Yesterday I went to Rutgers University to give a talk about medical ecology. Afterwards, I got a delightful surprise: Amy Chen Vollmer, the president of the Waksman Foundation for Microbiology, got on stage to announce I had won the Byron H. Waksman Award for Excellence in Public Communication of Life Sciences.
Byron Waksman, who passed away this June, was an immunologist who made important discoveries about auto-immune diseases and the signals white blood cells send to each other. Spreading the word about science was another of his passions; after he retired from his scientific work, he became a middle-school science teacher. Waksman was also the director of a foundation set up by his father, Selman Waksman, who won the Nobel prize for discovering many of the antibiotics we depend on today. Byron Waksman used the foundation’s resources to advance the understanding of science. One of the programs he initiated brings journalists to the Marine Biology Lab in Woods Hole to learn how science is done. All the journalists I’ve spoken to who have gone through it have sung its praises. It shows them the real science that lies beyond the press release and the phone call.
I’m hugely honored to get an award in Byron Waksman’s name. And it’s a particular pleasure to get an award decorated not with some non-descript humanoid, but with the Tree of Life. It’s a privilege to get to jump among its branches for a living.
Our skin is encased in a snug microbial suit, from our scalps to the tips of our toes. Bacteria begin to colonize our skin from the moment we are born, and they continue to coat us throughout life. They do us many favors. They moisturize our skin to keep it supple; they unleash anti-microbial toxins to ward off pathogens that might make us ill. Scientists know that our skin is home to many species, but they can’t yet say exactly how many–or why some species are found more often on the elbow than on the chin.
Two years ago at a conference in North Carolina, I ran into Rob Dunn, a biologist who was conducting a survey of this menagerie. He was interested in the life found in one particular spot on the human body: the belly button. At the conference, he was handing out Q-tips people could use to swab their navels, which he and his colleagues could then study to tally up the species dwelling there.
Five months later, Dunn sent me a preliminary report: “You, my friend, are a wonderland.” I was the proud host of 53 different types of bacteria, including some decidedly weird creatures, such as a microbe only known from the ocean, and another from the soils of Japan.
I was only one of many human hosts to offer up our navel’s residents to Dunn’s scrutiny. Today, Dunn and his colleagues published a scientific paper on the biological diversity found in 60 bellybuttons in the journal PLOS One. They show that the diversity of my navel was not freakish. Even in a tiny divot of human flesh, dozens or even hundreds of species of bacteria can coexist. All told, Dunn and his colleagues identified 2368 different species living in our 60 belly buttons. The average person had 67 species, with the number ranging from a low of 29 species to a swarming high of 107.
Out of those 2368 species, the majority–1458–are new to science. A few of them are very common, while most are exquisitely rare. Dunn and his colleagues found that eight types of bacteria made up nearly half the microbes the scientists detected. Each of them was present on over seventy percent of us. But the vast majority of the species–2188 all told–lived on six or fewer people. Most were found only on a single individual.
It’s possible that the rare microbes are only visitors, dropping by for a short stay in our navels before dying out or traveling on. The most common species the scientists found may have long-term leases, having evolved adaptation that help them thrive in the bellybutton’s distinctive habitat. Dunn and his colleagues found that these abundant species were also closely related to each other compared to the rarer ones. It’s a pattern similar to the one found in rain forests, were only a few lineages of trees dominate, with many species only contributing a few trees. Your belly button, in other words, really is a jungle.
For more information, read Dunn’s account of the study.
P.S. I refer to these bacteria as belonging to “species.” It’s a convenient term but, when it comes to bacteria, not a precise one. Feel free to mentally substitute “operational taxonomic unit” or “phylotype.”
In 1988, Richard Lenski, an evolutionary biologist now at Michigan State University, launched the longest running experiment on natural selection. It started with a single microbe–E. coli–which Lenski used to seed twelve genetically identical lines of bacteria. He placed each line in a separate flask, which he provisioned with a scant supply of glucose. The bacteria ate up the sugar in a few hours. The next day, he took a droplet of microbial broth from each flask and let it tumble into a new one, complete with a fresh supply of food. The bacteria boomed again, then starved again, and then were transferred again to a new home. Lenski and his colleagues have repeated this procedure every day for the past 24 years, rearing over 55,000 generations of bacteria.
I first reported on Lenski’s experiment 12 years ago, and since then I’ve revisited it every few years. The bacteria have been evolving in all sorts of interesting ways, and Lenski has been able to reconstruct the history of that evolution in great detail, thanks to a frozen fossil record. Every 500 generations Lenski and his students sock away some bacteria from each flask in a freezer. They can thaw out these ancestors whenever they wish and compare them to their youngest descendants. Biotechnology has improved drastically since 1988, giving Lenski an increasingly powerful evolutionary microscope. When he started out, it could take months to identify just one of the many mutations that arose in each lineage. These days, he and his colleagues can sequence an entire E. coli genome for a few hundred dollars and find every single new mutation in its DNA.
Four years ago, I wrote here about one particularly fascinating episode in the evolution going on in Lenski’s lab. It started in 2003, when the scientists there noticed something odd in one of the 12 flasks. It had become much more cloudy than the others. In a microbiology lab, that’s a sure-fire sign that the bacteria in a flask have experienced a population explosion.
At first the team suspected that some other species of bacteria had slipped into the flask and was breeding quickly. But they found that the flask was packed with E. coli—descendants of the original ancestor that Lenski had used to start the entire experiment. Somehow the bacteria in this one flask had evolved a way to grow much faster than the other bacteria.
The scientists determined that the bacteria had made a drastic switch: from feeding on the glucose to another compound, called citrate. Citrate is an ingredient in the broth where Lenski’s E. coli grows. It’s not food; instead, it helps keep the minerals in the broth in the right balance for E. coli to grow.
To a microbiologist, the emergence of E. coli that can eat citrate in a lab is deeply weird. E. coli typically can’t feed on citrate in the presence of oxygen. Some strains of E. coli can draw in citrate, but only if there’s no oxygen around. To make the reaction work, they have to pump out another compound called succinate at the same time. The ability of E. coli to feed on citrate in the presence of oxygen is extremely rare; it occurs when E. coli picks up the necessary genes from other species. In its normal environment (inside us), natural selection must not favor these mutants. Scientists have been studying E. coli in labs for over a century, making it the most intensely studied species, on Earth (as I explain in my book Microcosm). But in all that time, there has been only a single report of a citrate-feeding E. coli in a lab, back in 1982.
The inability of E. coli to grow on citrate is so stark, in fact, that microbiologists use it as a way to tell whether bacteria they come across are E. coli or not. It was thus a surprise to Lenski and his students to find a flask of E. coli suddenly feeding on citrate. The bacteria had not picked up the genes from another species. Instead, their new ability must have evolved after Lenski started his experiment with a single E. coli. This was not simply a case of natural selection enabling a species to do something better. This was a case of doing something new.
Zachary Blount–then a graduate student in Lenski’s lab and now a post-doctoral researcher there–led the investigation into this strange new development. Blount and his colleagues took away the glucose and found that the E. coli could thrive on citrate alone. They then defrosted the bacteria’s ancestors and fed them citrate to figure out when they acquired the ability. They found that a tiny fraction of the bacteria around generation 31,000 were able to grow very slowly on the citrate. Over a couple thousand generations, they got better at growing on citrate–so good, eventually, that they took over the flask and turned it cloudy.
Blount and Lenski first reported the evolution of the citrate-eaters in 2008. Now, after another four years of painstaking research, they’re back with a new paper that details what happened down at the molecular level. It’s a fascinating look at how new traits evolve by duplicating and recycling old parts.
The scientists found that the evolution took place in three chapters. In the first chapter, the stage was set for the transformation. In the second chapter, the bacteria became citrate feeders. And in the third chapter, they became much better citrate feeders.
It usually makes sense to start a story with Chapter One. But in this case, it’s better to start with Chapter Two: The Birth of the Citrate Feeders.
When E. coli finds itself in the absence of oxygen, it switches on a gene called citT. Like other species (including us), E. coli turns genes on and off by attaching proteins to short stretches of DNA nearby. When E. coli senses a lack of oxygen, proteins clamp onto one of these genetic switches near citT. Once they turn the gene on, it produces proteins that gets delivered to the surface of the cell. There they poke one end out into the environment and pull in citrate, while also pumping out succinate. After the citrate gets inside the microbe, the bacteria can chop it up to harvest its energy.
When E. coli is growing in oxygen, however, no proteins land on the genetic switch near the citT gene, and so it remains silent. The microbe wastes no energy making a protein that won’t help it grow.
Evolution has rewritten this little algorithm in the citrate eaters. As one cell in Lenski’s flask divided, it duplicated its DNA with one fateful mistake. It accidentally copied the citT twice. The new copy ended up near a different genetic switch–a switch that turns on neighboring genes in the presence of oxygen, not the absence.
While citT remained silent in the other bacteria in the flask, in the mutant cell, it switched on. The microbe began sticking citrate transporters on its surface and started drawing in the molecule. This mutation must have occurred by generation 31,500, when Blount found the earliest citrate eaters. The mutation was a crude hack; it produced a microbe that could draw in a little citrate, but not a lot. It still had to feed on glucose to get by.
Thus endeth Chapter Two.
In Chapter Three, life got better for the feeble citrate eaters. They copied the citT gene, along with its oxygen-switch promoter. Now the bacteria could make even more CitT channels, and thus pull in even more citrate. The bacteria made a third copy, and could pull in even more. Blount and his co-authors proved that the extra copies helped the bacteria this way by defrosting bacteria from Chapter Two and inserting copies of citT into them. Those early citrate eaters immediately got much better at feeding.
The scientists also found other mutations that arose during Chapter Three. While they have yet to figure out what those mutations did, the evidence they’ve gathered so far suggests the mutations allowed the bacteria to break down citrate more efficiently so they could get more energy from their food.
The most intriguing part of the story, however, is the first– Chapter One: Setting the Stage.
When Lenski and Blount first began to study the citrate eaters, they wondered what would happen if they wound back the evolutionary tape and let the bacteria re-evolve. Would the citrate feeding evolve again?
Blount thawed out ancestors from various moments in the history of the bacteria and started putting them through the same evolutionary experiment again. In some trials, the bacteria did indeed evolve into citrate eaters–but only if they came from after generation 20,000. This discovery suggested only after 20,000 generations were the bacteria prepared to evolve into citrate eaters. They must have already acquired other mutations that set the stage.
To test this idea, Blount and his colleagues thawed out some of the “prepared” bacteria: late-generation E. coli that had not yet gained mutations to citT. They created a miniature ring of DNA loaded with many copies of CitT and the oxygen-sensitive switch, and inserted it into the prepared bacteria. As they predicted, the bacteria now could suddenly feast magnificently on citrate.
But if Blount and his colleagues inserted the DNA ring into the original ancestor of the line, it grew poorly on citrate. That failure suggested that the early-generation bacteria were not ready to receive this evolutionary gift.
And thus a history takes shape:
Chapter One (from generaton zeo to at least generation 20,000): Our hero, E. coli, picks up mutations that don’t seem to have anything to do with feeding on citrate. They might have helped the bacteria grow better on their stingy rations of glucose. At least one of those mutations set the stage for feeding on citrate.
Chapter Two (around generation 31,500): The bacteria accidentally rewire their genome, so that a new copy of citT switches on in the presence of oxygen. Thanks to the mutations of Chapter One, this rewiring yields a modest but important improvement. Now the bacteria can feed a little on citrate, as well as on glucose.
Chapter Three (from about generation 31,500 to 33,000–and beyond): The bacteria make extra copies of the new and improved citT. They can pull in more citrate; new mutations fine-tune their metabolism to grow quickly on the molecule. World domination soon follows.
It’s remarkable how this experiment contains many elements of evolution that scientists have noted in other species. It’s common for genes to get duplicated, and for the new copy to be rewired for a new job. Snake venom, to pick one example, also evolved when genes were accidentally copied and then rewired. A gene that originally produced a digestive enzyme in the pancreas, for instance, now started making that enzyme in a snake’s mouth. It turned out to be a crude but effective venom. Later mutations fine-tuned the new venom gene until it became wickedly good.
The only important difference is that it took millions of years for snakes to evolve their arsenal of venoms, and scientists can only reconstruct their evolution by comparing living species. But in the case of E. coli, the transition unfolded fast enough for someone to track it from start to finish–and restart it when necessary.
Reference: Blount et al, “Genomic analysis of a key innovation in an experimental Escherichia coli population.” Nature, September 19 2012.
I have been meaning to read a book coming out soon called Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves. It’s written by Harvard biologist George Church and science writer Ed Regis. Church is doing stunning work on a number of fronts, from creating synthetic microbes to sequencing human genomes, so I definitely am interested in what he has to say. I don’t know how many other people will be, so I have no idea how well the book will do. But in a tour de force of biochemical publishing, he has created 70 billion copies. Instead of paper and ink, or pdf’s and pixels, he’s used DNA.
Much as pdf’s are built on a digital system of 1s and 0s, DNA is a string of nucleotides, which can be one of four different types. Church and his colleagues turned his whole book–including illustrations–into a 5.27 MB file–which they then translated into a sequence of DNA. They stored the DNA on a chip and then sequenced it to read the text. The book is broken up into little chunks of DNA, each of which has a portion of the book itself as well as an address to indicate where it should go. They recovered the book with only 10 wrong bits out of 5.27 million. Using standard DNA-copying methods, they duplicated the DNA into 70 billion copies.
Scientists have stored little pieces of information in DNA before, but Church’s book is about 1,000 times bigger. I doubt anyone would buy a DNA edition of Regenesis on Amazon, since they’d need some expensive equipment and a lot of time to translate it into a format our brains can comprehend. But the costs are crashing, and DNA is a far more stable medium than that hard drive on your desk that you’re waiting to die. In fact, Regenesis could endure for centuries in its genetic form. Perhaps librarians of the future will need to get a degree in biology…
Photo by Today is a good day – via Creative Commons
The world, it bears reminding, is far more complicated than what we can see. We take a walk in the woods and stop by a rotting log. It is decorated with mushrooms, and we faintly recall that fungus breaks down trees after they die. That’s true as far as it goes. But the truth goes much further. These days scientists do not have to rely on their eyes alone to observe the fungus on a log. They can drill into the wood, put the sawdust in a plastic bag, go to a lab, and fish the DNA out of the wood. A group of scientists did just this in Sweden recently, sequencing DNA from 38 logs in total. They published their results this week in the journal Molecular Ecology. In a single log, they found up to 398 species of fungi. Only a few species of fungi were living in all 38 logs; many species were limited to just one.
Consider that on your next walk in the woods. The one or two types of mushrooms you see on a log are an extroverted minority. The log is also filled with hundreds of other species that don’t make themselves known to you. Their invisible exuberance is a paradox. The fungi that live on rotting logs all make a living by releasing enzymes that break down wood. It’s puzzling that so many species can coexist in a log this way, instead of a single superior fungus.
The forces that drive up the diversity of fungi in a log are similar to the ones that fosterer the thousands of species of microbes in our bodies. For one thing, a log or a human body is not a uniform block of tissue. They both have geography. A microbe adapted to the acid bath of our stomach won’t fare well on the harsh desert of the skin. Likewise, what it takes to succeed as a fungus in a branch is different from what it takes in the heartwood of the trunk.
The human body changes over time, and a rotting log does, too. Babies are colonized by pioneer microbes, which alter the chemistry of their host and make it more welcoming to late-arriving species. The pioneers on a fallen log may include the spores of some species of fungi lurking in trees while they’re still alive. They burst into activity as soon as the tree crashes to the forest floor. Other species, delivered by the wind or snaking up through the soil, find it easier to infiltrate a log that’s already starting to rot. The early fungi may go after the easy sugar in the log, while later species unlock the energy in tougher tissues, like lignin and cellulose. Which particular pioneer starts to feed on a log first can make it inviting to certain species but not others.
Warfare also fosters diversity in a log. The fungi inside a log battle each other for food, spraying out chemicals that kill off their rivals. Each species has to balance the energy it puts into making enzymes to feed and weapons for war. Sometimes the war ends in victory for one species, but very often the result is a deadlock that leaves several species in an uneasy coexistence. There are more peaceful forces at work in a log, too. Many species of fungi in a log depend on each other. One species may feed on the waste produced by another, and supply another species with food in turn.
The world in a log influences the world as a whole. If it wasn’t for wood-rotting fungi, forests would be strewn with the durable remains of dead trees. When the first massive forests spread over the land 350 million years ago, fungi hadn’t yet adapted to decomposing logs. Instead of turning to soil, many trees ended up as coal. The great age of coal ended about 300 million years ago–right around the time that tree-rotting fungi emerged. Their emergence may have brought the age of coal to an end.
Three hundred million years later, that coal is coming back up to the surface of Earth to be burned. Some scientists are investigating fuels that could replace climate-warming ones like coal. One possibility is to pull out the energy-rich sugar locked up in the lignin and cellulose of crop wastes or switchgrass. On our own, we would not be able to perform the necessary alchemy. But fungi know how, and so scientists are sequencing the genomes of wood-rotting fungi to borrow their tricks. This is big-scale science: the genomes of over a dozen species have been sequenced or are in the sequencing pipeline. Yet a single log may contain twenty times more fungus genomes. At the moment, we can say for sure that the few mushrooms we see on a rotting log are far from its full reality. But it will be a long time before we know how all the parts of that reality fit together.
This month has seen a flood of new studies and reviews on the microbiome, the collection of creatures that call our bodies home. In tomorrow’s New York Times, I look at why scientists are going to so much effort to map out these 100 trillion microbes.
The microbiome is not just an opportunistic film of bugs: it’s an organ that play an important part in our well-being. It starts to form as we’re born, develops as we nurse, and comes to maturity like other parts of the body. It stabilizes our immune system, keeps our skin intact, synthesizes vitamins, and serves many other functions. Yet the microbiome is an organ made up of thousands of species–an ecosystem, really. And so a number of scientists are calling for a more ecological view of our health, rather than simply trying to wage warfare against infections.
Yesterday my Fresh Air interview was broadcast. You can listen to it here. I’ve been lots of emails with follow-up questions, and it occurred to me that I really ought to gather up some links to more information about the topics I discussed.
If I haven’t addressed a question you had listening to the show, leave a comment to this post and I’ll add a link.
The “virome”–the viruses that live in our body:
A Loom post about the swarms of viruses in the mouth, where they kill off bacteria
An article in Nature about a study of the viruses in identical twins
My article in the New York Times
My essay on the Loom about medical ecology
My Wired atlas of the human ecosystem
An example of microbiome research: extreme navel gazing
Maryn McKenna’s story in Scientific American on the struggle to mainstream fecal transplants to treat deadly infections
Ed Yong’s oeuvre on the microbiome at Not Exactly Rocket Science
Mayrn McKenna on her blog at Wired writing on the link between beneficial bacteria and protection from asthma, obesity, and other ills.
On March 20, I delivered a keynote talk at the Joint Genome Institute annual meeting. I talked about my experience of reporting on genomes over the past two decades–from my initial awe at the very first sequenced genomes to weary fatigue as thousands of genomes were published, and to a recognition of what the real news is about genomes today. Here’s the video.
One of the most interesting features of Google’s new social media service, Google+, is Google+ Hangout On Air. A group of people get onto G+ all at once, fire up their computers’ cameras, and have a conversation. Google puts whoever is speaking at the moment on the main screen. You can join a hangout if it’s public or if you have an invitation, and–coolest of all–it automatically records the conversation and throws it onto Youtube.
Right now only a few people have access to this service. I jealously watched fellow Discover blogger Phil Plait talk about exoplanets last month. (You can too.) And then I got invited to join the folks at the Singularity Hub for a hangout, too. It’s up on Youtube, and you can also see it embedded here below. We talked about all sorts of things–from mind-controlling parasites to bird flu to using viruses to cure antibiotic-resistant bacteria to the future of ebooks and much more.
I deeply crave this technology. I used to participate in a primitive forerunner of this, known as Bloggingheads. I bowed out due to editorial differences, but I still think the basic system is an exciting medium. I hope Google opens up their Hangout On Air service to more people, because it could be a whole lot of fun.