June 24, 2013
Sometimes, thinking about an old problem from a refreshing new angle is just the thing needed to find that eureka moment.
Cancer, one of the most notorious medical maladies, has been studied intensely in the current era of modern medicine. But a growing number of researchers think that bringing a fresh, out-of-the-box approach to understanding the disease may lead to some novel insights and, perhaps, solutions. And the subject that they’re hoping can serve as a window into the study of cancer may surprise you: ecology.
On face value, oncology and ecology seem vastly different. For starters, one is localized to specific cells in the body, while the other by definition spans the entire globe. But rather than labeling cancer as a group of mutated cells, as the thinking goes, we should see cancer as a disruption in the balance of a complex microenvironment in the human body. Like a damaging invasive beetle eating its way through forests in Colorado, a novel disease breaking out in populations of wild birds, or loggers mowing down parts of the Amazon rainforest, cancer throws a monkey wrench into an otherwise placid, balanced system.
This way of thinking makes cancer seem even more complex than it already is, but it could provide insights that ultimately make cancer more treatable, propose researchers from the Moffet Cancer Center in a paper published in the journal Interface Focus.
“Einstein is known to have said that everything should be made as simple as possible, but not simpler,” they write. “It turns out that complexity has its place and, as convenient as it would be for cancer biologists to study tumor cells in isolation, that makes as much sense as trying to understand frogs without considering that they tend to live near swamps and feast on insects.”
We tend to think of cancer only in terms of mutated cells, the authors continue. But adopting this narrow approach is like trying to understand why a frog has a sticky tongue without taking into account that frogs use their tongues to catch insects. Cancer cells, likewise, need context. A voracious cancer cell, for example, may situate itself next to a blood vessel not by chance, but so it can obtain more nutrients and oxygen to support its unlimited division.
Cancer cells must compete within the body for nutrients and other resources, just like animals living in an environment must compete with one another in order to survive. This means that cancer, like any organism, must adapt to its environment in order to thrive. The researchers explain:
It is now beginning to be widely accepted that cancer is not just a genetic disease but the one in which evolution plays a crucial role. This means that tumour cells evolve, adapt to and change the environment in which they live. The ones that fail to do so will ultimately become extinct. The ones that do, will have a chance to invade and metastasize. The capacity of a tumour cell to adapt to a new environment will thus be determined by environment and the cellular species from the original site, to which it has already painstakingly adapted.
So how can all of this theory be applied in real life? The environmental approach to understanding cancer is so complex that it rules out normal experiments; they could easily go awry with so many different components to consider. Instead, the researchers suggest turning to mathematics and computational for understanding the greater environmental context that leads to cancer. Ecologists use one such mathematical approach, game theory, as a way to study evolutionary biology and the way animals interact:
The force of natural selection keeps ecosystem denizens focused on optimizing the bottom line: long-term reproduction. In the games studied by evolutionary game theoreticians, individuals compete for available resources using a variety of strategies. These features and behaviours, known as the phenotypic strategy, determine the winners and losers of evolution.
Behavioral strategies may change depending upon both an animal’s nature and the situation’s context. Here’s a hypothetical example, based upon game theory thinking: If two hyenas are digging into a large, tasty wildebeest carcass, they’ll happily share that resource. But if two lions find that same carcass, they will fight for exclusive rights to eating it, meaning one lion emerges victorious and takes all the meaty spoils, while the other gets no food–plus is injured. Finally, if a lion meets a hyena at the carcass, the hyena will bolt, surrendering its goods to the stronger lion. In other words, game theory players can react one of three ways depending upon who they are and what’s going on: they can share, fight or forfeit.
Similar games may be played with tumor cells. “A good example would be a tumour with cells that move away when confronted with scarce resources (motile) and cells that stay to use them (proliferative),” the authors write. To make things even more complicated, however, tumor cells are known to change their behavior as they proliferate and metastasize throughout the body, meaning they could switch from a hyena to a lion.
One crucial thing that game theory at an ecosystem level shows us, they continue, is that indiscriminately focusing on killing as many tumor cells as possible might not provide the best outcome for the patient. According to game theory models, the eventual long-term result of the game depends upon specific interactions between the players, not on the number of players involved. Lions will continue to fight one another for food, regardless of whether two lions or 2,000 lions meet. “A treatment based exclusively on indiscriminately removing most (but not all) cancer cells may only have a temporary effect; as in most cases, the original number of tumor cells will eventually be restored and exceeded,” the authors write.
Instead, game theory indicates that a more effective alternative would be based on trying to change the ways that cells interact with one another and with their environment. This may affect the cells’ behavior, strength and reproductive success, the authors explain, which could drive a tumor’s evolution towards less aggressive cell types, or to a more stable coexistence with non-cancerous cells.
“The ecosystem view is, ultimately, a holistic one that sees cancer progression as a process that emerges from the interactions between multiple cellular species and interactions with the tumour microenvironment,” the authors write. “An ecosystem perspective presents us with intriguing implications,” they say, along with a host of questions about how far the analogy between ecosystems and cancer can be taken.
For example, if cancer cells spread like an invasive species through an ecosystem, what evolutionary gain is achieved when the closed off ecosystem (a body) is irreparably damaged (through a person’s death) such that the pestilence also dies? Unlike a virus, which may kill its host but spread to other hosts in the process, cancer cells themselves, for the most part, have no means of spreading from individual to individual. And are cancer cells taking their cues from processes driven by competition or from cooperation? Thinking more proactively, can non-cancerous cells be triggered so that they behave like lions and usurp cancerous cells’ resources until the cancer is manageable?
While ecology and mathematics likely will not defeat cancer on their own, viewing the disease from this perspective could allow doctors to better predict where in the body tumor cells have the best and worst chances of survival, and how to most effectively prevent them from proliferating.
“The heart of the matter is that an ecological view of tumours does not invalidate but complements and builds upon decades of cancer research and undoubtedly this will lead to a better understanding of the biology of cancer and to new and improved therapies,” the researchers conclude. “We need to properly understand the trees (e.g. every leaf, twig and branch) before we can understand the forest but we cannot afford to ignore the forest because the trees are so interesting on their own.”
June 20, 2013
You probably don’t feel much remorse when you bite into a raw carrot.
You might feel differently if you considered the fact that it’s still living the moment you put it into your mouth.
Of course, carrots—like all fruits and vegetables—don’t have consciousness or a central nervous system, so they can’t feel pain when we harvest, cook or eat them. But many species survive and continue metabolic activity even after they’re picked, and contrary to what you may believe, they’re often still alive when you take them home from the grocery store and stick them in the fridge.
The most recent evidence of this surprising phenomenon? A new paper, published today in Current Biology by researchers from Rice University and UC Davis, found that a range of harvested fruits and vegetables—including cabbage, lettuce, spinach, zucchini, sweet potatoes, carrots and blueberries—behave differently on a cellular level depending on their exposure to light or darkness. In other words, these fresh produce have an internal “body clock,” or circadian rhythm, just like we do.
Previously, Rice biologist and lead author Danielle Goodspeed had found that some plants depend on light cycles and their internal circadian rhythm to fend off predatory insects, at least while still in the ground. In experiments, she had noticed that thale cress plants used reliable daily exposure to sunlight as a basis for anticipating the arrival of insects during the day, and were able to build up reserves of defensive chemicals beforehand, during the night.
In this new study, she and others sought to determine whether already harvested samples of plant species that we commonly eat demonstrate the same kind of circadian behavior. They started by looking at cabbage, a close relative of thale cress, subjecting samples to similar experiments employed to arrive at the previous finding.
The team bought cabbage at the grocery store and took small leaf samples, and also acquired cabbage loopers, small moth larvae that like to feed on cabbage. The larvae were kept on a routine 24-hour light cycle: 12 hours of light alternating with 12 hours of darkness.
For three days, half of the cabbage samples were put on this same cycle, to “train” their circadian rhythms, but the other half were put on an entirely opposite cycle. As a result, plants in this second group would “think” it was night when the larvae behaved as if it were actually daytime, and vice-versa. If the harvested cabbage tissue depended on light exposure in the same way as the planted thale cress, then it’d build up defense chemicals at exactly the wrong time of day, and would likely suffer for it if the pests were given a chance to feed.
When the researchers let cabbage loopers loose on their favorite food, that’s exactly what happened. Cabbage leaves in the out-of-sync group showed significantly less resistance than the other samples, suffering more tissue damage and losing weight more quickly. The cabbage loopers feeding on these leaves also grew more quickly than those feeding on the first group. When the team directly measured levels of one specific class of chemicals involved in metabolic defense activity in the samples, they found that they did indeed cycle along with what the plants had been “trained” to anticipate as daytime.
The researchers put harvested lettuce, spinach, zucchini, sweet potatoes, carrots and blueberries through the same sort of experiment and arrived at the same results. All the plant samples “trained” to anticipate day at the correct time suffered less damage from the larvae than those with circadian rhythms that had been set incorrectly. It’s unclear why the root vegetables—carrots and sweet potatoes—would demonstrate a circadian rhythm (after all, they grow under the ground), but it’s possible that the entire plant simply uses the light cycle to orient its metabolic activity, and the pattern affects the roots as well as the leaves.
In a sense, the produce used in the experiment got jet lagged—their circadian rhythms told them it was nighttime, so they didn’t need to produce the defensive chemicals, when in fact it was day. It’s not so different from flying, say, to India, and your body telling you it’s time to sleep when you arrive, when in truth it’s 11 a.m. local time. Except, of course, that your jet lag doesn’t make you more prone to being consumed alive by insects.
Our burgeoning understanding of the circadian rhythms and metabolic activity of plants could eventually make an impact on another animal species that consumes fruits and vegetables: Homo sapiens.
The reason, the researchers say, is that some of the same chemicals involved in defense against insects appear to also act as anti-cancer agents. In trials, cabbage samples kept entirely in the dark (like, say, the vegetables in your refrigerator) suffered greater tissue loss than those with the circadian rhythm that aligned with the larvae, indicating they had lower overall levels of anti-pest (and anti-cancer) chemicals. So designing harvest, transport and storage systems with a focus on light exposure could be the next step in maximizing the nutrition we get when we eat fruits and vegetables.
March 1, 2013
Beijing’s terrible air quality is currently in the news, and for good reason: The level of pollution present in the air there is unprecedented for a heavily populated area, and several times worse than what any U.S. resident has likely ever experienced.
The New York Times recently reported on the air quality problems of Salt Lake City, Utah, and how the area’s geographical features and weather systems occasionally trap pollution in the city’s bowl-shaped basin. But the highest reading on the EPA’s Air Quality Index (AQI) scale ever recorded in Salt Lake City was 69 micrograms of soot and other particles per cubic meter.
In Beijing, that number frequently rises above 300—sometimes going much higher. Yesterday, a sandstorm blew into the city, mixing sand and dust with smog and pushing the AQI to 516. The scale was only designed to go up to 500, but on January 12, a measurement from the U.S. Embassy in Beijing read 755. For reference, the EPA recommends that for any number above 200, ”People with heart or lung disease, older adults, and children should avoid all physical activity outdoors. Everyone else should avoid prolonged or heavy exertion.”
What exactly makes physical activity in this sort of environment so dangerous? First, it’s important to understand exactly what AQI measures in the chart above: the weight of solid particles smaller than 2.5 micrometers wide (commonly known as fine particulates) that are suspended in an average cubic meter of air. In a heavily populated place like Beijing, most of the fine particulates are a result of industrial activity, the burning of diesel and gasoline for transport, or the burning of coal for energy or heat.
When we breathe in larger particles than those measured by the AQI (those typically bigger than 10 micrometers in size), they’re typically filtered out by cilia or mucus in our nose and throat. But those smaller than 10 micrometers can slide past these protections and settle in our bronchi and lungs. And the fine particulates commonly measured by the AQI can penetrate even further—entering the tiny air sacs known as alveoli where our bodies exchange carbon dioxide for oxygen—where they can cause some serious damage over time.
Researchers have linked many health problems to high levels of these tiny particulates in the air, but the most obvious effect has been lung cancer. One study spanning 16 years found that, over the course of an individual’s lifetime, an average increase of 10 on the AQI was associated with a 8 percent higher chance of developing the disease. When multiplied out over a broad area with a large population, the effect can be massive. A World Health Organization report estimated that fine particulates are responsible for 5% of the deaths resulting from lung cancer worldwide—800,000 deaths annually.
Fine particulates have also been linked with many other sorts of health issues, both long- and short-term. There’s evidence that, in individuals already predisposed to heart problems, they can trigger heart attacks. They can also exacerbate asthma, cause coughing or difficulty breathing in healthy people, and reduce the lungs’ ability to take in oxygen for people with COPD (chronic obstructive pulmonary disease).
Additionally, there are risks associated with even smaller particulates, known as nanoparticles, that are smaller than 100 nanometers in size. Only preliminary research on nanoparticles’ effect on the human body has been completed, but scientists believe that nanoparticles may be capable of penetrating even further into an organism, burrowing through cell membranes and potentially causing a range of problems, including damage to the lungs and circulatory system.
There has been limited research so far on the direct health impacts of air pollution in China, but one study found that, when air pollution was curtailed due to restrictions during the 2008 Olympics, several chemical biomarkers associated with cardiovascular disease in the blood of Beijing residents dropped off dramatically. Another study estimated that, if these same restrictions were extended permanently, lifetime risk of lung cancer for the city’s residents would be cut in half (a risk that has increased by 56 percent in the last 10 years, even as smoking has declined).
All told, there are very good reasons why many Beijing residents don’t venture out without a breathing mask—and why many Chinese are calling upon leaders to finally address the country’s air pollution problems in the coming political year, potentially by introducing rules that restrict industry and coal burning when air quality dips below acceptable levels.
January 22, 2013
Over thousands of years, gold has been used to treat rheumatoid arthritis, inner ear infections, facial nerve paralysis, fevers and syphilis. Now, preliminary findings suggest a new application for tiny grains of gold—destroying cancer cells.
Gold-carrying nanoparticles are capable of killing a common type of cancer that attacks antibody-making B cells in the blood, according to a study published today in the journal Proceedings of the National Academy of Sciences. This cancer, B-cell lymphoma, originates in the lymph glands and is the most common type of non-Hodgkin lymphoma. Last year, it resulted in nearly 19,000 deaths.
Developed by researchers at Northwestern University, the nanoparticle mimics the size, shape and surface chemistry of high-density lipoprotein—natural HDL—the preferred meal of these cancer cells. HDL is the “good” cholesterol that cruises through the bloodstream, removing dangerous buildups of LDL, the harmful, “bad” cholesterol.
The bits of gold tucked inside these particles are tiny—just five nanometers wide. A billionth of a meter, a nanometer is a measurement used to size bacteria, X-rays and DNA. The width of a double helix is about two nanometers.
Despite its microscopic size, the synthetic particle packs a big punch—more accurately, two of them. Recent research has shown that B-cell lymphoma is dependent on the uptake of natural HDL, from which it derives fat content, to spur cell proliferation. The nanoparticle cuts off its supply. Masquerading as natural HDL, the nanoparticle latched on to cholesterol receptors on deadly lymphoma cells. First, the nanoparticle’s spongy surface sucked out the cell’s cholesterol. Then, it plugged up the cancer cell, preventing it from absorbing natural HDL particles in the future. Deprived of this essential nutrient, the cell eventually died.
Natural HDL alone didn’t kill the cells or inhibit tumor growth in the study. The blinged-out particle was key to starving the lymphoma cell—and it did so without the help of cancer drugs.
It also didn’t appear to be toxic to other human cells normally targeted by HDL particles, to normal lymphocytes (a type of white blood cells) or to mice, in which the particle actually inhibited tumor growth. Developing a drug therapy using this nanoparticle depends on further extensive testing, but it could take chemotherapy off the table for the thousands of patients diagnosed with B-cell lymphoma.
June 20, 2012
Would you go on a mission to Mars? The Dutch startup company Mars One is planning to establish the first Mars colony in 2023, starting with four individuals and adding more people every two years, funded by turning the whole endeavor into a reality TV show.
It’s just the latest plan to colonize the Red Planet, but I’m doubtful it will happen. There’s the expense, for sure, and the trials of trying to convince anyone to go on a one-way journey with just a few other strangers (what if you don’t get along? It’s not like you can leave). And then there’s the radiation problem.
Out in space, there are gamma rays from black holes, high-energy protons from the Sun, and cosmic rays from exploding stars. Earth’s atmosphere largely protects us from these types of radiation, but that wouldn’t help anyone traveling to Mars. They would be exposed to dangers that include neurological problems, loss of fertility and an increased risk of cancer.
NASA scientists calculated in 2001 that a 1,000-day Mars mission would increase the risk of cancer somewhere between 1 and 19 percent. If the risk is on the lower end, then the outlook for Mars might be pretty good, but if it’s higher, then NASA, at least, wouldn’t send people (there’s no telling what a reality TV show might do). A 2005 study found even more to worry about—the radiation would be high enough to cause cancer in 10 percent of men and 17 percent of women aged 25 to 34 if they were to go to Mars and back.
The easy solution would seem to be to shield the vessel that carries the humans to Mars, but no one has figured out how to do that. When the thin aluminum currently used to build spacecraft is hit with cosmic rays, it generates secondary radiation that is even more deadly. Plastic might work—the shields on the International Space Station are made of plastic—but it’s not 100-percent effective. One scientist has suggested using asteroids to shield a vessel traveling between Earth and Mars. But somehow I don’t think Mars One is going to make that one work within a decade.
Or they could just send old people—a solution proposed a couple of years ago by Dirk Schulze-Makuch of Washington State University and Paul Davies of Arizona State University. “This is not a suicide mission. The astronauts would go to Mars with the intention of staying for the rest of their lives, as trailblazers of a permanent human Mars colony,” Schulze-Makuch and Davies wrote in the Journal of Cosmology. Loss of fertility wouldn’t be an issue for older astronauts and the radiation wouldn’t increase their lifetime cancer risk too much (since they’re already near the end of their lives).
That may be a solution more suited to NASA than Mars One, however, since television casting departments would probably want someone more like Snooki than Snooki’s grandma.
Editor’s note: In other Mars news, NASA is preparing for the August 5 landing of its massive unmanned science laboratory, Curiosity. The seven minutes between when the rover hits the top of the atmosphere and when it touches ground are the riskiest moments of the whole mission. The video below shows a few of the hundreds of things that need to go just right: