"It's like a zipper -- they open you and then close you back up."
The AP is running a story about the soaring rate of C-sections:
The rate of Caesarean sections in the U.S. has climbed to an all-time high, despite efforts by public health authorities to bring down the number of such deliveries, the government said Tuesday.
Nearly 1.2 million C-sections were performed in 2004, accounting for 29.1 percent of all births that year, the National Center for Health Statistics reported. That is up from 27.5 percent in 2003 and 20.7 in 1996.
The rate has increased from 5 percent in 1970, according to the article. There are lots of reasons, from an excess of caution by doctors and hospitals fearing malpractice, to "convenience":
Experts say many factors drove the rate: Mothers increasingly preferred the convenience of C-sections, which could be scheduled. Technological innovations let doctors better see problems before birth.
In praise of high-calorie coffee
There's an interesting convergence of health news today. Remember that story that overweight people live longer? Another conclusion was that underweight people died sooner. That's possibly surprising, since caloric restriction is supposed to increase longevity, a finding long known from studies in mice. Of course, the skinny people who are dying young may not be "calorie-restricted" in the sense the mice were, and it is perhaps very likely that the people don't have the vitamin and mineral balance promoted by caloric restriction advocates. But if you think that eating less will make you live longer, it should give you pause.
Well, now there is this Reuters story, reporting on research by John Phelan and Michael Rose:
"Our message is that suffering years of misery to remain super-skinny is not going to have a big payoff in terms of a longer life," said Phelan, an evolutionary biologist, in a statement.
Of course, how do you really test this in humans? Simple, find a natural experiment:
"In Japanese populations, for example, the normal male diet is approximately 2,300 kilocalories (calories) per day," they wrote Ñ and the average life span for a Japanese male is 76.7 years.
"Sumo wrestlers, however, consume an average of approximately 5,500 calories per day and have a life expectancy of 56 years," they added.
People living on the Japanese island of Okinawa eat somewhat less than the average Japanese. They also live slightly longer. This could give a basis for calculating the benefits of eating less.
Calculations based on the Okinawa and sumo wrestler data suggest that if Japanese people ate just 1,500 calories a day, the longest average life span attainable would be just under 82 years, Phelan and Rose wrote.
Of course, there is also the possibility that sumo wrestlers aren't exactly genetically representative of other Japanese, and likewise for Okinawans. And it's not obvious that the long-term effects in these samples will necessarily be like short-term effects in other populations. But still, it would sure give me pause before suffering through many years of not eating as much.
There is possibly another way to increase lifespan -- decrease the level of oxygen free radicals, which lead to many of the chronic diseases that induce early (and late) death.
In that vein, there is this story that coffee is the leading source of antioxidants for most Americans. Yes, drinking coffee might make you live longer.
They concluded that the average adult consumes 1,299 milligrams of antioxidants daily from coffee. The closest competitor was tea at 294 milligrams. Rounding out the top five sources were bananas, 76 milligrams; dry beans, 72 milligrams; and corn, 48 milligrams. According to the Agriculture Department, the typical adult American drinks 1.64 cups of coffee daily.
And get this part:
Men who drank more than six 8-ounce cups of caffeinated coffee per day lowered their risk of type 2 diabetes by about half, and women reduced their risk by nearly 30 percent, compared with people who did not drink coffee, according to the study in Annals of Internal Medicine.
Just doing my part to shift the "no-fat half-caff" crowd back to normal sugared-up caramel ventis...
Vasectomy dementia correlation
This press release about a possible link between vasectomy and dementia caught my eye. It just seems so, well, random.
The dementia is Primary Progressive Aphasia (PPA), a neurological disease in which people have trouble recalling and understanding words. In PPA, people lose the ability to express themselves and understand speech. It differs from typical Alzheimer's disease in which a person's memory becomes impaired.
Sandra Weintraub, principal investigator and professor of psychiatry and behavioral sciences and of neurology at Northwestern's Feinberg School of Medicine, began investigating a possible link between the surgery and PPA when one of her male patients connected the onset of his language problem at age 43 to the period after his vasectomy.
At a twice-yearly Chicago support group for PPA patients Weintraub sees from around the country, the male patient rushed into the room and asked the men sitting there, "OK, guys, how many of you have PPA?" Nine hands went up.
"How many of you had a vasectomy?" he demanded next. Eight hands shot up.
The actual association is much more slight, although highly significant in the sample. They haven't figured out a cause, but they have a hypothesis. It's the hypothesis that made the story really interesting for me, because it proposes a link between two rapidly-evolving tissue types: brain and testis:
Weintraub theorizes a vasectomy may raise the risk of PPA (and possibly FTD) because the surgery breeches the protective barrier between the blood and the testes, called the blood-testis barrier.
Certain organs - including the testes and the brain - exist in what is the equivalent of a gated community in the body. Tiny tubes within the testes (in which sperm are produced) are protected by a physical barrier of Sertoli cells. The tight connections between these cells prevent blood-borne infections and poisonous molecules from entering the semen.
After a vasectomy, however, the protective barrier is broken and semen mixes into the blood. The immune system recognizes the sperm as invading foreign agents and produces anti-sperm antibodies in 60 to 70 percent of men.
Weintraub said these antibodies might cross the blood-brain-barrier and cause damage resulting in dementia. "There are other neurological models of disease which you can use as a parallel," Weintraub said. Certain malignant tumors produce antibodies that reach the brain and cause an illness similar to encephalitis, she noted.
I suppose that if such antibodies actually do cause trouble in the brain, it is because neurons and sperm express one or more proteins in common that are rare elsewhere in the body. It seems not too surprising that two different systems closed off from the immune system might evolve to exploit similar protein networks in different ways.
Education and longevity
A Gina Kolata NYT article reviews the link between education and health.
The article keys off research by economist Adriana Lleras-Muney, who examined historical records to find whether increases in the length of compulsory education in different states had significant effects on lifespan:
"The idea was, when a state changed compulsory schooling from, say, six years to seven years, would the people who were forced to go to school for six years live as long as the people the next year who had to go for seven years," Dr. Lleras-Muney asked.
All she would have to do was to go back and find the laws in the different states and then use data from the census to find out how long people lived before and after the law in each state was changed.
"I was very excited for about three seconds," she says. Then she realized how onerous it could be to comb through the state archives.
After describing the results of this and other studies (all show education has a significant impact, increasing lifespan), the article discusses the interesting scientific problem -- just how does education have this effect?
There's really no answer, and the article discusses other factors like social networks and wealth, which are themselves not so easy to explain.
It's a mystery.
They don't make 'em like they used to
The New York Times Health section has a really well-written article about recent secular trends in longevity and body size, by Gina Kolata.
The article's point of departure is the health records of Civil War veterans. Of course, these have the shock value of describing terrible health problems that people don't even hear about anymore (the article mentions grapefruit-sized chronic hernias, and "dropsy"). But beneath these fairly startling differences, there is a huge statistical difference in death rates at ages that we today consider surprisingly young to die.
These people's genes were the same as people today, more or less. So the health differences are mostly due to our new environment. In particular, all those vaccinations, vitamins, and antibiotics really have made people bigger and healthier:
At a recent meeting of a Las Vegas chapter of the Sons of Confederate Veterans, eight burly men crowded into a library meeting room. All had experienced the equivalent of the Civil War tent problem.
"At the re-enactments, all the directors, all the costume directors say the re-enactors are just too darn big," said George McClendon, a hefty 67-year-old retired airline pilot.
Mr. McClendon is right. Men living in the Civil War era had an average height of 5-foot-7 and weighed an average of 147 pounds. That translates into a body mass index of 23, well within the range deemed "normal." Today, men average 5-foot-9½ and weigh an average of 191 pounds, giving them an average body mass index of 28.2, overweight and edging toward obesity.
You may be wondering, this is supposed to be better? Well, yes, at least when it comes to long-term health -- the Civil War veterans as a class were healthier and longer-lived in positive relation with body size. And diseases early in life (that themselves could stunt growth) caused problems later in life also:
"Suppose you were a survivor of typhoid or tuberculosis," Dr. Fogel said. "What would that do to aging?" It turned out, he said, that the number of chronic illnesses at age 50 was much higher in that group. "Something is being undermined," he said. "Even the cancer rates were higher. Ye gods. We never would have suspected that."
Men who had respiratory infections or measles tended to develop chronic lung disease decades later. Malaria often led to arthritis. Men who survived rheumatic fever later developed diseased heart valves.
Nor is it only effects during childhood or early adulthood. There seem to be prenatal effects as well:
So did a study of babies born to women who were pregnant during the Dutch famine, known as the Hunger Winter, in World War II.
That famine lasted from November 1944 until May 1945. Women were eating as little as 400 to 800 calories a day, and a sixth of their babies died before birth or shortly afterward. But those who survived seemed fine, says Tessa J. Roseboom, an epidemiologist at the University of Amsterdam, who studied 2,254 people born at one Dutch hospital before, during and after the famine. Even their birth weights were normal.
But now those babies are reaching late middle age, and they are starting to get chronic diseases at a much higher rate than normal, Dr. Roseboom is finding. Their heart disease rate is almost triple that of people born before or after the famine. They have more diabetes. They have more kidney disease.
It's a good article, and I think it makes a good stepping-off point for talking about the relationships of epigenetics and environment in the determination of disease risks. The one thing that we still know relatively little about is the extent to which late-life chronic diseases relate to different genotypes, and we will certainly be learning a lot more about that soon.
In essence, human genes respond to a history of relatively high early-life disease and high late-life mortality. We've gone and mucked up that killer environment, to our great advantage. Isn't it interesting, then, that these genes are capable of making bigger, healthier people when their environment has gone. After all, it didn't have to be that way.
And apparently it sometimes isn't that way. At least, it seems that those immune system genes that used to fight early childhood diseases now may be causing auto-immune disorders since they no longer have diseases to fight.
So we may be looking at a particular axis of disease and growth here, involving body size, status, nutrition, stress, cardiovascular health, and dementia. Which sure takes in a lot.
Building a better bone
According to Wired News, UC-Riverside scientists are working on repairing bones by using carbon nanotubes.
Human bones are both organic and inorganic. The organic part is made of collagen, the most abundant protein in mammals. The inorganic component is hydroxyapatite, a type of calcium crystal. The collagen forms a sort of natural scaffold over which the calcium crystals organize into bone. The idea in Haddon's research is to use the nanotubes as substitutes for the collagen to promote new bone growth when bones have been broken or worn down.
The appeal of nanotubes is their mechanical strength: they are intrinsically stronger than any other fiber in nature, and much lighter than most. The researchers have altered the chemistry of the ends of the nanotubes so that they attract hydroxyapatite.
My favorite quote:
Haddon hopes soon to test how the human body will respond to carbon nanotubes. Even though humans are carbon-based, that's not an iron-clad guarantee that the two will get along smoothly.
Redness
I've been meaning to link to this Gene Expression post on melanin variation in humans, and this AP story has given me an excuse.
Duke University researchers on Sunday reported the first direct evidence that those melanin differences indeed may be a culprit. It turns out that redheads' melanin is more vulnerable to a type of DNA-damaging stress from the sun's ultraviolet rays.
The study was a chemical experiment, where the effects of UV radiation on the pigments were viewed under a microscope. The next step would be to investigate epidemiological evidence to see if the apparent UV instability of pheomelanin translates into greater cancer risk.
"There has been speculation for years that pheomelanin could be a key pathway" in skin cancer formation, said Dr. Martin Weinstock of Brown University, a spokesman for the American Cancer Society. "The thought is that eumelanin does a reasonable job of protecting against UV and pheomelanin might in fact aggravate damage."
While more research is needed, Simon said in an interview that his study reinforces some practical advice: Slather on sunscreen that promises to protect against both UVA and UVB rays.
The distribution of pigmentation phenotypes and alleles is a story that has lately developed a few twists. Like this one:
East Asians tend to exhibit very high frequencies of the Arg163gln allele (as high as 80% among the Dai of Yunnan province in China, decreasing to 40% among the Uighers of Xinjiang and less than 10% in South Asia [ie; India]). The authors suggest that this allele might have been subject to strong directional selection in the recent past. They note that "under neutral expectation, the estimated arrival time of the Arg163Gln allele is older than the age of modern humans...."
Worth a raised eyebrow, but mainly just evidence for selection.
But then, most of the other non-African alleles are generally explained by relaxed selection instead of positive selection. This owes to the fact that none of them have risen to very high frequencies yet -- as one of them would if it were positively selected for very long.
Yet this is a rare evolutionary case in which the many ways that something could be messed up present an advantage. Usually, it is the single way that something could be made better that is the only path for selection. I wonder if we really have a good understanding of what alleles should look like in this unusual case. Maybe alleles like Arg163gln are the rare lucky ones that exceed the neutral expectation, while other alleles have as a sum faced a slight advantage, but haven't yet reached frequencies appreciable enough to battle it out for fixation. I wonder how MC1R allele frequencies compare to those of minor hemoglobinopathies around, say, the Mediterranean?
Stress, evolution, and disease
ScienceDaily has a good article profiling Robert Sapolsky's work on stress-mediated disease in wild baboons:
Why do humans and their primate cousins get more stress-related diseases than any other member of the animal kingdom? The answer, says Stanford University neuroscientist Robert Sapolsky, is that people, apes and monkeys are highly intelligent, social creatures with far too much spare time on their hands.
"Primates are super smart and organized just enough to devote their free time to being miserable to each other and stressing each other out," he said. "But if you get chronically, psychosocially stressed, you're going to compromise your health. So, essentially, we've evolved to be smart enough to make ourselves sick."
There's some simplification in the article, but it's a nice one for probing the relations between social life, evolution, and current-day chronic health problems.
But many of the qualities that make us human also can induce stress, he noted. "We can be pained or empathetic about somebody in Darfur," he said. "We can be pained by some movie character that something terrible happens to that doesn't even exist. We could be made to feel inadequate by seeing Bill Gates on the news at night, and we've never even been in the same village as him or seen our goats next to his. So the realm of space and time that we can extend our emotions means that there are a whole lot more abstract things that can make us feel stressed."
I'd like to see Bill Gates' goats.
Social hierarchies and health in primates
Wow, it's almost like Science is reading my mind! Just after this post on social status and this post on allostasis, the April 29, 2005 Science has printed this review article on social hierarchies and health by Robert Sapolsky (Stanford University).
The idea that the overall level of stress should affect health status is now well-established, due in large part to Sapolsky's prior work. Likewise, the idea that stress level is influenced by social position, especially rank, is clear. But which social ranks should be under the most stress?
Research in the 1950s, since discredited, argued that high rank was more physiologically stressful (that is, the "executive stress syndrome," which was purportedly valid for both humans and other primates). By the 1960s, the prevailing view had become that lower dominance rank carries the greatest risk of stress-related disease. It has now become clear that this is an incorrect generalization. The contemporary view reflects the heterogeneity that is the core of ethology: Rank means different things in different species and populations (Sapolsky 2005:648).
Ultimately, stress resulting from social interactions depends on the interactions themselves, and these are indefinitely varied. Sapolsky tries to break down the possible components of variation, arriving at ten separate dimensions along which social interactions may direct stress to some individuals more than others. These range from the strongly ecological, such as the whether high-rank individuals can dominate resources, to the ideosyncratic, such as culture and personality. Many include different aspects of the breeding system or competition related to mating. Sapolsky does not mention demographic factors that plausibly affect stress levels, such as group size and population density; his attention seems to be mostly directed to "species-typical" solutions. I would term these as "static" solutions, since they do not allow variation or envisage mechanisms of transition; compared to "dynamic" solutions that show any particular species as a flux of different social groupings that change over time. In any event, there appears to be little point in reductionism of social interactions with relation to stress -- a clear answer about whether dominant or subordinate individuals are more stressed in any particular species seems like a concrete step forward.
Sapolsky presents a table of binary tests of his ten factors, performed upon captive animals, to show the way that they influence the stress level in dominant and subordinate individuals. The assay of stress keys in on the level of glucocorticoids.
Consistently, animals who are more socially stressed by the dominance hierarchy show indices of hyperactivity of the GC system. This includes elevated basal levels of GCs, the enlarged adrenal glands that accompany such increased secretion, a sluggish GC stress response in the face of a major homeostatic challenge, and impaired sensitivity of the system to negative feedback regulation (Sapolsky 2005:651).
Unstable hierarchies, hierarchies in which dominant individuals must repulse many challenges, and cooperative breeding systems tend to stress high-ranking individuals. Low-ranking individuals are relatively stressed (compared to high-ranking individuals) in societies with low social support for subordinates and with nonviolent intimidation by dominants.
According to the review, chronic stress has many negative health effects, including:
- hypertension
- increased cholestorol and associated plaques
- inhibition of fertility and reproduction in males via suppression of testosterone
- reduction in fertility and reproduction in females via delayed maturation, anovulatory cycles, accelerated senescence, and reductions in estrogen and progesterone
- suppression of immunity
- neurobiological changes
Finally, the review discusses the analogy between the status-related stress in primates and SES as a factor in human health.
Are these findings relevant to humans? Initially, they seem to be of minimal relevance. Humans are not hierarchical in the linear, unidimensional manner of many species. For example, humans belong to multiple hierarchies and tend to value most the one in which they rank highest (for example, a low-prestige employee who most values his role as a deacon in his church). Furthermore, the existence of internal standards makes humans less subject to the psychological consequences of rank. Finally, health-rank relations that are easy to study can be highly artificial (e.g., examining the physiological consequences of winning versus losing an athletic competition) (Sapolsky 2005:652).
But Sapolsky concludes by noting that SES does correlate with several health indicators in Western societies.
There is no necessity to assume that humans must be hierarchical in the same style as many primate species to still have status-related chronic stress. The elements of the endocrine system that comprise the stress response are highly conserved in vertebrates; they can be expected to respond social interactions in any primate species, whether it has a rigid hierarchy or not. The cumulative effect of social interactions may be patterned in many different ways, some probably leading to an expression of chronic stress even if coping mechanisms (such as hobbies) are present. The endocrine system is about motivation for actions; and ancient humans needed motivating no less than any other kind of primate. Does it mean something for our evolution that low SES in today's humans leads to greater health impacts? I guess we'll have to wait and see.
References:
Sapolsky RM. 2005. The influence of social hierarchy on primate health. Science 308:648-652. Science online
Wanna be a zombie? Get in line!
In the wake of recent zombie-related films, there is this article from NEWS.com.au, by Nick Buchan:
US scientists have succeeded in reviving the dogs after three hours of clinical death, paving the way for trials on humans within years.
Pittsburgh's Safar Centre for Resuscitation Research has developed a technique in which subject's veins are drained of blood and filled with an ice-cold salt solution.
The animals are considered scientifically dead, as they stop breathing and have no heartbeat or brain activity.
But three hours later, their blood is replaced and the zombie dogs are brought back to life with an electric shock.
The next step is to test the method on humans, which the report says should occur within a year. The motive is to keep people alive after severe trauma or blood loss -- especially after battlefield injuries. When surgical repairs can be accomplished, the body would be restarted.
Is it creepy? I suppose if it leads to bloodlust (or brainlust), then yes.
Climbing holes into your brain
I often lecture to my 100-level classes on human adaptations to altitude and the effects of hypoxia. Our picture of these adaptations and other physiological changes associated with high altitude has been changing in recent years. One reason is a better assessment of the variability among high-altitude populations in their response to hypoxia.
The other reason is better technology. The "Mind Matters" feature of the Scientific American blog has a feature this week on the neuroscience of altitude sickness. It details some of the effects of hypoxia on the brain, including details from recent studies involving MRI scans of elite climbers:
This acute high-altitude disease has long been known to cause brain damage. But one of the sobering things about the Fayed study is that none of the Everest climbers experienced high altitude cerebral edema, and the only acute case of mountain sickness was a mild one suffered by the expedition's amateur climber. Yet even all the professional mountaineers showed lasting brain damage -- presumably suffered on previous ascents to the high mountains, because their MRI scans were abnormal before the Mt. Everest ascent and unchanged after.
The essay is by R. Douglas Fields, describing work by Nicholas Fayed and colleagues. The results are true not only for Everest but for lower-altitude summits as well. The first discussed is Aconcagua:
The body is remarkably resilient--does the brain recover from these mountaineering wounds? To answer this important question, the researchers re-examined the same climbers three years after the expedition, with no other high-altitude climbing intervening. In all cases, the brain damage was still evident on the second brain scan.
Still, Aconcagua is one of the world's highest mountains -- in the top 100. Mont Blanc, in the Alps, is less extreme. With a summit at 4810 meters, it is climbed each year by thousands of mountaineers who probably do not expect injury to their "second favorite organ," to use Woody Allen's nomenclature for the brain. Yet the researchers found that of seven climbers reaching the summit of Mount Blanc, two returned with enlarged VR spaces.
Of course, if you've seen any of the various Everest documentaries, you will remember the cognitive impairment that results from low oxygen. Climbers often can't think straight, and particularly inexperienced climbers really need someone at a lower altitude to help supervise their summit attempts. But the sobering thing about these MRI results is that the altitude of Mont Blanc is substantially lower than the Everest base camp at 5500 meters.
Social networks and Alzheimer's disease
This seems interesting (press release via Science Blog):
"Many elderly people who have the tangles and plaques associated with Alzheimer's disease don't clinically experience cognitive impairment or dementia," said Bennett. "Our findings suggest that social networks are related to something that offers a 'protective reserve' capacity that spares them the clinical manifestations of Alzheimer's disease."
We already know that Alzheimer's progression is slower or less severe in people with higher education levels, higher verbal expression early in adulthood, and continued mental exertion later in life. But what seems interesting here is the autopsy data, which show that the Alzheimer's-related plaques are still developing in people with less severe symptoms, so that it appears the social networks are having a protective effect in the context of people who would otherwise have had worse symptoms:
The relationship between the amount of Alzheimer's disease pathology and cognitive performance changed with the size of the social network. As the size of the social network increased, the same amount of pathology had less effect on cognitive test scores. In other words, for persons without much pathology, social network size had little effect on cognition. However, as the amount of pathology increased, the apparent protective effect on cognition also increased. Thus, social network size appears to have offered a protective reserve capacity despite the fact that their brains had the tangles and plaques indicative of Alzheimer's disease.
One hypothesis would be that people have differing reserve capacities to make up for plaque-related declines in function, and that these depend on social interactions. But in that case, the mechanism would be of great interest with respect to the evolution of social interactions -- for example, is it neurotrasmitter-mediated, or hormonally mediated, or does it require the use of particular anatomical structures?
Depending on the mechanism, we might expect social networks to have strong effects on cognitive performance in non-Alzheimer's older people -- or maybe even in younger people also.
The complex landscape of diabetes
An Amanda Schaffer article, "In Diabetes, a Complex of Causes" in the Science Times covers recent research on Type 2 diabetes. The interesting part of the research is the extent that insulin resistance and related hormonal signaling have been linked to processes ranging from inflammation, bone metabolism, and the brain:
In previous work, Dr. Karsenty had shown that leptin, a hormone produced by fat, is an important regulator of bone metabolism. In this work, he tested the idea that the conversation was a two-way street. "We hypothesized that if fat regulates bone, bone in essence must regulate fat," he said.
Working with mice, he found that a previously known substance called osteocalcin, which is produced by bone, acted by signaling fat cells as well as the pancreas. The net effect is to improve how mice secrete and handle insulin, the hormone that helps the body move glucose from the bloodstream into cells of the muscle and liver, where it can be used for energy or stored for future use. Insulin is also important in regulating lipids.
The common theme seems to be this: Once, doctors focused on easy-to-measure biomarkers, like blood glucose level. But these are in turn affected by many different physiological processes -- far from the pancreas --- many in feedback relations regulated by multiple signaling molecules.
The brain in particular exerts a powerful drain on blood glucose. So you might expect something like this:
"If the brain is getting the message that you have adequate amounts of these hormones and nutrients, it will constrain glucose production by the liver and keep blood glucose relatively low," said Dr. Michael W. Schwartz, a professor at the University of Washington. But if the brain senses inadequate amounts, he continued, it will "activate responses that cause the liver to make more glucose, and new evidence suggests that this contributes to diabetes and impaired glucose metabolism."
There's a lot more, although the article doesn't touch on the recent genomic scans for diabetes-related genes.
Coverflow for data
The current Discover magazine is running an interview with international health researcher Hans Rosling. A man with a tremendous resumé, Rosling also has a blog tracking his research and public lectures.
His most recent venture was the development of the Trendalyzer software, which is a really cool way to represent changing data over time. The link goes to a demo site, preloaded with world demographic data. I can't wait until the software goes public.
Here's what Rosling had to say about the project:
I explained [to my students] that we have a continuum of life conditions in the world -- we can't put countries into two groups. But when I showed them graphs of this [with time as one axis], it didn't impact them.
Then in 1994, I got the idea to show each country as a bubble, with economic factors on one axis and child survival on the other. My son strated writing the code that made the bubbles move through time, and his wife joined as designer. When you show time as an x-axis, you violate the way we think. But when you show time as graphic movement, as animation, people suddenly understand.
The graphs are startling. I will say that it's not obvious to me that you can tell the difference between linear and geometric growth by watching the moving bubbles -- in other words, while they make people intuitively understand the change, they may hide important details of process. But for the audiences Rosling is addressing, the distinction is unimportant:
So far, we have had a major hit with two target groups: children under 12 and heads of state. What they have in common is that you have only 5 to 10 seconds to impress them.
I'm thinking that a 10-second timeflow graph in a presentation will always beat the static version when time is an axis. Imagine tooth MD and BL diameters represented in many species over time...
Blood type O resists severe malaria
Who knew? Blood type O protects people from falciparum malaria. That's a study by Alexandra Rowe and colleagues, studying a case-control sample from Mali.
And it's not just some little piddling effect. Check out the chart:
Figure 1, A and B, from Rowe et al. 2007.
Type O seems to have a large preventative effect in the severe malaria cases. It doesn't protect people from initial infection, according to these comparisons, but it seems to reduce the disease severity by a lot. The paper attributes that to a reduction in "rosetting" -- that is, the parasites make blood cells tend to clump together, allowing the parasites to spread more quickly through the blood. The mechanism for that clumping makes use of the ABO antigen. Type O people lack the functional trisaccharide antigen, and so they have less rosetting when infected by P. falciparum.
Here's a mystery: if O has such a large effect on malaria severity, then why isn't it fixed? Certainly it is at a higher frequency in subsaharan Africa than in many other parts of the world, but from an initially substantial frequency and no apparent disadvantages it should have become rapidly fixed anywhere P. falciparum infects a substantial proportion of people.
Now, you might point out that O is recessive, and so selection would not be as effective. But this is mostly true for the initial, very low-frequency stages of selection on an allele. Type O blood exists at a substantial frequency already in most human populations. It's not a very young mutation. So selection should have been very effective right away, despite it being recessive.
Clearly, one of two things must be true: either "severe" malaria as documented in this study haven't long been a strong selective factor, or type A and B have counterbalancing advantages.
I could imagine either scenario -- for example, maybe in the past the selective impact of "severe" and non-severe malaria was about the same, and the two only become relevantly different given a mimimal degree of medical care. Or maybe a new P. falciparum strain causing more "severe" malaria hasn't existed very long, but is resisted by type O.
Or, maybe A and B respond effectively to later stages of infection (there's some precedent, with a CD28 allele showing resistance to cerebral malaria, for example). It seems like if there were another important pathogen selecting strongly for A and B, we'd have noticed -- but then, I would have thought that an ABO-malaria association this strong would have been noticed earlier!
Here's the review section:
Earlier studies have found no consistent effect of the ABO blood group on the incidence of uncomplicated malaria, parasite density, or levels of anti-malarial antibody (for review, see ref. 16). The effect of the ABO blood group on severe falciparum malaria has received little attention, although previous studies have suggested that in African children, blood group A may predispose to severe malaria (17, 18), and in Southeast Asian adults, blood group O may confer resistance to the multiorgan failure form of severe disease (19). A rigorous study of the effect of ABO blood group on susceptibility to severe malaria using a matched case-control design with adjustment for known host protective factors such as hemoglobin variants has not been per formed (20). The possibility of a rosette-mediated protective effect of blood group O has been raised previously (17â21); however, the effects of ABO blood group on rosetting and susceptibility to severe malaria have not yet been examined in a single study (Rowe et al. 2007:17471).
There you have it: it takes some doing to tease out these associations of alleles with disease stage and severity. And yet, these are precisely the associations that might be important to selection on an evolutionary timescale.
(via Gene Expression)
Rowe JA, Handel IG, Thera MA, Deans A-M, Lyke KE, Koné A, Diallo DA, Raza A, Kai O, Marsh K, Plowe CV, Doumbo OK, Moulds JM. 2007. Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting. Proc Nat Acad Sci 104:17471-17476. doi:10.1073/pnas.0705390104
"Linus Pauling was right, but he was off by one letter"
That's the final line in this story from the Globe and Mail about vitamin D and cancer risk.
The new findings that prompted the story haven't yet been published, and the story seems one-sided (no prominent skeptics are quoted), but it's a story that mixes traditional anthropological narratives about adaptation with new medical research, and it's full of punchy quotes. Here's the lede:
In June, U.S. researchers will announce the first direct link between cancer prevention and the sunshine vitamin. Their results are nothing short of astounding.
A four-year clinical trial involving 1,200 women found those taking the vitamin had about a 60-per-cent reduction in cancer incidence, compared with those who didn't take it, a drop so large — twice the impact on cancer attributed to smoking — it almost looks like a typographical error.
The story can potentially pull in several other kinds of information, including the lower cancer rates in developing countries, the different rates in U.S. racial groups, and the increase in cancer rates over time. Still, we've seen other correlations in the past that could pull these together, such as diet, stress, and substance use (smoking, alcohol) -- which are sometimes interrelated -- so we'll have to see how the result accounts for multiple correlations. It sounds like a simple treatment-control experiment, which should lead to a strong conclusion.
If vitamin D at the "normal" levels is actually a deficiency, then the obvious conclusion is that people should get out in the sun more. The article doesn't miss this:
Those studying the vitamin say the hide-from-sunlight advice has amounted to the health equivalent of a foolish poker trade. Anyone practising sun avoidance has traded the benefit of a reduced risk of skin cancer — which is easy to detect and treat and seldom fatal — for an increased risk of the scary, high-body-count cancers, such as breast, prostate and colon, that appear linked to vitamin D shortages.
The sun advice has been misguided information "of just breathtaking proportions," said John Cannell, head of the Vitamin D Council, a non-profit, California-based organization.
"Fifteen hundred Americans die every year from [skin cancers]. Fifteen hundred Americans die every day from the serious cancers."
The article includes lots of quotes from the vitamin D industry guy -- it almost sounds like a press release -- so we'll have to see if the results are really as provocative as suggested here. Last year there were other stories that pointed in this direction, so it seems not too unlikely. Vitamin D isn't just for rickets anymore.
The spread of acne
I found this article by Loren Cordain et al. while I was looking for something else, and thought I'd point it out:
Acne vulgaris: a disease of Western civilization
Background In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95% of the adolescent population. In men and women older than 25 years, 40% to 54% have some degree of facial acne, and clinical facial acne persists into middle age in 12% of women and 3% of men. Epidemiological evidence suggests that acne incidence rates are considerably lower in nonwesternized societies. Herein we report the prevalence of acne in 2 nonwesternized populations: the Kitavan Islanders of Papua New Guinea and the Aché hunter-gatherers of Paraguay. Additionally, we analyze how elements in nonwesternized environments may influence the development of acne.
Observations Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade 1 with multiple comedones or grades 2-4) was observed. Of 115 Aché subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed.
Conclusions The astonishing difference in acne incidence rates between nonwesternized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing environmental factors. Identification of these factors may be useful in the treatment of acne in Western populations.
The observations are well-summarized there in the abstract. The introduction points out in addition other populations where acne was apparently rare or absent before Westernization, including Inuit and Okinawan peoples. Also, acne is less prevalent in more rural samples of mixed-ancestry populations, such as Peruvians or South Africans.
In the context of an apparent increase in acne with the introduction of urbanization and Westernized diet, the paper suggests that acne mainly results from diet, in particular depending on the insulin response. This mechanism is a bit involved, so if you are interested, you should refer to the paper.
The journal accompanied that article with an editorial, which notes the interest of recent research into links between obesity, insulin resistance and hyperandrogenism.
This is a great couple of paragraphs:
Cordain et al (1) suggest that diet-induced hyperinsulinemia elicits endocrine responses that may affect the development of acne through mediators such as androgens, insulinlike growth factor (IGF) 1, IGF binding protein 3, and retinoid signaling pathways. The role of diet in endocrine activity is supported by the observation that improvements in nutrition have been linked to an earlier onset of sexual maturation and the development of acne in young girls and boys. Numerous studies have shown that improvements in general nutrition in girls have led to an earlier onset of menses and that menses is delayed in girls with low body fat such as athletes and ballet dancers. (7) In 1970, the mean age of onset of menarche in the United States was 12 years compared with age 16 years for girls in 1835. (8) Of interest is the observation that the mean age of onset of menarche in the Kitavan population is 16 years, which is significantly older than girls in westernized societies. In a 5-year longitudinal cohort study of 439 black girls and 432 white girls in Cincinnati, Ohio, Lucky et al (9) demonstrated that those with severe comedonal acne had a significantly earlier age of onset of menarche and higher serum levels of dehydroepiandrosterone than girls with mild comedonal acne. This study demonstrated that the early development of comedonal acne might be one of the best predictors of later, more severe disease. In a similar 5-year longitudinal study of 219 black and 249 white early adolescent boys in Cincinnati, black boys had higher pubertal maturation scores than white boys of the same age. (10) The prevalence and severity of acne correlated well with advancing pubertal maturation. Is the late onset of menarche in Kitavan girls "protective" against the development of acne or severe acne? Although Cordain et al do not present data regarding the age of sexual maturation of the Kitavan or Aché boys, is it also possible that their relative lack of acne might relate to a later age of pubertal maturation and sebaceous gland exposure to higher circulating levels of androgen?
If acne results from hyperinsulinemia, as proposed by Cordain et al,1 one would expect that obese individuals, who are relatively chronically insulin resistant, would have a higher prevalence of acne. Bourne and Jacobs (11) evaluated 2720 military recruits for obesity and the presence of acne and noted an association between the 2 in the older recruits (ages 20-40 years) but not in those in the age range of 15 to 19 years. This observation suggests that the presence of acne in a younger population may be associated with factors other than obesity or insulin resistance. In fact, serum levels of IGF-1 are highest during periods of the adolescent growth spurt and taper off in the 20s, which coincides with the pattern in the peak incidence of acne. (12) Insulinlike growth factor 1 functions similarly to insulin in that it can promote the growth of keratinocytes and sebaceous glands. It is possible that that the effects of the hyperinsulinemia on acne in obese adolescents may be overshadowed by the effects of high levels of circulating IGF-1. As pointed out by Cordain et al, acne has been associated with elevated serum levels of IGF-1 in adult women with acne. (13) All adolescents, including the Kitavan and Aché, would experience increases in IGF-1 during adolescence, so increases in IGF-1 alone cannot explain the presence of acne.
Yes, IGF-1 is the tiny dog gene, in case you're wondering what kind of search led me to this!
The editorial is receptive but still skeptical of the diet-acne link proposed by Cordain et al.:
Although Cordain et al. (1) make a strong argument for the role of diet in acne, we believe that it is difficult to dissociate environmental factors such as diet from genetic factors in their study. The Aché and Kitavan people live in closely knit communities, and therefore genetic factors may play a role in the relative lack of acne in these populations. Several studies point to an association of genetic factors with acne, including studies that demonstrate variations in the prevalence of acne among ethnic groups and the high degree of concordance of acne in twins. (15-19)
There are a number of later references that cite the paper by Cordain et al., if you're interested in following up -- a link between acne and diet has always been problematic, but this is probably more or less because expression of the disease also depends on several genetic factors that are difficult to untangle.
References:
Cordain L, Lindeberg S, Hurtado M, Hill K, Eaton SB, Brand-Miller J. 2002. Acne vulgaris: a disease of western civilization. Arch Dermatol 138:1584-1590.
Thiboutot DM, Strauss JS. 2002. Diet and acne revisited. Arch Dermatol 138:1591-1592. Abstract
Ancient hemorrhagic fever in Mexico?
I was reading through next month's Discover, and there is an article covering the work of Rodolfo Acuna-Soto, who has proposed that some of the most major epidemics that killed the Aztecs and other ancient American populations may have been caused by an indigenous hemorrhagic fever. This 2000 paper and this 2002 paper lay out the case.
The abstract of Acuna-Soto et al. (2000) describes the disease:
In 1545, twenty-four years after the Spanish conquest of the Aztec empire, an epidemic of a malignant form of a hemorrhagic fever appeared in the highlands of Mexico. The illness was characterized by high fever, headache, and bleeding from the nose, ears, and mouth, accompanied by jaundice, severe abdominal and thoracic pain as well as acute neurological manifestations. The disease was highly lethal and lasted three to four days. It attacked primarily the native population, leaving the Spaniards almost unaffected. The hemorrhagic fevers remained in the area for three centuries and the etiologic agent is still unknown. In this report we describe, and now that more information is available, analyze four epidemics that occurred in Mexico during the colonial period with a focus on the epidemic of 1576 which killed 45% of the entire population of Mexico. It is important to retrieve such diseases and the epidemics they caused from their purely historical context and consider the reality that if they were to reemerge, they are potentially dangerous.
There are several lines of evidence leading to this interpretation, including contemporary accounts of symptoms by doctors and priests, the lack of correspondence of these symptoms to known epidemics like smallpox, typhus, yellow fever, malaria and the other usual candidates, the fact that the indigenous people used a distinct word, cocolitzi to describe the epidemics, which was different from their description of smallpox (often assumed to have been the cause), and the association between epidemics and droughts.
The papers suggest that the transmission pattern is similar to the hantavirus that caused Four Corners disease: years of drought followed by rainfall, which caused an explosion of rodent populations and greatly increased human-rodent contacts. They substantiate the hypothesis with analysis of tree-ring data, which show a correspondence between drought years and plague years, as well as a massive drought and wet sequence associated with the largest epidemic in 1545.
A big problem with the hypothesis could be the fact that the cocolitzi epidemics did not greatly affect Spaniards, despite the expectation that they should have had no immunity to a native American disease. Acuna-Soto and colleagues propose that this is a reflection of their high status -- they would have been under less stress during droughts than the indigenous people, and they might not have had as extensive contact with rodents.
The 2002 paper speculates that the epidemic may derive from either a hantavirus or an arenavirus, both of which have caused rodent-borne disease in the New World, but no known species of either has been found in the right place. Perhaps the closest analogue would be the Machupo virus that causes Bolivian hemorrhagic fever. It's an awful disease.
Will it return?
Cocoliztli was an emerging disease of its time and it appeared at a time of intense social and ecologic change. The illness ran without control and caused catastrophic damage to the Indian population for at least a century. Today, there are no reported human or animal diseases resembling cocoliztli in the area. The disease has not been reported for a long time and the probability of an epidemic reemergence
remains unknown. As for potential risk factors, it is important to remember that poverty, a key element in the epidemic, remains prevalent in some areas formerly affected by the disease. In the small towns around the city of Tehuacan, in the state of Puebla where cocoliztli once flourished, the word cocoliztli is still used as synonymous with lethal disease. Perhaps it is only representative of a historical vestige, but if the word and the concept remain active, we may well wonder if the etiologic agent is also alive and waiting to emerge again (Acuna-Soto et al. 2000:737).
It makes a good detective story, with quotes from unpublished historical documents, dendrochronology, and all the rest.
References:
Acuna-Soto R, Romero LC, Maguire JH. 2000. Large epidemics of hemorrhagic fevers in Mexico 1545-1815. Am J Trop Med Hyg 62:733-739. PubMed
Acuna-Soto R, Stahle DW, Cleaveland MK, Therrell MD. 2002. Megadrought and megadeath in 16th century Mexico. Emerg Infect Dis 8:360-362. PubMed
The appendix: not just for appendectomies anymore?
In a paper in press in the Journal of Theoretical Biology, Randal Bollinger and colleagues suggest that the human vermiform appendix functions as a "safe house" for bacteria:
The observations described above, in conjunction with the survival advantages afforded to bacteria by biofilms(Costerton, 1995; Costerton, 1999; Costerton et al., 1995) and the architecture of the human large bowel, give rise to the idea that the appendix is a compartment well suited for maintaining beneficial or commensal microorganisms, being well positioned to avoid contamination by pathogenic organisms present transiently in the fecal stream. Indeed, the narrow lumen of the appendix as well as its location at the lower end of the cecum are both factors that afford relative protection from the fecal stream as it is propelled by peristalsis. Given the metabolic advantages (Bradshaw et al., 1994; Bradshaw et al., 1997) and other advantages (Costerton, 1995; Costerton, 1999; Costerton et al., 1995) that biofilms are known to afford bacteria, biofilm formation in the appendix is expected to be a relatively effective means of preserving and protecting commensal bacteria. In essence, the structure of the appendix is expected to enhance the protective effect of biofilm formation for commensal bacteria. Effective biofilm formation by commensal bacteria in the appendix is expected to facilitate not only the exclusion of pathogens, but also the adherence of the non-pathogenic commensal organisms within that cavity. Regular shedding and regeneration of biofilms within the appendix would be expected to re-inoculate the large bowel with commensal organisms in the event that the large bowel became infected by a pathogen and was flushed out as a defensive response to that infection (Bollinger et al. 2007:7-8).
So in other words, the appendix supposedly facilitates the use of diarrhea as a pathogen-shedding mechanism, because it would preserve the beneficial gut flora when the body sheds the biofilm coating the rest of the colon.
It's a hypothesis.
So here's a problem: The authors note that the appendix may now be relatively useless because of the lower importance of fecal-borne diseases "in the face of modern medicine and sanitation practices." But before people started living in sedentary settlements, with high population densities, fecal-borne diseases must have been vastly less important than they have been historically, when people regularly have drunk from contaminated water supplies. Throughout human evolution up until the Holocene, diarrheal diseases would not have been absent (food poisoning and incidental contact with fecal-borne disease from other species always being possible), but they must have been vastly less important than they have been recently.
Indeed, maintenance of a reserve supply of commensal bacteria in the event of infection by pathogens may be unnecessary in areas where outbreaks of enteric pathogens do not affect the vast majority of the population at any one time. Certainly this idea is consistent with the well-known observation that appendectomy is without currently discernable long-term side effects in societies with modern medical and sanitation practices (ibid.:9).
If it's adaptive, it must be not to the recent environment of high enteric pathogen load, but the ancestral environment. And not just to meat-eating: the apes have appendices, too. In fact, Fisher (2000) points out that many primates, including non-anthropoids, have similar structures. Others have thickened "biofilm"-like mucosal layers in the cecum that would seem to approximate this microbe-harboring function. Since this includes primarily fruit-eating and leaf-eating species, there is no reason why contact with meats, bacteria from spoiled meats, or enteric bacteria from consumed animals should necessarily be involved. I'm not sure why the current paper (Bollinger et al. 2007) didn't cite any of this comparative work; it certainly seems relevant to their hypothesis.
The appendix looks functional to me, I'm just not sure that it is specifically a "safe harbor" in the face of enteric pathogens. It may just be a "safe harbor" in the face of normal elimination.
I guess that last is an unfortunate turn of phrase...
References:
Bollinger RR, Barbas AS, Bush EL, Lin SS, Parker W. 2007. Biofilms in the large bowel suggest an apparent function of the human vermiform appendix. J Theor Biol (in press) doi:10.1016/j.jtbi.2007.08.032
Fisher RE. 2000. The primate appendix: a reassessment. Anat Rec B 261:228-236. doi:10.1002/1097-0185(20001215)261:6<228::AID-AR1005>3.0.CO;2-O
Circumcision and Cyberchase, revisited
This is me, last year, writing about a study on circumcision and HIV risk in Africa:
The study was stopped before its scheduled completion, because the reduction in risk was significant. But arguably, this reduction would itself reduce as the study went on longer -- men who maintained high-risk sexual activities might see a delay in infection with circumcision, but if those activities continued, they would likely ultimately be infected. In other words, we can't assume that the reduction in risk would project linearly with time. Instead, as time passes, the high-risk population would become increasingly saturated with infections. If this model held, then circumcision would become less and less effective over time.
This is from a press release about a current study showing that circumcision has less of an impact than thought last year:
The study has important policy implications. Several international AIDS organizations have begun to provide funding for male circumcisions as a deterrent to AIDS. While male circumcision may indeed reduce the risk of transmission by some 50% to 60% in each sexual encounter, reducing single encounter transmission rates alone cannot control the epidemic. The reason is that individuals in highly infected countries have multiple contacts with the infected so reducing transmission rates only defers the inevitable.
Now, the idea is that the rate of infection among prostitutes is the key factor, because it is the most important determinant of the long-term risk over many sexual encounters.
The mystery and terror of Ebola
Tara Smith at Aetiology has a recent post discussing the Ebola virus. Personally, I think it's much scarier than influenza, but that's just me. She points out that much of the fear comes from the mystery -- we just don't know so much about where it comes from or what natural variability may be hiding in some animal reservoir.
But there's plenty of scary stuff there:
Additionally, I mentioned above that there are 4 known distinct lineages of Ebola: Zaire, Sudan, Ivory Coast, and Reston. This study only focused on the most virulent; the Zaire strain. It doesn't answer the question of whether EBO-Z is spreading into a population where other filoviruses already exist, but EBO-Z is out-competing them, or if it's spreading into regions where no Ebola relatives are present. Just based on other epidemiologic data, I'd guess it's the former. Serologic studies in several regions of Africa have shown that many people possess antibodies to the Ebola virus, even though they report never having had a hemorrhagic fever (or experiencing an outbreak of Ebola-like illness in their village). It seems likely that filoviruses are present somewhere in the environment already, but these strains are probably low-virulence, and do not cause overt disease. The Reston strain already has been shown to cause asymptomatic infection with humans; there is no reason to think others like this cannot be out there as well. Are they losing an evolutionary battle with EBO-Z? If so, that suggests that we may see more frequent outbreaks in the future.
The whole blog is excellent for discussion of health and evolution. I'm adding it to my blogroll.
Evolutionary medicine intro
I ran across an HTML version of an article by Lori Oliwenstein, originally from Discover, that introduces evolutionary medicine. It's a good link for my students, and for anybody else who's interested. And it has a great Paul Ewald quote:
"You're doing to these organisms what we did to wolves," says Ewald. "Wolves were dangerous to us, we domesticated them into dogs, and then they helped us, they warned us against the wolves that were out there ready to take our babies. And by doing that, we've essentially turned what was a harmful organism into a helplful organism. That's the same thing we did with diphtheria; we took an organism that was causing harm, and without knowing it, we domesticated it into an organism that is protecting us against harmful ones."
Gorilla and chimpanzee Ebola transmission
I've been following the story of the Ebola epidemic in wild lowland gorillas, in posts here, covering research by Magdalena Bermajo et al., and here, sampling research on disease spread in wild primates. Now, a new contribution to the story comes from Peter Walsh and colleagues, studying the movements and interactions of gorilla groups with each other and with chimpanzees.
Of particular interest was the fact that overlaps pivoted on a few social units that were frequently present during the mast fruiting event (fig. 1C). One unit visited the Nauclea trees on 26 of the 36 September and October days on which gorillas were observed in Nauclea trees. It accounted for 38% of same-day overlaps, 49% of consecutive-day overlaps, and 56% of 2-day overlaps. It overlapped with nine of the other 15 units in at least one of the three time intervals (four, seven, and nine units, respectively). These observations suggest that some gorilla social units may play a disease-transmission role analogous to that of prostitutes in the spread of HIV in southern Africa (Anderson et al. 1991), rapidly disseminating Ebola among networks of individuals that would otherwise interact little. Such "super spreaders" have recently been shown to play a critical role in the dynamics of explosively emerging diseases, including Ebola in humans (Lloyd-Smith et al. 2005) (Walsh et al. 2007:687-688).
In the next paragraph, the authors discuss coforaging in the same trees by gorillas and chimpanzees in the Goualougo Triangle:
From 2002 to 2004, we observed chimpanzees from four different communities foraging in fruiting trees from the genus Ficus. On 5 of 75 days (i.e., once for every 15 days of feeding observations at Ficus trees) chimpanzees occupied a tree simultaneously with gorillas (see video 3). Co-occupancy lasted for an average of 47 min, with an average of 10.4 chimpanzees and 3.8 gorillas involved. True rates of co-occupancy are probably higher because gorillas appeared to be deterred by the presence of observers. Although shared use of resources has been reported (Kuroda et al. 1996), this is the first study documenting that co-feeding occurs on a regular basis (Walsh et al. 2007:688).
The study doesn't document actual transmission of Ebola, but is intended to provide details of the social context in which transmission could occur. In addition to the cross-specific interactions, they also report one group coming across and inspecting a dead bloody gorilla corpse. Inspection isn't new, but what is interesting is that lowland gorillas live at population densities high enough to run across dead individuals from other groups -- making disease transmission by this mechanism plausible.
References:
Walsh PD, Breuer T, Sanz C, Morgan D, Doran-Sheehy D. 2007. Potential for Ebola transmission between gorilla and chimpanzee social groups. Am Nat 169:684-689. Abstract
Gorillas and ebola
Just a pointer to this Reuters article about the spread of the Ebola virus through a wild gorilla population:
A 2004 outbreak of the virus, which also kills people, killed 97 percent of gorillas who lived in groups and 77 percent of solitary males, Damien Caillaud and colleagues from the University of Montpellier and the University of Rennes in France reported.
Overall, it wiped out 95 percent of the gorilla population within a year, they reported in the journal Current Biology.
The paper in Current Biology (DOI link) is super-short, and ends with this paragraph:
These results provide new insights into the epidemiology of a still largely unknown disease. In an evolutionary perspective, this study provides direct evidence that, in hominoids other than humans, group individuals face a higher disease risk. This cost has probably been an important constraint to sociality evolution in early humans [10]. In a conservation perspective, the demographic impact of Ebola virus is dramatically enhanced since it disproportionately affects females and young individuals, which are essential for population recovery (Figure 2C,D). Censuses conducted in 1994â5 revealed that Odzala-Kokoua National Park gorilla density was the highest ever recorded, averaging 5.4 ind/km2 [11]. Preliminary surveys we conducted show that EBOV may have affected this population heterogeneously, with some large areas being now almost devoid of gorillas and others seeming intact. Thousands of gorillas have probably disappeared. As the impact of EBOV on apes is still difficult to control, reinforced protection of gorillas and chimpanzees is required throughout their range, especially against poaching and logging, the two major additional threats to these species [6] (Caillaud et al. 2006:R490, emphases mine).
This kind of risk from living in a social group would probably strike most people as highly irregular. I mean, how often can a killer virus come through? Maybe it is a unique recent risk because of human activities that incur on gorilla habitat.
On the other hand, a disease doesn't have to be so deadly to have important impacts on fitness, and sociality also has the increased risk of parasites (reviewed by Altizer et al. 2003). This passage from Semple and colleagues (2002) applies to primates:
However, many studies have identified social and ecological correlates of parasite abundance and disease prevalence that would be predicted to play a role in shaping the evolution of the immune system.
Two parameters of particular interest in this respect are population density and group size, which may affect parasite transmission rate between hosts. Comparative analysis has indicated that parasite abundance can be strongly correlated with host population density among mammals (Arneberg et al. 1998), and meta-analysis has demonstrated that the prevalence and intensity of contagious parasites can be positively correlated with host group size
among social animals (Cote & Poulin 1995). More specifically among primates, prevalence of parasitic infection has been found to increase with higher population density (e.g. howler monkeys; Stuart et al. 1990), and group size has been found to be positively related to parasitic infection rate (e.g. Amazonian primates; Davies et al. 1991).
Epidemics may be a more serious risk for primates than for many other mammals; since:
- primates are highly social
- multiple primate species are often sympatric (chimpanzees and gorillas being the operant example here, although both are widely sympatric with cercopithecine and colobine species also)
- primates interact more closely than most other mammals with bats and birds, the major long-distance disease dispersers
This is one of the problems with optimality models for group dynamics -- you never know which important variables you are leaving out.
For instance, why don't orangutan social groups spend much time around each other? The usual answer is that it is energetically expensive to forage together through much of their habitat. But then, there is this:
Sylvatic transmission of arboviruses among Bornean orangutans
ND Wolfe, AM Kilbourn, WB Karesh, HA Rahman, EJ Bosi, BC Cropp, M Andau, A Spielman, and DJ Gubler
Wild populations of nonhuman primates live in regions of sylvatic arbovirus transmission. To assess the status of arbovirus transmission in Bornean forests and the susceptibility of wild orangutans to arboviral infection, blood samples of wild orangutans, semi-captive orangutans, and humans were examined. Samples were tested by plaque reduction neutralization test for antibodies to viruses representing three families (Flaviviridae, Alphaviridae, and Bunyaviridae), including dengue-2, Japanese encephalitis, Zika, Langat, Tembusu, Sindbis, Chikungunya, and Batai viruses. Both wild and semi-captive orangutan groups as well as local human populations showed serologic evidence of arbovirus infection. The presence of neutralizing antibodies among wild orangutans strongly suggests the existence of sylvatic cycles for dengue, Japanese encephalitis, and sindbis viruses in North Borneo. The present study demonstrates that orangutans are susceptible to arboviral infections in the wild, although the impact of arboviral infections on this endangered ape remain unknown.
A habit for avoiding social contacts might be expected to reduce the risk of infection, just as it did for gorillas faced with Ebola. This strategy may well be resource-mediated: relatively low local resource densities may restrict any advantages of high social contacts to an extent that the benefits for resisting disease outweigh them. In other words, disease is not the only factor encouraging low social contacts, but it may modify the balance among the other factors in ecology-dependent ways.
The strategy may also be body mass-mediated. For instance, Davies et al. (1991) found that malaria risk in New World primates depends not only on group size but also body weight. Semple et al. 2002 also show that body size and immune system activity are also related to disease and infection rates.
On the other hand, Bonds and colleagues (2005) describe a model in which higher disease prevalence can increase the advantages of sociality. There is some entertaining dancing at the end of that paper, since empirical studies have pretty consistently shown a positive association between disease risk and social group size -- but Bonds et al. argue that these studies aren't finding evolutionary responses, but instead positive relationships that are expected within static populations. Whatever the case, there is some interesting math in this paper, which has the chief weakness of assuming that the host population is homogeneous. Working out optima with different host strategies possible would be more difficult but worthwhile -- for instance, a long solitary period for males would be a strategy that appears to be adaptive in the gorilla-Ebola case, and plausibly is generally so for large-bodied primates.
At any rate, this area of research is developing quickly. In 2002, Kappeler and van Schaik reviewed determinants of sociality in primates and had only this to say about disease:
Finally, potential main determinants of some aspects of social systems, as well as some important consequences, remain virtually unexplored. There are few studies on diseases of natural primate populations, and their effects on behavior (Freeland, 1976; Davies et al., 1991; Heymann, 1999; Nunn et al., 2000) (Kappeler and van Schaik 1998:728).
There have been several studies in the interim, including some of the ones listed here. A bit more theory, particularly with respect to variability in strategies and multispecific interactions, would help. And of course, there is the possibility that direct adaptations to diseases had important effects on social group sizes. This is where I think there may be important impacts on human evolution, since we seem to have had some fairly unique immune system adaptations during the course of the last couple million years.
References:
Altizer S, Nunn CL, Thrall PH, Gittleman JL, Antonovics J, Cunningham AA, Dobson AP, Ezenwa V, Jones KE, Pedersen AB, Poss M, Pulliam JRC. 2003. Social organization and parasite risk in mammals: integrating theory and empirical studies. Annu Rev Ecol Evol Systematics 34:517-547. DOI link
Bonds MH, Keenan DC, Leidner AJ, Rohani P. 2005. Higher disease prevalence can induce greater sociality: a game theoretic coevolutionary model. Evolution 59:1859-1866. Abstract
Caillaud D and 8 others. 2006. Gorilla susceptibility to Ebola virus: the cost of sociality. Curr Biol 16:R489-R491. DOI link
Davies CR, Ayres JM, Dye C, Deane LM. 1991. Malaria infection rate of Amazonian primates increases with body weight and group size. Functional Ecology 5:655-662.
Kappeler PM, van Schaik CP. 2002. Evolution of primate social systems. Int J Primatol 23:707-740. DOI link
Semple S, Cowlishaw G, Bennett PM. 2002. Immune system evolution among anthropoid primates: parasites, injuries and predators. Proc Roy Soc B 269:1031-1037. DOI link
Wolfe ND and 8 others. 2001. Sylvatic transmission of arboviruses among Bornean orangutans. Am J Trop Med Hyg 64:310-316. Abstract
Affliction with little dragons
If you can stomach a story about guinea worm, there is an excellent one in the NY Times today (via Althouse). It covers the difficulties faced in current eradication efforts, and specifically the Carter Foundation's role, but is a good story about the interplay between traditional cultures, disease and Western medicine.
"We have paid people to put Abate in the sacred ponds secretly," he admitted.He described a northern village that practiced both ancestor worship and Islam, which considers dogs unclean.
"They refused the Abate," he said, adding with a grin: "But someone killed a dog and threw it in their sacred pond. People stopped drinking the water -- and Guinea worm cases went down."
The thing that strikes me is this:
Guinea worm's Latin name is dracunculiasis, or "affliction with little dragons," but in Africa it is often called empty granary because of its tendency to erupt at harvest time, rendering farmers unable to work. It ought to be almost ridiculously easy to wipe out, because it has a complex life cycle in which humans, worms, fleas and shallow ponds each must play their parts perfectly. Any missing link disrupts the chain of transmission.
Yet this complex parasite has spread across subsaharan Africa and into the Indian subcontinent. Amazing how effective a strategy afflicting humans has proven to be.
Syphilis origin pinpointed?
John Noble Wilford covers a new article on the New World origin of syphilis, researched by Kristin Harper and George Armelagos.
In her investigation, Ms. Harper studied 22 human Treponemal pallidum strains. The DNA in their genes was sequenced in nearly all cases, examined for changes and eventually used in constructing phylogenetic trees incorporating all variations in the strains.
An Old World yaws subspecies was found to occupy the base of the tree, indicating its ancestral position in the treponemal family, she said. The terminal position of the venereal syphilis subspecies on the tree showed it had diverged most recently from the rest of the bacterial family.
Specimens from two Guyana yaws cases were included in the study, after they were collected and processed by Dr. Silverman. Genetic analysis showed that this yaws strain was the closest known relative to venereal syphilis.
The research article is open access in PLoS Neglected Tropical Diseases. It is a pretty standard phylogenetic analysis, somewhat complicated by the high recombination rate in these bacteria, but the results seem very straightforward. The sister-group relationship of syphilis with Guyana yaws is based on four SNPs, three of which are plausibly selected, so we'll likely hear more on this story in the future.
People sometimes wonder why it matters where syphilis came from. Or worse, they suspect that it is just a front -- a way to play "blame the victim" by putting the origin of the scourge in ancient Americans. This is truly an anthropological topic -- the science of origins is confounded with the subsequent cultural interactions of these populations.
But I think that Armelagos, who has been deeply involved in the problem of syphilis origins for a long time, makes the most relevant connection, as quoted by Wilford:
Dr. Armelagos said research into the origins of syphilis would continue, because "understanding its evolution is important not just for biology, but for understanding social and political history."
Noting that the disease was a major killer in Renaissance Europe, he said, "It could be argued that syphilis is one of the important early examples of globalization and disease, and globalization remains an important factor in emerging diseases."
That to me is an important point worth bringing to my classes. Studying the origins of these epidemics gives us insight about the relationships of global cultural interactions and ecological disruption for new emerging diseases. Syphilis did not merely originate and spread. It also fundamentally changed its nature, with increased virulence and sexual transmission. These changes were adaptive in the context of 16th century global contacts and ecological changes. Maybe the most important changes were in sexual ecology, but sheer numbers may also have been an important catalyst for change. Yaws is a long-term infection that can be sustained in small-scale populations of thousands. Syphilis was introduced and rapidly spread through a population of millions.
The research paper raises an unusual point: answering this question for syphilis may become impossible because its pathogen relatives have been declining:
The large-scale comparative genetic studies possible on the pathogens that cause diseases such as malaria and anthrax will never be possible in T. pallidum [syphilis + yaws], because of the disappearance of the non-venereal treponematoses and the strains that cause them [60],[61]. The prevalence of yaws in Guyana, the last country in South America in which yaws has been documented in recent years, has decreased annually, and surveys carried out by our group in 2006 and 2007 in endemic yaws territory demonstrated no active cases of the disease. Analysis of South American strains is necessary in order to assess the relationship between subsp. pallidum and non-venereal treponemal strains. Because it is not clear whether an opportunity to examine such strains will arise again, the results presented in this paper are of special importance in the debate over the origins of treponemal disease.
Two of the samples in the paper come from degraded old sources -- and they turn out to be the key comparisons. If these species are eradicated it will be a triumph for human health, so there is no reason for sadness (and I suspect no volunteers will be stepping forward to preserve them!). But it does raise an interesting prospect: in at least a few cases, maybe the study of pathogen evolution will become as difficult as the study of human evolution.
References:
Harper KN, Ocampo PS, Steiner BM, George RW, Silverman MS, et al. (2008) On the Origin of the Treponematoses: A Phylogenetic Approach. PLoS Negl Trop Dis 2(1): e148. doi:10.1371/journal.pntd.0000148
HIV, Africa, circumcision, and PBS Kids
My daughter really likes Cyberchase. She likes it because it is all about how math can solve problems. If you're unfamiliar with the show, a crew of three ordinary kids and their Gilbert Gottfried-voiced toucan-looking cyberbird get to tool around cyberspace helping the beneficent leader, Motherboard, to beat back the nefarious schemes of the evil Christopher Lloyd-voiced Hacker.
It's not that often that kids' shows interact with real life, but yesterday was one of those days. I was reading this study about how men were circumsized for a random trial in Kenya to see how much circumcision cut the risk of HIV infection. It has been recognized for many years that circumsized men in Africa have a lower infection rate from heterosexual sex than do non-circumsized men. But circumcision is a fairly drastic intervention compared to other methods to prevent infection, notably condoms. It's one thing to observe that men who undergo circumcision for cultural reasons have a lower infection rate, it's another to suggest that all men get circumcized as a routine prophylactic measure.
The study reported yesterday was fairly remarkable:
The clinical trial, funded by the National Institute of Allergy and Infectious Diseases and the Canadian Institute of Health Research, enrolled 2,784 HIV negative, uncircumcised men between 18 and 24 years old in Kisumu, Kenya.
Half the men were randomly assigned to circumcision, half remained uncircumcised. All men enrolled in the study received free HIV testing and counseling, medical care, tests and treatment for sexually transmitted infections, condoms and behavioral risk counseling for 24 months.
Study results show that 22 of the 1,393 circumcised men in the study contracted HIV, compared to 47 of the 1,391 uncircumcised men. In other words, circumcised men had 53 percent fewer HIV infections than uncircumcised men.
The report indicates that all the men in the study tended to reduce their sexual risk behavior, although it doesn't indicate whether that was because of the availability of condoms, medical care, information, or because volunteers were more likely to be health-conscious to begin with.
The conclusion of the report was clear -- based on a 53 percent reduction in HIV infection rate,
Until now, public health organizations have not supported circumcision as a method of HIV prevention due to a lack of randomized controlled trials.
"With these findings, the evidence is now available for donor and normative agencies, like WHO and UNAIDS, to actively promote circumcision in a safe context and along with other HIV prevention strategies," [study PI Robert] Bailey said.
Back to Cyberchase.
You see, in yesterday's episode, Hacker was carrying out a nefarious plot to destroy the Cybrary:
Hacker poses as a virus exterminator. He fools Ms. Fileshare into entering her lair, the Cybrary, with bogus bar graph comparisons. Hacker releases his bugs, but it's Hacker who pays the price with a bout of amnesia. (He's forced to work for Buzz!) But the bugs are still out in the Cybrary, seizing control of various sections. Ms. Fileshare insists the CyberSquad that, if she is to believe them, they must provide an easy way to compare the number of bugs in each Cybrary section.
How could Hacker possibly get hired as a virus exterminator, you wonder? Well, he showed the Cybrarian Ms. Fileshare two graphs -- the number of bugs he eliminated, and the number eliminated by his competitors. Hacker's bar was much higher, and Ms. Fileshare assumed that Hacker had eliminated many more bugs than his competition.
But there was a catch. Hacker's two graphs had different scales. Even though his bar was much higher, it represented only a few bugs. His competitor had a much lower bar, but it had a much smaller scale, so it represented many more bugs than Hacker's graph.
In other words, Cyberchase is teaching my daughter and who knows how many other kids just how people can lie with statistics. A very good thing, I would say.
So what does Cyberchase have to do with HIV infection rates? Well, if you're clever you'll have already figured it out. Look at those numbers again:
Study results show that 22 of the 1,393 circumcised men in the study contracted HIV, compared to 47 of the 1,391 uncircumcised men. In other words, circumcised men had 53 percent fewer HIV infections than uncircumcised men.
In other words, uncircumcised men in the study had a 3.4 percent infection rate, and circumcised men had a 1.6 percent infection rate. True, that is a 53 percent reduction, and every case of HIV is well worth preventing.
But how many men would sign up for circumcision if they knew that their actual risk reduction was the mere 1.8 percent difference between the two numbers? And how does this reduction compare to other measures, like the consistent use of condoms?
The 1.8 percent reduction puts this quote into another perspective:
The study also evaluated the safety of circumcision in a community health clinic with specially trained practitioners. There were no severe or lasting complications from circumcision. However, 1.7 percent of surgeries resulted in mild complications, such as bleeding or infection.
Granted that HIV infection is much more serious than most instances of complications from circumcision. But the study is assuming that circumcision has no other downsides, which is far from obvious.
The study was stopped before its scheduled completion, because the reduction in risk was significant. But arguably, this reduction would itself reduce as the study went on longer -- men who maintained high-risk sexual activities might see a delay in infection with circumcision, but if those activities continued, they would likely ultimately be infected. In other words, we can't assume that the reduction in risk would project linearly with time. Instead, as time passes, the high-risk population would become increasingly saturated with infections. If this model held, then circumcision would become less and less effective over time.
Increasing the rate of circumcisions might make a big system-wide difference. Every infection has a cascade of economic and social effects, and every prevented infection limits the rate of spread of the epidemic.
But the costs of circumcision very well might exceed the reduced risks -- especially if high-risk sexual behavior is not reduced as well. To me, the study is sufficient to suggest that already-established circumcision traditions should be encouraged, but not enough to suggest that it should be adopted en masse by other populations. It almost certainly shouldn't be given money that would otherwise go to increase consistent condom use.
And consider yourself blessed if, like me, you have a daughter who likes math!
Malaria immune evasion
Tara Smith of Aetiology has a fascinating post on gene switches in malaria.
Here's an excerpt:
A question asked is how does P. falciparum regulate expression of the var gene family, a highly polymorphic family of genes which encode the P. falciparum erythrocyte membrante protein 1(PfEMP1). PfEMP1 is a major virulence factor that plays a role in immune evasion. In each individual P. falciparum parasite, only one var gene is expressed; the other 59 are silent. However, the parasite can switch expression: a parasite that initially expresses, say, var29 can switch and later express only var 40, for instance. This would protect the parasite, as a host that was mounting an immune defense targeted to the protein produced by var29 would have to essentially start back at square one. This was previously known, but what wasn't known was just how P. falciparum carries out this switching, and more importantly, just how it keeps the other 59 silent while expressing the one of choice.
She answers the question, and illuminates a lot about how P. falciparum manages to steer clear of immune defenses -- I mean, literally steer red blood cells around.
Parasites. To paraphrase Elwood Blues: I hate those guys.
A fungus among us
What an awesome science story:
First, researchers grew enough fungus to give dandruff to 10 million people. Next, they sequenced its genes. Then they found out that not only does an icky fungus live on your head and cause dandruff - but it could be having sex. On your head. Right now.
It's Malassezia globosa, and it's another one of those commensal organisms that has a varying range of pathological effects, including serious systemic infections in some infants. Here's what Wikipedia has to say:
Recently, identification of Malassezia on skin has been aided by the application of molecular or DNA based techniques very similar to those used by forensic scientists to identify criminal suspects. These investigations show that in humans the species causing most skin disease, including the most common cause of dandruff and seborrhoeic dermatitis is M. globosa. The skin rash of tinea versicolor (pityriasis versicolor) is also due to infection by this fungi [sic].
As the fungus requires fat to grow, it is most common in areas with many sebaceous glands: on the scalp, face, and upper part of the body. When the fungus grows too rapidly, the natural renewal of cells is disturbed and dandruff appears with itching (a similar process may also occur with other fungi or bacteria).
Aside from the details about this fungus, the story is interesting because it illustrates the extent to which genome sequencing has become available in disease research. This work -- entire genome sequencing and analysis -- was done by a lab at Procter and Gamble. There's a bunch of stuff in Nature this week on the uses of whole-genome sequencing in evolutionary analysis and functional inference.
For research into pathogen-host interactions, like this work, ha