The Genetics of ResearchBy Meredith Sell Published: Oct 26, 2017
“There’s been a lot of hype about genetics since about 2000, since the Human Genome Project,” said Garrett Shanks, a 2016 Taylor biology graduate, “and it’s just turned out to be a lot more ambiguous than people predicted.”
February 2001, when Shanks was in early elementary school, the Human Genome Project published a 90 percent complete “genetic blueprint for a human being.” Expectations were high. With so much information at their fingertips, scientists and health care providers, it was assumed, would be able to understand and treat genetic diseases with little trouble.
Now, about 16 years later, Shanks is closing out a year of full-time genetic research, a process he likens to searching for a needle in a haystack—with no guarantee that such a needle even exists.
The general public understanding of genetics is an oversimplified use of mathematical probabilities with a strong concept of genetic mutations that is heavily influenced by the origin stories of comic book superheroes and typically tied to extreme radiation.
The actual science is more complicated.
“Everyone used to call it a mutation,” Shanks said, “until we started doing all this [genetic] sequencing and realized everyone has hundreds of what were formerly called mutations. They can’t be mutations, because they’re really common, so now they call them variants.”
A harmful variant is pathogenic, harmless is benign, and most variants are of “unknown significance.”
Since last June, Shanks and Dan Clemens ’15, a fellow Taylor graduate, have been working in the Windland Smith Rice Sudden Death Genomics Laboratory at Mayo Clinic. Under the direction of Dr. Michael J. Ackerman, the lab investigates a variety of heart diseases and conditions with a specific focus on their known or unknown underlying genes.
A typical day finds Shanks and Clemens in different corners of the lab. Shanks spends most of his time in front of a computer screen, first filtering through genetic variants, then narrowing down which variants he’s going to investigate, then using resources—scientific literature, in silico tools, online databases—to learn what he can about the scientific community’s knowledge of particular variants.
Clemens does more lab experimentation, including almost daily cell culture work. “That’s just a fancy way of saying, ‘growing cells,’” he explained.
Both are working on related, but very different, investigations. The variants Shanks is working with belong to a group of young people who died suddenly for no known reason.
“We’re looking through their DNA to try to understand if there’s a genetic basis for their death,” Shanks said. “Maybe they had one of these heart diseases that were below a diagnosable level when they were alive, so let’s see if in their genetic code there’s some kind of explanation for their death.”
Clemens’ cell culture work ties to two related objectives:
“I’m working on functionally characterizing a disease that our lab discovered,” he said, “which means that we’re trying to use cells that have this disease to better understand the disease.”
He’s also running experiments to better understand the genetics of a patient they think has the disease.
The disease, Triadin Knockout Syndrome, causes severe heart arrhythmia at an early age—all of the patients they’re working with have had a cardiac arrest before the age of two.
“A lot of the work that we do, the questions that we’re trying to answer come directly from Dr. Ackerman’s patients,” Clemens said. “That’s kind of the motivation to study this disease and better understand it, so that he can continue to treat them better.”
When Shanks was a senior in high school, he was given an assignment to write a letter to himself four years later. Not long ago, his mother found it and told him that he’d written about wanting to be at Mayo.
“I was attracted to Mayo because … their slogan is ‘The needs of the patient come first,’” Shanks said, “so in a world where it seems like money has taken over medicine, they seem to be—at least, try to be more geared towards the patients that they care for.”
His sophomore year at Taylor, Clemens took Cellular and Molecular Biology with Dr. Jeff Regier and a crop of juniors who were preparing for the MCAT and starting to fill out medical school applications. Up until that point, medical school had been his plan for his future, but that semester:
“I was more excited about being in that class.”
He remembers being fascinated by the material and, for the first time, he started thinking about looking into areas of biology outside of medicine. “That’s when I started leaning more towards research,” he said.
The leap from undergraduate biology studies to full-time biomedical research has offered its share of challenges for both of them.
“When you’re in undergrad, you think, ‘Okay … here’s the problem and I can look up how to solve it,’” Shanks said, “but [when] you start to research, you realize that there are roadblocks and the field doesn’t know how to solve them—and that’s why you’re doing the research.”
They’ve adopted a mindset toward research shared by Dr. Jessica Vanderploeg, Assistant Professor of Biology:
“Be cautiously optimistic, but emotionally unattached.”
Go to the lab. Ask the questions. Do the work. Poke and prod from one angle and then another and another. Don’t get your hopes up, but expect to learn something.
And when another day, week, month in the lab brings more questions than answers:
“This may be hard and it may be frustrating and I’m losing my patience with this scientific work,” Clemens said, “but I know that in the long run, it’s going to be helpful for someone who has a really terrible disease.”
This fall, Garrett Shanks ’16 is entering medical school at Loma Linda University. Dan Clemens ’15 is starting the PhD program at Mayo and will continue his work in the Windland Smith Rice Sudden Death Genomics Laboratory.