Friday, August 8, 2008

.Contagious cancer: The evolution of a killer

By David Quammen

During the early months of 1996, not long before Easter, an amateur wildlife photographer named Christo Baars made his way to the Australian island-state of Tasmania, where he set up camp in an old airport shack within the boundaries of Mount William National Park. Baars’s purpose, as on previous visits, was to photograph Tasmanian devils, piglet-size marsupials unique to the island’s temperate forests and moors. Because devils are nocturnal, Baars equipped his blind with a cot, a couple of car batteries, and several strong spotlights. For bait he used road-kill kangaroos. Then he settled in to wait.

The devil, known to science as Sarcophilus harrisii, lives mostly by scavenging and sometimes by predation. It will eat, in addition to kangaroo meat, chickens, fish, frogs, kelp maggots, lambs, rats, snakes, wallabies, and the occasional rubber boot. It can consume nearly half its own body weight in under an hour, and yet—with its black fur and its trundling gait—it looks like an underfed bear cub. Fossil evidence shows that devils inhabited all of Australia until about 500 years ago, when competition with dingoes and other factors caused them to die out everywhere but in Tasmania, which dingoes had yet to colonize. More recently, Tasmanian stockmen and farmers have persecuted devils with the same ferocity directed elsewhere at wolves and coyotes. The devils’ reproductive rate, opportunistic habits, and tolerance for human proximity, however, have allowed localized populations to persist or recover, and at the time of Baars’s 1996 visit, their total number was probably around 150,000.

On his earlier visits, Baars had seen at least ten devils every night, and they were quick to adjust to his presence. They would walk into his blind, into his tent, into his kitchen, and he could recognize returning individuals by the distinctively shaped white patches on their chests. This trip was different. On the first night, his bait failed to attract a single devil, and the second night was only a little better. He thought at first that maybe the stockmen and farmers had finally succeeded in wiping them out. Then he spotted a devil with a weird facial lump. It was an ugly mass, rounded and bulging, like a huge boil, or a tumor. Baars took photographs. More devils wandered in, at least one of them with a similar growth, and Baars took more pictures. This was no longer wildlife photography of the picturesque sort; it was, or anyway soon would become, forensic documentation.

Back in Hobart, Tasmania’s capital, Baars showed his pictures to Nick Mooney, a veteran officer of Tasmania’s Parks and Wildlife Service who has dealt with the devil and its enemies for decades. Mooney had never seen anything like this. The lumps looked tumorous, yes—but what sort of tumor? Mooney consulted a pathologist, who suggested that the devils might be afflicted with lymphosarcoma, a kind of lymphatic cancer, maybe caused by a virus passed to the devils from feral cats. Such a virus might also be passed from devil to devil, triggering cancer in each.

More evidence of contagion began to accumulate. Three years after Baars shot his photographs, a biologist named Menna Jones took note of a single tumor-bearing animal, something she had not seen before. Then, in 2001, at her study site along Tasmania’s eastern coast, her traps yielded three more devils with ulcerated tumors. That really got her attention. She euthanized the animals and brought them to a lab, where they became the first victims to be autopsied by a veterinary pathologist. The “tumors” (until then the term had been only a guess or a metaphor) did seem to be cancerous malignancies, but not of the sort expected from a lymphosarcoma- triggering virus. This peculiarity raised more questions than it answered. Tasmanian devils in captivity were known to be quite susceptible to cancer, at least in some circumstances, possibly involving exposure to carcinogens. But the idea that the cancer itself was contagious seemed beyond the realm of possibility. And yet, during the following year, Menna Jones charted the spread of the problem across northern Tasmania. Nick Mooney, meanwhile, had done some further trapping himself. At a site in the northern midlands, he captured twenty-three devils, seven of which had horrible tumors. Shocked and puzzled, he remembered the Baars photos from years earlier.

Further trapping (more than a hundred animals, of which 15 percent were infected) showed Mooney what Jones had also seen: that the tumors were consistently localized on faces, filling eye sockets, distending cheeks, making it difficult for the animals to see or to eat. Why faces? Maybe because devils suffer many facial and mouth injuries—from chewing on brittle bones, from fighting with one another over food and breeding rights, from the rough interactions between male and female when they mate. The bigger tumors were crumbly, like feta cheese. Could it be that tumor cells, broken off one animal, fell into the wounds of another, took hold there, and grew? This prospect seemed outlandish, but the evidence was leading inexorably to a strange and frightening new hypothesis: the cancer itself had somehow become contagious.

Under ordinary circumstances, cancer is an individuated phenomenon. Its onset is determined partly by genetics, partly by environment, partly by entropy, partly by the remorseless tick-tock of time, and (almost) never by the transmission of some tumorous essence. It arises from within (usually) rather than being imposed from without. It pinpoints single victims (usually) rather than spreading through populations. Cancer might be triggered by a carcinogenic chemical, but it isn’t itself poisoning. It might be triggered by a virus, but it isn’t fundamentally viral. Cancer differs also from heart disease and cirrhosis and the other lethal forms of physiological breakdown; uncontrolled cell reproduction, not organ dilapidation, is the problem.

Such uncontrolled reproduction begins when a single cell accumulates enough mutations to activate certain growth-promoting genes (scientists call them oncogenes) and to inactivate certain protections (tumor suppressor genes) that are built into the genetic program of every animal and plant. The cell ignores instructions to limit its self-replication, and soon it becomes many cells, all of them similarly demented, all bent on self-replication, all heedless of duty and proportion and the larger weal of the organism. That first cell is (almost always) a cell of the victim’s own body. So cancer is reinvented from scratch on a case-by-case basis, and this individuation, this personalization, may be one of the reasons that it seems so frightening and solitary. But what makes it even more solitary for its victims is the idea, secretly comforting to others, that cancer is never contagious. That idea is axiomatic, at least in the popular consciousness. Cancer is not an infectious disease. And the axiom is (usually) correct. But there are exceptions. Those exceptions point toward a broader reality that scientists have begun to explore: Cancers, like species, evolve. And one way they can evolve is toward the capacity to be transmitted between individuals.

Devil tumor isn’t the only form of cancer ever to achieve such a feat. Other cases have occurred and are still occurring. The most notable is Canine Transmissible Venereal Tumor (CTVT), also called Sticker’s sarcoma, a sexually transmitted malignancy in dogs. Again, this is not merely an infectious virus that tends to induce cancer. The tumor cells themselves are transmitted during sexual contact. CTVT is widespread (though not common) and has been claiming dogs around the world at least since a Russian veterinarian named M. A. Novinsky first noted it in 1876. The distinctively altered chromosome patterns shared by the cells of CTVT show the cancer’s lineal continuity, its identity across space and through time. Tumor cells in Dog B, Dog C, Dog D, and Dog Z are more closely related to one another than those cells are to the dogs they respectively inhabit. In other words, CTVT can be conceptualized as a single creature, a parasite (and not a species of parasite, but an individual), which has managed to spread itself out among millions of different dogs. Research by molecular geneticists suggests the tumor originated in a wolf, or maybe an East Asian dog, somewhere between 200 and 2,500 years ago, which means that CTVT is probably the oldest continuous lineage of mammal cells presently living on Earth. The dogs may be young, but the tumor is ancient.

Unlike devil tumor—now known as Devil Facial Tumor Disease, or DFTD—CTVT is generally not fatal. It can be cured with veterinary surgery or chemotherapy. In many cases, even without treatment, the dog’s immune system eventually recognizes the CTVT as alien, attacks it, and clears it away, just as our own immune systems eventually rid us of warts.

The case of the Syrian hamster is more complicated. This tumor arose around 1960, when researchers at the National Cancer Institute, in Bethesda, Maryland, performed an experiment in which they harvested a naturally occurring sarcoma from one hamster and injected those cells (as cancer scientists often do) into healthy animals. When the injected hamsters developed malignancies, more cells were harvested. Each such inoculation-and-harvest cycle is called a passage. The experiment involved a dozen such passages, and over time the tumor began to change. It had evolved. The later generations, unlike the first, represented a sort of super tumor, capable of getting from hamster to hamster without benefit of a needle. The researchers caged ten healthy hamsters together with ten cancerous hamsters and found that nine of the healthy animals acquired tumors through social contact. The hamster tumor had leapt between animals—or anyway, it had been smeared, spat, bitten, and dribbled between them. (The tenth hamster got cannibalized before it could sicken.) In a related experiment, the tumor even passed between two hamsters separated by a wire screen. The scientists had in effect created a laboratory precursor of what would eventually afflict Tasmanian devils in the wild: a Frankenstein malignancy, a leaping tumor, which could conceivably kill off not just individuals but an entire species.

Early last summer I went to Tasmania, where I met Menna Jones for an excursion to the Forestier Peninsula, a long hook of land that juts southeastward into the Tasman Sea. Jones supervises an experimental trapping program aimed at ridding the peninsula of tumor disease or, at least, determining whether that goal is achievable. The Forestier is a good place for such trials because the peninsula (and its lower extension, a second lobe called the Tasman Peninsula) is connected to the rest of Tasmania by only a narrow neck—just a two-lane bridge across a canal. If the disease could be eradicated from the entire peninsula, by removing all sick animals and leaving the healthy ones, Forestier and Tasman might be protected from re-infection by a devil-proof barrier across the bridge; and if that worked, the protected population could rebound quickly. The Forestier Peninsula, full of good habitat, might become a vital refuge for the species. Those measures might even validate a method—defense by tourniquet—that could be used on some of Tasmania’s other peninsular arms.

Jones, who is a brisk, cordial woman with a mane of brown hair, picked me up in an official state Land Cruiser, and as she drove she described the effects seen so far. Her field people had culled more than a hundred devils within the past four months, she said, and though the size of the Forestier population seemed to be holding steady, the demographics had changed. Mature adults, the four- and five-year-olds, were being lost, and so three-year-olds, adolescents, were accounting for most of the parenthood. The biting associated with breeding brings fatal disease, and the disease kills fast—sex equals death, a bad equation for any species. “We think extinction is a possibility within twenty-five years,” Jones said.

We crossed the little bridge onto the peninsula and, after a short drive through rolling hills of eucalyptus forest, rendezvoused with the trapping crew. The chief trapper was a young woman named Chrissy Pukk, Estonian by descent, Aussie by manner, wearing a pair of blue coveralls, a dangling surgical mask, and a leather bush hat. She had been trapping devils here for three years. Jones and I tagged along as Pukk and two volunteers worked a line of forty traps placed throughout the forest. The catch rate was high, and most of the captured devils had been caught previously and injected with small electronic inserts for identification. These devils came in on a regular basis, as if the traps were soup kitchens, and Pukk recognized many of them on sight. She and only she handled the animals, cooing to them calmingly while she took their measurements, checked their body condition, and, most crucially, examined their faces for injuries and signs of tumor. One devil, a robust male Pukk called Captain Bligh, showed wounds from a recent mating session: broken teeth, a torn nose, a half-healed cut below his jaw, and a suppurating pink hole on the top of his snout, deep enough that it might have been made by a melon scoop. But he seemed to be clean of tumor. ’s just a brawler,” Pukk said. She released him, and he skittered off into the brush.

“You see a lot of old friends come and go,” Pukk told me as she examined another animal. For instance, there was one she had caught the day before, a male called Noddy. She had last trapped him less than a week earlier, noted inflamed whisker roots, and released him; but in the brief passage of days, those inflammations had become tumors, and now Noddy was awaiting his fate in a holding trap.

Colette Harmsen, a veterinarian who had made the long drive south from Tasmania’s Animal Health Laboratory at Mount Pleasant, was there to euthanize and autopsy any animal Pukk found unfit for release. She wore her black hair cut short, her jeans torn at the knee, a lacey black dress over the jeans, a black T-shirt reading save tassie’s forests over the dress, and, over it all, a pale blue disposable surgical smock. She was waiting at her pickup truck along with her pit bull, Lily, and her pet rat, CC, when Pukk arrived to deliver the unfortunate Noddy. Pukk and her crew returned to the trap line, Menna Jones went back to Hobart, and I stayed to watch Harmsen work. I had never seen anyone cut open a Tasmanian devil.

Her working slab was the tailgate of her pickup, spread with a clean burlap sack; her scalpels, syringes, and other tools came from a portable kit. First she anesthetized Noddy with gas. Then, after drawing blood samples from deep in his heart, she injected him with something called Lethabarb, which killed him. She measured his carcass, inspected his face, and then sliced an olive-size lump off his right cheek just below the eye. She showed me the lump’s interior: a pea-size core of pale tissue surrounded by normal pink flesh. She put a chunk of it into a vial; that would go to a lab up at Mount Pleasant, she said, to be grown for chromosome typing. From the left side of the face, among the whiskers, Harmsen cut another tumor. Noddy lay limp on the burlap, both cheeks sliced away, like a halibut. When she slit open his belly and found an abundance of healthy yellow fat, she sighed. “He was in good condition.” The disease hadn’t progressed far. There was no sign of metastasis. But the protocols of the trapping program on Forestier don’t include therapeutic surgery and chemo. Harmsen put a bit of Noddy’s liver, a bit of his spleen, and a bit of his kidney into formalin. Those samples, too, would go back to Mount Pleasant for analysis. She wrapped the rest of Noddy in his burlap shroud, put him in a plastic garbage bag, and sealed that with tape. He would be incinerated. Then she cleaned up, fastidiously, to eliminate the chance that tumor cells might pass from her tailgate or her tools to another animal.

The phenomenon of transmissible tumors isn’t confined to canines, Tasmanian devils, and Syrian hamsters. There have been human cases, too. Forty years ago a team of physicians led by Edward F. Scanlon reported, in the journal Cancer, that they had “decided to transplant small pieces of tumor from a cancer patient into a healthy donor, on a well informed volunteer basis, in the hope of gaining a little better understanding of cancer immunity,” which they thought might help in treating the patient. The patient was a fifty-year-old woman with advanced melanoma; the “donor” was her healthy eighty-year-old mother, who had agreed to receive a bit of the tumor by surgical transplant. One day after the transplant procedure, the daughter died suddenly from a perforated bowel. Scanlon’s report neglects to explain why the experiment wasn’t promptly terminated—why they didn’t dive back in surgically to undo what had been done to the mother. Instead, three weeks were allowed to pass, at which point the mother had developed a tumor indistinguishable from her daughter’s. Now it was too late for surgery. This cancer moved fast. It metastasized, and the mother died about fifteen months later, with tumors in her lungs, ribs, lymph nodes, and diaphragm.

The case of the daughter–mother transplant and the case of the Syrian hamsters have one common element: the original sources of the tumor and the recipients were genetically very similar. If the genome of one individual closely resembles the genome of another (as children resemble their parents, and as inbred animals resemble one another), the immune system of a recipient may not detect the foreignness of transplanted cells. The hamsters were highly inbred (intentionally, for experimental control) and therefore not very individuated from one another as far as their immune systems could discern. The mother and daughter were also genetically similar—as similar as two people can be without being identical twins. Lack of normal immune response, because of such closeness, goes some way toward explaining why those tumors survived transference between individuals.

Low immune response also figures in two other situations in which tumor transmission is known to occur: pregnancy and organ transplant. A mother sometimes passes cancer cells to her fetus in the womb. And a transplanted organ sometimes carries tiny tumors into the recipient, vitiating the benefits of receiving a life-saving liver or kidney from someone else. Cases of both kinds are very rare, and they involve some inherent or arranged compatibility between the original victim of the tumor and the secondary victim, plus an immune system that is either compromised (by immuno-suppressive drugs, in the organ recipient) or immature (in the fetus).

Other cases are less easily explained. In 1986, two researchers from the National Institutes of Health reported that a laboratory worker, a healthy nineteen-year-old woman, had accidentally jabbed herself with a syringe carrying colon-cancer cells; a colonic tumor grew in her hand, but she was rescued by surgery. More recently, a fifty-three-year-old surgeon cut his left palm while removing a malignancy from a patient’s abdomen, and five months later he found himself with a palm tumor, one that genetically matched the patient’s tumor. His immune system responded, creating an inflammation around the tumor, but the response was insufficient and the tumor kept growing. Why? How? It wasn’t supposed to be able to do that. Again, though, surgery delivered a full cure. And then there’s Henri Vadon. He was a medical student in the 1920s who poked his left hand with a syringe after drawing liquid from the mastectomy wound of a woman being treated for breast cancer. Vadon, too, developed a hand tumor. Three years later, he died of metastasized cancer because neither the surgical techniques of his era nor his own immune system could save him.

The tumor that I had watched Colette Harmsen harvest from Noddy’s face would be examined at the Mount Pleasant labs by Anne-Maree Pearse and her assistant Kate Swift. Pearse is a former parasitologist, now working in cell biology, and she has a special interest in the genetics of Devil Facial Tumor Disease. She and Swift were the researchers who, in 2006, published a dramatic report in the British journal Nature that, with eight paragraphs of text and a single photographic image, had answered the lingering question about whether DFTD is a genuinely transmissible cancer.

Pearse came out of retirement (she had turned to running a flower farm) in response to the scientific conundrum of DFTD. A back injury has forced the use of a cane on her, but she is vigorous when describing her research. Although she was originally trained as an entomologist, her work with fleas drew her into the world of parasitology, and from there it was just a few more steps into oncology and the study of lymphomas among the devil and its close marsupial relatives. “Somehow my whole life was preparing me for this,” she said when I visited her lab at Mount Pleasant. She added, almost appreciatively: “This disease.” Pearse tends to think, as she put it, “outside the square”—a useful trait in the case of DFTD, she said, because the disease isn’t behaving like anything heretofore known. “It’s a parasitic cancer,” she told me. “The devil’s the host.”

For the 2006 study, Pearse and Swift examined chromosome structure in tumor cells from eleven different devils. They found that the tumor chromosomes were abnormal (misshapen, some missing, some added) compared with those from healthy devil cells, but that the tumor chromosomes, from one cell or another, from one tumor or another, were abnormal in all the same ways. You could see that comparison graphically in the photo in Nature: fourteen nice sausages matched against thirteen variously mangled ones. Those thirteen chromosomes, wrote Pearse and Swift, had undergone “a complex rearrangement that is identical for every animal studied.” The mangling was unmistakable evidence. It appeared in each tumor, but not elsewhere in each animal. “In light of this remarkable finding and of the known fighting behavior of the devils,” Pearse and Swift wrote, “we propose that the disease is transmitted by allograft”—tissue transplant—“whereby an infectious cell line is passed directly between the animals through bites they inflict on one another.”

Pearse and Swift had proved that DFTD is a highly infectious form of cancer, its transmission made possible by, among other factors, the habit of mutual face-biting. When I visited Menna Jones, she expressed the same idea: “It’s a piece of devil tissue that behaves like a parasite.” Jones was using the word “parasite” in its strict biological sense, meaning: any organism that lives on or within another kind of organism, extracting benefit for itself and causing harm to the other. The first rule of a successful parasite is, Don’t kill your host—or at least, Don’t kill one host until you’ve had time to leap aboard another. DFTD, passing quickly from devil to devil, killing them all but not quite so quickly, follows that rule.

How does any parasite, whether it is a species or merely a tumor, acquire the attributes and tactics necessary for survival, reproduction, and continuing success? The answer is simple but not obvious: evolution.

Cancer and evolution have traditionally been considered separately by different scientists with different interests using different methods. You could graduate from medical school, you could follow that with a Ph.D. in cell biology or molecular genetics, you could become a respected oncologist or a well-funded cancer researcher, without ever having read Darwin. You could do it, in fact, without having studied much evolutionary biology at all. Many cell and molecular biologists tended even to scorn evolutionary biology as a “merely descriptive” enterprise, lacking the rigor, quantifiability, and explanatory power of their disciplines. There were exceptions to this disconnect, cancer scientists who even during the early days thought in evolutionary terms, but those scientists had little influence.

In recent decades, however, the situation has changed, as molecular genetics and evolutionary biology have converged on some shared questions. One signal act of synthesis occurred in 1976 when a leukemia researcher named Peter Nowell published a theoretical paper in Science titled “The Clonal Evolution of Tumor Cell Populations.” Nowell proposed what was then a novel idea: that the biological events occurring when cells progress from normal to pre-cancerous to cancerous represent a form of evolution by natural selection. As with the evolution of species, he suggested, the evolution of malignant tumors requires two conditions: genetic diversity among the individuals of a population and competition among those individuals for limited resources. Genetic diversity within one mass of pre-cancerous cells comes from mutations—copying errors and other forms of change—that yield variants as the cells reproduce. That is, in the very act of replicating themselves (sometimes inaccurately), the cells diversify into a population encompassing some small genetic differences between one cell and another. Each variant cell then replicates itself true to type, constituting a clonal lineage (a lineage of accurate copies), until the next mutation creates a new variant. The fittest variants survive and proliferate. By this means, the genetic character of the cell population gradually changes, and with such change comes adaptation, a better fit to environmental circumstances. What constitutes “the fittest” among clonal lineages within a pre-cancerous growth? Those that can reproduce fastest. Those that can resist chemotherapy. Those that can metastasize and therefore escape the surgeon’s knife.

Nowell’s hypothesis about tumor evolution became widely known and accepted within certain circles of cancer research. (Among other researchers, it wasn’t adamantly disputed but merely ignored.) Those circles have more recently produced a lot of rich theorizing, and a smaller amount of empirical work, supporting Nowell and carrying his idea forward. A culmination of sorts occurred in 2000, when the cancer geneticist Robert Weinberg, discoverer of the first human oncogene and the first tumor suppressor gene, published a concise paper titled “The Hallmarks of Cancer.” Weinberg and his coauthor, Doug las Hanahan, described six “acquired capabilities,” such as endless self-replication, the ignoring of antigrowth signals, the invasion of neighboring tissues, and the refusal to die, that collectively characterize cancer cells. How are those capabilities acquired? By mutations and other genetic changes, giving cells with one such trait or another competitive advantage over normal cells. Hanahan and Weinberg added that “tumor development proceeds via a process formally analogous to Darwinian evolution.” With this cautious phrasing, they gave authoritative endorsement to the idea that Peter Nowell had proposed: Cancers, like species, evolve.

In 1998 a young researcher named Carlo Maley began looking for a way to study the evolution of cancer. Educated at Oxford and MIT as an evolutionary biologist and a computer modeler, Maley had no training in medicine and not much in molecular biology. During a postgraduate fellowship, though, he became interested in infectious disease. He figured that if evolution was cool, then coevolution—wherein both parasite and host are evolving—would be doubly cool. Then he stumbled across a description of cancer as an evolving disease. He read that Sir Walter Bodmer, a British geneticist and the former director of the Imperial Cancer Research Fund, had urged his cancer- research colleagues to “think evolution, evolution, evolution” when they considered tumor cells. Maley typed “evolution and cancer” into a search engine for the scientific literature, which turned up very little. He did learn of Nowell’s hypothesis, but that was just theory. He was groping. He had done plenty of theoretical modeling, but for this task he needed the desperate realities, and the data, of clinical oncology.

And then, at a workshop in Seattle, Maley met Brian Reid, an experienced cancer researcher studying something called Barrett’s esophagus, a pre-cancerous condition of the lower throat. They hit it off. Reid had the right clinical situation but wasn’t deeply versed in evolutionary biology; Maley had the right background. They agreed to collaborate.

Reid and his colleagues possessed sixteen years of continuous data on Barrett’s patients and a tissue bank going back to 1989. They knew which patients had developed esophageal cancer and which hadn’t, and they could match those outcomes against what they had seen in cell cultures and genetic work from earlier in the patients’ history. So they could ask evolutionary questions that were answerable from patterns in the data. The most basic question was: Did tumors become malignant through evolution by natural selection? The other big question was: Can doctors predict which pre-cancerous growths will turn malignant? Maley and Reid, along with additional collaborators, found that case histories of Barrett’s esophagus tend to confirm Nowell’s hypothesis. Cancerous tumors, like species, do evolve. And from the Barrett’s data, predictions can be made. The higher the diversity of different cell variants within a pre-cancerous growth, the greater the likelihood that the growth will progress to malignancy. Why? Because of the basic Darwinian mechanism. Genetic diversity plus competitive struggle eliminates unfit individuals and leaves the well-adapted to reproduce.

Maley and Reid have more recently taken such thinking one step beyond evolution—into ecology. Along with Lauren M. F. Merlo (as first author) and John W. Pepper, they published a provocative paper titled “Cancer as an Evolutionary and Ecological Process,” in which they discussed not just tumor evolution but also the ecological factors that form evolution’s context, such as predation, parasitism, competition, dispersal, and colonization. Dispersal is travel by venturesome individuals, which in some cases allows species to colonize new habitats. Merlo, Maley, and their colleagues noted three ways in which the concept of dispersal is applicable to cancer: small-scale cell movement within a tumor (not very important), invasion of neighboring tissues (important), and metastasis (fateful).

Reading that, I remembered Devil Facial Tumor Disease and wondered whether there might not be a fourth way: transmissibility. An infectious cancer is a successful disperser. It colonizes new habitat. DFTD seems to be dispersing and colonizing, much as pigeons disperse across oceans, colonizing new islands. This wasn’t just evolution; it was evolutionary ecology.

I called one of the paper’s coauthors, John W. Pepper, an evolutionary biologist at the University of Arizona, and asked whether I was stretching the notion too far. No, he said, you’re not. If he could revise that paper again, Pepper told me, he would insert the idea that tumors evolve toward transmissibility.

Eight hundred million years ago there was no such thing as cancer. Virtually all living creatures were single-celled organisms, and the rule was Every cell for itself! Uncontrolled, undifferentiated cell growth wasn’t abnormal. It was the program of all life on Earth.

Then, around 700 million years ago, things changed. Paleontologists call this event the Cambrian explosion. Complex multicellular animals, metazoans, appeared. And not just metazoans but metaphytes, too—that is, multicellular plants. How did it happen? Very gradually, as single-cell creatures resembling bacteria or algae began to aggregate into colonial units and discover, by trial and error, how they could benefit from division of labor and specialization of shape and function. To enjoy those benefits, they had to set aside the old rule of absolute selfishness. They had to cooperate. They couldn’t cheat against the interests of the collective entity. (Or anyway they shouldn’t cheat, not very often; otherwise the benefits of collectivity wouldn’t accrue.) Cooperation was a winning formula. Primitive multicellular creatures, roughly along the lines of jellyfish or sponges or slime molds, began to succeed, to grow, to occupy space, and to claim resources in ways that loner cells couldn’t. You can see their imprints in the Burgess Shale: weird things like sci-fi vermin, pre-vertebrate, pre-insect, that seem to have been built out of bubble wrap and old Slinkys. They succeeded for a while, then gave way to still better designs. Multicellularity offered wide possibilities.

But uncontrolled cell replication didn’t disappear entirely. Sometimes a single atavistic cell would ignore the collective imperative; it would revert to the old habit—proliferating wildly, disregarding all signals to stop. It would swell into a big, greedy lump of its own kind, and in so doing disrupt one or more of the necessary collective functions. That was cancer.

The risk of runaway cell replication remained a factor in the evolutionary process, even as multicellular creatures increased vastly in complexity, diversity, size, and dominance on our planet. And species responded to that risk just as they responded, incrementally and over long periods of time, to other such risks as predation or parasitism: by acquiring defenses. One such defense is the amazing ability of living cells to repair mutated DNA, putting the cell program back together properly after a mishap during cell replication. Another defense is apoptosis, a form of programming that tells a cell not to live forever. Another is cellular senescence, during which a cell continues to live but no longer is capable of replicating. Another is the distinction between stem cells and differentiated cells, which limits the number of cells responsible for cell-replacement activity and thereby reduces the risk of accumulated mutations. Another is the requirement for biochemical growth signals before a cell can begin to proliferate. Many of these defenses are controlled by tumor-suppressor genes, such as the one that produces a protein that prevents cells from replicating damaged DNA. Nobody knows just how many anti-cancer defenses exist within a given species (we humans seem to have more than mice do, and possibly not so many as whales), but we do know that they make our continuing lives possible.

Tumors, in the course of their own evolution from one normal cell to a cancerous malignancy, circumvent these natural defenses. They may also change in response to externally imposed defenses, such as surgery, chemotherapy, and radiation. The fittest cells, in Darwinian terms, are those that reproduce themselves most quickly and aggressively, resisting all signals to desist and all attempts to kill them. The victim (that is, the human or the Tasmanian devil or the Syrian hamster) suffers the consequences, having become the arena for an evolutionary struggle at a scale far different from that of its own struggle to survive. But the principles of the struggle are the same at each scale.

This process, whereby cells mutate, reproduce, and proliferate differentially within a body, is called somatic evolution. It stands as a counterpoint to organismic evolution (progressive changes at the scale of whole bodies within a population), and the opportunities for it to proceed are abundant. According to one count, at least 291 genes in the human body contribute, when damaged by mutation, toward somatic evolution.

Mutations occur when something goes wrong during cell replication. A cell replicates by copying its DNA (sometimes inaccurately), sorting the DNA into two identical parcels of chromosomes, then splitting into two new cells, each with its own chromosomes. This process is called mitosis. The goal is not to generate an ever-higher number of cells during a creature’s adult lifetime but simply to replace old cells with new ones. Mitosis counterbalanced with apoptosis, cell death, should provide a constant supply. But each time a mitotic division occurs, there is some very small chance of mutation. And the many small chances add up. A human body contains about 30 trillion cells. The number of cell divisions that occur in a lifetime is far larger: 10,000 trillion. A disproportionately large share of those divisions occurs in epithelial cells, which serve as boundary layers or linings, such as the skin and the interior surface of the colon. That’s why skin cancer and colon cancer are relatively common—more cell turnover, more chance of mutation and evolution.

How many mutations does it take for a malignancy to occur? Estimates range from three to twelve, in humans, depending on the form of cancer. Five or six is considered an operational average for purposes of discussion. Here’s some good news: For a cell to acquire those five or six changes, at the usual rate of mutation, is highly, highly, highly unlikely. The odds are great against quintuple mutation in any given cell, making cancer seem impossible within a human lifespan. One form of mutation, however, can vastly increase the later rate of mutation, which gives the pre-cancerous cells many more chances to become malignant.

In the United States, about 40 percent of us will eventually get cancer bad enough to be diagnosed. And autopsies suggest that virtually all of us will be nurturing incipient thyroid cancer by the time we die. Among octogenarian and nonagenarian men, 80 percent carry prostate cancer when they go. Cancer is terrible, cancer is dramatic, but cancer isn’t rare. In fact, it’s nearly universal.

The biological mystery of how the Tasmanian devil’s rogue tumor manages to establish itself in one animal after another is still unsolved. But a good hypothesis has been offered by an immunologist named Greg Woods at the University of Tasmania. Woods and his group studied immune reactions in Sarcophilus harrisii, which seem generally to be normal against ordinary sorts of infection. Against DFTD cells, though, no such reaction occurs. “The tumor is just not seen by the immune system, because it just looks too similar,” Woods told me when I stopped by his lab. The devils have low genetic diversity, probably because they inhabit a small island, they colonized it originally by way of just a few founders, and they have passed through some tight population bottlenecks in the centuries since. They’re not quite so alike one another as a bunch of inbred hamsters, but they’re too alike for their own good in the current sad, anomalous circumstances. Their immune systems don’t reject the tumor cells because, Woods suspects, in each animal the critical MHC genes (the major histocompatibility complex, which produces proteins crucial to immunological policing) are all virtually identical, and the devils’ police cells can’t distinguish “him” from “me.”

Most of the DFTD team are, like Greg Woods and Anne-Maree Pearse, located in Hobart or Launceston. Most of the animals aren’t. So, two days after the autopsy on Noddy, I drove back to the Forestier Peninsula for another round of trapping with Chrissy Pukk and her crew. It wasn’t that I expected to learn any new angles on the science. I just wanted to see more Tasmanian devils.

This time, Pukk issued me my own pair of blue coveralls. As we set off along the trap line, she exuded the contentment of a joyously crude tomboy enjoying the best job in the world: trapping devils for the good of the species. The only downside was the necessity of issuing a death sentence to any animal with a trace of tumor. “You get attached to the individuals,” she admitted. “But you’ve got to remember all the other individuals you can save if you take that animal out early on.”

Wouldn’t this be less difficult emotionally, I asked her, if you gave them numbers instead of names? She answered the question—saying she couldn’t do her work properly if she wasn’t emotionally invested, plus which, names were easier to remember—and then she continued to answer it throughout the day. These creatures, they all have their memorable eccentricities, their little histories, she explained. Some she could recognize almost by smell. You couldn’t do that with numbers.

There were forty traps again today, and about a dozen trapped devils to process, all recaptures, previously tagged and named. Trap by trap, animal by animal, Pukk worked through the measurements and the facial exams, handling each devil firmly but with a steady touch that provoked no devilish squirming: Captain Bligh (looking glum, or maybe a little embarrassed at having been caught again so soon), Hipster, Isabel, Masikus (Estonian for “strawberry”), Miss Buzzy Bum (her rump had been full of burrs), Rudolph (thus called for a nose that had been rubbed raw), Sandman, Skipper, and many others. They may have been virtually indistinguishable in the terms by which immune systems operate, but Chrissy Pukk knew each devil at a glance.

Rudolph’s condition gave her pause. He was a two-year-old, nicely grown since she had first trapped him, his red nose healed . . . but there was something on the edge of his right eye. A pink growth, no bigger than a caper. “Oh shit,” she said. Tumor? Or maybe it was just a little wound, puffy and raw. She looked closely. She peered into his mouth. She palpated lymph nodes at the base of his jaw. The volunteers and I waited in silence. Evolution had shaped Rudolph for survival, and evolution might take him away. It was all evolution: the yin of struggle and death, the yang of adaptation, DFTD versus Sarcophilus harrisii. The leaping tumor, well adapted for fast replication and transmissibility, has its own formidable impulse to survive. And no one could know at this point, not even Chrissy, whether it had already leapt into Rudolph.

“Okay,” she said, sounding almost sure of her judgment, “I’m gonna give him the all clear.” She released him and he ran.

At latest report, Devil Facial Tumor Disease has spread across 60 percent of Tasmania’s land surface, and in some areas, especially where it got its earliest start, the devil population seems to have declined by as much as 90 percent. In November, the Tasmanian government classified the devil as “endangered.” DFTD specialists differ strongly on how such a crisis should be met. One view is that suppressing the disease— trapping and euthanizing as many infected animals as possible and then establishing barriers, as on the Forestier Peninsula—is the best strategy. Another view is that the species, virtually doomed on mainland Tasmania, can better be saved by transplanting disease-free devils to a small offshore island. Still another view, maybe the boldest and most risky, is that doing nothing— allowing the disease to spread unchecked—might yield a small remnant population of survivors, with natural immunity to DFTD, who could repopulate Tasmania.

Weeks after my last outing with the trappers, back in the Northern Hemisphere and wanting a broader perspective—not just on the fate of the devils but on the evolution of cancer—I met Robert Weinberg at a stem-cell conference in Big Sky, Montana. Because it was a Sunday, with the first session not yet convened, and because he is a genial man, Weinberg gave me a two-hour tutorial in a boardroom of the ski lodge, fortifying some points by flipping through his own four-pound textbook, The Biology of Cancer, a copy of which I had lugged to our meeting like a student. He was incognito in a plaid Woolrich shirt. He’d be called on that evening to deliver the keynote address, but never mind, he was prepared.

“Infectious cancer is really an aberration,” Weinberg told me, affirming what Greg Woods had said. “It’s so bizarre. It has happened only rarely.” Maybe it’s possible only in cases where there’s close physical contact between susceptible tissues. “That, right away, limits it to venereal tumors, or tumors that can be transmitted by biting.” Weinberg knew that I’d walked in with a head full of Tasmanian devils.

Does this mean that cancer cells are harder to transmit than, say, virus particles? “Much,” he said. “Cells are very effete. Very susceptible to dying in the outside world.” They dry out, they wither, they don’t remain viable when they’re naked and alone. Bacteria can form spores. Viruses in their capsules can lie dormant. But cells from a metazoan? No. They’re not packaged for transit.

And that’s only one of two major constraints, Weinberg said. The second is that if cancer cells do pass from one body to another, they are instantly recognized as foreign and eliminated by the immune system. Each cell of any sort bears on its exterior a set of protuberant proteins that declare its identity; they might be thought of as its travel papers. These proteins are called antigens and are produced uniquely in each individual by the MHC (major histocompatibility complex) genes. If the travel papers of a cell are unacceptable (because the cell is an invader from some other body), the T cells (one type of immunological police cell) will attack and obliterate it. If the invader cell shows no papers at all, another kind of police cell (called NK cells) will bust it. Only if the antigens on the cell surface have been “downregulated” discreetly but not eliminated altogether can a foreign cell elude the immune system of a host. That’s what Canine Transmissible Venereal Tumor seems to have done: downregulated its antigens. It shows fake travel papers—blurry, faded, but just good enough to get by.

Nice trick! How did CTVT do that? Although nobody knows exactly, the best hypothesis is evolution by natural selection—or by some process “formally analogous” to it.

Weinberg went on to explain that the process is a little more complicated than classic Darwinian selection. Darwin’s version works by selection among genetic variations that differentiate one organism from another, and in sexually reproducing species those variations are heritable. But evolution in tumor lineages occurs by that sort of selection plus another sort—selection among epigenetic modifications of DNA. Epigenetic means outside the line of genetic inheritance: acquired by experience, by accident, by circumstance. Such secondary chemical changes to the molecule affect behavior, affect shape, and pass from one cell to another but do not, contrary to the analogy, pass from parent to offspring in sexual reproduction. These changes are peeled away in the process of meiosis (the formation of sperm and egg cells for sexual reproduction) but preserved in mitosis (the process of simple cell replication in the body). So cancerous cell reproduction brings such changes forward into the new cells, along with the fundamental genetic changes.

Does that mean tumors don’t evolve? Certainly not. They do. “It’s still Darwin,” Weinberg said. “It’s Darwin revised.”

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How To Get Better Results In Less Time At The Gym

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By: Sheamus (see more of Sheamus's blogs)

As an experienced strength trainer, one of the biggest mistakes I see new members make is working out for too long, too often. Arnold Schwarzenegger’s two-hour, twice-daily workouts back in the 1970s are the stuff of legend, but times have changed.

Schwarzenegger was a pioneer, but he was also a genetic freak – what worked for him almost certainly won’t work for you. Lifting weights was Schwarzenegger’s life – this is a luxury working people can rarely afford.

Here’s the good news – you can achieve outstanding results by spending less time at the gym! Just follow these simple tips:

Everything Is In The Preparation

The time you spend at the gym is not limited to those minutes when you’re actually working out. Getting your gym kit ready, driving to the gym, getting dressed, getting undressed, showering afterwards, driving home – all this stuff adds up. Get in the habit of considering your total gym time, which includes all of these things plus the actual workout itself. Now, consider what you can do to shave off some precious minutes before and after your workout.

For example:

  • Join a gym that is close to home.
  • If possible, only visit the gym at off-peak, or less busy times
  • Prepare your gym bag the evening before your workout.
  • Consider showering when you get home, rather than at the gym.

Lift Weights No More Than Three Times A Week

As a new gym user, it’s easy to want to get the most value out of your expensive membership, and it’s not uncommon to see people hitting the gym five, six or even seven days a week! Even for a veteran this is counter-productive – your muscles need rest and recovery. By overtraining them you will encourage atrophy. Not only will they not grow, they might even shrink!

For the first 4-6 months of your membership, three visits to the gym each week is more than sufficient to obtain great results without risking damage to your health. It’s also a regimen that is easy to maintain.

Don’t Worry If You Miss A Workout

Life has a habit of putting things in your way, particularly when you’re trying to do something productive. From time to time something will happen that will mean you will have to skip a workout.

Here’s the thing – don’t worry about it. Just make up the workout the next day, or as soon as you can. One great method I’ve used to ensure I get to workout three times per week is to not plan my days off in advance. Many people like to take the weekends off, or only go to the gym Monday, Wednesdays and Fridays. That sounds great on paper, but what if life gets in the way?

While it is essential that the body gets sufficient rest (see below), if you don’t plan your days off and attempt to go to the gym whenever you possibly can, you will find that you miss very few workouts. Think of your gym visits and recovery periods as constantly ongoing – by taking a day off in between each visit, you’ll automatically hit your target of three sessions each week.

Do A Full-Body Workout

None of us are professional bodybuilders, so why do so many of us attempt to follow their workouts? Bodybuilding magazines are notorious for this, endlessly publishing the routines of modern pros that are far too advance and strenuous for regular people.

A full-body workout is a great time-saver but also a regimen that offers the most benefits for beginner and intermediate gym users. Many new gym users concentrate entirely on the so-called ‘beach muscles’ – chest, shoulders and particularly biceps. This is counterproductive, as the largest muscle groups – back and legs – are often completely ignored. The body likes to grow proportionately, so by favouring some muscle groups over others you won’t see the best results.

Focus on the larger muscle groups through compound exercises. These move the body through multiple joint movements and provide complete muscle fibre stimulation, as opposed to isolation exercises, which focus on a single joint.

Example compound exercises include barbell squats, pull-ups, dead lifts, bent-over rows, bench press, military press, dips and lunges. (Tip: search YouTube for working examples of all of these exercises.)

Each full-body workout should contain six or seven of these compound exercises, performed in reverse-order of muscle size, i.e., legs, back, chest and then shoulders. (See example workout below).

Workout For No More Than 40 Minutes!

Your total time at the gym should take no more than 40 minutes, which includes preparation. Ideally, you should be lifting weights for no more than 30 minutes in total, which includes all exercises and rest between sets. Keep the intensity high.

To achieve this, it’s important to look at your workout program intelligently. Each exercise should be broken down into ‘warm-up’ and ‘working sets’ – the former prepares the muscle for the more intensive shock of the latter, which should be heaviest possible weight you can lift while maintaining proper form.

The size of the muscle group will determine the number of sets and repetitions necessary. Additionally, as a muscle group is warmed up there is less of a need for ‘warm-up’ sets with each new exercise.

Here’s an example workout:

Barbell Squat: 2 x 10 (warm-up sets), 2 x 8 (working sets)

Pull Ups: 2 x 10 (weight-assisted), 1 x 8
Dead Lifts: 1 x 10, 1 x 6-8
Bent-Over Rows: 1 x 6-8

Bench Press: 2 x 10, 1 x 6-8

Military Press: 1 x 10, 1 x 6-8

Total Exercises Performed: 6
Total Sets:

Each set, with rest, should last about two minutes, which makes 30 minutes in total.


A superset involves performing two exercises back-to-back without rest. For best results you should use opposing muscle groups. For example, one could superset back with chest by doing one set of pull-ups immediately followed by one set of dips. This counts as one superset. Then rest and repeat. It’s a great way to save time and produces great results. Consider using the superset method on alternate months, as the impact on the body, particularly with compound exercises, is significant.


Rest is essential to muscle gain. If you visit the gym too regularly or don’t have sufficient rest between sets, your progress will suffer.

A good rule of thumb is to rest 45-60 seconds between each set. Consider resting an additional 30 seconds between exercises (i.e., 90 seconds). Be mindful of your total workout time!

If you plan to workout three times per week, you need a minimum of 48 hours of rest between workouts. This is essential. Your body needs the recovery time, and trying to do too much will lead to poor results.

Don’t Waste Time

Increasingly gyms have become places for people to meet and chat with their friends. Don’t waste time chatting at the gym. Leave your mobile phone in your locker and if you workout with friends, keep it as professional as possible.

By following the advice above, you can ensure that your gym sessions will be as productive as possible. Because you’ll be spending less time there but still seeing great results, you'll also have a strong motivation to keep going.

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Woman kills boyfriend for drinking her beer, officials say

Bail set at $500,000 in West Side stabbing death in car

|Chicago Tribune reporter

A West Side woman who allegedly stabbed her elderly boyfriend to death because he was drinking her beer was ordered held Thursday in lieu of $500,000 bail.

Regina Williams, 55, of the 1000 block of North Waller Avenue appeared in Cook County Bond Court before Judge Israel Desierto, charged with first-degree murder in the slaying of Willie Anderson, 77, of the 2200 block of West Monroe Street.

About 6 p.m. Wednesday, the two were sitting in Anderson's car outside his home when Williams became angry that he was drinking her beer, authorities said. They began to quarrel, and Williams allegedly pulled a knife she carried for protection and began stabbing Anderson.

Anderson yelled for help, but Williams continued to stab him, Assistant State's Atty. Susanne Groebner told Desierto.

Afterward, Williams got out of the car and called down the street to Anderson's nephew, saying, "You better come get your uncle—I just killed him," according to her arrest report.

Groebner said Williams got back in the vehicle and finished drinking her beer.

Williams is on probation for a 2007 felony conviction for aggravated battery. In that case she was convicted of spitting in the face of a Chicago Fire Department paramedic who was giving her medical treatment.

Williams has a history of mental illness, according to the Cook County public defender's office.

Her next court date was set for Aug. 26.

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Cutting Back on "Bad" Carbs

Good Carb, Bad Carb

Thanks to the popularity of low-carb diets, nearly half of Americans say they are watching the amount of carbohydrates they eat. If you're among them, we're providing these 16 tips so your carb control is stealthy, healthy, and wise!

Bear in mind that there is a huge difference between Cheese Doodles and oatmeal. Both might be categorized as carbs, but their benefits are on opposite ends of the health spectrum. What is a "bad carb"?. Here's the simplest answer: white flour, refined sugar, and white rice. More broadly, any food made primarily of a carb that has been processed in such a way as to strip out ingredients that hinder quick and easy cooking. Why are refined carbs a problem? Easy: They digest so quickly that they cause blood sugar surges that lead to weight gain and other health troubles.

The carbs in most salads are
The carbs in most salads are "good" because they are also high in fiber.
The carbs in most salads are
The carbs in most salads are "good" because they are also high in fiber.
Here we'll give you ways to avoid troublesome carbs while still getting the fuel you need for good health. Carb-counting meets common sense, right this way...

1. Tell the waiter to hold the bread. At almost every restaurant, your meal starts with a basket of rolls, breads, and crackers made from white flour. If it's not put on the table, you won't eat any. Or, if you really need something to nibble on, ask if they have whole wheat varieties.

2. At Chinese restaurants, ask for brown rice, and limit how much you eat to one cup. In fact, some Chinese restaurants have started offering to swap a vegetable for the rice in their combo dinners, knowing that many people are on low-carb diets. At home, always cook brown rice instead of white. Brown rice hasn't been processed and still has its high-fiber nutrients.

3. Instead of bread, use eggplant slices to make a delicious sandwich. Broil two thick slices of eggplant until brown, then add mozzarella and tomato, olive oil and basil to one slice, suggests Nicole Glassman, owner of Mindful Health in New York City. Top with the other slice of eggplant and broil again until the cheese melts.

4. Wrap your food in lettuce leaves. Yes, skip the bun, tortillas, and bread slices and instead make a sandwich inside lettuce leaves. Glassman suggests going Mexican with a sprinkle of cheddar cheese, salsa, and chicken; Asian with sesame seeds, peanuts, bean sprouts, cut up green beans, and shrimp with a touch of soy sauce; or deli style with turkey, cheese, and mustard.


5. Buy old-fashioned snacks in kid-size bags. Truth is, pretzels, tortilla chips, potato chips, and cookies are mostly bad carbs, made primarily of refined flour, sugar, salt, and/or oil. You want to remove as many of these foods from your daily eating as you can. But if you can't live without them, buy them in small bags -- 1 ounce is a typical "lunch box" size -- and limit yourself to just one bag a day.

6. Break yourself of your old spaghetti habits. Almost everyone loves a big bowl of pasta, topped with a rich tomato sauce. The tomato sauce couldn't be better for you; the spaghetti, however, is pure carbohydrate. While spaghetti is fine to eat every now and then, for those sensitive to carbs or wishing to cut back on their noodle intake, here are some alternatives to the usual spaghetti dinner:
  • Here's the easiest choice: Switch to whole wheat pasta. It is denser than traditional pasta, with a firm, al dente texture similar to what you'd get in Italy.

  • Grill vegetables such as eggplant, zucchini, bell peppers, and onion and slice them into long, thin pieces. Mix up and pour your spaghetti sauce over the vegetables for a delicious and immensely healthy meal.

  • Substitute spaghetti squash for the pasta. Boil or microwave the squash until soft, then scoop out the seeds and pull the strands of squash from the shell with a fork. Top with your favorite sauce and a grating of real Parmesan.

  • Try healthy whole grains as a replacement for pasta. Spaghetti sauce goes better than you'd expect on brown rice, barley, chickpeas, and such.

7. Cut up 1-ounce portions of cheese and divvy up 1-ounce portions of nuts into tiny snack bags. Now you have a handy snack at the ready.

8. Eat potatoes boiled with the skin on. The effect of potatoes on blood sugar depends on how the potatoes are prepared. No need to unspud yourself completely! Also, new potatoes tend to have fewer simple carbs than other types of potatoes.

9. Eat lightly of the new low-carb products. More than 1,000 low-carb products were introduced in 2003, but the FDA has yet to publish any guidelines as to what "low carb" really means. Instead, many new "low carb" foods are to carb-cutting what "low fat" cookies were to fat-cutting: just a new way of pitching foods high in calories and low in nutrient value. In fact, Consumer Reports found that many packaged low-carb foods are actually higher in calories than their regular counterparts. For instance, a serving of Keto's low-carb Rocky Road ice cream has 270 calories, almost double the calories found in many regular ice creams and twice as much fat.

Be Careful

10. Think lightly of the new net-carb measurements. Many of the low-carb weight-loss programs are trying to get their followers to use "net carbs" as the measurement of choice for the appropriateness of a carb food in their diet. This is a measurement of the "bad carbs" left in a food after you adjust for those carb ingredients that don't immediately affect blood sugar. The folks at Atkins Nutritionals say the proper way to measure net carbs is to subtract fiber (as well as sugar alcohols and glycerin, when applicable) from the total carbs listed on the nutrition facts panel of a product. But that's just their version, and that's the problem. "Net carbs" is not a regulated or standardized measurement -- manufacturers can define it how they want, and say what they want on product packaging. And there is no science to say that tracking net carbs offers any unique weight-loss benefit.

11. Never let yourself get too hungry. Eat every three to five waking hours, and eat only until you're satisfied but not stuffed. You should never reach the point where you feel ravenous. Not only is that a recipe for overeating, but your body will want sugary, quick-to-digest "bad carbs" to quickly satiate your need for fuel.

12. Instead of eggs and bacon, try low-carb versions of cereals. For example, the Nature's Path cereal line offers all the benefits of whole grains without the "problem" carbs found in added sugar. Another option is low-carb, high-fiber muffins and breads (spread with no-sugar-added jams or nut butter).

13. At the movies, skip the popcorn. Popcorn isn't a bad food, but it does happen to be a simple carb with little other nutritional value and, when bought at the theater, is often drowning in salt and fat as well. Better movie snacks are small bags of nuts or seeds and fresh or dried fruit. Just sneak them into the theater in your purse or a backpack.

14. Mix up a sweet dessert. Combine nonfat cream, unsweetened cocoa, sugar substitute, and ice in a blender. Or mix mascarpone and sugar substitute with whipped cream and a hint of lemon zest.

15. Make your own quickie low-carb pizza. Lightly toast a whole grain, low-carb tortilla and top with chopped tomatoes and shredded, part-skim, mozzarella cheese. Season with salt and pepper and return to the toaster oven until cheese is melted and bubbling.

16. Make french fries with turnips. Missing those fries with that bun-less burger? Heimowitz suggests cutting turnips into sticks and tossing with olive oil and salt. Bake at 425°F for 30 minutes, turning frequently. Voilà! A crisp side dish with none of the fat of frying and far fewer carbs than from potatoes.

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10 mispronunciations that make you sound stupid

Author: Toni Bowers

Right or wrong, people often judge you by the way you pronounce things. Say a word incorrectly and POW — they’ve pegged you as a provincial, poorly educated moron. Toni Bowers offers a list of commonly mangled words so you can double-check your own pronunciation.

Previously, TechRepublic ran an article about 10 grammar mistakes that make you look stupid. The examples cited involved the misuse of words in written and verbal communications. I’d like to go a step farther here and talk about words that may be used correctly but are pronounced wrong. They also may be much more flagrant examples of stupidity.

A caveat: My ear may be abnormally sensitive to mispronunciations since in college I developed an unnatural affinity for linguistics (can you say “Get a life?”). However, people often make snap decisions about character and intelligence based on their language biases, so it’s something you should be aware of. Here are some of my pet peeves, which you may or may not ever use in your life.

Note: This article originally appeared in our Career Management blog.

#1: Realtor

Many people — I’ve even heard it from people on national TV — pronounce this word REAL-uh-ter. Is this a case of wide-spread dyslexia, transposing the a and the l? It’s REAL-tor. That’s it. You’d think only two syllables would be easier to pronounce, but apparently not.

#2: Nuclear

Do you know how tough it is to be an advocate for the correct pronunciation of this word (NU-clee-er) when the president of the United States pronounces it NU-cu-lar? I don’t buy that it’s a regional thing. Ya’ll is a regional thing; nu-cu-lar is not.

#3: Jewelry

It’s not JOO-la-ree, it’s JOOL-ree. Again with the making things harder by turning a word into three syllables. What’s with that?

#4: Supposedly/supposably

The latter is a nonexistent word.

#5: Supposed to/suppose to

I think this one is more a matter of a lazy tongue than of ignorance. It takes an extra beat in there to emphasize the d at the end, but it’s worth it. And never omit the d if you’re using the term in a written communication or people will think you were raised in a hollowed-out tree trunk somewhere.

#6: Used to/use to

Same as above.

#7: Anyway/anyways

There’s no s at the end. I swear. Look it up.

#8: February/Febuary

As much as it galls me, there is an r between the b and the u. When you pronounce the word correctly it should sound like you’re trying to talk with a mouthful of marbles — FEB broo ary.

#9: Recur/reoccur

Though the latter is tempting, it’s not a word. And again, why add another syllable if you don’t need it?

#10: Mischievous/mischievious

I know, I know, it sounds so Basil Rathbone to say MIS cha vous, but that’s the right way. Mis CHEE vee us is more commonly used, but it’s wrong.

And last but not least, my personal all-time pet peeve — the word often. It should be pronounced OFF un, not OFF tun. The t is silent.

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BP Invests $90 Million in Verenium’s Cellulosic Ethanol Technology

Incredible sand sculpture

Swedish teen girls have more sex with one another

More teenage girls than boys have had sex with someone of the same gender, according to a new dissertation from the Sahlgrenska Academy in Gothenburg.
The result comes as no surprise to the researcher, midwife Gun Rembeck, who works at the primary care clinic in southern Älvsborg.

“I work at the youth health centre and asked the staff there what they thought before I told them about the results. They answered right away that there are more girls,” she said.

Altogether 440 girls and boys aged 17 were questioned for the study.

“It was 6.1 percent of the girls who answered that they had had sex with someone of the same gender, while 1.7 percent of boys said the same thing,” Rembeck explained.

No one is quite sure why the answers are so different between the sexes.

“It may be that girls feel their way forward without identifying themselves as either homo- or heterosexual,” said Rembeck.

She thinks that girls are also more inclined to experiment than boys.

“There is less of a taboo for girls. During their teenage years girls are often a bit more intimate with each other in their own way. Boys are often more worried, afraid to diverge, and the expressed norm is to not be homosexual," Rembeck said.

The study also found that somewhat more girls than boys had also made their sexual debuts.

“It’s possible that girls who know they are oriented toward homosexuality have become sexually active earlier than boys,” she added.

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How To Build a World: The Basics

By Michael Harrison

Fantasyworld Kids love to build their own worlds. They do it without prompting as they "play pretend" with toys and with one another, but some excel and go on to greatness. Everyone takes joy in a good story, but one that is set in a dynamic, believable world really stands out.

When he was a young boy, C.S. Lewis and his brother created the world of Boxen, inhabited by anthropomorphic animals. Lewis later went on to integrate many of his childhood creations into his Narnia books. At age 8, Ed Greenwood wrote of the "stoic swordsman Durnan, the blustering old rogue Mirt, and the all-wise, ancient wizard Elminster." Today, those denizens of the Forgotten Realms are familiar to millions of Dungeons and Dragons players worldwide. Both authors are well-known for their stories, but they're even more renowned for the worlds that they created.

Since August is World Building Month and I've been hard at work on creating the setting for my new D&D campaign, I'll be detailing the hobby, discussing some well-known created worlds, and outlining some tools and tricks that modern worldbuilders can use to craft their own imaginary universes. Read on for an introduction to the basics.

So, why build a world? For GeekDads (and moms), this is a great opportunity to spend some engaging creative time with your kids. If you have a kid who is involved in a roleplaying game like D&D, this is also a wonderful way to put them into the Dungeon Master seat and let them tell some stories of their own.

One other thing I've noticed in my years of world building: creating a new universe makes you ask questions about your own universe. Whether it's philosophical quandaries about gods and warfare, or curiosity about real-world historical events, building your own world inevitably teaches you an awful lot about your own.

Now, the level of detail for your freshly-minted world depends on the age and attention spans of your participants. My own son, at two years, isn't quite ready for a cohesive gazetteer-style "world bible"—he's content to build tiny, throw-away worlds consisting of his toy cars and the garage the cars inhabit—but your mileage may vary.

Before you begin, you should think about your approach. The two basic philosophies for creating a world are the "outside-in" and the "inside-out" methods. I've found that your personality and how you plan on using the world itself will determine the best method for you to use.

Outside-In: Start at the top and paint your world in broad strokes. Create a map that outlines all major continents of the planet, define the nations, determine climate and race, touch on religion and myth and creation.

After you're done with the big stuff, focus on the details. What cities or towns exist within the nations that you created earlier? Create a time line and find out what happened during the Second Age of Man. You put a snowdrift on your map, smack dab in the middle of the otherwise-arid Desert of Drer. Why?

The benefit to the outside-in approach is that your world is very well-defined and cohesive. This makes for fewer plot holes and more realism.

While this completism is certainly satisfying for many, the drawback is that it takes time. A lot of time. There's a reason why Wikipedia has nearly 2.5 million articles. A world that has seen even just a few hundred years of history will have thousands of notable people, places, and things. If that seems like a bit too much work, then the inside-out approach is for you.

Map Inside-Out: Focus instead on one location of the world and give it as much detail as you can. Along the way, develop back stories and personality for important figures and features of the world.

Areas and individuals outside of your initial area are blurry and out-of-focus for now. When you need those parts of the world—usually when characters in your roleplaying campaign or stories reach them—you'll have to flesh them out in more detail.

Benefits? It's easier, for sure, and it's more efficient. If no one ever makes it to the Steppes of Jarkas to investigate the evil temple of the Blind God, then aren't you glad you never wrote up ten pages of descriptions? By focusing on the starting area, you can also hop right into the action.

Sometimes, though, when you don't prepare information ahead of time, you can feel rushed to detail new locales and the world can begin to feel inconsistent. If your characters somehow make a side trek to that temple, you haven't put a lot of thought into this Blind God fellow, so unless you're good at adapting and improvising, the whole scene might fall flat.

Both methods have their ups and downs, and many people feel that a combination of the two is the best approach. Start with an overview but don't worry about details for every little thing. Then switch over to inside-out mode and focus on the part of the world that really strikes your fancy.

Regardless of how you begin, focus on milestones. Try not to get sidetracked by each detail that you come upon. I have a hard time following this advice myself and it can be very time consuming. You find yourself discussing the world's pantheon, only to be distracted by a specific god or goddess. Unless you leave yourself a trail of breadcrumbs, you might find yourself utterly lost within your own creation. This is not necessarily a bad thing, of course, but it's not very effective at getting your world fully fleshed out.

You don't need to be as compulsive as Tolkien, inventing everything down to the genealogies and languages of Middle Earth's inhabitants. When Margaret Weis and Tracy Hickman set about establishing the fantasy world of the Dragonlance novels, they took some cues from the Good Professor. They also realized that the modern reader doesn't really care that the Quenya language has ten basic vowels, six diphthongs, and uses the Tengwar alphabet. Thus the elven languages of Dragonlance were developed with less philological fervor.

Focus on the things that interest you. Tolkien loved his languages, so he started there and built up cultures around them. If you like warfare, start with an epic battle and then figure out who was fighting who and what they were fighting about. If you like magical weapons, start with a cool artifact and then create a back story. Fascinated with monsters? Dragons are a good place to begin.

Next time, I'll talk about some major questions you should ask about your world as you go about creating it, and some tools you can use to organize your burgeoning world.

Original here