In science, creativity is at first hypothetical

Neil Caudle

A mother, a child, and the question of nurture.

 

For biologist Lesly Temesvari, a strong hypothesis requires more than mere method.

Lesly Temesvari would like to bury the notion that creativ­ity and science are somehow at odds, that creativity is all about making stuff up and science is all about mining data and build­ing knowledge as ants assemble anthills, grain upon grain. It’s just not that simple, she says.

A biologist who studies parasitic diseases (see Dysentery’s life raft), Temesvari has learned that the make-or-break moment for any new line of research may well be the leap of induction, invention, or pure inspiration that leads to what if… and then to a sometimes outrageous proposition called the hypothesis. Proceeding step-by-step through the scientific method does not automatically hand you this prize, a testable hypothesis. The scientist has to create one.

I ask her for an example of how this works, and she tells me a story. It’s a story about her science, her little girl, and a magazine sort of like this one.

Rat pups need a licking

“I graduated from McGill University, so I get the alumni mag­azine,” she begins, “and there was a story in it about two scientists at McGill from different fields—one was a behavioral scientist and one was a molecular biologist—who happened to meet at a confer­ence. The behavioral scientist had been interested in maternal nurturing, and its effects on behavior, and he had a rat model he was using to study this. He used two groups of rats—nurtur­ing and non-nurturing. Apparently you can tell the difference by whether or not they lick their pups. And he’d found that rats that were not nurtured had significant behavior changes; they were more anxious, and they didn’t nurture their own pups. At the conference he started talking to the molecular biologist, who said maybe nurturing can actually change the genetics in some way. Now this interested me, because I have an adopted daughter who is from China. So because she is not my biological daughter I am especially interested in the question of how much influence I can have on her development. If nurturing actually changes behavior at the genetic level, I want to know about it.”

The researchers at McGill had been studying the epig­enome, a code of biochemical tags that turn genes on or off.

Something that affects these switches is called epigenetic, and the biochemical tags are methyl groups. So the process that alters gene function is called methylation, a topic of special interest in Temesvari’s lab because parasites could very well interfere with the on-off switches. From the rat studies at McGill, it appeared that mother rats licking their pups had an epigenetic effect by changing the patterns of methylation.

“At McGill, they found some real changes at the genetic level,” Temesvari says. “They took non-nurtured pups and moved them into a colony of nurturing rats, and genetically, these pups began to look more like the nurturing rats.”

Applying it to people

But finding these epigenetic changes in rats does not guaran­tee finding them in humans. So the researchers looked for a way to study methylation in people, too. They had access to postmor­tem tissue samples from the Montreal Neurological Institute. The samples were from people who had committed suicide and who also had not been raised in nurturing homes.

“When the researchers looked at the samples, the pattern of methylation matched those in non-nurtured rats,” Temesvari says.

In other words, a lack of nurturing apparently affects the genetics and behavior of people and rats in similar ways.

That’s when Temesvari made her leap of induction.

“It dawned on me,” she says, “that if something as extrane­ous as maternal nurturing can affect methylation patterns, the parasites I study may have some influence as well. One example is Toxoplasma, which you have been exposed to if you’ve ever had a cat. Toxoplasma is a very common parasite that goes into cells, and people have always assumed that it’s harmless. Recently, there’s been some research that shows Toxoplasma is not as harmless as we’d thought. One study out of Sweden showed that people with past Toxoplasma infections were seven times more likely to commit suicide. Another study showed that people with Toxoplasma antibodies circulating in their blood were more likely to be risk takers, and therefore more likely to have car wrecks or other seri­ous accidents.”

Before we begin blaming our cats for our foul moods and fender benders, Temesvari cautions that the findings are so far correlations, not proofs. No one has established cause and effect. But the correlations seem strong enough to take the next step: forming a hypothesis. And for her, the what-if questions went something like this: What if a parasite like Toxoplasma alters methylation patterns? And if it does, wouldn’t it also influence behavior?

These were the kinds of questions that pointed Temesvari toward a hypothesis that did not bubble up from her research alone. She read a magazine. She thought about her daughter. She connected the two with her science. And there it was.

She is applying for a grant from a private foundation, hoping to test the hypothesis that if maternal nurturing can change the methylation patterns and the expression of genes, causing a change in behavior, then there might be a similar connection between a parasitic infection and changes in behavior. In her lab, she will infect living cells with Toxoplasma and see what happens with the methylation.

This is not a safe little puzzle to solve in the lab. It’s a big and outrageously daring proposition that will raise a few eyebrows in her field.

“The whole idea is totally harebrained,” she says, laughing.

Out of her comfort zone

Harebrained or not, Temesvari’s idea is too big for her lab to handle alone. She will need help.

“I’m really out of my comfort zone on this project,” she says. “Elena Dimitrova in math is going to help because she’s good at analyzing very large data sets. June Pilcher is a behavioral scientist, and she’s agreed to help us think about the behaviors involved.”

The project will be daunting, and its implications could be huge. For years, researchers have labored to explain, for example, the effects of poverty or trauma on health and behavior. If conditions at home expose a child to parasites, will the child be at greater risk not just for infection but for behavioral problems as well? Is this one factor in the link between poverty and mental illness or crime?

As a scientist and a mother, Temesvari would like to help settle the question of how much a parent can matter in the life of a child. And she is only half joking when she finishes our conver­sation with a quip:

“When people meet my daughter and they say, ‘She’s so beautiful, or she’s so smart,’ I say, ‘Yes, and it’s epigenetic. It’s me affecting her methylation patterns.’”

Lesly A. Temesvari is an Alumni Distinguished Professor of biologi­cal sciences in the College of Agriculture, Forestry, and Life Sciences. Elena Dimitrova is an associate professor of mathematical sciences in the College of Engineering and Science. June J. Pilcher is an Alumni Distinguished Professor, Department of Psychology, College of Business and Behavioral Science.

The story Temesvari read, “Are Your Genes Your Destiny? (Not if your mom has anything to say about it),” by Hannah Hoag, appeared in the Spring/Summer 2011 edition of McGill University’s alumni magazine.

In 2010, Temesvari won a Fulbright fellowship, which took her to Italy to teach science writing. Building on that experience, she and Steven B. Katz, a colleague from English (see Connecting two cultures), led Creative Inquiry teams that helped Clemson undergraduate students produce a science journal and a radio program about research.

Photos by Craig Mahaffey.