What Nobody Needs to Know About Airborne Infection

RICHARD L. RILEY

	ARTICLE

TOP ARTICLE

John Barnwell, Director of Research and Education at the Veterans Administration (VA) Central Office in Washington, D.C., took a gamble to answer the question: is tuberculosis (TB) transmitted by droplet nuclei? He went to the new VA Hospital in Baltimore where there were wards for TB patients, and had them hand over a six-room semi-isolated suite of rooms and penthouse directly above to three outside investigators. William F. Wells was an eccentric genius, originator of the droplet nucleus hypothesis, and demonstrator of droplet nucleus transmission of bovine TB in rabbits; Cretyl C. Mills was Wells' devoted, single-minded, and obsessively thorough assistant, inadequately called a technician; and yours truly, Richard L. Riley, was a professor at Johns Hopkins University in Baltimore, a disciple of Wells, and Principal Investigator on the project. By the time results were written up eight years later (Riley, Mills, O'Grady, Sultan, Willstadt, Shivpuri, Infectiousness of air from a tuberculosis ward. Am Rev Respir Dis 1962;85:511-525), Barnwell had retired, Wells lay dying, and Cretyl Mills had been infected with TB.

The plan of attack was simple: to see if guinea pigs breathing air vented from a human TB ward would be infected under conditions that precluded transmission by any means other than airborne droplet nuclei.

In 1954 Wells and I spent many hours at the hospital ensuring that organisms from the research ward could not escape into the rest of the building, installing in the penthouse an exposure chamber designed by Wells to house 150 guinea pigs, getting the amount of fresh air make-up to the room ventilating system controlled and measured, performing preliminary experiments to show that rabbits in a patient's room could be infected with bovine TB atomized into the ventilating system, and satisfying all concerned that we were ready to start studying human patients. When male guinea pigs had been purchased, quarantined, demonstrated to be tuberculin-negative, and installed in the exposure chamber, infectious patients from the hospital were transferred to the six single-bed rooms. A two-year period of data collection followed during which Wells seldom appeared at the hospital, and I made a couple of visits a week. Cretyl Mills was the one on the spot, feeding and caring for the guinea pigs, tuberculin testing all 150 in the exposure chamber every month, keeping all the records, and fending off people with complaints.

Consider the effect of this project on the operation of the hospital: apprehension on the part of administrators, doctors, nurses and patients; extra work for the doctor assigned to rotate patients on the research ward so that patients becoming sputum-negative were removed and replaced by patients thought to be infectious; extra work for the bacteriology laboratory because of frequently repeated sputum tests; extra work for the pathology laboratory autopsying infected guinea pigs, culturing suspected lesions, and performing drug-susceptibility tests on the organisms; extra housekeeping chores; and added responsibilities for the administrators. In a word, a damn nuisance for everybody. And this went on for years.

Meanwhile Wells' wife died, leaving him in charge of their mentally retarded son. Their house was in a remote part of the eastern shore of Maryland where an outhouse still served its classic function. Wells kept in touch by phone, invariably at dinner time and at length and much to the annoyance of my wife.

Two years of data collection were completed. Just as Wells had predicted, out of 150 exposed, three guinea pigs a month, on average, caught TB. This was the monthly take for which the exposure chamber was designed. It was an example of Wells' uncanny ability to foresee the quantitative implications of the droplet nucleus concept. Furthermore, as predicted, the infected animals had single tubercles in the lungs, indicating infection by a single infectious particle, the effect of enormous dilution by uninfected air. But objections were raised. Maybe the guinea pigs were infected by the feed, the water, the caretaker, who knows. There were no controls to disprove routes of infection other than aerial ones. To deal with these objections a second exposure chamber with capacity for an additional 150 guinea pigs was constructed and run in parallel with the first. On the way to this control chamber the air was disinfected by ultraviolet irradiation, so that no animal could be infected by air. Any infection would have to be by some other route; lack of infection would indicate the absence of any other route. The second two-year study was underway.

Then Wells collapsed at his eastern shore home, paralysed from the waist down, unable to reach the phone and unable to get his son to call for help. Two days later he was found and brought to the Johns Hopkins Hospital. A vertebral metastasis, probably from the prostate, was found. He was a veteran of World War One, so we were able to get him transferred to the VA Hospital where the research was in progress.

Dr. Solbert Permutt, a close friend of mine from Hopkins, came to visit Wells. By this time Wells had become frankly psychotic. For the first fifteen minutes he described with conviction and some anger the electric shocks that were being applied to his paralysed legs by some hidden enemy. We let this paranoid outburst run its course. Wells then became totally lucid, and we discussed the progress of the research exactly as in the past. The abrupt change was beyond belief. Permutt could scarcely trust the testimony of his own senses.

Cretyl Mills carried the work forward to its successful conclusion. When we sat down together to write up the findings, I was astounded at the details she had recorded. She not only kept records of the monthly tuberculin tests, as expected, but also ancillary data that now became important. She knew where in the exposure chamber every infected guinea pig was housed and where in the lungs every tubercle was located. She also kept detailed reports of the findings of the pathologist, Dr. Walenty Nyka, and of the drug-resistance patterns of the infecting organisms. From the latter, specific human sources could often be identified. And, of course, she found no infections in the control chamber receiving disinfected air.

At the time of the completion of the study in 1961, Cretyl Mills was still healthy and thriving on her largely independent responsibilities. She subsequently came down with TB and was put to bed in the very hospital where she had carried the torch for airborne infection. Wells died in 1963 after months of physical restraint. Thus ended the career of a truly "mad genius" who gave us the droplet nucleus hypothesis and changed our thinking about aerial transmission of infection. He never saw the final confirmation. To my eternal shame, his name was not included among the authors of the final paper.

John Barnwell's gamble paid off in spite of all the mischief along the way. I wish to mention three reasons. The VA facilities were well suited to the needs of the project, and VA personnel, gently nudged from above, were accommodating. The three primary investigators represented well defined areas of responsibility: intellectual leadership by Wells, reliable performance by Cretyl Mills, and administration by me. Finally, Wells, in his cranky way, gave us an ingredient that scientists seldom mention: a mission to convince unbelievers.

	Footnotes

Correspondence and requests for reprints should be addressed to Richard L. Riley, M.D., 32 Sunset Lane, Petersham, MA 01366.