Scientific American

New Revelations about the Biodiversity of Belly Buttons

When it comes to science, I have the patience of a rabid fox, trapped in a cage, in front of which a wounded rabbit is standing. My family, the folks in my lab and the need for sleep balance this nascent madness. But sometimes the caged fox of mania escapes; sometimes when everyone else sleeps I can’t resist the run.

Image 0. A young fox pretending it isn’t thinking about a rabbit. Image courtesy Rob Lee.

Today was one of those days. We saw another glimpse into the life inside belly buttons. Belly buttons are ridiculous and yet the life we study in them is not; it includes both dangerous and life saving species though in just what mix and why, well, that is what we’d like to know. As a result we have, over the last few years, worked with more than 500 people to sample the life in their belly buttons. It has not always been pretty (Imagine emails from concerned and infected citizens that include photos. Yes, we see those. No, please don’t send them.), but the aim was to have a consistent part of the body through which we might understand the differences more generally, person to person, in what lives on skin.

Your skin is covered in life, a fine featheriness of single-celled organisms, your verdant cloak of existence, a cloak so woven into your existence that it is not clear where it ends and you begin. This is life that colonizes you during or before birth and accumulates through living. It also sheds. The more you sit in a place, the more that place is filled with the microbes from your skin.  We are all like Pigpen, tracking a cloud of our microbes wherever we go.

But which life? And can we understand what determines which life? That is our rabbit-hopping quarry. Or it was. In route we stumbled into something else and ran after it down another trail. That something else was the realization that, at least in our first datasets, if you knew which species were abundant (present in many cells on the average person) and frequent (present on many people) in one group of folks you could predict the same for another group of folks, and perhaps any other you examined. In other words, some bacteria are predictably abundant and frequent AND those bacteria appear to come from just a small subset of the many lineages of life, an unusually small subset, a handful of sun-shaped life forms in a universe filled with stars. To us this was a big deal because thousands of species live on skin, but if only a minority is predictably important, knowing the story of the life of the skin might actually be tractable.

This is what we found, but here is where I tell you about a thing scientists know but don’t share with the public. I think the formal term for it is soul-crushing self-doubt. Scientists are taught to be skeptical. They are taught that most of what they learn about the world, most of what we know about the world, is wrong. They are taught to poke relentlessly at our existing knowledge, to look for weakness, errors, things into which the finger sinks deeply. What wakes them up at night is the sense that the thing they have just discovered will be found out to be the thing that is wrong.

The only recourse for this crushing, scientific self-doubt is, of course, to repeat observations and experiments, or to cry. So in the mornings after sleepless nights, we do more science to check, again and again, our ideas hoping that if something is wrong or not quite right that we will find it out before our peers do. The only thing worse than realizing you have totally misunderstood the gears behind the clock of life is having one of your colleagues realize it for you. Colleagues are, of course, not the same as friends.

If an idea stands the test of this additional prodding then, it just might be true. (The doubt never disappears, it just diminishes, just as science never reaches the truth, it just approaches it ever more closely). It is for this reason that what happened to me tonight, on one of those reckless evenings of plunging headlong into data was so exciting.

We recently got our first glimpse at the data from the last 284 people who sampled their own belly buttons. The process works more or less like this. People sample their belly buttons. We extract DNA from their samples (which takes more time than you think), we amplify that DNA (which takes more time than you think), we find the money to pay for that DNA to be sequenced (which takes more time than you think), we then send that DNA off to a company that does the sequencing, the DNA then comes back in an email as data (after more time than you might think). Someone then processes those data to turn them from zillions of nucleotides into something that can be jammed into a spreadsheet or statistical software or other programs (which takes WAY more time than you might think) and then and only then we have a data matrix you might recognize, one with the kinds of bacteria in the columns and the identity of the belly buttons in the rows. With that matrix, we can begin to see our quarry.

It so happens, that thanks to the work of many people, including the citizens who sampled their belly buttons, the students who processed those samples, the postdocs who coordinated the processing, Holly Menninger who made sure the bill was paid, and another postdoc who processed the data further, we now have a data matrix. And so if you sent us a sample of your belly button and are waiting to hear what lives in your belly button, we will tell you very, very, soon (It also takes WAY more time than you might think to write 284 emails plus the emails to folks whose samples didn’t work). But before we do, I am going to tell you what I peeked at. I went through and with these new data I looked to see whether what we found for the first data, those that we already published on, held. It was not what we proposed to study next, it was not the big question, but it was the wounded rabbit in front of my fox cage, the thing on which I could seize to see for myself whether my sleepless nights were deserved. I wanted to know if, as in our first samples, the common and frequent species were predictably common and frequent and the uncommon and infrequent species were predictably uncommon and infrequent. It might, for a million reasons, have been otherwise. Part of me was sure it would be.

I should have gone to bed. It was late when I first saw the data. I had things to do the next day. I had a morning to wake up to, but I could not resist and so I split the data into, for a starting point, three random hunks of the same number of people and examined the ability of the frequency of different kinds of bacteria in each hunk to predict that in each other hunk.

Here are the results as I first saw them. You should think like a scientist and, as a starting point, assume that I was wrong. But I was not.

Image 1. The number of people on which bacterial taxa occur as a function as their total number of occurrences. Species that are common overall are common in each random subset of the data.


In short, it seems as though across very different people, our rule of commons and uncommons, the law of oligarchs as we have called it elsewhere, holds. The most frequent species are taxa of Corynebacterium and Staphylococcus (which are also among the most frequent bodily taxa we find in houses). This is lovely for a million reasons, but it is most lovely tonight because I poked my finger hard into what we discovered and my finger didn’t sink in. The idea held against the pressure, which doesn’t mean it was right, but it certainly means, it is not yet wrong.

Image 2. One (crude) measure of the relative abundance of different kinds of bacteria in our most recent 274 samples. Number on the x-axis is a person. The y-axis shows the relative number of reads of each kind of bacteria. On many people, a Corynebacterium is, by this metric, the most abundant kind of bacteria in the belly button, but a Staphylococcus is also very common. The third most common kind of bacteria does not even have a genus name.

Now we get to explore the question that started us off in the first place, but we do not need to study all of the species. The predictable presence of the common, frequent species means that they are the big story, what we most need to explain. It is late tonight, but I may go try now to figure them out. How could I not? The rabbit waits a little further down the trail.

A Wild Bet: Can Inoculating Newborns with Innocuous Strains of Bacteria Save Them from Deadly Ones?

Recently, one of Paul Cezanne’s missing paintings was rediscovered. The painting shows Paulin Paulet, a gardener on Cezanne’s family estate, looking at his poker cards. Cezanne painted Paulet as part of a series of paintings between 1890 and 1896. This particular painting is called A Card Player. It had not been seen since 1930; its whereabouts were unknown. When the owner of the painting came forward, the art world was agog. The painting was small but stunning. It sold for 19.1 million dollars at Sotheby’s. Hidden for decades, it was now among the more valuable pieces of art in the world.

Image 1. Another painting from the same series as “A Card Player.” This one, entitled “The Card Players” also shows Paulet, at right.

I was thinking about this painting recently while reading through an old scientific paper (link). Like A Card Player, this paper seems to have a worth that is hard to calculate. It will not fetch millions of dollars (I got it for free from D.H. Hill Library) but it could improve millions of lives. It too features a gardener placing his bets.

The story begins in an undisclosed hospital in which newborns were getting skin lesions and other infections. A nurse in the hospital was inadvertently carrying a pathogenic strain of Staphylococcus bacteria (Staphylococcus aureus type 80/81, hereafter 80/81) from one newborn to the next. She had had contact with 28 newborns with the first 24 hours of their lives. Six of those newborns were colonized by the 80/81 strain. But the nurse also held and cared for 31 infants who were more than a day old. None of those infants was colonized by 80/81. Herein was a mystery in among the fates of newborns. It was a mystery to which Heinz Eichenwald, a professor at the University of Texas, Southwestern Medical Center, was drawn.

Eichenwald imagined two possible explanations for the mystery. The first and more ordinary explanation was that age conferred some sort of immunological maturity that better allowed the newborns to defend themselves. Alternatively, perhaps the older babies had had more of a chance to be colonized by other bacteria species and that those species conferred resistance to newly arriving pathogens such as 80/81. Just how the bacterial species might confer resistance was unknown, but it was speculated that they might outcompete the pathogens by taking up space or resources before the pathogens could gain a foothold. This second possibility seemed much more far fetched and yet it was, to Eichenwald, inescapably interesting.

Eichenwald devised an experiment. It was well known that in hospitals around the U.S. the incidence of colonization of newborns by 80/81 was very variable. In one nursery, just 11% of newborns were colonized by 80/81 whereas in another 50% were. What if, Eichenwald imagined, newborns who were initially placed in a nursery with a low incidence of 80/81 were moved to the nursery with a high incidence. Would they be protected by their early colonization by bacteria other than 80/81? The experiment was done and, yes, they were, even though they were just a day old, too young for their immune systems to have become any more developed with age.

This experiment was clever (though ethically dubious). It suggested a role for bacterial interference, maybe. Yet it left open a range of other possible explanations. Eichenwald could not convince himself something else wasn’t going on and so he did the perfect experiment, a technically unassailable, but, again, ethically challenged, experiment; he decided to try to garden the bodies of hundreds of babies.

Eichenwald found hospitals around the country in which 80/81 was epidemic. He and his colleagues then inoculated the nasal cavities or umbilical stumps (belly button nubs) of half of a group of newborns with an innocuous strain ofStaphylococcus (502). They then examined whether the inoculated individuals stood a reduced risk of 80/81. They were, in essence, gardening the bodies of newborns, or trying to anyway. They were planting one species, a crop, and hoping that it would ward off another, a weed. This was risky gardening, a poker game in which the bet was the fate of newborns and yet Heinz  F. Eichenwald placed his bet. He placed it hundreds of times, one time for each newborn he inoculated with the good bacterium but also once for each of the control infants he did not inoculate. Then he waited.

The results to a study like this one were potentially important (if heeded) in the 1970s, they were important to each newborn infected with 80/81 or any other pathogen in each hospital around the world. They were probably of relevance to, at that point, hundreds of thousands if not millions of lives. With time, the potential value of this study, however, has increased. It has increased in direct proportion to the number of infections in hospitals but also the severity of those infections. Infections with 80/81 were often problematic (producing boils and lesions) and sometimes dangerous. Now, infections with bad Staphylococcus strains are often a matter of life and death. Times and bacteria have changed.

In the 1960s and 1970s when this study was done, even when strains ofStaphylococcus aureus, in particular 80/81, were serious they could usually be treated with antibiotics. 80/81 was susceptible to Methicillin, for example. However, since that time antibiotic resistance has evolved in and spread among strains ofStaphylococcus aureus. Many strains of Staphylococcus aureus are now categorized as MRSA, Methicillin resistant Staphylococcus aureus. These resistant strains include strains very closely related to 80/81, strains one might reasonably describe as 80/81’s far more dangerous descendants. In this regard, one might wonder not only whether the infants in the hospital who were dosed with a good/innocuousStaphylococcus were spared 80/81 but also whether, in modern hospitals, dosing infants with good bacteria might reduce their risk of infection with MRSA or, by the same token, whether living a life that doses us with good bacteria might, more generally, decrease our risk of MRSA. These seem to be important questions.

Meanwhile, Heinz  Eichenwald did not have to wait long for results. Of the 108 infants in which the good Staphylococcus established, 4.6% became colonized with 80/81. More than one might hope for. But in the 143 infants in which the good Staphylococcus was not established, 39.1%, nearly ten times as many, became infected with 80/81 or one of its close relatives. Gardening the body in self defense seemed to unambiguously work. But this was not enough. Eichenwald would try something else. He would inoculate all of the newborns in the hospitals he was studying with the good Staphylocccus. When he did, 80/81 entirely disappeared from those hospitals. The results could not have been more clear and so, on their basis, Heinz  F. Eichenwald concluded, “during the presence of a severe epidemic of staphylococcal disease, the use of 502-A represents the most immediate, safest and effective method of terminating the epidemic. I feel that we now have enough data, involving several thousand babies to indicate that this is a completely safe procedure.”

In the immediate aftermath of this work, excitement boiled. The other scientists who reviewed the paper clearly imagined instituting similar approaches in their own hospitals. It seemed like an approach that might spread ward to ward around the world and it might spread not only among nurseries but also among doctors treating adults. Could inoculation prevent us all from MRSA? Or reduce the risk? Recently, a great deal of attention has been given to the value of fecal transplants or transplants of microbes among ears for those with depauperate or severely infected microbial faunas. But it would be much simpler if we could actually just inoculate those individuals faced with depauperate microbiota with a few good lineages, lineages such as the good Staphylococcus (Recent work has shown that one of the factors that allows beneficial Staphylococcus to exclude pathogens is the production of enzymes that prevent the pathogens from forming biofilms). Eichenwald’s idea really seems like a multi-million dollar one. But this value is unrealized as much as if it were, well, a forgotten painting by Cezanne. After its initial success, Eichenwald’s idea enjoyed modest popularity and then floundered (Perhaps in part due to one fatality associated with the accidental introduction of the “good” Staphylococcus into the blood of a newborn; Eichenwald himself moved on to other things.

Since 1990, Heinz Eichenwald’s study has been mentioned in a scientific paper just once (at least according to Google Scholar) and even then only in passing, but a few new studies have begun to suggest his approach anew, often as though it were a new frontier rather than an old one being revisited. There seem to be complexities. Eichenwald might have gotten lucky in his choice of species to consider and yet his results are beyond reproach  for those species. Could Eichenwald’s approach save lives if it were implemented now? Maybe. Dosing young mice with beneficialStaphylococcus (S. epidermidis) seems to ward off pathogenic Staphylococcus, including deadly MRSA.  In a way, I’m auctioning Eichenwald’s idea off here. Why don’t you see what you can get for it, how much traction or progress. You can join the small group of scientists now considering the idea. Meanwhile, I should mention a final irony. Cezanne’s painting, the one that lay hidden all those years, was hidden, and I kid you not, with Eichenwald. The man who gardened life in human bodies and did so while taking risks, was the keeper of Cezanne’s card playing gardener. Eichenwald’s father appears to have bought the painting from a gallery in Berlin around 1930. The family then fled to New York to escape the Nazi’s and brought the painting with them. It stayed with the family until, upon Heinz’s death in September of 2011, his widow, Linda, decided to sell the work. When she did she found that in the time that the painting lay hidden it had appreciated many fold in value and relevance. Time will tell whether the same is true of Eichenwald’s greatest work, his idea to garden bodies. It remains his tremendous but unplayed hand.


The Sieve Hypothesis: Clever Study Suggests an Alternate Explanation for the Function of the Human Stomach

You have a stomach. I have a stomach. It is one of our few universals. Humans, mate, sing, talk, and raise their children in many different ways, but we’ve all got stomachs. The question is why.

Stomachs help to digest food; they get the process rolling, boiling and grinding by coating our food in slime, enzymes and acid. This is the textbook explanation and no one is saying it is wrong, but in one of my treasured meanders through the library, I recently stumbled upon a paper suggesting this explanation is incomplete, perhaps woefully so. Just as important to our survival may be the stomach’s role in separating, sieving one might say, bacteria that are good for our guts from those that are bad. The study I found was led by Dr. Orla-Jensen, a retired professor from the Royal Danish Technical College. Orla-Jensen tested this new idea about the stomach by comparing the gut bacteria of young people, healthy older people and older people suffering from dementia. What Orla-Jensen found is potentially a major piece in the puzzle of the ecology of our bodies.

Image 1. A diagram of the human stomach. The stomach may act as a sieve, allowing only some kinds of microbes through to the small intestines.

Orla-Jensen and colleagues began by positing, or perhaps assuming is the better word, that a key function of the stomach is to kill bad bacteria with acid. The acid, they argue, serves as a sieve. It stops bad bacteria, particularly the most opportunistic of pathogens, but it does not stop all bacteria. It lets those beneficial bacteria that have adaptations for dealing with stomach acid–adaptations honed over many thousands of generations–on down the gastrointestinal road. In their model, if the stomach fails to kill bad bacteria, pathogens dominate the intestines. They do so in place of the beneficial microbes that help our bodies to digest food and produce nutrients. And when they do… death or at least the failure to thrive is nearly inevitable.

Orla-Jensen and colleagues knew from earlier work that the pH of the human stomach increases with age; the stomach becomes less acidic. This effect is most acute in individuals over seventy years of age. In these individuals Orla-Jensen predicted that the stomach’s effectiveness as a killer of bad microbes might be compromised. In turn, the intestines, recipients of everything that leaves the stomach, living or dead, might become dominated by pathogenic species such as the weedy and deadly Clostridium dificile or by oral species, that while beneficial in the mouth can become a pathogen in the gut. It was a simple enough prediction, but perhaps too simple. The biota of the gut is complex. It can contain thousands of species and is influenced by many, many factors which have proven in many ways intractable. Could the stomach’s pH really matter enough to make a measurable difference? As I read Orla-Jensen’s paper, I was skeptical, but I was curious enough to read through to the results. I sat down on the floor in the library and prepared to stay a while.

Image 2. Micrograph of Clostridium dificile. Image courtesy of CDC/ Lois S. Wiggs (PHIL #6260), 2004.

To test their hypothesis, Orla-Jensen and colleagues cultured bacteria they had collected from fecal samples of ninety human participants, one third of whom were between 30 and 40 years old and two thirds of whom were over seventy. They then compared the microbes found in the samples from these different age groups. Again, they would expect that in the older individuals that the bad bacteria and oral bacteria should be more common and, in their abundance, displace the good necessary bacteria, such as Bifidobacterium.

Remarkably, the authors’ predictions from the sieve hypotheses held up. I have reproduced and slightly modified their main table below. Nine percent of the individuals over seventy had more than a million cells of the bad news Clostridumbacteria per gram of feces; none of the thirty to forty-year-olds did. What was more, a third of the individuals over seventy had more than a billion cells per gram of feces of the oral bacteria, Streptococcus salivarius. Again, none of the thirty to forty-year-olds did. But were these pathogenic and oral bacteria doing well enough to actually compromise the success of good bacteria in the gut? Yes. While all of the thirty to forty year olds had at least a million cells of the good gut bacteria Bifidobacteriumper gram of sample, less than half of the individuals over seventy did.

Interestingly, the guts of those individuals over seventy years of age who had dementia were in the worst shape, by far. Nearly each and every one of their guts was dominated by Clostridium and oral bacteria. Other studies seem to lend support to these general findings, albeit from different angles. A study comparing healthy individuals and individuals with low stomach acidity found that those with low stomach acidity were less likely to have Bifidobacterium even though their total density of intestinal bacteria, particularly the pathogens, increased. Another study found that individuals with low stomach acidity tend to be more likely to suffer from diarrhea, as would be expected if their guts were being taken over by pathogens.

The  differences seen here as a function of age are much more pronounced than those seen in another study, recently published in the journal Nature. The Naturearticle compares the gut microbes of more than  five hundred individuals of different ages and ethnicities. In the Nature study the authors found little effect of age on gut microbes after the first few years of life (during which there was a large effect as newborns slowly acquired adult microbes). However, the Nature study only considered four individuals over seventy years of age (they also did not specifically look for shifts in beneficial versus problematic species, perhaps they will in the future). Orla-Jensen’s work suggests that it is precisely the very old individuals in whom the differences begin to be pronounced.  Sometimes it takes the perspective of many studies and time to see the full picture. This is probably where I should point out that the Orla-Jensen study I’m discussing was published in 1948. Interesting ideas can get lost in unread scientific articles; many, perhaps most, are. Orla-Jensen’s paper has only rarely been cited and never in the context of the discussion of the function of the stomach or even in the context of aging and the microbial wilderness of our bodies.

Table 1. Reproduced (with updates) from Orla-Jensen et al., 1948. Sample size for each group = 30 individuals. The author of this paper, Prof. Orla-Jensen was 77 at the time of the publication of this paper in 1948 and so had a personal interest in these results. One wonders if he sampled himself.

Percent of individuals with > than 1 billion cells of each bacteria per gram of feces, or, in parentheses, percent of individuals with > 1 million cells per gram.
Volunteers MutualistBifidobacterium PathogenClostridium Oral bacteria,Streptococcus salivarius
Aged 30-40 (Healthy) 57  (100) 0 0
> 70 years (Healthy) 25 (44) 9 31
> 70 years (w/ Dementia) 7 (9) 48 35

More than sixty-five years later it is now up to us to figure out what other predictions the sieve hypothesis might make <sup>2/<sup>. Perhaps the most obvious prediction is that as one travels the body, from the skin to the mouth to the stomach and on into the intestines, that one should encounter, at each step, diminishing subsets of microbial lineages. Is this true? It seems hard to believe. After all, a huge number of studies have proudly announced the great diversity of microbes in the gut, a terrible diversity. Let’s look.

The best study I know of included samples from mouth and gut, and considered which taxa of microbes were found in the different habitats. The diversity of major lineages drops by half as you go from the mouth to the stomach AND the lineages present in the gut, particularly the colon, are a subset of those in the stomach which are a subset of those in the mouth (see Figure 2). Comparing the results of this studies with those of others suggests the mouth itself also serves as a kind of filter, winnowing the species that land on the skin and lips or in the mouth to the subset that are most beneficial. From this subset, the stomach further cleaves.

If the sieve hypothesis holds, there must be additional predictions. I have not thought this through terribly well, but I think I would probably expect differences in the stomachs of animals eating different foods. Animals that eat foods that are more likely to include pathogens ought to have filters that are more finely tuned to weeding out bad microbes; they ought, I think, to err on the side of killing too many. This does appear to be the case for some vultures. The stomach of the white-backed vulture has a pH of 1! Conversely it seems plausible to predict that animals that eat diets less likely to lead them to pathogens, fruit eaters for example, should be expected to relax the sieve, open it up a little to make sure that many good microbes make it through.  I don’t know that it has been tested. There must be more predictions for the differences one expects among species. A broad survey of the evolution of the stomach seems in order.

Image 3. White backed vultures feeding on a wildebeest. These vultures need to very actively fight the pathogens in the dead meat on which they indulge. One way they do so is by having very, very, acidic stomachs. Photo by Magnus Kjaergaard.

Modern living also presents us with another testable prediction about the stomach and its effects on microbes. Bariatric surgery is an ever more common medical intervention in which the size of a patient’s stomach is reduced so as to reduce the amount of food he or she can eat in one sitting. The surgery also has the consequence, however, of increasing the pH in the stomachs of those who have the surgery, making their stomachs less acidic. If the sieve hypothesis is right these individuals ought to have gut bacteria that look more like those of seventy years old than those of thirty year olds. They do. Recently a study has found that goodBifidobacterium species become more rare after bariatric surgery while oral bacteria (in this case Prevotella) and  E. coli, which can be a pathogen, become more common. These results seem to be what the sieve hypothesis would predict.

I am sure there are more predictions. I’ll leave you to them. The good news is that if there are more predictions now is a great time to look, to test them. The study of the microbes of our body is now hip, as sexy as a field of study that often involves the word fecal can be (see Image 4 or check out your own sexy fecal bugs at American Gut). New data are published every day. If we can develop good predictions they can be tested. We might finally figure out what the stomach does, or rather the complex mix of its roles, its churning melange of duties. No one denies that the stomach helps to break down proteins, it just might not be its most important job.

Image 4. Microbiologist Jonathan Eisen wearing his microbiome. Image courtesy of Jonathan Eisen.

Meanwhile, there is an interesting coda to this story. In addition to considering the difference between old and young individuals, Orla-Jensen, as you might remember, considered the difference between healthy individuals over seventy and individuals over seventy with dementia. The individuals with dementia had even more pathogens and oral microbes in their guts than did the healthy seventy-year-olds. This is interesting, but what is the cause and what is the effect here? Could a poorly functioning stomach lead to a pathogen heavy microbe community in the gut and could that gut community in turn lead to dementia? Could our minds really fail because our stomachs do? A few recent studies have begun to explore the possibility that dementia might result from infection, but it is WAY too soon to say anything conclusive. One is left to imagine the mechanism behind such a decline. I have some ideas, but I’ll need to think them over some more. Meanwhile, you can offer your hypotheses too, and I’ll go back to the library and see what other gems I can find, old studies that are as revolutionary as the new ones you read about in the press, studies that whether right or wrong confirm just how little we know and how slow and circular progress can be.


1- They did not sequence the genes of these microbes—now a common technique—and so their results represent just part of what was going on in the sampled guts, a few kinds of common trees in a diverse forest, and yet it was probably a reasonable measure of those trees.

2- Which, I will confess, I’ve named here. Orla-Jensen and colleagues thought the idea so obvious as to not even deserve a name.


How a Tiny Wasp May Save Your Life

Nature knows no real balance, just moments of apparent equilibrium before some rise or fall.

We are studying scale insects—a kind of immobile (scientists say “sessile”) animal that lives on plants and sucks at them until, in some cases, they die (and by we, I mostly mean one of my students, Emily Meineke, and her other advisor, Steve Frank). Scale insects are everywhere once you learn to look for them, under nearly every leaf, sucking.

The sucking of scale insects is mostly harmless, an indiscretion, an innocent obsession, but scale insects can kill trees and maybe worse. A year or so ago, we began to wonder whether or not they might also affect humans. This is the kind of thing one wonders when contemplating whether the obscure topic one has chosen to spend one’s life on might have some meaning. It was lovely and unadulterated speculation, then we read a new paper about emerald Ash borers and everything changed. Well, not everything. Actually not so much at all, but it was a cool paper.

Image 1. Look closely. These are the scale insects who blend in with tree bark all over the city and world, convincing you and me to move along. There is nothing to see.  Photo by Becky Kirkland/NC State University Communications

Ash trees are brush-topped, lovely  and, in many cities in North America among the most common urban trees. Or they were. In 2002 emerald ash borers arrived from Asia in Michigan where they began to kill ash trees. At last count tens of millions of ash trees had been killed in Michigan and surrounding states.

If there is any good news about the emerald ash borer, it is that it set the stage for a clear study of what happens when you lose trees (I know, this is like saying that the good news about the titanic is that it taught us how giant ships sink). This beetle kills trees anywhere it invades and so, with each death, the consequences of their loss can be studied relative to what was observed where ash trees have not died. Trees offer–people who study, love and hug trees argue–many health benefits, including their effects on air quality and urban climate. The presence of trees, it has been suggested, might even lead to a local decrease in some pollutants and hence the incidence of those human health problems associated with pollution (heart disease, respiratory problems, low birth weight babies, etc…).

The anticipated effect of the loss of many trees, in this case many ash trees, would be that in areas where the trees died the health of humans should be more negatively affected. More beetles = fewer trees = more human health problems. More beetles might even = more human death.  Such are the hypotheses one can come up with when sitting on the patio of a favorite bar, but typically elegant bar hypotheses get messy when they are brought out into the clear headed air of morning and confronted with data.

Not this time. The results held. The beetle and its effects on trees were statistically associated with more than 21000 extra deaths (yes, 21000!). In counties where the emerald ash borer killed more trees, more deaths occurred. Indirectly, the emerald ash borer may be killing people (it is also possible that something else has happened in concert with the tree deaths to affect human health, but it is unclear what this might be). Other studies have been found links between the number of trees around houses and the birth weight of babies (more trees = reduced risk of  having a low birth rate baby. See similar results from a separate study from Spain). These new results do not prove the positive effects of trees on human health, but they certainly do not reject the possibility. All of this brings me back to the scale insects we are studying. It gets me wondering anew about the effects of scale on health and well-being.

Recently, Emily Meineke has shown that scale insects are becoming more abundant in the warmer parts of cities.Emily’s story goes something like this. Warm cities make scale insects do better (this we know). Because scale insects sometimes kill trees, this probably leads them to kill more trees. Because the death of trees can negatively affect human health, it may even be the case that warm cities lead to more scale insects, which lead to fewer trees, which leads to more negative human health outcomes. At least we can hypothesize that these are possibilities (And then Emily can go test them. Advising can be fun.).

Image 2. Emily Meineke, scale insect whisperer. Photo by Becky Kirkland, NCSU.

But there is one more fun piece in this living puzzle. There is the question of why the scale insects don’t always kill the trees. This is an old question, one might pose it more simply as, “why is the Earth green?,” green rather than the brown that would result if all the insects ate all of the plants.

The answer is not immediately obvious. One might argue that it is in the best interest of the insects to not eat all of the plants, but insects aren’t so smart. I’ve never seen a beetle or a scale insect turn down an edible tree. They are not in the habit of leaving one for the future.

Instead, the Earth is green in large part because animals eat and kill herbivores.  It is always shark week up among the leaves of the trees. Bless the predators who keep things green. In the case of the beetles, it may really be the predators. But in the case of the scale insects, more than predators it appears to be another clan of organisms— the real monsters of the backyard—parasitoids.

Parasitoids are animals that lay their eggs inside the bodies of other animals. They are among the most common life forms on Earth, far more diverse and common than birds and mammals combined (and yet they have, as one measure of how little we take note of them, never been mentioned in the Atlantic Monthly or the New Yorker). Many parasitoids specialize on scale insects; in as much, they are defenders of trees. It appears that these parasitoids are, in part, what keeps them in check and so to the extent that scale insects threaten trees, whose absence threatens our health, these parasitoids might just be saving our lives.

Image 3. A tiny defender of trees (about 2 mm), a parasitoid wasp of the genus Encryrtus.  This wasp is one of the most common parasitoid wasps found living inside the female scale insects on willow oak trees. We haven’t been able to figure out the species, despite having contracted a parasitoid expert to identify the wasps of scale insects. Maybe it is a new species. Maybe it is just a species so hard to ID that there is just one old guy in the Czech republic who can do so. Photo by Andrew Ernst (the contracted parasitoidologist).

But life is never easy.  There is another group of organisms, the hyperparasitoids. They lay their eggs inside the eggs or bodies of parasitoids that are, in turn, inside of other organisms. If the parasitoids are the friends of humanity (and trees), “hypers” are, once again, like the scales themselves, our enemy.

Image 4. A tiny hyperparsitoid wasp (about 1 mm) of the genus Pachyneuron, nemesis of Encryrtus wasps and, indirectly, trees and humanity. Photo by Andrew Ernst.

I’ve now walked ten steps past what we know is to what might be and so I should return to the ash trees, which in their absence appear to make us sick or even dead, and simply suggest that all around us the trees and our health depend on a diversity of forms that, without meaning to, keep the tree eaters in tenuous check, a check that constantly slipping this way and that as the trees, herbivores, parasitoids and hyperparasitoids win battles (but seldom wars).  Who knows, your life may have already been saved by a tiny wasp. The world is green because of such organisms, but, as the case of the emerald ash borer (who, in leaving Japan for the U.S. has escaped both predators and parasitoids) makes clear, it could be, at any moment, otherwise.  Some of the things we need to do to keep the world green are relatively beyond your control as an individual (now that the emerald ash borer has arrived, your ability to check its spread is limited, for example), but one thing that definitely tips the balance of power, one thing that keeps the green team winning is planting a tree. Planting a tree brings back all the benefits that turn into costs when trees are killed. A planted tree (and its menagerie of scale insects, parasitoids and hyperparasitoids)  also helps to cool hot streets and so reduces the impact of scale insects. If you plant the right tree, it will grow fruit you can eat, big branches to hang a swing on, or broad leaves beneath which you can walk in admiration, keeping an eye on the scale insects and  the deadly parasitoids flying leaf to leaf, searching for the one they love, and then shoving a needle into its back and implanting a near microscopic, alien egg.


Why Mosquitoes Like You and Not Me

The mosquito is so small it takes almost nothing to ruin it.–Mary Oliver

Mosquitoes devour some people and ignore others. If they like you, swat a dozen and a dozen more appear in their place, inserting their mouthparts into your capillaries and imbibing as quickly as they can. Why? We can consider this question in two ways. The version we usually think of is “why me?” What is it about my body that calls the mosquitoes in? But there is also a bigger why. Why does variation in human attractiveness to mosquitoes exist in the first place?

With regard to the second why,  let’s be responsible and begin with some hypotheses.  Mosquitoes are one of the most deadly groups of organisms on Earth, more deadly than tigers, snakes or even other humans.  Mosquitoes kill by proxy. They transmit pathogens such as dengue, yellow fever and, that real devil among demons, big daddy malaria.

Over the last twelve thousand years (since the dawn of agriculture) malaria has killed enough people, particularly children, that those human populations exposed to malaria have evolved in response. Malaria’s sickle altered human genomes in nearly all of the regions in which it was historically present.  It was the high jump over which much of humanity never made it and those that did make it often did so at a cost. Populations long-exposed to malaria are more likely to have sickle cell anemia but also each of tens of other adaptations that either prevent infection or make its consequence less deadly. Nearly all of these adaptations have side effects, sometimes dangerous ones, just less dangerous than malaria. No organism has influenced human evolution more than the malaria parasite (and its chariots, theAnopheles mosquitoes).  This leads me to three hypotheses.

Hypotheses—First, we might imagine that the descendants of those peoples who have lived with malaria might be less attractive to mosquitoes (because those who were more attractive died). Let’s call this hypothesis “odorant camouflage.” It will be my focus here. A second (and, frankly, less exciting) hypothesis might be that humans just happen to vary in terms of whatever it is that attracts mosquitoes. Perhaps some humans just happen to be more apparent to mosquitoes, lovely by accident. A third, but not final, hypothesis  is that mosquitoes choose people whose smells indicate they will be better hosts.

Everyone attracts mosquitoes to some extent, so as long as they shall breathe. From the perspective of mosquitoes the world is composed of rivers of carbon dioxideflowing from the headwaters of animal’s mouths. Carbon dioxide flows from us all.  Mosquitoes fly in the direction of higher carbon dioxide concentration and this leads them close enough, having found a warm body, to make more discerning decisions.

Because all adult humans breathe about the same amount (our hearts require this basic parity) the differences among us in our appeal to mosquitoes have to do not with our carbon dioxide but instead with our bodily odors. Most of your up close and personal odor, the mélange of you, is produced by the bacteria on and in you. You are densely covered in a fine and fuzzy patchwork of hundreds of species of bacteria. Kill all the bacteria in a patch of skin  and that skin will be odorless (save a hint of whatever cleaning agent you used). When it comes to odor, you are your bacteria.

Image 2. Anopheles (A and B) and Culex (C) species resting in their characteristic yoga poses. From USDA Miscellaneous Publications No. 336: "The mosquitoes of the southeastern states."

Image 2. Anopheles (A and B) and Culex (C) species resting in their characteristic yoga poses. From USDA Miscellaneous Publications No. 336: “The mosquitoes of the southeastern states.”

The perfect test—If we were to test our first hypothesis, we would want to compare the attractiveness of people from different regions to mosquitoes. Based on this hypothesis, we expect that malaria mosquitos, for example Anopheles gambiae, should be less attracted to the smell of the bacteria of humans from malarial zones, since any of the humans from these regions who were less attractive to mosquitoes would have been more likely to survive. One might then isolate which microbes or other sources produce the attractive (or unattractive) smell (and maybe even use them as a probiotic mosquito repellent).

After completing such a study with Anopheles gambiae, we would then need to test other mosquitoes. You might be surprised to learn that there are no fewer than three thousand species of mosquitoes on Earth and perhaps as many as six, seven or even ten thousand. There is no reason for the stories of these different species of mosquitoes (most of which avoid humans altogether), or what they are attracted to, to be terribly similar. They all perceive the river systems of carbon dioxide, but choose differently once they near bodies. To take one example, the common native mosquito species  of eastern North America were never exposed to primates until humans came over the Bering straight and then wandered over the Rockies all the way to North Carolina. One can guess that these mosquitoes were then attracted to those humans who smelled most like the hosts that the mosquitoes had evolved to be attracted to, bison, elk, deer, giant sloths and the like. There are many mosquito stories.

But back to what we might discover. It appears no one has addressed the evolutionary “why” behind the differences among humans in their attractiveness to mosquitoes. Recent studies have, however, considered many aspects of “why me.” Studies initially found variation in attractiveness to mosquitoes that could not be associated with diet, body size or gender. More recent studies, found that thesedifferences appeared to be due to host odor. Then, in 2006, researchers found that cultured skin bacteria would attract mosquitoes.

Most recently, Dutch scientist Niels Verhulst led a study in which he and his team  gently rolled beads on the feet of  forty-eight volunteers (A. gambiae, the mosquito being studied, is an ankle biter). The beads were then put in a bag which was then presented to the mosquitoes (for their judgement). Based on the relative attraction of the mosquitoes to the different bags of beads the scientists established a kind of Zagat score for the discerning proboscis. Anopheles gambiae appears to have evolved to live with humans with the dawn of agriculture. But it loves some humans more than others. Perhaps, Verhulst reasoned, this is because of the specific mix of bacteria species on the ankles of each human.  All but two of Verhulst’s volunteers were Caucasian. I’ll note here that this is not the group of individuals it makes the most sense to expose to malaria mosquitoes  for the simple reason that Anopheles gambiae and its malaria have never lived in the Netherlands. Yet, the researchers were in the Netherlands and it was a start. If Caucasian folks of the Netherlands differ in their appeal to mosquitoes, it might add insight into the “why me?”

The results were fascinating. The odors of seven of the volunteers were strongly preferred by the mosquitoes. Verhulst studied the bacteria on the feet of those and all of the other volunteers. The individuals with more kinds of bacteria (on their feet) tended to have fewer individual bacteria (you either have lots of kinds or lot of individuals, but not both). Those individuals whose odors mosquitoes preferred tended to have a lower  diversity and higher abundance of microbes. Boom. The microbes did it, at least when it comes to 48 Dutch guys and a bunch of African mosquitoes. Or at least this is what we know so far (Verhulst thinks that where the diversity of bacteria is high, those diverse bacteria actually suppress the populations and odors of the bacteria that would otherwise be common. Were this true, these bacteria could be considered to be actively helping to disguise our odor, our stinking mutualists.).

But what about the other mosquito species? What about populations historically exposed to malaria versus those that have not been? What about inoculating people with bacteria that reduce bacteria odor? Nothing, none of it. We don’t know.

Stuck mid-story–For millions of people, the specific attractiveness of their skin is a thing of life or death. Hundreds of studies have considered why some people attract mosquitoes and others don’t. Bacteria were only invoked recently, but appear to be a big part of the story. The evolutionary context of this attractiveness has not been well considered. Given the strong impact malaria has had on human survival, it would be very surprising if there were no evolutionary element to the story of why some of us are more edible than others. But because the approach to malaria mosquitoes has primarily been medical, the lens has been narrow. Here is call for a big lens.

The good news is that at least as concerns hypothesis one, it would be easy to test the hypotheses that can be generated using evolution’s big lens.  All  Niels Verhulst and his colleagues would have to do would be to repeat their initial study and see if individuals from different ethnic groups differ in their bacteria as a function of the historic exposure of their peoples to malaria (surely the diversity of immigrants to Holland would help this endeavor) and if those bacteria differ in predictable ways in terms of their attractiveness to mosquitoes. This wouldn’t be fully conclusive, but it would be a start. There are other approaches too.

In the meantime, if you are highly attractive to mosquitoes, you can thank your odor, an odor produced by your bacteria which might or might not have been influenced by the evolutionary history of your people.

I ended this article here and then I emailed Niels Verhulst to check that I hadn’t missed something important about his work.  He read the article and wrote,” I agree.” This, I thought, was good news, but he continued… ” however we have some evidence that HLA genes are involved. HLA genes determine our body odor (and probably skin bacterial profile) and we found that individuals with a particular gene were more attractive to this mosquito (…) this gene occurs less frequently in Africa (where the most deadly malaria has long been prevalent) than in Europe or the US (where malaria’s history has been more patchy).”

Here was a tantalizing result, a result that makes me want to start studying mosquitoes, a result that while it neither confirms nor rejects any of the hypotheses laid out above, offers the tantalizing suggestion that our relative attractiveness to mosquitoes is/might be/could be part of a more ancient story of agriculture, immigration, agriculture, mosquitoes and malaria. Unless, of course, it is not.

I love you science.

What Is Wrong with Dissections?

Here is a story you might find a bit laughable. At the end of the dark ages in what is now Italy, when knowledge was being reborn, anatomists would read from an ancient Greek text while their assistants dissected a human body and pointed out its parts. If the body looked different from what was written in the thousand year old text it was seen to be mutant, deviant, wrong. No matter that the ancient Greek knowledge was flawed and many of the rather ordinary observations that were being made would have improved dramatically upon what was known. Man, those early anatomists were dopes. It would take a major scientific revolution for anatomists to begin to actually observe and learn from dissections. The idea that more knowledge could be gained was a breakthrough. Isn’t it crazy how hard it was for early scientists to figure out obvious things? Boy oh boy.

Image 1. An early anatomy theater at the University of Leiden.

I was thinking about this the other day when I walked past a classroom in which undergraduates were dissecting cats.  Around the world, millions of cats, dogs, pigs and other mammals, including thousands and thousands of humans are dissected in anatomy classes. They are dissected in order to teach students—including all of those who will eventually operate on your body—about how an average mammal, amphibian or other body works.

One can discuss the merits of having students perform dissections.  One can also discuss the morality of such dissections. I won’t do either. I want to get at something else, the issue of whether these students are doing exactly the same sort of science that was being done at the end of the dark ages.

In an average anatomy class dead animals are handed out to students. A tired/sometimes grumpy/overworked/underpaid teaching assistant discusses how the dissection should be done. Students perform various forms of butchery. Students label/point to/remove parts of the body on which the teaching assistant has told them to focus. In focusing on these parts of the body, the students are told about how it works, or at least how it works in general. More body parts are dissected. More knowledge is provided. The bodies are then thrown away in special trashcans. The teaching assistant goes home to work on their thesis and to wonder if he/she will ever get the job. The students go home to think about other students/beer/ or other students. The whole process repeats with a new group the next morning.

I don’t mean to make fun of the hard work of students or teaching assistants. What I do mean to make fun of is that we seem to now teach anatomy in exactly the same way that it was being taught at the end of the dark ages. Specifically, students look at bodies of animals, but are not encouraged in any way to make real observations. Instead, they are encouraged to look for what is already known and then if it does not look quite right, do depict it the way it “should,” look. Even where the differences among bodies are noted, they are seldom measured. Even when measurements are taken, they are seldom recorded.

Now, you might say, Rob, you are confusing things. At the end of the dark ages we were ignorant about the body. Simple measurements could produce new knowledge. Now we understand the body. Of course, there is that difference. You are right, or you would be except that we still don’t understand the bodies of animals all that well. The function of the appendix is under new scrutiny. The stomach too. In fact, when it comes to basic morphology, the sorts of things that can be measured by preoccupied students in large classes, we haven’t made that much progress in the last hundred years (This is where you, as the reader, cue in on your favorite exception to my sweeping generalization and then go on to mention it in the comments section). How and why do intestines vary among individuals? How frequent are different deformations of particular organs. Are there tradeoffs between investment in one organ and in another? How frequent are rare mutations in the bodies of cats, pigs or even humans, mutations that we still don’t understand very well at all. Such mutations are hard to study because of their very rarity, but we dissect so many pigs, cats and other animals that even something that turns up in just one in a million animals turns up somewhere in some class each year. What else could be studied? I’m sure you can think of obvious features I am missing. The point is there are discoveries right beneath students as they look up at their teaching assistants or teachers, but we are training them to ignore them, to see the general story at the expense of the truth.

What now? I have one idea, probably an overly simple one, inspired by work in citizen science.  I would have students take real measurements along with high-resolution digital images of the animals, including humans, that they dissect. They would also take a sample of some tissue of each animal (This might need to occur before the animals were preserved which would be harder, but still possible). The images and measurements would be sent to a database where they could be compared with others of the same. The tissue would be shipped to a tissue bank. With the database, anyone could compare the features of animals to understand how much they vary. With the tissue bank, the genes associated with unusual features could be narrowed down upon. With every moment in class, the students, however sleepy, however focused on the girl or boy in front of them, would be reminded that the body they are looking at is, like their own body, still imperfectly, understood. That was the revelation that would come after the dark ages, in the late renascence. It is a revelation we would do well to build upon as we consider how our own science and education might, together, be reborn, or, if not reborn, just done in such a way as to allow students to pay a little more attention to the dead pig in the hand, which, as they say, is worth ten in the book. Maybe they don’t really say that, but you get the idea.

I was going to end there but then I remembered the one place, the only place in which students are actually taught to pay attention to the bodies they see before them, art classes. In figure drawings classes a naked man or woman stands in front of a room of students and is observed, drawn, piece by piece. We could learn something from these art students and their teachers. Ironically, the same was also true at the end of the dark ages, when, long before the scientists began to pay attention to bodies, the artists did. The artists had to, they were charged by their instructors with portraying truths in contrast to the science students who were (and are) charged only with portraying what is already known.

Note: I use the term “dark ages” here. As one commenter notes, Early Middle Ages is the term historians now tend to use. However, from the point of view of biology in general and anatomy in particular, the times were dark. For many fields of biology more was known in 100 BC than was known in 1400 AD. Whatever you call the intervening years, scientifically they were illuminated by precious little light.

Science Reveals Why Calorie Counts Are All Wrong

At one particularly strange moment in my career, I found myself picking through giant conical piles of dung produced by emus—those goofy Australian kin to the ostrich. I was trying to figure out how often seeds pass all the way through the emu digestive system intact enough to germinate. My colleagues and I planted thousands of collected seeds and waited. Eventually, little jungles grew.

Clearly, the plants that emus eat have evolved seeds that can survive digestion relatively unscathed. Whereas the birds want to get as many calories from fruits as possible—including from the seeds—the plants are invested in protecting their progeny. Although it did not occur to me at the time, I later realized that humans, too, engage in a kind of tug-of-war with the food we eat, a battle in which we are measuring the spoils—calories—all wrong.

continue reading…