Your hands are, roughly speaking, 360 million years old. Before then, they were fins, which your fishy ancestors used to swim through oceans and rivers. Once those fins sprouted digits, they could propel your salamander-like ancestors across dry land. Fast forward 300 million years, and your hands had become fine-tuned for manipulations: your lemur-like ancestors used them to grab leaves and open up fruits. Within the past few million years, your hominin ancestors had fairly human hands, which they used to fashion tools for digging up tubers, butchering carcasses, and laying the groundwork for our global dominance today.
We know a fair amount about the transition from fins to hands thanks to the moderately mad obsession of paleontologists, who venture to inhospitable places around the Arctic where the best fossils from that period of our evolution are buried. (I wrote about some of those discoveries in my first book, At the Water’s Edge.)
By comparing those fossils, scientists can work out the order in which the fish body was transformed into the kind seen in amphibians, reptiles, birds, and mammals–collectively known as tetrapods. Of course, all that those fossils can preserve are the bones of those early tetrapods. Those bones were built by genes, which do not fossilize. Ultimately the origin of our hands is a story of how those fin-building genes changed, but that’s a story that requires more evidence than fossils to tell.
A team of Spanish scientists has provided us with a glimpse of that story. They’ve tinkered with the genes of fish, and turned their fins into proto-limbs.
Before getting into the details of the new experiment, leap back with me 450 million years ago. That’s about the time that our early vertebrate ancestors–lamprey-like jawless fishes–evolved the first fins. By about 400 million years ago, those fins had become bony. The fins of bony fishes alive today–like salmon or goldfish–are still built according to the same basic recipe. They’re made up mostly of a stiff flap of fin rays. At the base of the fin, they contain a nubbin of bone of the sort that makes up our entire arm skeleton (known as endochondral bone). Fishes use muscles attached to the endochondral bone to maneuver their fins as they swim.
Our own fishy ancestors gradually modified this sort of fin over millions of years. The endochondral bone expanded, and the fin rays shrank back, creating a new structure known as a lobe fin. There are only two kinds of lobe fin fishes left alive today: lungfishes and coelacanths. After our ancestors split off from theirs, our fins became even more limb like. The front fins evolved bones that corresponded in shape and position to our ulna and humerus.
A 375-million-year-old fossil discovered in 2006, called Tiktaalik, had these long bones, with smaller bones at the end that correspond to our wrist. But it still had fin rays forming fringe at the edges of its lobe fin. By 360 million years ago, however, true tetrapods had evolved: the fin rays were gone from their lobe fins, and they had true digits. (The figure I’m using here comes from my more recent book, The Tangled Bank.)
Both fins and hands get their start in embryos. As a fish embryo grows, it develops bumps on its sides. The cells inside the bumps grow rapidly, and a network of genes switches on. They not only determine the shape that the bump grows into, but also lay down a pattern for the bones which will later form.
Scientists have found that many of the same genes switch on in the limb buds of tetrapod embryos. They’ve compared the genes in tetrapod and fish embryos to figure out how changes to the gene network turned one kind of anatomy into the other.
One of the most intriguing differences involves a gene known as 5′Hoxd. In the developing fish fin, it produces proteins along the outer crest early on in its development. The proteins made from the gene then grab other genes and switch them on. They switch on still other genes, unleashing a cascade of biochemistry.
Back when you were an embryo, 5′Hoxd also switched on early in the development of your limbs. It then shut off, as it does in fish. But then, a few days later, it made an encore performance. It switched back on along the crest of the limb bud a second time. This second wave of 5′Hoxd marked a new pattern in your limb: it set down the places where your hand bones would develop.
Here, some scientists proposed, might be an important clue to how the hand evolved. It was possible that mutations in our ancestors caused 5′Hoxd to turn back on again late in development. As a result, it might have added new structures at the end of its fins.
If this were true, it would mean that some of the genetic wherewithal to build a primitive hand was already present in our fishy ancestors. All that was required was to assign some genes to new times or places during development. Perhaps, some scientists speculated, fishes today might still carry that hidden potential.
Recently Renata Freitas of Universidad Pablo de Olavide in Spain and her colleagues set out to try to unlock that potential. They engineered zebrafish with an altered version of the 5′Hoxd gene, which they could switch on whenever they wanted by dousing a zebrafish embryo with a hormone.
The scientists waited for the fishes to start developing their normal fin. The fishes expressed 5′Hoxd at the normal, early phase. The scientists waited for the gene to go quiet again, as the fins continued to swell. And then they spritzed the zebrafish with the hormone. The 5′Hoxd gene switched on again, and started making its proteins once more.
The effect was dramatic. The zebrafish’s fin rays became stunted, and the end of its fin swelled with cells that would eventually become endochondral bone.
These two figures illustrate this transformation. The top figure here looks down at the back of the fish. The normal zebrafish is to the left, and the engineered one is to the right. The bottom figure provides a close-up view of a fin. The blue ovals are endochondral bone, and the red ones display a marker that means they’re growing quickly.
One of the most interesting results of this experiment is that this single tweak–a late boost of 5′Hoxd–produces two major effects at once. It simultaneously shrinks the outer area of the fin where fin rays develop and expands the region where endochondral bone grows. In the evolution of the hand, these two changes might have occurred at the same time.
It would be wrong to say that Freitas and her colleagues have reproduced the evolution of the hand with this experiment. We did not evolve from zebrafishes. They are our cousins, descending from a common ancestor that lived 400 million years ago. Ever since that split, they’ve undergone plenty of evolution, adapting to their own environment. As a result, a late boost of 5′Hoxd was toxic for the fishes. It interfered with other proteins in the embryos, and they died.
Instead, this experiment provides a clue and a surprise. It provides some strong evidence for one of the mutations that turned fins into tetrapod limbs. And it also offers a surprise: after 400 million years, our zebrafish cousins still carry some of the genetic circuits we use to build our hands.
Freitas et al, “Hoxd13 Contribution to the Evolution of Vertebrate Appendages.” Developmental Cell dx.doi.org/10.1016/j.devcel.2012.10.015
Schneider and Shubin, “Making Limbs from Fins.” Developmental Cell dx.doi.org/10.1016/j.devcel.2012.11.011
Slate is running a “pandemics” series, and I’m offering up the view from deep time. Koalas are getting hammered by a viral epidemic right now, and we’d do well to understand their woes. Because over the past 60 million years, we’ve experienced much the same thing, and it’s helped make us who we are today. Check it out.
In May I wrote in Discover about a major experiment in neuroscience. Ahmad Hariri, a neuroscientist at Duke, is gathering lots of data from hundreds of college students–everything from genetic markers to psychological profiles to fMRI scans. He hopes that the Duke Neurogenetics Study, as he’s dubbed it, will reveal some of the ways in which the variations in our genes influence our brain circuitry and, ultimately, our personality and behavior.
Hariri plans to collect data from over 1000 people, but he and his colleagues are already starting to analyze the hundreds of students they’ve already examined to look for emerging patterns. In the open-access journal Biology of Mood and Anxiety Disorders, they’ve just published some of their first results. While the results are, of course, preliminary, they do offer an interesting look at the future of neuroscience. Rather than pointing to some particular gene or brain region to explain some feature of human behavior, neuroscientists are learning how to find patterns that emerge from several factors working together.
For their new study, Hariri and his colleagues looked in particular at problem drinking. They hoped to find factors that predicted whether students would start imbibing worrisome amounts of alcohol. Other scientists have previously found evidence that a stressful event–the death of a parent, failing a class, and such–sometimes leads students to hit the bottle. But plenty of students endure these hardships and don’t end up getting drunk so often. Hariri and his colleagues suspected that the difference might have to do with how our brains respond to both stress and alcohol.
When they sifted through their data from 200 students, they found two factors helped predict whether a student was a problem drinker or not. One was how strongly their brains responded to rewards. Hariri and his colleagues tested this reward response by having students play a guessing game while having their brains scanned. They had to guess the value of a number on a card, and then they saw whether they got it right or not. Success brought a surge of blood to a region of the brain called the ventral striatum–a region that responds to many pleasures. Recovering alcoholics who see a picture of a bottle will experience a surge in the ventral striatum, for example. The surge was stronger in some students than others. Students who had a stronger surge in the ventral striatum had higher levels of problem drinking in the wake of stressful events.
But that wasn’t the whole story, Hariri found. There was one more requirement. In another test, he and his colleagues tested how people’s brains responded to fearful images–pictures of scared faces, for example. Such sights usually trigger a surge of activity in a region called the amygdala. And some people have a stronger response there than others to the same picture. Hariri found that people with a strong reward response started drinking after a stressful event if they also had a weak response from the amygdala to fearful images.
The suffering that comes from losing a job or being assaulted can lead people to seek solace through alcohol. Hariri’s research suggests that the stronger a reward a person experiences from a drug like alcohol, the more they’ll drink. But that’s not the case if a high-reward person also has a high fear response in the amygdala. A person with a strong amygdala response may feel anxiety about the dangers of getting too drunk and back away from problem drinking. If people don’t sense the threat so keenly, however, then they may have nothing standing in the way of taking in too much alcohol. The scientists found this three-way interaction between stress, reward, and threat when they looked at students who were problem drinkers at the time of the study, and they also found it when they followed up three months later and discovered some of their students had developed a new drinking problem.
As with any study like this, we’ll have to wait and see if it gets supported by replicated studies. Hariri himself will be able to run that sort of study when he has collected more data from other students. If it holds up, scientists may eventually be able to find gene variants that are associated with the high-reward low-threat brain. Some studies even have suggested that a single variant can produce both changes. Perhaps a report from a DNA-sequencing company might include a list of the variants that make some people more prone to drink in stressful situations. On the other hand, it’s also possible that the problem drinking among the students came first, and led to their experiencing stressful events. Teasing apart all the strands will take some time.
PS: For the data geeks, here’s a figure from the paper. The brain in (A) shows the reward-related activity in the ventral striatum. B shows the amygdala’s response to fear. The graphs show how likely people are to experience problem drinking after a stressful event. The left graph shows the response from people with a low reward response from the ventral striatum, and the graph to the right shows high-responders. In each graph, the scientists break out the high amygdala response (green line) and low (blue). The one line that stands out belongs to the high-reward, low-threat subjects.
I was recently invited to write an essay for a promising new web site that launches today, called Being Human. It’s all about what it means to be Homo sapiens, and I chose to focus on our brain, which is so fundamental to our unique place in the natural world. In fact, we like to think of ourselves as our brains. You could, after all, imagine yourself as just a brain in a vat. It might be hard to manage, but if someone could figure out the right liquids to put in the tank and the right wires to stick into it, it “ought” to work. Hence, The Matrix.
A new look at retracted papers since 1975 paints a picture that’s none too pretty. Retraction rates are zooming up, and most of those retractions, a new study finds, are due to misconduct such as fraud and plagiarism. I write about the study in tomorrow’s New York Times. Check it out.
New England’s fisheries are in such bad shape that the Department of Commerce has now declared them a disaster. It’s not merely the sheer volume of fish we’re catching that explains the woeful state of these fish stocks. Even in places where governments have established strict limits on fishing, some fisheries have been unexpectedly slow to recover. That’s because fish don’t exist in isolation. They’re part of ecological networks. And when we hammer these networks, they can suddenly flip into a new state. Getting them back to their old state can be surprisingly hard.
In the new issue of Scientific American, I’ve written a feature on recent research into how ecological networks flip, along with attempts to detect warning signs of food webs on the brink (subscription required).
P.S. A needless snarky commenter objected to having to pay for the article. As I pointed out to him or her, if you want to read two lengthy scientific reviews on the subject for free, here is a pdf and here’s another one.
For all the progress scientists have made in studying Neanderthals since then, the answer remains tough–in part because it’s not that easy to define a species.
NOVA asked me to write about this enduring question. You can read my answer here.
Every now and then we science writers come face to face with how much science there is to write about–and how limited our powers to write about it are. This week, I’m on the road to report a magazine feature–a week that just so happens to be the one that a team of scientists chose to publish dozens of papers at once on the nature of the human genome. The purpose of the project, called ENCODE, is to systematically measure the function of every bit of the human genome. ENCODE has been going on for quite some time. In 2008, I wrote about the first chunk of results from ENCODE in the New York Times, and I followed up in 2010 here with a report on the work of some skeptics who challenged some of ENCODE’s results. If I wasn’t already insanely busy with another story, I’d be all over this one.
If you’re interested in the debate over how our DNA works, let me direct you to some coverage:
Last year, a Cornell University psychologist named Daryl Bem published a study which he claimed showed that events in the future can influence our minds at the present. I wrote about the study in an essay for the New York Times on the workings of science–how science relies on replication to move forward, and how scientists often struggle to make this happen. When other scientists replicated Bem’s experiments, they failed to get his results. But they found it difficult to get their results published in prominent journals, which frown on replication studies.
Over at Science-Based Medicine, Steve Novella writes about a newly published replication study appearing in the same journal where Bem’s original research was published. Once again, the scientists failed to get Bem’s results. That the future does not affect the present is not exactly news, but Novella’s post is still very much worth reading, because he takes this moment as an opportunity to talk about the reason that studies like Bem’s turn out the way they do in the first place, and how scientists can design experiments better in the future. Check it out.