There's an old sarcastic saying about flying pigs. As in, say, "The Cubs will win the World Series, when pigs fly!" Wiltz Wagner, PhD, knows about flying pigs. He's taken them flying, roaring across the Gulf of Mexico in a NASA jet called the Vomit Comet. The plane - whose proper name is the KC-135 - is what the National Aeronautics and Space Administration uses to give its passengers the experience of weightlessness. Scientists, students and astronauts fly on it regularly, bringing experiments to run, equipment to test and a few toys to play with as they float.
Dr. Wagner, the V.K. Stoelting Professor of Anesthesiology and professor of physiology and pediatrics at Indiana University School of Medicine, and his colleagues from the University of Washington took pigs in flight eight times last year. They wanted better answers to questions they've been asking for more than a decade: How does blood flow through our lungs, and why does it flow that way?
Building A Theory
Why did that question bring a group of pulmonary physiologists and their
pigs to NASA's Johnson Space Center? The story begins more than forty years
ago in London, where researcher John B. West, PhD, MD, was trying to answer
the same questions. In the 1950s, it was known that the heart pumped blood
through the lungs, where waste carbon dioxide was removed and oxygen was
added. But there was much we didn't know. Exactly how and where did the
blood flow? Did some parts of the lungs get more than other parts? If so,
where and why? There was no good model of the process.
So Dr. West and his colleagues at Hammersmith Hospital in London came up with one. First, they measured blood flow in human lungs using radioactive gases. By measuring how quickly the radioactivity was removed via the blood in different parts of the lung, they could monitor circulation.
"When we made the measurements, we were very, very surprised - we were astonished," Dr. West said recently from his office at the University of California at San Diego.
Blood flow in the lung, it turned out, was anything but uniform. There was much more blood flowing at the bottom of the lung than at the top. In later experiments, Dr. West and his team came up with what's now called the zone theory, the first powerful model of pulmonary blood flow. According to the theory, the lung is tall enough that gravity affects blood pressures inside the lung. As a result, at the top, relatively little blood flows through the system for exchanging gases. As you go down the lung, more blood flows. The blood flow is the greatest at the bottom.
Dr. Wagner keeps a metal Slinky toy in his IU office to help illustrate this. Pull up on the Slinky and it stretches at the top, but the springs stay clumped together at the bottom. Or think of an apartment tower, he says, when many people want to take a shower at the same time. Those on the bottom floors will enjoy lots of hot water. Those at the very top may be lucky to get a thin stream dribbling out.
"It's a good model. It's simple to understand. It's simple to explain. We all believe it," says Dr. Wagner, who also is director of research in the IUSM Department of Anesthesiology. In fact, he says, virtually every medical student studying physiology learns Dr. West's zone theory of the lung. But because of the Vomit Comet flights and other experiments, the theory may need some serious repairs.
Going Against The Grain
A scientific theory is a little like a window that scientists use to view
their part of the world. At first, the theory may not be very good - the
window is small. Then additional experimentation leads to a better model,
and scientists build a new, bigger window.
In this case, the scientists are the University of Washington team led by Robb W. Glenny, MD, a physiology professor who believes Dr. West's theory needs significant updating. Dr. Glenny has been studying pulmonary circulation for more than a decade, using a system that injects tiny colored microspheres into the blood. The microspheres, about twice as large as a red blood cell, lodge in the lungs. Later the lungs can be analyzed in much finer detail than was possible with the radioactive gas used decades ago.
When Dr. Glenny started doing his microsphere experiments, he found that while gravity did have an effect, something else was going on as well. At each level of the lung there were big differences in blood flow. It was as if, returning to the apartment tower, you walked along one of the upper floors and found that in some apartments the showers barely worked, but from others hot water flowed full blast.
"The discrepancies started stacking up until it got to the point that the old model didn't hold together any longer, and it required a new perspective," Dr. Glenny says.
Journal Article Spurs Debate
In 1991, Dr. Glenny challenged conventional wisdom by publishing a paper
in the Journal of Applied Physiology that was headlined "Gravity is a minor
determinant of pulmonary blood flow distribution."
Dr. West did not let it pass. He wrote the journal a letter attacking Dr. Glenny's paper as "misleading in several respects." The way the experiment was done, Dr. West said, didn't support Dr. Glenny's position. In a scientific journal, those are strong words.
"It was a little bit naughty of them to title the article in this very provocative way," Dr. West says. "I think they've sort of got a bit of a bee in their bonnet about this, which is a shame."
And so the debate began. Dr. Glenny's group has pressed on throughout the 1990s with experiments it says support its position. That is what brought Dr. Glenny and Dr. Wagner on board the Vomit Comet . . . that and Dr. Wagner's trips to the Bonneville Salt Flats to race motorcycles. Dr. Wagner's wife and daughter race the machines, trying to set land speed records.
As it happened, one "guy who spun wrenches with us at Bonneville" had a day job at NASA's Johnson Space Center in Houston, Dr. Wagner recalls. In fact, the "guy" was Sam Pool, MD, chief of the medical science branch in Houston, and he invited Dr. Wagner down. As a visitor, Dr. Wagner got a tour. And the tour included the Vomit Comet. Aha! What better way to test the effects of gravity on the lungs than see what happens in weightlessness?
Of course, they don't call it the Vomit Comet for nothing. The jet, being pushed to its limits, flies in huge parabolic arcs. During the upper arcs, everything aboard the plane is weightless for about thirty seconds. During the lower arcs, everything weighs about twice as much as usual. The human body was not meant for this sort of flying. It makes a lot of people sick. One member of the team got so sick on the first flight that he had to be replaced on later flights. Dr. Wagner fought nausea every single time, although he says it's amazing how much fun floating weightless is. "It's the fantasy; it's Peter Pan," he says. "Everybody was just giggling like a kid."
But Dr. Wagner and his Seattle colleagues were all business when it came to the science being tested. A special machine to hold a pig was built that allowed different colored microspheres to be injected into the pig's bloodstream at different parts of the flight, particularly when the pig was weightless, and when it was pulled by twice normal gravity. Each flight was a frenzy of activity, with team members conducting the tests and monitoring vital signs of the animal - which was almost completely enclosed in the machine. The NASA Animal Care Committee at Johnson Space Center approved the research.
Team To Present Findings
Drs. Glenny and Wagner and their teams are still studying the results.
They made their first presentations at a scientific meeting this spring. It
may be another year before their work is published. But they think they
have enough data to start building that picture window.
They suspect that although there are zones, gravity is responsible for perhaps fifteen percent of the differences in blood flow in the lung. The structure of the lung circulatory system - the way the blood vessels divide and differentiate - accounts for perhaps eighty percent.
In fact, Dr. Glenny believes the best way to model blood flow in the lung is not to divide it into three zones, but to use fractals. Fractals are a relatively new branch of mathematics that scientists have found useful in understanding complex patterns in nature, such as rainfall patterns and waves.
A Meeting Of The Minds?
All this is "interesting," counters Dr. West, but he still "would have to
disagree with the statement that gravity is not a very important factor. In
the upright human lung, there is absolutely no doubt that gravity plays an
extremely important role." When it comes to medicine, he says, it's the
human lung that's important, after all. "What happens in a pig in a KC-135
aircraft is perhaps interesting, but most interesting is what happens in
you and me."
And, Dr. West adds, it's not like he never said there was no difference in blood flow at any given level of the lung. In fact, Dr. West's team has done its own experiments aboard a space shuttle, and those experiments show that something besides gravity is at work.
From his Midwest vantage point, Dr. Wagner says he thinks the two West Coast camps in fact are coming closer together. "If you hear these guys at meetings, it seems pretty polarized. Then they'll write things (in scientific journals) that don't seem so polarized," he says.
And taking part in these new discoveries is exciting, Dr. Wagner says. It's not every day you get to take the prevailing theory on something and turn it upside down.
On one of last year's trips to Houston, Dr. Wagner thought up another test. It could head off some critics who might say the Vomit Comet experiments didn't measure what Drs. Glenny and Wagner say they did. The new test involves videotaping blood cells flowing through tiny capillaries in the lung. Watching the tape in his lab recently, Dr. Wagner saw the results he expected, and he grinned. It was like picking up a hammer to build that big new window.
"How often do you get to think of something like this that drives the nail in? Not very often." RDepartment Of Pediatrics Sets Pace In NIH Funding
The Department of Pediatrics at IUSM received $8.3 million in National Institutes of Health funding in 1998 and now ranks eleventh among the ninety-one pediatric departments in the country who receive NIH funding.
Pediatrics has climbed steadily in the rankings since 1990 when it was fiftieth out of 124 U.S. medical schools. A significant portion of the funding has been generated by researchers in the Herman B Wells Center for Pediatric Research, which opened in 1991 in Riley Hospital for Children and expanded, along with other research laboratories, in the Cancer Research Institute in 1997. Recent advances in molecular biology and genetics in the Wells Center have provided tremendous insight into the molecular basis of many pediatric diseases.
Also outstanding was the Department of Medicine, which ranked in the top fifteen percent in the country with $36.1 million in NIH funding. It is fourteenth among the 107 NIH-funded departments in the U.S. A significant amount of its funding is focused on research in cancer, alcoholism, diabetes, arthritis, and infectious (sexually transmitted) diseases, as well as on bone studies and the General Clinical Research Center (GCRC).
Other departments in the School that received approximately $1 million or more from NIH are the Departments of Anatomy, Biochemistry, Genetics, Microbiology, Otolaryngology, Pathology, Pharmacology, Physiology and Psychiatry.
IU physiology professor Wiltz Wagner (left) conducts research aboard a NASA KC-135, a.k.a. the Vomit Comet, using a pig (inside the cylinder at lower right). Other team members include Dowon An, H. Tom Robertson, MD, Myron Chornuk, and Robb Glenny, MD (also floating). Not pictured is principal investigator Mike Hlastala, PhD, Susan Bernard, DVM, and Wayne Lamm. NASA-approved experiments take place on every Vomit Comet trip.