Past to Present
Evolutionary biologist Joe Thornton rolls up his sleeve and reaches into a blue and white plastic cooler, just like the one you might take to a soccer game or the beach.
But you won't find cold sodas or turkey sandwiches in this one, and its contents might be among the grossest things you've ever seen.
Inside, sand-colored, snakelike hagfish writhe like hoses bursting with water. They lunge against the side of the cooler and squirm under Thornton's grip as he reaches in with his arm. When he pulls out his hand, it drips with wads of clear, snotty goo.
"A few of these hagfish can fill a 5-gallon bucket with slime in a few minutes," Thornton says. "It's amazing."
Hagfish are slimy, slithery creatures that offer a clue to our deep past. By studying the DNA of hagfish and other unusual animals, Thornton has been able to resurrect 450-million-year-old genes and use them to make equally ancient proteins. This archaic biology, he says, can help us better understand who we are today.
"Science isn't just about shining a bright light on nature and seeing the truth," says Thornton. "It's a way to reflect on the human condition and to see our place in the world."
Thornton's research focuses on our endocrine system, a complex network of glands and hormones found in most animals with well-developed nervous and circulatory systems. Glands like the thyroid, adrenal and ovary make hormones, which travel through the bloodstream as chemical signals that trigger our bodies to do all the things we need to survive.
Thornton studies a specific group of hormones called steroids. Examples include estrogen and testosterone. While known mostly for their role in reproduction, these hormones are also key players in bone and cardiovascular health, our stress response and diseases like cancer.
To do their jobs, all hormones must latch onto specific proteins called receptors on or inside cells. Think of them as part of a lock-and-key system. When you have a match, the door opens—triggering a cascade of biochemical changes within the cell.
"Virtually everything a living cell does is controlled by specific interactions between molecules, like hormones and their receptors," explains Thornton. "But despite their importance, we know very little about how these kinds of specific interactions evolved."
Origin of a Scientist
Thornton wasn't always interested in studying steroid hormones. Before graduating from college with a degree in English, Thornton says he wanted to "connect with reality" and began working for Greenpeace, an international organization that educates the public on global environmental problems and solutions for a greener future.
"Science isn't just about shining a bright light on nature and seeing the truth. It's a way to reflect on the human condition and to see our place in the world."
For about 10 years, Thornton traveled to communities with major sources of chemical pollution. Part of his job involved reading about scientific studies and translating the results for local residents.
Thornton wrote dozens of reports and articles describing the health hazards posed by chemical pollution and arguing for specific solutions. He explained these ideas to the press and testified before Congress.
"I became a specialist in helping communities understand the scientific literature to protect themselves and the environment," says Thornton.
The experience sparked his interest in endocrine disruptors, synthetic chemicals that mimic our natural hormones. They enter the air, water or food supply as byproducts of many chemical, manufacturing and agricultural practices.
Because they are so widespread, everyone is exposed to them. Endocrine disruptors have been linked to reproductive problems, impaired immune function and various cancers.
Endocrine disruptors affect animals, too. Scientists suspect they're responsible for a decline in Florida's alligator population, the feminization of male marine organisms, and damage to fish and bird populations.
Alarmed by these potential threats to our environment and our bodies, Thornton started asking questions of his own.
Why do these chemicals have such a big effect on biology? How did hormones and their receptors evolve? Can we predict which chemicals are likely to cause endocrine disruption if we have a better basic understanding of receptors?
"When it came time for me to move on [from Greenpeace], I was so fascinated with the science that I wanted to pursue it directly," says Thornton.
So he went back to school and took his first biology class at age 30. Now 43 and running his own lab at the University of Oregon in Eugene, Thornton is finding the answers to the questions that drove him to science and environmental activism.
Molecular Time Machine
Like a historian studying the past to make sense of current events or an anthropologist examining ancient cultures to understand today's customs, Thornton goes back in time to piece together the evolution of hormones and their receptors. His main objective: to unravel the history of our endocrine system. The findings could help other researchers understand the origins of hundreds of diseases related to the endocrine system and identify new ways to treat or prevent them.
Thornton starts by studying hormone receptors in living animals. On any given day, Thornton's lab might have a cooler full of undulating octopi, jawless lampreys, predatory worms, sea slugs or the slimy hagfish. These organisms, he says, occupy critical spots on the evolutionary tree of animal life for understanding the evolution of the endocrine system. Each species shares an ancient common ancestor with humans and split off the evolutionary tree around the time that certain receptors first evolved.
"My kids like coming in and seeing us dissect these fantastic creatures," says Thornton, whose children are 8 and 11.
"I think that exposure to what I'm doing gives them an appreciation for how old and diverse life on Earth is," he adds. (And it makes their dad seem forever young.)
Thornton extracts genetic material and hormone-containing serum from the hagfish and other organisms. Then, he examines the DNA to find ancestral receptor genes.
He does this with the help of computers and other molecular biology tools. Thornton looks in huge databases of DNA sequences to search for similarities between the gene sequences from his living creatures and those of hundreds of other receptors cataloged in the database. Software programs can turn this information into phylogenies—family trees that show varying degrees of relatedness.
For centuries, these "trees" were based mainly on visible traits, such as bone structure, wings or the presence of fur. But as more tools for studying DNA have become available, evolutionary trees have expanded to include genetic information.
Thornton then uses biochemistry techniques to actually synthesize the DNA for ancient genes and molecular biology methods to find out how they functioned. The search has taken him back 450 million years to the time of the last common ancestor of you.and a hagfish.
Back then, the only vertebrates around were fish without jaws. The climate, which had been quite warm, cooled. Water temperatures dropped to about what they are today, making the sea a more hospitable environment. That was a good thing, because the ocean offered just about the only real estate.
It might seem nearly impossible to imagine we'd share anything in common with the ocean dwellers that lived hundreds of millions of years ago. But Thornton has a fridge of tiny test tubes and incubators with petri dishes to prove that we do.
Each tube contains millions of copies of resurrected receptor genes. Cells living on the plastic plates in the incubator produce the receptor proteins encoded by these ancient genes. Thornton and others can use these proteins to see how they respond to different hormones. By changing the ancient DNA, they can retrace the process by which evolution tweaked the receptors' sensitivity to various hormones.
With the help of a technique called structural biology, they can also see how the receptor proteins' shapes changed over time. Under certain conditions, proteins form crystals that can be bombarded with high-energy X-rays to determine their shape. By using these methods, Thornton has determined the precise atomic structure of several ancient receptors and has shown how that structure changed as the receptors evolved to bind new hormones in a lock-and-key fashion (see receptor image).
Often called the father of evolution, biologist Charles Darwin thought of evolution as a tree where all species branched from a common ancestor. As nature selected for certain advantageous traits, he reasoned, organisms with helpful genetic changes survived to pass those genes to offspring.
Repeated over long periods of time, populations would adapt to their environments. Isolated populations that evolve independently would diverge, eventually forming new species.
Can this explanation of such gradual adaptation apply to the evolution of systems in which the function of the whole requires all the parts to be present? If a hormone needs a receptor and a receptor needs a hormone, then how do you explain the evolution of one without the other?
Or, for that matter, how do you explain the evolution of any complex system with many parts?
The explanation is beautifully simple, Thornton says.
"These systems were assembled by evolution in a piece-by-piece fashion from molecules that once did other jobs." And his research tells the whole story, from beginning to end.
Here's what Thornton has learned. In distant times, there was a single ancient hormone receptor that worked in partnership with a single ancient hormone. That receptor was only as specific as it needed to be at that time. Other hormones with slightly different shapes could have activated it, but only one of these was actually available.
Then, about 450 million years ago, the gene for the ancient receptor got duplicated. Over millions of years, the two copies gradually amassed different sets of genetic changes, leading to two different receptors present in most vertebrates living today.
One of these duplicate receptors retained the ancestral shape and continued to partner with the ancient hormone and other similarly shaped hormones that emerged later in evolution. Today, this receptor interacts with aldosterone, the hormone that regulates salt and water balance in humans and fourlegged animals.
As for the other duplicated copy, Thornton has tracked the changes in its DNA over time. He showed that two mutations altered the receptor's shape in a way that changed its lock-and-key fit. As a result, the receptor lost its ability to interact with the ancestral hormone but gained an ability to partner with cortisol, a hormone that today controls our response to long-term stress.
Thornton explains that the specific hormone-receptor pairs we have in our bodies today came about by subtle modifications of hormones and receptors that already existed for different purposes. He calls this idea "molecular exploitation."
"It's taking old parts and reusing them for new purposes by bringing them into newly built systems," he says.
Because of modern scientific tools and technologies like ancestral gene resurrection, Thornton says evolutionary biologists can now study evolutionary changes and the processes driving them in a much more detailed and decisive way than has ever been possible.
But understanding evolution can also help us to understand the present and future, Thornton says. The concept of molecular exploitation, for example, helps him explore endocrine disruption and try to make sense of it.
The discovery that hormone receptors are only as specific as they need to be at any one time in evolution, he says, explains why they are susceptible to disruption by pollutants.
"The chemical industry has produced tens of thousands of chemicals in the last 60 years, but our receptors evolved hundreds of millions of years ago and have not had a chance to evolve resistance against them," he says.
Could our bodies evolve to shut out endocrine disruptors? That process could take thousands of generations, "and I'm not willing to wait for evolution to solve the problem for us," Thornton says.
So Thornton does what he can for the environment. After his time with Greenpeace, Thornton wrote a 600-page book, Pandora's Poison, outlining the health dangers of chemical pollution. It was printed on chlorine-free paper.
On a more personal level, Thornton and his family try to leave a small environmental footprint. When he and his wife built their house, they avoided using materials containing polyvinyl chloride (PVC, a type of vinyl). The Thorntons buy organic food and leave the car at home as often as they can.
"We try to be as low-impact as possible," Thornton says, but admits, "We're not perfect. Very few families are."
He assists environmental groups, and he uses his knowledge about the evolution of hormones to teach a course that inspires students to explore the intersections of science and policy.
"I take every opportunity I can to discuss how research can affect our understanding of the effects of chemicals on health and what we can do about it," says Thornton.
He considers sharing his work and its implications with the public and the broader research community to be among the most crucial—and rewarding—jobs of a scientist.
"One of the most important aspects of doing science well is being able to communicate your findings, to tell their story," he says. "A great experiment won't contribute anything if you can't make other people understand it and appreciate why it's important."
Thornton says this perspective didn't come from working in the lab. It came from reading literature, writing a book and simply talking to people. These activities also prepared him well for thinking about science and doing experiments, he says.
Thornton believes that scientists leave an important mark on society.
"By doing science, we're contributing to culture in the same way novelists and philosophers and historians and artists are," Thornton says.
"Science allows us to reflect on our condition and our place in the world, and what it means to be who we are."
Joe the Scientist
I became a scientist for two reasons. I wanted to use knowledge to help protect the environment and human health. And I wanted to contribute to culture—our shared understanding of ourselves and our world—the same way writers and artists do.
Think of an interesting or controversial issue, and science probably has something important to offer on it. For some issues, like global warming or high breast cancer rates, science's role is obvious. But science has a lot to say about less technical questions, too, including some that go right to the core of our self-understanding.
Consider the biggest one of all: What does it mean to be human? Writers and philosophers have been wrestling with this one for centuries. But scientific discoveries have radically reshaped the answers we can give today.
We have learned that we share many behaviors—and even more aspects of the nervous and endocrine systems that produce them—with chimpanzees, zebrafish and even sea slugs. In my lab, we are discovering precisely when and how some of these features first evolved.
Big cultural issues will never be answered by science alone, because they also involve values, ethics and spirituality. But our biology is a significant part of who we are, and science is the best way to generate knowledge about nature.
When a scientific discovery changes the lens through which we see ourselves and the world, we can appreciate it the same way we do a van Gogh painting or a Shakespeare play.
My job is to go to the lab each day and try to continue that tradition.
How cool is that? —Joe Thornton