State Patients Once Used as Guinea Pigs

By Peter Hardin, Times-Dispatch Washington Correspondent
Sunday, November 25, 2001 A1

WASHINGTON–In the last war that touched American soil, there was a biological killer and a federal investigation.

Attempting to isolate the sometimes deadly biological agent, federal scientists used patients at a Virginia asylum as their laboratory subjects.

The biological killer was an accident: A widespread vaccination of U.S. troops against yellow fever backfired awfully.

Tens of thousands of soldiers were sickened with hepatitis early in 1942. Scores died. The vaccine had been given in part to protect against a possible biological attack.

The human guinea pigs were patients at the Lynchburg State Colony, a mental retardation facility. They were powerless, voiceless and anonymous.

Scientists from the U.S. Public Health Service infected dozens of them with hepatitis as part of their research, according to a trail of documents, archival information and interviews pieced together by The Times-Dispatch.

For his work advancing medical knowledge of hepatitis, the lead federal researcher, Dr. John W. Oliphant, was acclaimed as a pioneer.

About the human “volunteers,” history has been silent.

Many of these patients at the former Virginia Colony for Epileptics and Feeble-Minded were labeled mentally defective. As part of a push for selective human breeding, Virginia carried out a majority of its 8,000 involuntary sterilizations of such people at the Colony during the 1900s.

In the Lynchburg study during World War II, medical investigators cooperating with the Army sought to pinpoint what had tainted the yellow fever vaccine. They inoculated teen-agers and adults with tainted vaccine batches and also with serum taken from people who had contracted the disease after vaccination.

At least 273 “volunteers” were inoculated. At least 37 of them – and perhaps 13 more – developed symptoms of what now is known as hepatitis B as a result.

Surviving records and histories strongly indicate that the Public Health Service research was carried out over three years at the facility, now called the Central Virginia Training Center. Comprehensive records about the Colony study, including names of the subjects, have been lost, destroyed or misplaced.

The Lynchburg experiment was spurred by forces and events in places as distant as Japan and New York City. Although the study was launched almost 60 years ago, parallels exist with the nation’s new struggle against terrorism, a biological attack and a debate over compromising human rights in wartime.

Army vaccination was made compulsory

A man carrying a diplomatic letter of introduction walked into a laboratory of the Rockefeller Institute in New York City on Feb. 23, 1939.

The institute lent space to the Rockefeller Foundation for the manufacture of yellow fever vaccine, using a live, but weakened, yellow fever virus.

Ryoichi Naito introduced himself as a faculty member at the Army Medical College in Tokyo, Japan. He asked for two strains of the yellow fever virus. He was refused.

Three days later, a Rockefeller technician was approached by a well-dressed stranger with “a trace of foreign accent” who offered first $1,000, then $3,000 for the highly infectious yellow fever virus, according to a report given to authorities.

The technician, sitting in his parked car on a New York street, repeatedly demurred. The stranger made an intimidating remark and grabbed the technician’s car key before fleeing in his own 1939 Buick.

These back-to-back incidents were among the first to raise U.S. suspicions about the Japanese trying to obtain the yellow fever virus.

Other intelligence included reports in early 1941 of two Japanese battalions trained in biological warfare.

By August 1941, Col. James S. Simmons of the Army Medical Corps wrote a memorandum about the suitability of yellow fever for “offensive military use.” He voiced concern that “the possibility of its use is recognized by the experts of certain foreign countries.”

In addition, the War Department was worried about sending troops to foreign lands where they might be exposed to yellow fever. It ordered vaccination early in 1941 of troops stationed in the Western Hemisphere’s tropics.

As the United States drew closer to war, these recommendations were broadened. Vaccination of the entire army was made compulsory in January 1942.

Soon an outbreak of a disease called “jaundice” hit U.S. troops with widespread impact. Thousands of soldiers were affected in the United States, in the Pacific, Alaska, Iceland and England. Military circles expressed alarm.

“It was incapacitating great sections of the Air Force, particularly at the time of the Battle of Midway,” retired Brig. Gen. Stanhope Bayne-Jones, a coordinator of the investigation, would recall later.

“It was a great worry. It was investigated in greatest secrecy, too.”
An epidemic was declared by March 1942. Medical detectives hunted the biological culprit, not knowing whether the disease was contagious or if it might actually be yellow fever. The patterns they found suggested a strong correlation between soldiers who had fallen sick and being vaccinated.

On April 15, the Army surgeon general ordered use of the vaccine discontinued. The military recalled supplies.

The suspect vaccine had been made by the International Health Division of the Rockefeller Foundation using human serum, the clear fluid portion of blood plasma that’s left after the clotting factors have been removed.

A vaccine without serum was substituted. The U.S. Public Health Service made large amounts of the replacement vaccine.

On July 24, Secretary of War Henry L. Stimson publicly announced the development of 28,585 cases of “jaundice.” He disclosed 62 deaths.

Even with the old vaccine shelved, the government sought to examine traits of the disease-causing agent and to determine how to prevent contamination of vaccines or important fluids, such as blood and plasma.

One outcome was this memorandum:
“Tentative outline for proposed yellow fever vaccine study at Lynchburg State Colony, Colony, Virginia.”

It was dated Aug. 4 and was written by three Public Health Service scientists. The Times-Dispatch located the document in the National Archives.

The team emphasized the need for a safe yellow fever vaccine. It lamented the “unexpected serious consequences” following recent vaccination of U.S. troops.

“It is clear that a prompt solution to the problem of the etiology [cause] of jaundice following vaccination against yellow fever is a matter of extreme national urgency,” the memo said.

Because of the problem’s national importance and because satisfactory laboratory animals were lacking for such studies, the scientists said, “it is deemed by us to be justifiable and necessary to use human beings as experimental subjects.”

The team laid out careful plans for testing and observing the Virginia patients. It called for weekly examinations until one of two things appeared: either symptoms of the disease or “some evidence of liver damage.” The memo gave no clue why patients at the Lynchburg Colony were chosen.

Joining Dr. John Oliphant, whose medical degree was from Indiana University, were Drs. Alexander G. Gilliam, a Petersburg native with his medical degree from the University of Virginia; and Carl L. Larson, a physician from the University of Minnesota.

The three scientists who drafted the memo reported to National Institute of Health. At that time it was the laboratory and epidemic-tracking arm of the Public Health Service.

There was a handwritten notation on the document.

“Approved,” wrote R.E. Dyer, NIH director.

Human serum taken for further research

The team just had investigated an outbreak of “jaundice” in the Virgin Islands. Thousands of people there had been given one of the same vaccine batches administered to U.S. troops.

From some Virgin Islanders who got the disease, investigators took samples of human serum to use in further research.

They shifted their research to an unnamed “institution with a population of about 1,700,” according to published studies. On June 30, 1942, the Lynchburg Colony had 1,649 patients.

By March 1944, a total of 273 subjects ranging in age from 13 to 57 had been inoculated, Oliphant reported in a medical journal. Of the 37 who developed “jaundice,” most cases suffered a mild form. At its most severe, hepatitis B can cause liver damage or death.

Anorexia, a lack of appetite for food, was usually present for those having the sickness, he wrote; before onset of the sickness there was often discomfort in the front of the stomach and nausea. In a few cases there was vomiting. Some people had a slight fever. No deaths were reported.

Among those infected were some “volunteers” inoculated with a batch of vaccine that had sickened soldiers and Virgin Islanders. This outcome provided important proof that the tainted vaccine could cause hepatitis.

Also sickened were some of the “volunteers” inoculated with serum taken from other people who had hepatitis. Scientists reasoned that the serum alone could cause the disease, which Oliphant at one point called “serum jaundice” and which later became known as “serum hepatitis.”

Oliphant also reported that the disease apparently wasn’t spread by human contact. And irradiating the serum apparently inactivated the sickness-causing agent.

The investigator kept the military closely informed of his findings. For his research he sometimes used hepatitis materials provided by the Army, according to correspondence at the National Archives that is now declassified. At least once, an Army officer screened an Oliphant report before its contents were published in a medical journal.

Oliphant’s research drew high praise.

“I think this is the most important contribution which has been made to knowledge of the nature of the agent causing this type of jaundice,” Col. Bayne-Jones wrote to Oliphant in August 1943, responding to an interim report.

Immunity of people who had developed “jaundice” after inoculation and recovered, and a method to irradiate human serum were topics of two later medical journal reports by Oliphant.

In these studies, groups totaling 99 people, 20 of whom had been infected before, were inoculated. Thirteen got “jaundice.” The articles, published in medical journals in December 1944 and April 1946, didn’t say where the studies were carried out.

But the site clearly appears to have been the Lynchburg Colony.

Themes of Oliphant’s formal articles were mirrored by an annual report of the Colony from 1944.

“Dr. John W. Oliphant and his two assistants were in charge of the [Public Health Service] research,” said the report, which was spotlighted by the Lynchburg News & Advance in a 1995 article. Archival research and interviews by The Times-Dispatch turned up additional information about the federal investigators’ proposal for the Lynchburg study and the role of possible biowarfare in the unfolding events – two issues with special timeliness after Sept. 11.

Evidence from the Lynchburg study pointed to a virus sometimes present in human blood as causing hepatitis that resulted from the yellow fever vaccine, the 1944 Colony report said. It mentioned findings on immunity and irradiation, and it described hopes for finding a way to make blood products safe from the virus.

One year later, in 1945, the annual Colony report stated, “The United States Public Health Service .*.*. finished its work here.”

Oliphant’s death a ‘staggering blow’

Oliphant, 50, died in January 1952 from accidental carbon monoxide poisoning at his home in Washington, D.C. He had just returned from an inspection trip to a federal penitentiary in Washington state.

A national authority on viruses, Oliphant had started an experimental study using prisoners at the penitentiary. He was head of a joint Department of Defense and Public Health Service project.

His death came as “a staggering blow,” the Public Health Service said.
A history of the Army’s Medical Department described Oliphant as “a pioneer in this country on transmission experiments in serum hepatitis.”

Vaccine given to troops was contaminated

With the passage of time, historians and researchers have shed light on the 1942 epidemic and on Japanese biological warfare.

Medical researchers determined that seven batches of the yellow fever vaccine given to troops at the start of World War II were contaminated with the hepatitis B virus.

Human serum for the vaccine had been taken from medical school volunteers. Several of them had a history of the disease, unknown to the vaccine’s maker.

Ultimately 50,000 soldiers were affected by epidemic, and 330,000 persons “may have been infected,” researchers wrote in the New England Journal of Medicine. Many of those who were infected may not have developed symptoms of the sickness.

One hundred soldiers died, according to a history of the Public Health Service published in 1951.

Meanwhile, Max Theiler of the Rockefeller Foundation Virus Laboratory won the Nobel Prize in medicine and physiology in 1950 for developing a successful yellow fever vaccine.

Japan’s use of biological weaponry in more than a decade preceding 1945 has come to the attention of historians.

Japan attacked China using germ weapons. Some scholars estimate that several hundred thousand people were killed. The death toll is debated.

The Japanese also killed thousands of prisoners. Gruesome experiments by the main biological warfare arm of the Japanese Imperial Army, Unit 731, included disease germs ranging from anthrax to yellow fever, according to historian Sheldon H. Harris.

More is known, too, about the Japanese doctor who requested the yellow fever virus at a New York laboratory in 1939.

Ryoichi Naito was a protege of Shiro Ishii, the foremost exponent of Japan’s biological and chemical warfare research, according to Harris, an emeritus history professor at California State University, Northridge. He wrote “Factories of Death,” a book about Japanese biological warfare.

After the United States launched its own program to build biological stockpiles, yellow fever was part of its arsenal.

Inmate experiments not unusual in that era

Now the United States is at war against terrorism. The nation has been battling a biological attack on the home front.

Today, it may seem shocking to think of government scientists giving “feeble-minded” patients a vaccine that they suspected of causing an epidemic and infecting the patients with disease. In that era, however, experimenting on inmates of institutions was not unusual.

It may be easier today to understand both the concern over enemy bioweapons on the eve of World War II and some military planners’ alarm over a vaccination of troops that went terribly awry.

The Lynchburg saga may lend itself to the intensifying debate over threats to human rights in wartime, when national security is under attack.

Victoria A. Harden, chief historian for the National Institutes of Health, believes the federal scientists who drew up the Lynchburg Colony study were aware of ethical issues.

“When you’re between a rock and a hard place, you’ve got to make a choice. Are you going to conduct human experiments, or are you going to live with the disease? It’s not an easy choice,” Harden said.

Rules for human experimentation have been made far more restrictive since World War II.

“We’ve seen a change in perception, about who we do experiments on; the rules have changed. The level of scrutiny has changed,” said Jonathan D.

Moreno, a University of Virginia bioethics professor and author of “Undue Risk: Secret State Experiments on Humans.”

He is a former member of President Clinton’s Committee on Human Radiation Experiments. It investigated the government’s decision during World War II to inject people with plutonium without their knowledge or consent.

One of the best-known experiments affecting modern attitudes was the Public Health Service-sponsored Tuskegee Syphilis Study, between 1932 and 1972.

Poor black men with syphilis were promised free therapy but were denied penicillin so investigators could study the way the disease progressed.
Another controversial study took place at the Willowbrook State School for the Retarded in Staten Island, New York.

Some children at the school – where many had contracted hepatitis already – were injected with a mild hepatitis serum, in research with echoes of Lynchburg. Ultimately the Willowbrook research played an important role in development of a vaccine for hepatitis B.

Paul A. Lombardo, a U.Va. professor of bioethics and of law, said the Lynchburg Colony patients could not have truly been volunteers for science.

“It would be the height of irony to say that people who were taken out of society because they were allegedly unable to make proper choices” were the same people “whom we endow with the privilege of volunteering their personal health for national good,” Lombardo said.

Colony patients would have been least likely to understand the risks they were taking and would have had difficulty dealing with sickness, he added.

Lombardo declined to label the Lynchburg episode as shameful, however.

“It’s probably less fruitful to try to come up with a word for how much we, in retrospect, disapprove of what happened in 1942, than it is to reflect on whether or not we would allow something like that to happen today,” Lombardo said. “I certainly hope not.”

Posted in My Work, Thu, 28/05/09