How Carcinogens Cause Cancer
Siddhartha Mukherjee is the author of The Emperor of All Maladies: A Biography of Cancer, winner of the 2011 Pulitzer Prize in general nonfiction, and The Laws of Medicine. He is the editor of Best Science Writing 2013. Mukherjee is an assistant professor of medicine at Columbia University and a cancer physician and researcher. A Rhodes scholar, he graduated from Stanford University, University of Oxford, and Harvard Medical School. He has published articles in Nature, The New England Journal of Medicine, The New Yorker, The New York Times, and Cell. He lives in New York with his wife and daughters.
Siddhartha Mukherjee: So we’ve talked a little bit about the Cancer Genome. We’ve talked about the genetic changes, but I want to take one step back even before these genetic changes arise. Dr. Schwartzentruber, tell us what we know about how carcinogens cause cancer.
Doug Schwartzentruber: Well that is a challenging question because there are multiple ways for carcinogens to cause cancer and I probably should defer to some of the other panelists as well who have studied that much more than I have, but the obvious first step is how the environment which from the minute we’re born begins to interact and create feedback to say our normal cells that could then potentially be cancerous and maybe I'll stop at that point and lead into others.
Lewis Cantley: Well I can. I mean most carcinogens we think cause cancer by mutating DNA, but there are examples of carcinogens for example, forballesters [ph] which can cause skin cancers that almost certainly are to working through mutating DNA directly, although in the long run you always end up getting mutations in DNA. They are rather probably causing cells to grow at a higher rate and the higher the rate cells grow the more frequently they get mutations in DNA. Basically a cell has to go through a division cycle and make a daughter cell in order for a mutation to get locked in and that- But most really do it by directly damaging DNA, UV light, radiation directly damage the nucleotides in the DNA and many other chemical carcinogens interpolate into the DNA and at the time of cell division interfere with proper base replacement.
Harold Varmus: No, I agree entirely with this, but I would like to add two important points. First we as individuals grow up from a single cell and through many, many rounds of cell division many errors are going to occur because the ability to copy and distribute the three billion base pairs of DNA into daughter cells is an inherently error prone mechanism. We have ways to try to correct it, but nevertheless damage will occur and over the course of many cell doublings there will be damage that can be carcinogenic, so you don’t need to have external factors for cancer to arise. Cancer is probably part of our heritage. Genetic change is a good thing at the species level because we generate diversity throughout living systems.
The other point I would make is that not all carcinogens are UV light or radiation. Some of them are viruses and it’s very important to keep that in mind. It has been estimated that in developing countries for example maybe a third of cancers are caused by viruses. We actually have vaccines that are effective against some of those viruses. The human papillomavirus vaccine, the human hepatitis B virus vaccine can prevent a very large amount of cancer in those countries if the vaccines are made available, brought to patients, made affordable in poor countries. Cervical cancer is largely controlled in this country by pap smears, by early detection, and we only have about 3,000 deaths a year in this country, but in many parts of the world, India for example, and large parts of Africa, cervical cancer is the most common cause of death from cancer among women, and we now have the potential to reduce the incidence of that cancer by two-thirds using the human papillomavirus vaccine.
Seemingly every year there are new reports that something we consume or use on a daily basis is carcinogenic. But what exactly does that mean on a biological level?
These questions can help us think more critically about new developments in artificial intelligence.
- The media often exaggerate and overhype the latest discoveries in artificial intelligence.
- It's important to add context to new findings by asking questions: Is there a demo available? How narrow was the task the computer performed?
- A more robust approach to artificial intelligence involves solving problems in generalized situations rather than just laboratory demonstrations.
Most elderly individuals' brains degrade over time, but some match — or even outperform — younger individuals on cognitive tests.
- "Super-agers" seem to escape the decline in cognitive function that affects most of the elderly population.
- New research suggests this is because of higher functional connectivity in key brain networks.
- It's not clear what the specific reason for this is, but research has uncovered several activities that encourage greater brain health in old age.
At some point in our 20s or 30s, something starts to change in our brains. They begin to shrink a little bit. The myelin that insulates our nerves begins to lose some of its integrity. Fewer and fewer chemical messages get sent as our brains make fewer neurotransmitters.
As we get older, these processes increase. Brain weight decreases by about 5 percent per decade after 40. The frontal lobe and hippocampus — areas related to memory encoding — begin to shrink mainly around 60 or 70. But this is just an unfortunate reality; you can't always be young, and things will begin to break down eventually. That's part of the reason why some individuals think that we should all hope for a life that ends by 75, before the worst effects of time sink in.
But this might be a touch premature. Some lucky individuals seem to resist these destructive forces working on our brains. In cognitive tests, these 80-year-old "super-agers" perform just as well as individuals in their 20s.
Just as sharp as the whippersnappers
To find out what's behind the phenomenon of super-agers, researchers conducted a study examining the brains and cognitive performances of two groups: 41 young adults between the ages of 18 and 35 and 40 older adults between the ages of 60 and 80.
First, the researchers administered a series of cognitive tests, like the California Verbal Learning Test (CVLT) and the Trail Making Test (TMT). Seventeen members of the older group scored at or above the mean scores of the younger group. That is, these 17 could be considered super-agers, performing at the same level as the younger study participants. Aside from these individuals, members of the older group tended to perform less well on the cognitive tests. Then, the researchers scanned all participants' brains in an fMRI, paying special attention to two portions of the brain: the default mode network and the salience network.
The default mode network is, as its name might suggest, a series of brain regions that are active by default — when we're not engaged in a task, they tend to show higher levels of activity. It also appears to be very related to thinking about one's self, thinking about others, as well as aspects of memory and thinking about the future.
The salience network is another network of brain regions, so named because it appears deeply linked to detecting and integrating salient emotional and sensory stimuli. (In neuroscience, saliency refers to how much an item "sticks out"). Both of these networks are also extremely important to overall cognitive function, and in super-agers, the activity in these networks was more coordinated than in their peers.
An image of the brain highlighting the regions associated with the default mode network.
How to ensure brain health in old age
While prior research has identified some genetic influences on how "gracefully" the brain ages, there are likely activities that can encourage brain health. "We hope to identify things we can prescribe for people that would help them be more like a superager," said Bradford Dickerson, one of the researchers in this study, in a statement. "It's not as likely to be a pill as more likely to be recommendations for lifestyle, diet, and exercise. That's one of the long-term goals of this study — to try to help people become superagers if they want to."
To date, there is some preliminary evidence of ways that you can keep your brain younger longer. For instance, more education and a cognitively demanding job predicts having higher cognitive abilities in old age. Generally speaking, the adage of "use it or lose it" appears to hold true; having a cognitively active lifestyle helps to protect your brain in old age. So, it might be tempting to fill your golden years with beer and reruns of CSI, but it's unlikely to help you keep your edge.
Aside from these intuitive ways to keep your brain healthy, regular exercise appears to boost cognitive health in old age, as Dickinson mentioned. Diet is also a protective factor, especially for diets delivering omega-3 fatty acids (which can be found in fish oil), polyphenols (found in dark chocolate!), vitamin D (egg yolks and sunlight), and the B vitamins (meat, eggs, and legumes). There's also evidence that having a healthy social life in old age can protect against cognitive decline.
For many, the physical decline associated with old age is an expected side effect of a life well-lived. But the idea that our intellect will also degrade can be a much scarier reality. Fortunately, the existence of super-agers shows that at the very least, we don't have to accept cognitive decline without a fight.
Can Impossible Foods beat other brands — like Beyond Meat and Tyson — in the war to dominate the alternative meat industry?
- The Impossible Burger will be available in 27 Gelson's Markets stores in Southern California starting Sept. 20.
- Beyond Meat and Impossible Foods sell plant-based burgers in restaurants, but only Beyond Meat sells products in grocery stores.
- Tyson could begin to edge out these smaller companies with its unique meat product that contains plant and animal components, appealing to health-conscious "flexitarians."