There are two things that move the world, at least in Dr. Amelia Woolums’s opinion.
“Money and passion are the two things that really motivate people to get things done,” said Woolums, a professor in the Department of Pathobiology and Population Medicine in the College of Veterinary Medicine (CVM) at Mississippi State University.
For Dr. Peter Ryan, passion for relaxin physiology has inspired more than three decades of research.
“This is my therapy. I love administration. I love working with students and faculty. But I love being involved in research too,” said Ryan, a professor in the CVM, and the MSU Executive Vice Provost and Dean of the Graduate School.
First discovered as a hormone of pregnancy, relaxin is a reproductive peptide hormone found in humans and animals; one of its functions is to help “relax” muscles and ligaments in the pelvis for delivery.
“One of the things that really interest us is the high incidence of difficult deliveries in cattle, particularly first-time calving cows (heifers),” said Ryan.
“Calves that are born from a difficult delivery are often not as healthy,” said Woolums. “They are more likely to not get enough of the mother's antibodies vital in the first few weeks of life, and as a result, they're more at risk for infections and more likely to die or not grow to be productive animals.”
Studies by Ryan and Dr. Frederico Hoffman at MSU show that at some point during their evolution, cattle, and other members of the Bovidae family, lost the relaxin gene, so they cannot produce this beneficial hormone. However, they still carry a receptor for relaxin, which means they can respond to the hormone if they are treated with it.
“As a post-doc, I worked for one of the pioneers of relaxin research in the 1980s at the University of Guelph in Canada. We did a study using synthetic recombinant human relaxin in dairy heifers and got a positive response. The problem is you have to use an awful lot of it, and it’s not manufactured commercially, so it's very expensive and not very practical,” explained Ryan.
Ryan took a position at Rutgers University in New Jersey; his post-doc advisor at Guelph had passed away from an aneurysm, and to the best of his knowledge the work was never published. Ryan continued research in the field of relaxin with other domestic species, including porcine and equine, but he said the research for the bovine relaxin hormone “has always been in the back of my mind.” But, two years ago, the research came to the forefront when he sat next to Woolums during lunch at a conference at MSU, and they connected their pieces of the puzzle.
“I think this a lovely story of serendipity and research,” said Woolums.
“We were discussing the research, and Amelia suggested, ‘why don't we use a molecular approach.’ She had already done a successful study on another project using this technology,” said Ryan.
Another piece to the puzzle was Woolums’s husband, a biomedical engineer at Emory University.
Collaborating with Dr. Phil Santangelo at Emory University, Ryan and Woolums worked with CVM Doctor of Veterinary Medicine-PhD (DVM-PhD) Student Caitlyn Burke to treat bovine cells with a molecule that can induce cells to make relaxin, messenger RNA (mRNA). This mRNA is what cows' cells made before they lost the gene for relaxin. Burke's research showed that this treatment could indeed cause the cells from cows to produce relaxin as they once could. The next step will be to determine whether treatment of whole live cows can also lead to relaxin production.
“That was an exciting moment,” said Burke. “When Dr. Ryan first pitched me this project, I immediately thought I would absolutely love to do this. I’ve been really fortunate to have his insight and work under Dr. Woolums who is so highly respected in the scientific community.”
“In a way this approach is similar to using insulin to treat people with diabetes,” explained Woolums. “The insulin molecule is normally made in the body, but if people don't make it, they develop diabetes. Because scientists figured out how to make insulin ‘in the lab,’ people with diabetes can take insulin, and stay healthier longer.”
Ryan added "The common endpoint is to replace the loss of endogenous hormone production. One condition is addressed with hormone therapy, in this case insulin, and in the other condition in heifers, the plan is to address the condition using relaxin mRNA therapy."
“Right now, the global effort is producing more food efficiently and effectively in the same footprint as we have today, and technology like this is going to enable us to do that,” said Ryan.
The research will need to expand to a larger number of cows to confirm they consistently produce relaxin when treated with the mRNA. If that is successful, the next step will be to treat heifers likely to have difficult deliveries to determine if the relaxin produced can improve outcomes. This will take time and more resources, but as Woolums and Ryan explained, the outcome is worth the effort, even if it takes decades.
“As a scientist, you would like to be able to leave your profession having done something that has helped advance the field,” said Ryan. “I'm not looking for accolades. To me, that's the most bankrupt approach to pursuing anything in life.”
Contact: Mary Kathryn Kight