The Devil Is in the Details

WILLIAM W. STEAD

University of Arkansas College of Medicine, Little Rock, Arkansas^* 

	ARTICLE

TOP ARTICLE

In 1949, after a tour of duty in the Navy and a residency in Internal Medicine at the University of Minnesota, I was offered a junior staff position on the Tuberculosis Service of the Minneapolis Veterans Administration Hospital. The hospital had recently become affiliated with the Medical School of the University of Minnesota. I soon joined Dr. Richard Ebert, the young and enthusiastic Chief of the Medical Service, in a project that eventuated in a pair of papers (D. L. Fry, W. W. Stead, R. V. Ebert, R. I. Lubin, H. S. Wells. Measurement of intraesophageal pressure and its relationship to intrathoracic pressure. J. Lab. Clin. Med. 1952;40:664-673 and W. W. Stead, D. L. Fry, R. V. Ebert. The elastic properties of the lung in normal men and in patients with chronic pulmonary emphysema. J. Lab. Clin. Med. 1952;40:674-681).

First we had to find a minimally invasive way to measure intrathoracic (or intrapleural) pressure to facilitate study of the retractile force of the lungs and dynamics of breathing. We were interested in studying patients with pulmonary emphysema in comparison with normal subjects. Don Fry and Bob Lubin were junior residents in Internal Medicine rotating through the Tuberculosis Service.

There were few studies of intrathoracic pressure, because it required the percutaneous insertion of a needle into the pleural space and measurement of intrathoracic pressure with a water manometer. Obviously this did not lend itself to the study of either patients or normal subjects. In the system we envisioned we would simply attach the end of a tube in the esophagus to one side of a new and very sensitive device called a "strain gauge" and one from the mouthpiece to its other side. Then, with air flow interrupted and the glottis open, the retractile force of the lung, PL, could be measured at various degrees of expansion as the difference between the pressure in the lung, PL, minus the esophageal pressure, PT. In addition, the dynamics of breathing could be assessed from pressure- volume curves during breathing.

However, we soon saw that this was not as simple as it seemed, because of peristalsis of the esophagus. To minimize this effect, we used a small bore plastic tube with holes in the distal several centimeters. The multiple holes helped but still did not solve the problem, because of fluid entering the tube. To exclude the fluid we tried sheathing the holes with some thin impervious material. We first tried a child's balloon, then a finger cot, a polyethylene plastic, a latex condom, a "fish-skin condom", etc., etc. Some of these helped, but introduced other artifacts because of the redundancy of the sheath.

After a number of weeks of such futile efforts, we decided that we needed a "condom designed for a snake." Thus, while attending the annual meeting of the Central Society for Clinical Research in early November 1949, we took a cab and visited several factories that made latex products. At one of the condom factories the manager took an interest in our problem and agreed to make a "condom" 18-cm long by 1-cm diameter with the usual thin wall of 0.05 mm. These proved satisfactory for our purpose, and the company made them available to us and to any other groups doing similar studies.

The frustrating search for this essential item for our research evoked an interesting difference in our two young residents. Dr. Fry was assigned to the TB ward where I was the Attending Physician. Realizing that the pace on any TB Service would be much slower than on the Medical Service, I offered Dr. Fry an opportunity to join Dr. Ebert and me in the laboratory. Without hesitation, he drew himself up to his full height and told me that he was not interested in research, that if he ever did any, it would be in clinical endocrinology, with a technician doing the laboratory work. I apologized and quietly withdrew.

I was both surprised and pleased a week later when Dr. Lubin, who was assigned to another TB ward, approached me saying that his ward was not very busy and since he was going into academic medicine he thought that he would like to come to the laboratory to see what we were doing. Naturally, I welcomed him, as did Dr. Ebert. Some two weeks later, Dr. Fry appeared, saying his ward was so slow that maybe he would like to see what we were doing in the lab.

It was fascinating to observe the change that developed in the interests of these two bright young men over the next few months. The one who was interested in academic medicine became more discouraged with each of our many failures, while the one who had no interest in research became ever more determined to solve this problem. Bob Lubin dropped out after a while, but went on to become a well respected cardiologist in Tulsa. Don Fry was stimulated by the challenge and took to this hands-on project like a duck to water. He found research stimulating and went on to become Chief of the Clinical Biophysics Section at the National Institutes of Health, distinguishing himself through his work on the biophysics of the cardiovascular system, using many of the same principles involved in our work together. Upon retiring from the NIH he joined the faculty of the School of Medicine at Ohio State University, where he is still active.

Dr. Fry figured out a way to adapt a solenoid apparatus from an automatic sander used on trucks in icy weather to make instantaneous interruptions of air flow with the glottis still open. This produced consistent measurements of the static retractive force of the lung at various degrees of inflation. It is this property that makes exhaling largely passive for normal people, while losing it contributes to shortness of breath. This part of our work (Am. Rev. Respir. Dis. 1967;96:656-665) eventually became useful in the 1990s. The test proved to be a useful way to quantify the pulmonary retractive force in patients with pulmonary emphysema who are being considered for lung reduction surgery. By repeating the test a few weeks postoperatively one can assess the effect of the procedure.

Another part of our project involved studying the effect of the density and viscosity of the respired gas mixture on airway resistance. We did this by substituting other gases for the 80% nitrogen in air. For example, the much less dense helium and oxygen mixture was easier for patients with emphysema to breathe. The only odd effect was that it changed a bass voice to a soprano. We used hydrogen and oxygen with similar results. As a precaution for this portion, we taped all electrical switches in the room and corridor to prevent their use, which might ignite the hydrogen-oxygen mixture and blow me to kingdom come.

For a gas of a density similar to that of nitrogen but of greater viscosity we went to the Handbook of Chemistry and Physics. We found that argon and neon would both fill the bill. Extensive inquiry finally turned up a source for argon, but it was too expensive for us. So, we searched further for another gas that might be more accessible. We found one with density similar to nitrogen but with greater viscosity and which was available in Minneapolis.

We bought a tank of this gas and filled the spirometer with 80% of it and 20% oxygen and set our usual subject (WWS) up for one of our usual runs. After a few minutes I felt "sort of funny," but not much more so than I often did in the artificial setting of breathing from the spirometer. When I fell to the floor, Dr. Fry grabbed the mouthpiece and put it into his mouth. It was not long before he was beside me on the floor. Dr. Ebert didn't think a third person breathing the mixture would be of any help and so he ran down the hall for the Handbook of Chemistry and Physics. Upon reading it, he quickly understood the problem. By this time Don and I were conscious and all was well.

This episode is my nominee for the best example of the Law of Unintended Consequences. Our attention had been so fixed on the detail of one particular property we needed that we failed to recognize that the propane we were using might have anesthetic properties similar to its well known "cousin," cyclopropane. We all felt stupid but relieved that we had escaped tragedy, not just once but twice in a single day.

As for the stupidity of the three of us, I can only say that each of us has managed to live out a full life and arguably were a little wiser for the experience. The effort to create new knowledge was an intellectually stimulating adventure. It helped us understand how bumpy the road to new knowledge can be.

My life in the laboratory took a sharp turn in 1953 when I was drafted for a second opportunity in the service, this time for 18 months as Assistant Chief of the TB Service at Fitzsimons Army Hospital. I had to switch from experimental research to gaining insight into tuberculosis by honing my observational skills. I became hooked on TB as a fascinating infection and stayed with it as others drifted toward use of the fiberoptic bronchoscope and critical care medicine. In my 25 years as Director of TB control in Arkansas I found that practicing the best medicine I know and keeping good records can also be a good way to remain active and to create new and useful knowledge.

I regret to report that we and many others were saddened to lose Dr. Ebert four years ago when, after a long and distinguished career as Chairman of Medicine at the Universities of Arkansas and Minnesota, he died quietly in his sleep at age 83. He is survived by his beloved wife, Shirley and their five children.

	Footnotes

Correspondence and requests for reprints should be addressed to William W. Stead, M.D., Tuberculosis Program, Arkansas Department of Health, 4815 West Markham Street, Mailslot 22, Little Rock, AR 72205.