UB team explores cancer defenses of big, long-lived animals

When UB evolutionary biologist Vincent Lynch was in graduate school studying life history evolution, a scientific enigma known as Peto’s paradox intrigued him.

Cancer arises from an accumulation of mutations in individual cells over their lifetime, so it is to be expected that animals that live a longer time and have more cells would have a higher chance to acquire cancer. But they do not. Peto’s paradox revolves around this idea.

Lynch decided that when he started his faculty job, leading his own research, he wanted to explore why larger, long-lived animals didn’t develop cancer more often.

Growing up, Lynch, a first-generation college student, only knew of two occupations involving a biology major: doctor and teacher. It wasn’t until he got to college that he learned about research-based careers.

He hopes his work can lead him to discover information that can aid in advancements for cancer treatment and prevention in humans.

“Understanding how some animals evolved to be relatively cancer-free despite having giant bodies and living a really long time is all about understanding how evolution works,” says Lynch, associate professor of biological sciences, College of Arts and Sciences. “If you can figure out how it is these animals evolved to be relatively cancer-free, we can learn something about evolution and maybe that can teach us something about how we can treat cancer in humans.”

In the lab, Lynch’s team uses evolutionary genomics and comparative cell biology to study Peto’s paradox. Evolutionary genomics focuses on how an organism’s DNA has evolved over time. Comparative cell biology focuses on the similarities and differences between varied species’ cells.

To obtain cells and DNA for different critters, Lynch collaborates with “frozen zoos,” one of his favorites being the San Diego Zoo’s. These organizations collect and freeze cells of many species, including rarer or potentially at-risk species. By keeping and preserving cells, there is a record of these animals’ genetic information. 

As part of their work, Lynch and colleagues “stress out” animal cells in the lab as much as possible, and record and analyze the cells’ reactions to the stresses. Some cells persevere and adapt to the stresses, while other cells die. Once a cell is dead, scientists conduct further analysis on how it died and how long it took to die.

The results show that some animals, including elephants and Galápagos giant tortoises, are very sensitive to these stresses. This sensitivity makes their cells more susceptible to death, which can actually be beneficial. As Lynch explains, certain types of cell damage can increase cancer risk, so if potentially cancerous cells die quickly, tumors will be less likely to develop.

Another finding is the existence of multiple copies of tumor suppressor genes in these species.

In addition to elephants and tortoises, other creatures of interest in the Lynch lab’s cancer research include whales, bats, sloths, armadillos and aardvarks.

Work in the lab is a collaborative experience between Lynch, postdoctoral scientists and graduate students.

The lab is heavily driven by curiosity, and documentation is very important: If you have an idea or revelation, write it down. Writing everything down also helps keep track of any progress or setbacks.

“Basically, it is all about being curious,” Lynch says. “It’s about understanding how biology and evolution work. For the most part, once grad students and postdocs become familiar with what we do, they can do their own curiosity-driven experiments. It is pretty collaborative. We all learn from each other.”

Outside the lab, in a workspace shared by scientists from across the department, are huge dry erase boards filled with biological terms in an array of different colors: phenotype, recombination, selection, DNA, segments, duplication, interference. These words are all connected to each other with arrows and graphs, resembling a vision board.

Inside the lab, cells are kept in freezers until they are ready for use. One recent morning, the scientists are growing and experimenting with African elephant cells.

Growth media, which helps keep the cells alive when they aren’t frozen, and trypsin, an enzyme that breaks down proteins, are kept warm at 37.1 degrees Celsius.

In future research, the team will insert genes of elephant ancestors into the modern elephant cells. One of the questions the researchers are trying to answer is if the rate of apoptosis, also known as cell death, can be changed through the insertion of ancestor genes that suppress tumors.

Some important work related to the research is also done outside of the lab. Jacob Bowman, a postdoctoral scientist who has been a member of Lynch’s group for a year and a half, focuses in part on computational work, analyzing large amounts of genetic-sequencing data, which allows him to see how genes are evolving.

Bowman became interested in Lynch’s work after Lynch paid a visit to Ohio State University, which Bowman attended at the time. After hearing a lecture by Lynch, Bowman applied for a position with the lab. Bowman and Meaghan Birkemeier, a master’s student who recently joined Lynch’s research team, both share the sentiment that the lab environment is very nice and fluid.

“I’m excited to have such a fascinating research project for my master’s degree. Dr. Lynch is approachable with any questions I have about my project and provides direction for my experiments as I work toward answering my research question,” says Birkemeier. “My fellow students make the lab a fun environment, and we learn from one another as we collaborate in our research.”

“The lab environment is like a playground where we get to try a whole bunch of techniques and just explore new ideas all the time,” says Bowman. “We’re not expected to tackle a problem with one method, but with a myriad of tools that give us new information. Vinny’s excitement for the work and the process is infectious. It creates a positive and communicative lab atmosphere that is ideal for science.”