their energies into making poison.

Whatever the answer turns out to be, this picture already makes one thing clear: there’s more than one way to be a granular poison frog.

Champions of the Cold: My New Story on Life That Thrives At Low Temperatures

I’m no fan of the cold, so it’s remarkable to me that there are so many species that can thrive at temperatures that would kill me from hypothermia. At Nova Next, I’ve written a feature about these so-called psychrophiles. I take a look at the biochemical secrets to survival at sub-zero temperatures, what psychrophiles can tell us about life on other chilly planets, and how biotechnology might harness their remarkable proteins for all sorts of applications. Check it out.

Today on NPR Talk of the Nation: Second Skeletons and Rare Diseases

AT 3 pm ET today on NPR’s Talk of the Nation, I’ll be talking about my article this month in the Atlantic about a rare disease that creates a second skeleton, as well as the quandary of people with rare diseases more broadly. I’ll be on with Jeannie Peeper, who has the condition I write about and who is one of the main subjects in my piece.

Brilliant Blunders: My Review for the New York Times

Science is not a string of successes. It has its share of errors and misconduct, and acknowledging them does no disservice to the value of scientific research that stands the test of time. So it was a pleasure to review a new book, Brilliant Blunders, by Marco Livio, for the New York Times Book Review. No one is perfect, Livio shows us, even some of the greatest scientists of the modern age. Check it out.

Bird Sex and Why It Matters: My New Column For the New York Times

[image error]

No penis required. Google “cloacal kiss.” Photo by PWIO via Creative Commons [Photo linked to original]

Sex is intriguing in all its forms, and bird sex is particularly intriguing. Some male birds have giant corkscrew-shaped penises, but most have none, thanks to its evolutionary disappearance millions of years ago. For “Matter,” my weekly New York Times column, I take a look at the case of the disappearing penis, and why it’s important to study, despite what some cable news pundits may say. Check it out!

(And for you anatomy junkies, Ed Yong has more!)