These seem like two very disparate ideas: the embryonic development of a single specimen and the evolution of a whole species. How did they get connected?
At first paleontologists were studying evolution on vast timescales through fossils. Then geneticists came on the scene, and they were studying small-scale differences within species based on mutations in genes. What has been called the modern synthesis of the two fields emerged in the 1940s with the idea that the sorts of genetic differences you could observe in populations, right out your window, when compounded and extrapolated over vast periods of time, could account for the large-scale changes we see in the fossil record. So the modern synthesis was a harmonization of those two scales.

But the modern synthesis did not explain evolution in full. It was still just a theory. Where was the empirical evidence? Darwin’s theory of descent was a black box. You could not see exactly what kinds of changes were taking place to account for the differences in forms. But the study of embryonic development has allowed us to peer into the machinery of making these creatures. We can study their DNA text and their developing embryos and ask, where do the differences arise? That gave us the empirical data for the theory. You can’t necessarily see the change happening in the adult, but you can see that if you change that nucleic acid base right there in that gene, at that particular point in embryonic development, that animal is darker. If you change those three bases over there, that limb is longer. This is the fundamental basis of evolution: changes in DNA. By experimenting with it and visualizing it all the way up the ladder of differences, we now understand that the modern synthesis is correct.

You’ve said evolution is like compounding interest. How so?
Just like a good money market account, evolution works through incremental change. If variants within a species provide an advantage, no matter how slight, then that form, that capacity, will be favored. If evolving spots on wings makes you more attractive to mates or more evasive to predators, those patterns will dominate. Those varieties will have more offspring. Added up over centuries, millennia, and longer periods of time, natural selection—the competition that takes place in nature between variant forms—is powerful enough to forge all the changes that we’ve seen on the face of the earth.

It is hard for most people to wrap their brains around such vast stretches of time.
A century ago, Teddy Roosevelt was president and cars were barely in use. That seems like an unimaginable amount of time ago, but biologically and geologically speaking, it was a split second. A million years is just a fraction of the time that upright hominids have had to evolve. It takes time for sea levels to rise, for rivers to cut their course. As temperatures change, as rain forests grow up or deserts emerge, the creatures that live in these regions are adapting and changing too.

You call the combination of evolution and embryonic development evo devo. What is that, exactly?
It is just shorthand for “evolutionary developmental biology,” a mini-syllabic description of this field that’s concerned with the evolution of development. It’s related probably to Devo, the new-wave band of the early 1980s—those were the guys who played with dog dishes on their heads. Before then you could describe evolution as change over time, but we did not have any grip on that process until the 1980s.

And that’s when you entered the scene?
Right. I was in graduate school doing research in immunology at Tufts University in Boston. I would just hop on the subway and go to seminars at three or four different schools. It’s stimulation, right? It’s hard to know how all the dots got connected, but I kept hearing that things were not well understood in evolution and things were not well understood in development, and I started thinking: How can I get at the meat? I was looking around for insights when I came across the very thin literature on the genes that sculpt fruit fly bodies, including the study of spectacular mutants. In these mutants, or Frankenflies, a single gene could put legs on the head in place of antennae. Other single-gene mutations gave the flies an extra set of wings or removed its eyes or wings completely. The fact that single-gene mutations could have such dramatic effects raised the question: What were these genes, and what were they meant to do? The quest was to figure out how these genes sculpted the fruit fly body form.

You saw the fruit fly as a window into evolution and development. How did you make the connection?
It was not an obvious call, because the expectation was that fruit flies didn’t have anything to do with the development of furry creatures. But in 1983 I found a laboratory where I could do the work, with Matt Scott at the University of Colorado at Boulder. Just as we were getting started, it became clear from our research and others’ that these body-building genes were not restricted to fruit flies; they were shared throughout the animal kingdom. It was a real jolt. All of a sudden we could do deep experiments at the most fundamental level to understand how form actually evolved.

So scientists were seeing the same master genes at work in many different species?
Yes. One shocking discovery was the relationship between our eyes and bug eyes. You wouldn’t think they had anything in common, right? Bug eyes, with 800 facets, work by different optical principles than human eyes. For almost a century and a half, biologists thought that they had evolved independently, from scratch, and that eyes had been invented many times in the animal kingdom by completely different means—different recipes in different groups of animals. We have now discovered that these eyes are formed by what is recognizable as the same gene, even though those animals have been evolving separately for 500 million years. When we took the mouse version of this gene—the same gene we find in the human—and put it in the fly and tweaked it, we induced fly eye tissue.

Our team showed that the same common gene is critical to building limbs in humans and fruit flies. It turns out that this gene is critical to building virtually everything that sticks out of the body: antennae, legs, horns, whatever. These kinds of experiments shattered our preconceptions and forced people to think differently. Beneath these extremely diverse exteriors was a deeply shared common genetic tool kit. If I had five minutes with Charles Darwin, I’d start right there. It would blow his mind.

Clearly we have entered the age of experimental Darwinism. What are the experiments like, specifically?
We look at lots of species to figure out the ancestral form of a particular molecule. We can reconstruct that ancestral molecule and then retrace the steps that must have taken place to forge the new forms and functions we see today. If you think that the difference between two species involves changes in certain genes, you can swap those genes between the species. We’re doing those experiments trait by trait. There’s a powerful set of experiments that people have done on vision. Lots of animals differ in the parts of the color spectrum that they see best because of how they are tuned to their environments —whether they live in the deep sea or in caves, whether they mostly go out in the day or at night, or whether they’re trying to pick up ultraviolet patterns on flowers or on prey. Sight is really important in helping animals live, and since animals live in lots of different habitats, vision has evolved a lot.

Experiments that look at these changes are very doable in the lab. You can swap genes and change the retinal proteins that detect light. Then you can make very clear predictions about what certain changes mean and verify those things experimentally. For example, mice have been given an extra color vision gene in the lab, and it has been shown that the protein manufactured by that gene expands the scope of their vision by enhancing their ability to see longer-wavelength light without any other changes in the brain.

Can we apply these discoveries to the human realm?
We now know that the human genome and the chimp genome differ by only about 1 percent. Yet our bodies and brains are so different. How can we be so different from other primates if our genes are so much the same? How did we get the dexterity in our hands? How do we walk upright? How are we able to hold this conversation? How did we get big brains? Once you identify the meaningful functional changes that have taken place between us and chimps, you realize that pretty big differences in anatomy and behavior can result from a small degree of genetic divergence. Evo devo has given us the tools to explore this mystery: The same genes are being regulated and then used in a different way. Something is happening a little earlier or in another place or is staying on a little bit longer. These are the time and space dimensions of development. It’s like choreography. You’ve got the same dancers, but the ballet is different based on different cues.

In your book Endless Forms Most Beautiful, you refer to the Cambrian explosion, a time when a vast number of new life-forms appeared at nearly the same time. Evolutionary skeptics often point to this kind of abrupt shift—doesn’t such rapid change contradict your description of a single master tool kit and slow evolution over long stretches of time?
Prior to about 543 million years ago, you saw things like jellyfish and spongelike creatures, but you didn’t see bilateral creatures: worms and trilobites and things like this. Then in the Cambrian explosion, large and complex animal forms erupted. These forms in the Cambrian represent a lot of the major divisions of the animal kingdom we see today. The Cambrian explosion looks abrupt in the fossil record, but the surprising message from evo devo is that all the genes for building big, complex animal bodies long predated the appearance of those bodies. Most of what was needed to create this incredible complexity already existed. The genes were expressed prior to the Cambrian in those more modest, soft-bodied creatures, but they had fewer jobs to do. Complexity evolved by expanding the uses of these genes rather than inventing lots more of them.

It makes you wonder what kind of potential is just waiting to burst out today.
Dinosaurs were the dominant vertebrates right up until the end of the Cretaceous. Mammals existed, but they were smaller, carving lifestyles out of the dinosaurs’ way. Take out the dinosaurs and in 10 or 15 million years mammals had evolved into all sorts of large forms and dominated terrestrial ecosystems. When genetic potential met ecological opportunity, you got elephants and bison and giraffes. Think about ecology as corking the bottle; take the cork out and things explode.

When genetic potential met ecological opportunity, you got elephants and bison and giraffes. Ecology is like corking the bottle; take the cork out and things explode.

You mention in your book The Making of the Fittest that every species contains fossil genes.
These are remnants that are no longer used, and the integrity of the genetic text starts to erode. One of my favorite stories concerns the ice fish of Bouvet Island. These creatures live in the cold waters of the Antarctic. They are the only vertebrates without red blood cells to carry oxygen to nourish their tissues. If you look at the genes for hemoglobin, the oxygen-carrying proteins in red blood, one of those genes is completely gone and another is a broken remnant, rotting away. From this we understand that the ancestors of these fish had red blood, but these guys have left that red-blooded lifestyle behind.

The explanation is ecological. The ice fish are living in this extremely cold water, and it may well be that red blood cells are really hard to pump around capillaries in such cold water. Instead, the fish have larger gills and pretty much a scaleless skin. So they’re just getting their oxygen passively from the surrounding ocean water. They’ve abandoned a way of life that has nourished vertebrates for some 500 million years. As for us, humans have junked about 800 genes in the course of our evolution from mammalian and earlier ancestors going back millions of years. Who knows, those lost genes might be useful to us 1,000 years from now, but there’s no way to preserve them. I guess we could always try to engineer some things back in.

By contrast, you’ve said that some genes are immortal.
These genes date back to the early origin of life on the planet, and they’re so essential that their text has been preserved for more than 3 billion years. They’re involved in very fundamental ways with the decoding of the genetic machinery shared among all organisms. Without these genes you couldn’t express your genetic information and produce the proteins you need to live.

You’ve presented an avalanche of irrefutable evidence, yet opponents of evolution seem to refute it all. How do you respond?

You can hear me almost chuckling, because it’s not reasonable, it’s not rational, and as the years click by, it’s ever more preposterous, but people still stick to their guns.

Is there anything we can do to help persuade the skeptical public to accept the evolutionary way of looking at life?
Seriously, teach evolution as a core theme in science from the early grades. The universe changes, the earth changes, and life changes with the evolving earth.

Where do you see evolutionary biology going next?
Today we’re in a second golden age. We’re not collecting the menagerie of critters that Darwin did or hauling them back to a museum. Instead, we’re collecting the genetic recipes of creatures across the planet and trying to figure out how they came to be. We’re looking right into the text of evolution, and even into the text of extinct creatures like woolly mammoths and Neanderthals, and we’re asking what made them similar to or different from elephants or from us.

A third golden age will come when we understand life beyond earth. How many times has life evolved, and how many origins have there been? Has life moved from planet to planet? Is the chemistry of extraterrestrial life different from that of life on earth? This will be difficult work, but we have to look ahead. Finding life elsewhere in the universe would bring a scientific revolution as big as any we’ve ever had.

Click here to see DISCOVER's special package on Darwin in honor of his 200th birthday and the 150th anniversary of The Origin of Species.