Dr. Solbert Permutt is a giant in the world of lung research, a gregarious, outspoken 76-year- old professor with the enthusiasm of a teen-ager, a flamboyant taste for large bow ties and a history of teaching generations of doctors at Johns Hopkins Medical School.
His friend, Dr. Alkis Togias, 43, is quiet and conservative, a scientist who doesn't mind dirtying his hands studying cockroaches as a possible cause of asthma in Baltimore's public housing.
"This is the kind of catastrophe - the nightmare scenario - that everybody fears will happen in human experimentation," said Jeffrey J. Fredberg, director of the physiology program at the Harvard School of Public Health. "The feeling among many of us is, 'There but for the grace of God go I.'"
The death June 2 of Ellen Roche, a 24-year-old Reisterstown resident, has sent shock waves through Hopkins and out among scientists across the nation. It was the first death of a volunteer in a medical experiment at Hopkins in more than a decade.
The death was especially devastating to the doctors, colleagues say, because Roche worked with them as a lab technician at the Asthma and Allergy Center at the Bayview campus.
Roche was enrolled in a federally funded study overseen by Permutt and Togias into how the lungs of asthmatics and healthy people work differently. After inhaling a chemical, Roche developed a dry cough and flulike symptoms. Her lungs failed during a nearly monthlong hospitalization.
Last week, the federal Food and Drug Administration released a preliminary report that faulted Togias, the principal investigator in the experiment, saying that he neglected to follow several safety requirements.
These included failing to obtain FDA approval for using an unapproved drug and failing to adequately warn his volunteers of the risks. The consent forms signed by Roche and nine others warned of dizziness and temporary coughing, but did not mention any risk of death or say that a chemical used in the experiment was no longer approved as a drug by the FDA.
Medical journals in the 1950s and 1960s linked the chemical, hexamethonium, to rare cases of fatal lung disease. However, more recent articles have reported that inhaling small amounts of the chemical in experiments has not caused problems.
Along with the FDA, the federal Office of Human Research Protection is investigating the death, the cause of which is not yet known.
Daniel A. Kracov, an attorney with the Washington law firm Patton Boggs, said it would be inappropriate for his clients to talk publicly while the death is under investigation.
"They are obviously extremely upset and concerned about the situation, and are concerned about the family of the patient - that has always been their top concern," Kracov said.
Many of their fellow scientists say the suggestions of improper conduct are puzzling because Permutt and Togias have led distinguished careers.
"Here are two very serious, very sensible doctors who have contributed a great deal to science - it is very difficult to understand, and very sad," said Dr. Thomas A. E. Platts-Mills, chief of the asthma division at the University of Virginia.
Permutt was inspired to become a researcher when he was 5 years old, according to a 1994 book, "The Pulmonary Circulation and Gas Exchange," to which Permutt contributed a chapter that is partly biographical.
Permutt's mother took him to see the 1932 movie "Arrowsmith," based on a novel by Sinclair Lewis. The lead character, Dr. Martin Arrowsmith, tests a serum to prevent the spread of bubonic plague in the West Indies. When his wife dies of the plague in a laboratory accident, Arrowsmith denounces experimentation on human subjects. But then his serum proves successful, and he continues his research.
"From the time I saw that movie, I dreamed of becoming a medical scientist like Arrowsmith," Permutt wrote in the 1984 book. "Although the work might be dangerous, it would also be adventurous, and I was willing to take the risks in the same way that a policeman or a fireman does."
As a young student, Permutt became intoxicated by the "beautiful and mysterious" mathematical symbols he saw in books, he wrote.