Are We Breathing All Wrong?
Michael Joyner, M.D., has a cold. But it doesn't decrease his obvious excitement for a project that really started over two decades ago. And like everything he's studied since his undergraduate days, it has to do with oxygen.
"One of the things that has bothered me for about the last 20 or 25 years is that birds flying over Mount Everest have left-shifted hemoglobin," he says.
Hemoglobin is a protein that gives red blood cells their color. It carries oxygen throughout the body, and different factors affect the amount of oxygen that can attach to the hemoglobin. When oxygen saturation is measured, the normal value is expressed as an S-shaped curve, but that curve can shift to the left or right depending on quite a few variables. Currently, medical textbooks say a shift to the right means hemoglobin gives up oxygen to tissues more easily and protects against low levels of oxygen, while a left-shift means less oxygen is released.
"It's literally the first thing they teach you in medical school," says Dr. Joyner.
Textbooks or Evolution
But that doesn't square with the left-shifted geese. They fly at altitudes of more than 20,000 feet through high mountain passes where oxygen is scarce. So, Dr. Joyner wondered, why wouldn't the geese be right-shifted to maximize what little oxygen was present? When he started to look further, the oddities increased.
"And it turns out, llamas are left-shifted, as are a bunch of other animals that live at very high altitudes," says Dr. Joyner. "This bothered me for a while, and I started wondering, 'Okay, why would evolution pick a different solution than the biochemistry textbooks tell us is correct?'"
Now, Dr. Joyner, his laboratory, and collaborators get to find out.
He recently received the National Heart Lung and Blood Institute's Outstanding Investigator Award to study this question. The award provides support for "projects of unusual potential" by providing more money than a typical grant does and for a longer period of time. The goal is to give researchers more time and flexibility to pursue a risky scientific question that could pay off big. And, Dr. Joyner says, it does help in one big way.
"I've been let out of grant-writing jail," Dr. Joyner laughs. "Even somebody who's pretty successful at writing grants fails a lot. It's very competitive. So this frees up two or three months of the year to think about other things."
Geese, Llamas . . . People?
Before they received the award, Dr. Joyner and his team started answering the hemoglobin question by looking for humans who were naturally left-shifted.
"Left-shifted people sometimes have a high blood count," explains Dr. Joyner. "It's sort of an incidental finding, and it’s a very small fraction of the population."
To find people with left-shifted oxygen saturation, Dr. Joyner pulled in colleagues James Hoyer, M.D.; Jennifer Oliveira, M.D.; and Shelly Roberts, R.N. The team found a 1970s report in Mayo Clinic Proceedings, and other resources on patients studied by Virgil Fairbanks, M.D., a member of the Mayo Clinic emeritus staff. Dr. Joyner also found patients who had been studied at the University of Minnesota and whose exercise capacity was remarkably high at high altitudes. Ultimately, Dr. Joyner's team was able to identify and recruit a large family for the project.
The Final Piece of the Puzzle
Dr. Joyner notes that a big advantage for the project is access to a specialized human clinical research area in Mayo Clinic's Center for Clinical and Translational Science called the Clinical Research and Trials Unit (CRTU). The CRTU provides support from specially trained nurses and other staff, and procedural and laboratory services, allowing researchers to undertake detailed studies of key aspects of physiology.
"We are one of the few institutions left that have something like the CRTU," says Dr. Joyner. "We have developed capabilities where we can measure how air gets into the lungs, how it gets across the lungs into circulation, how much blood the heart actually pumps, how much blood goes to each organ, and how each organ is using that blood."
The CRTU was built for just these sorts of investigations and has contributed to significant findings in heart failure, aging, and exercise benefits.
"We can also start to understand the other adaptations these people have made and start thinking about how we can intervene in patients with disorders," says Dr. Joyner. For example, he says, in people who have trouble oxygenating their blood due to lung disease or an acute lung injury, might a drug for left-shifted hemoglobin patients help their lungs pick up more oxygen, provided it can be off-loaded at the tissue level? Or on the other hand, for people without sufficient blood flow, a right-shift might help.
"I'm attempting to keep pushing the envelope a bit, and hopefully, we’ll make some discoveries about oxygen transport in humans that will be of general interest to the whole field and that may provide insights into patient care," says Dr. Joyner.
The Mayo Model of Research
And, Dr. Joyner says, because Mayo Clinic has the CRTU, other infrastructure, and a culture of collaboration, when you get a novel idea, you're in a position to pursue it.
"One of the things that’s helpful to keep you going in research long-term," explains Dr. Joyner, "is to be willing to pursue the interesting things you stumble onto.”
And he's looking forward to stumbling over many more interesting scientific finds as this new project ramps up.
"It's nice later in your career to get an award like this," Dr. Joyner says. "You always have to worry about aging, but hopefully, I can channel our long-practicing Mayo clinicians and clinician investigators who are still going strong in their 80s. Every day, I come in and say, ‘What adventure awaits me today at Saint Marys Hospital?’ And if you keep your eyes open, something will. If you don't learn something new every day at Mayo Clinic, it's not Mayo Clinic's fault. It's because your eyes weren't open."