Fighting the Invisible: The Struggle to Eliminate Viral Hepatitis
Interviewer: Lauren Heywood Interviewee: Dr. Robert H. Purcell Instructor: Mr. Alex Haight February 17, 2009 Table of Contents
Interview Release Form.…………………………………………………………………………..2
Statement of Purpose……………………………………………………………………………...3
Biography…………………………………………………………………………………………4
Historical Contextualization: “A Race for the Cures”…………………………………………….6
Interview Transcription…………………………………………………………………………..23
Time Indexing Recording Log…………………………………………………………………...53
Interview Analysis……………………………………………………………………………….54
Appendix…………………………………………………………………………………………59
Works Consulted…………………………………………………………………………………65
Statement of Purpose
Far too often, the study of history is reserved for wars, battles, and economic upheavals, rather than the vital study of the history of scientific and medical research. The purpose of this
American Century Oral History project is to enlighten many to the struggles fought and victories won behind the doors of the laboratory, often far out of the public view, with the interview of Dr.
Robert Purcell, a main character in the fight against the elusive viral hepatitis. This project aims to impart a verbal illustration to those already aware of and involved in the process of scientific or medical research and to inspire those who are not. Dr. Purcell’s vivid description of the effort against this worldwide epidemic will hopefully provide detail to the frightening abstract of disease and research. Biography
Dr. Robert Harry Purcell was born on December 19, 1935, in Keokuk, Iowa. In his youth, he moved to Dallas, Texas, in 1936 and in 1944 to Haileyville, Oklahoma, where he attended high school. As a child, Dr. Purcell was fond of playing football and of nature.
Following an insufficient high school education, Dr. Purcell attended Eastern Oklahoma A&M
Jr. College, receiving an A.S. in Chemistry in 1955, and Oklahoma State University, where he graduated with a B.A. in Chemistry in 1957. In 1960, Dr. Purcell received his M.S. in
Biochemistry as a Student Fellow from Baylor University College of Medicine, and in 1962 he obtained his M.D. from Duke University School of Medicine, also as a Student Fellow. In 1963,
Dr. Purcell completed his internship in Pediatrics at Duke Hospital; he traveled to the CDC in
Atlanta, Georgia, for eight weeks of epidemiology training to become an Epidemic Intelligence Officer. Following those weeks of training, Dr. Purcell was transferred to Bethesda, Maryland, to work at the National Institute of Health (NIH) on vaccine efficacy trials; he has worked at the
NIH ever since. In 1974, Dr. Purcell was appointed to be the Head of the Hepatitis Viruses
Section and, in 2001, the Senior Investigator and Co-Chief of the Laboratory of Infectious
Diseases at the NIH. In addition, Dr. Purcell has been an elected member of the National
Academy of Sciences since May 1988, and a co-inventor of several of the Hepatitis A vaccines.
He is a co-inventor of 47 patents and co-author of six books. Dr. Purcell currently lives in
Bethesda, Maryland, and has two sons. Historical Contextualization: A Race for the Cures
Historian David McCullough, in speaking of the influenza epidemic of 1918, spoke also of the tragedy of all epidemics, saying, “It would be as if today, with our present population, more than 1.4 million people were to die in a sudden outbreak for which there was no explanation and no known cure…Could it happen again? Yes, indeed” (McCullough 7-8).
There is very little more terrifying than hundreds of people dying of one devastating disease all around without knowledge of the origin or the remedy. Throughout the world, epidemics take the lives of more and more people, and even animals, in just this way as scientists struggle to find the causes, preventions, and cures for the diseases at hand. The process of discovery and research is long and arduous, but the result, if successful, is irreplaceable. The terror of polio, smallpox, influenza, and countless other epidemics and pandemics was largely due to the mystery and widespread death surrounding them. Thus, to discover a vaccine is to give security to those without the disease, and even hope of a cure to those already infected. Hepatitis is among these epidemics of history, and remained a threat to many lives, even as polio and smallpox were neutralized. Therefore, in order to understand the perspective of someone who participated in hepatitis research, it is important to first examine earlier epidemics, the history of hepatitis throughout the world, and the struggles of hepatitis research in its very early stages.
Dr. Rob DeSalle defined an epidemic as, “any disease, injury, or health-related event” that precipitously strikes more than the average number of people in a certain area (DeSalle 153).
An epidemic may be confined to the country where it emerged, or it may pass through the surrounding countries as well. If a disease becomes a worldwide epidemic, it is classified as a pandemic. If it is confined to the very small region of its origin, it is considered endemic.
Throughout epidemics, the source of movement is usually other humans, animals, or parasites, such as fleas. Wars, increased traveling, trade, urbanization, and climate changes can cause or exacerbate an epidemic or pandemic (DeSalle 153). Epidemiology, or the study of a population’s health and diseases, was important to the discovery and eradication of many of these epidemics. The first documented epidemiology followed the 1832 cholera epidemic in
London, England (Friedlander 15). In 1848, Dr. John Snow traced the epidemic to the polluted water of the Thames River. In addition, after the 1854 relapse, he traveled among the citizens of the city, keeping research records that earned him his title, Father of Epidemiology (Friedlander
16-18). Throughout history, men like Dr. Snow helped to discover the source of epidemics around the world, leading to safer living conditions and a higher awareness of disease.
However, epidemics ravaged civilizations long before the study of epidemiology began.
One ancient epidemic was the historic “Black Death,” also known as the Bubonic Plague, of the fourteenth century (Giblin 11). The first outbreak, recorded between 541 and 544 AD, killed 40 million people (Ryan 120). However, it recurred in the fourteenth century, around the Black
Sea. The plague was especially devastating in its mysterious nature; few could even speculate on how one contracted the disease. At first, victims endured rather indistinct symptoms; fatigued and plagued by headaches, they could barely walk. However, after the lymph nodes in the groin expanded to the size of eggs and victims’ blood pressure began to escalate, their nervous systems failed, resulting in a painful death, by the fifth day in most cases (Giblin 11-12). This terrifyingly swift demise threw societies into an uproar. With increased travel to escape and excitement about the disease, it turned into a pneumonic plague, easily contagious by coughing
(Ryan 122). Agnolo di Tura, of Siena, Italy, wrote of the mass burials and shocking disrespect for the dead at the time, saying, “This is the end of the world” (Giblin 20).
Various societies channeled their terror in several ways in response to the epidemic. In the areas surrounding the Black Sea, the native Muslims claimed that the Christian Italian traders in the area were responsible for the numerous deaths, forcing the Italians to flee for their lives
(Giblin 12). Some believed that the disease was due to earthquakes, the Devil, or even a climatic change. Historian Giovanni Boaccaccio wondered in his book, The Decameron, if the plague could be from God’s anger (Giblin 16-18). Many devoutly religious people took to this approach, praying and fasting in hopes of ending the terrible plague, and often casting out misfits and outsiders, as the natives did in the regions around the Black Sea. In Germany, the
Flagellants1, after the Catholic Church outlawed their practices, blamed the Jews for the plague, establishing the first holocaust in 1348 (Giblin 37). Many believed that eradication of the Jews from society would bring relief in the plague’s death toll, and the Flagellants took advantage of this suspicion and fear in pursuit of their former respected reputation.
Almost as dangerous, physicians of the time knew very little, often harming rather than helping their suffering patients. As a result, many turned to prayer, and to Saint Roch, saint of the plague, who had died in 1327 after a life spent patiently nursing those thus afflicted (Giblin
28). The various reactions to the Bubonic Plague in the fourteenth century increased the fear that accompanied the disease, sending people into frenzy and, with increased travel, spread the disease throughout Europe.
In reality, black rats and their fleas spread the Bubonic Plague of the fourteenth century with devastating efficiency on trading vessels. Its origins were of Southeast Asia, and increased trade and travel exacerbated the epidemic (Ryan 4). As more and more residents fled from the
Black Sea region, the plague spread to Italy, France, Great Britain, and Germany. Aggravating
1 Flagellants were a group of German Christians who whipped themselves and roved through towns, hoping for God’s forgiveness of their sins. The flagellants commanded much respect from the religious people of the century until they challenged the Church’s power in their declaration that they, not the Church’s ministers, were God’s chosen envoys on earth. In 1349, Pope Clement denounced them and asked officials to outlaw them all over Europe (Giblin33-35). the situation, this increased travel and trade were only one factor of the period of social and environmental upheaval (Ryan 357). The plague affected port cities in particular; in Venice,
Italy, the government enacted the first quarantine on a ship infected with the disease. Although unsuccessful, the terrified inhabitants finally began to take a rational approach to ending the devastating pandemic (Giblin 17).
By 1351, about 23,840,000 people had died in Europe of the Black Death, or almost 32% of the current population. However, this was not the end; about every ten years in the fourteenth century it returned, with a death toll of 50% of the population at its conclusion (Giblin 39-40).
Today, the plague still recurs, but it can be held in check by modern antibiotics, if quickly recognized (Grady 43). The families of the many victims of the Bubonic Plague could never forget the misery and consternation of what became a cataclysmic pandemic. Even those who did not get the disease lived in constant fear for themselves and for their families. However, the terror of the Black Death gently receded into myth as modern epidemics took the public’s attention.
One such modern disease, poliomyelitis, was commonly known as simply polio or infantile paralysis and bore alarm akin to that of the Black Death in its mystery and swiftly catastrophic symptoms. The American media of the 1940s and 1950s created much of the terror with extreme exaggeration of the new epidemic. In addition, the National Foundation for
Infantile Paralysis turned polio into an amplified, menacing disease, but one with a potential for a cure. Through furious campaigning for resources and scientists, the foundation generated, in historian David Oshinsky’s words, a “new model for giving in modern America, the concept of philanthropy as consumerism” (Oshinsky 5). However, the truly frightening factor of polio for the people of the United States was its attack on the defenseless young children of America. Polio is a virus, spread by exposure to fecal waste, that assaults and distends the spinal cord’s grey nerve tissue. In the worst cases, it causes partial or complete paralysis (Grady 56-
57). Victims of polio suffer headaches, nausea, or nothing at all, and only in one percent of the cases does it conquer the central nervous system and lead to paralysis. Victims rarely die unless theirs is the bulbar polio, when the lungs are paralyzed and the victim is unable to breathe at all
(Oshinsky 8-9). This virus went through three stages in America before losing its publicity of fear: endemic, epidemic, and post-vaccine. After the vaccine passed through its exhilarating climax, the vast majority in America considered the polio issue to be solved and therefore inconsequential.
The path to the vaccine was paved with the new idea of American consumerist philanthropy. With the National Foundation for Infantile Paralysis funding research, scientists discovered more and more about the feared virus, including the antibodies for each of three separate types of polio and the troubling fact that immunity to one does not provide immunity to all (Oshinsky 9). As for the vaccine itself, the Foundation financed a veritable competition for the honor of a polio vaccine. In the end, the three contestants were Albert Sabin, Jonas Salk, and
Hillary Koprowski, and the feud was fierce. In 1952, Jonas Salk of the University of Pittsburgh patented the first vaccine: a killed-virus2 version to yield the polio antibodies without any danger of a true infection. He tested his theory in the Salk Vaccine Field Trials of 1954, with two million elementary school children throughout the United States, covered closely by the media.
For this, he received the Congressional Gold Medal in 1955 and the Presidential Medal of
Freedom in 1957 (Oshinsky 6-7). Right behind him in 1957, Albert B. Sabin produced the
2 A “killed virus vaccine” is a vaccine without a living virus, but one that supposedly produces the desired antibodies. Some scientists argue over the efficacy of this, insisting that while it lacks the danger of a true infection, it may fail to produce a truly strong immunity to the virus that could wipe out a disease over time. These experts prefer the live-virus vaccine with more natural effects, despite the slight danger of infection (Oshinsky 6). favored method: a live-virus vaccine to provide a weak, natural virus creating immunity without the full disease. He successfully commandeered testing in the USSR, as most children in the
United States already had Salk’s vaccine (Ryan 7). The two men, intensely competitive, lived with the feud for years, as scientists still dispute the benefits of both vaccines.
The American media coverage of the race for the polio vaccine was unusually large for a science experiment in the 1950s. While it lost that coverage after the success of the Salk and
Sabin vaccines, the fight against polio remains in several regions of the world, especially in Asia and Africa. In 1987, the World Health Organization initiated a campaign to end the crippling spread of polio around the world with the approval of the United Nations. In addition, the organization declared an attempt to turn the world in favor of Salk’s killed-virus vaccine, in hopes of entirely eradicating the polio virus (Oshinsky 287-288). Polio was no longer a large problem for the United States, and it grew faint in the domain of faraway and less fortunate countries.
However, as scientists discovered and struggled to eliminate poliomyelitis, the world faced a new threat in the form of hepatitis, also known as yellow jaundice3 (Anchord viii).
Newly discovered, hepatitis is a virus-induced inflammation of the liver. Liver complications accompany this virus, such as liver failure and liver cancer. With fear thick in the air, scientists studied the new peril diligently, as technology slowly developed to aid them. Soon, they discovered that the new danger was not in the form of a single, simple virus, but in several different viruses.
First known as catarrhal jaundice, hepatitis confused and befuddled scientists through its many different strains and treatments. Men first wrote down cases of jaundice and various other
3 Jaundice is a common symptom of most types of hepatitis; it is a yellowing of the eyes and skin, indicating liver disorders. symptoms of hepatitis in 2000 BC (Gallagher 28). Later on, around 400 BC, Hippocrates also wrote about the symptoms of hepatitis. In addition, mentions to such a disease arose in the
Talmud and primeval Chinese medical records. Even in those ancient times, physicians struggled to identify and treat epidemics like hepatitis, using scanty knowledge in pursuit of a dangerous disease. From the time of the seventeenth century until the twentieth century, many people called hepatitis the “campaign disease.” The epidemic, quickly turning pandemic, raged in Napoleon’s Egyptian campaign, the U.S. Civil War, Great Britain’s World War I operation in
Mesopotamia, World War II, Korea, Vietnam, and various civilian populations (Anchord vii).
The disease directly resulted from the travel and trade involved in the various wars of these centuries, and it devastated the efforts of these armies and the civilizations they encountered.
The epidemics occurred cyclically, once every ten to fifteen years (Berkman 6). These recurrences discouraged the people of these regions, as the disease itself could often precipitate chronic complications of the liver, and before there was much knowledge of the disease, few could know how to prevent or cure it.
In 1912, Dr. L. Cockayne suggested the name infective hepatitis as a substitute for the earlier common name of catarrhal jaundice. In 1937, Findlay and MacCallum distorted the new term as they reported the first case of acute hepatitis in England amid the receivers of the yellow fever vaccine, calling it common infective hepatic jaundice and clinging to the association between hepatitis and jaundice. Finally, in 1943, scientists reaffirmed infectious hepatitis as the appropriate term. In establishing the official name of the disease, scientists identified hepatitis as a devastating disease throughout the world, and declared their own variety of war upon it, intent upon bringing its terrible consequences to an end. In his paper in the 1993 edition of the magazine Gastroenterology on “The Discovery of the Hepatitis Viruses,” Dr. Robert H. Purcell declared that the “Silver Age” of hepatitis research occurred from 1943 to 1963, especially as
World War II and its effects took their toll on the world and as scientists focused their attention on the spreading disease (Purcell 955).
In 1947, MacCallum introduced the difference between Hepatitis A and Hepatitis B. He identified Hepatitis A Virus (HAV) as infectious hepatitis, and Hepatitis B Virus (HBV) as hepatitis linked to injections of serum, blood, or plasma. In World War II, various vaccines were devised in pooled human serum, making many recipients prone to hepatitis and other transfusion-related diseases. Scientists increasingly struggled to discover the causes and treatments for both forms of hepatitis as soldiers and civilians alike fell to disease as well as to war. With the increased attention to this devastating problem, Saul Krugman, while experimenting on mentally retarded children in Willowbrook State School in New York, confirmed the existence of the two different kinds of hepatitis and a lack of heterologous immunity4 (Purcell 955). In addition, he found that HBV could be killed with heat but still produce immunity when the dead virus was given to patients. While the testing encountered opposition for moral issues in choice of test subjects, it led to the affirmation of MacCallum’s ideas and to the discovery of a vaccine for HBV (Purcell 956).
Hepatitis A, or infectious hepatitis, can be spread by oral exposure to infected human fecal waste and, occasionally, by infected blood. It frequently occurs in families and among sexual partners (Berkman 4-5). Fortunately, most infected people do not experience symptoms, and are not diagnosed with hepatitis (Anchord 34). However, because of this, these unsuspecting carriers can inadvertently infect others, and only a specific blood test shows the resultant antibodies to the virus. Up to one month may pass before a patient encounters the average
4A lack of heterologous immunity occurs when immunity to one strain of a virus fails to cause immunity to the other. symptoms, if ever. As with many diseases, the elderly and weak often deteriorate more quickly than the young and strong in the face of symptoms such as fever, decreased appetite, nausea, stomachaches, and jaundice for two to six months (Berkman 5). These symptoms, though uncomfortable and damaging to health, were reassuring; if one contracted HAV, it would not lead to chronic hepatitis, as HAV can only instigate an acute infection. However, other types of hepatitis do not run their course so quickly.
Hepatitis B, or serum hepatitis, has both an acute and a chronic guise. Not all victims have symptoms, and most will recover with a protecting immunity against further HVB assaults.
However, the chronic infection strikes about a tenth of those afflicted and these patients die by the thousands each year from the liver disease and liver cancer complications that accompany
HBV. Often young adults contract HBV, usually between the ages of 20 and 39 (Berkman 7).
However, many mothers pass the disease to their children in childbirth, resulting in a life of HBV for the infected child. The symptoms of HBV, other than the results of liver disease and cancer, are very similar to those of HAV; in addition, the virus can be detected using a blood test
(Berkman 8). The disease is quite distressing to its victims if they show symptoms, and the chronic strain is devastating. Consequently, since its discovery, scientists have made an HBV vaccine a top priority.
Hepatitis C, almost always chronic, was identified in 1989 as a health risk, following a year of 230,000 new cases (Anchord viii). HCV spreads to others through infected blood only; the casual passer-by is not at risk. The symptoms are primarily jaundice, but the troubling complications of HCV come later in life, with the chronic phase (Berkman 10-11). HCV is a primary cause of cirrhosis5 and hepatocellular carcinoma6. In 1991, blood tests became available
5 Cirrhosis is a case of widespread nodules, or irregular spherical groups of cells, in the victim’s liver, and fibrosis, or buildup of scar tissue, often caused by hepatitis (Worman 39). 6 Hepatocellular carcinoma is a liver cancer and the number two cause of cancer death throughout the world in clinics for HCV, a vast improvement for those who feared the disease. Though most of those infected die with HCV, it does not normally precipitate death (Anchord 65-66). This ruinous disease has been a major health issue in blood transfusions throughout the twentieth century; in
1996 there were 36,000 new cases (Anchord viii). Crippling liver disorders that accompany this disease have driven scientists to search for a vaccine and a universal treatment.
Hepatitis D is very uncommon in the United States, but it has precipitated epidemics in the Amazon basin, Africa, and around the Mediterranean Sea (Anchord 82). It can only be contracted if the patient has HBV, and there is a large risk of chronic hepatitis and acute liver failure in HDV patients (Anchord 83). HDV’s symptoms and transference are identical to those for HBV. However, there is a much larger risk for chronic liver diseases in a patient with HDV; seventy to eighty percent of HDV victims get chronic liver disease, in contrast to the mere fifteen to thirty percent of those with HBV. In addition, while prevention of HDV is possible before the transaction of HBV, afterwards, it is impossible (Berkman 12-13). Thus, while HDV is devastating to those who have already suffered through HBV, there was a hopeful message upon its discovery; if scientists eradicate HBV, they simultaneously destroy HDV.
Hepatitis E, not yet reported in the United States, is a potential threat to the country due to a recent epidemic in Mexico. HEV was first recognized in the 1955-1956 epidemic in Delhi,
India, where it was transmitted through oral contact with infected feces, as in HAV epidemics
(Anchord 83). Scientists Doris Wong, Mohammed Sultan Khuroo, and Mikhail Balayan announced the epidemic and its characteristics in India (Purcell 959). Its symptoms include gastric pains, fever, nausea, retching, and jaundice, with no treatment or vaccines available
(Berkman 15). Scientists suspected animal carriers harbored the disease between each endemic.
While quite uncomfortable, scientists have not found a chronic HEV strain, causing a less fearful
(Worman 205). potential for epidemic.
Hepatitis F, hepatitis G, and transfusion transmitted virus (TTV) have been subjects of interest for scientists, but very little is known about them. They are not prevalent in the United
States, and certainly not as devastating to the world’s populations as are other hepatitis viruses.
Hepatitis F, though naturally the next subject for discussion, was misidentified at its discovery, and is not considered to be a type of hepatitis anymore. In regard to hepatitis G, scientists, according to Dr. James L. Anchord, “do not test for this inconsequential virus,” as it results in no observable damage to the body. HGV is transmitted through blood transfusions (Anchord 83).
It can arise with HCV and rarely causes a chronic disease. Though the most recently discovered form of hepatitis, HGV is not a common subject for vaccine research due to its absence as a medical threat (Berkman 16). TTV is another form of hepatitis that is not considered a danger to society; it causes no discernible damage to its victims (Anchord 83). Scientists have identified
HGV and TTV in order to monitor their progress in society, but they have spent their time and energy in treating more harmful types of hepatitis.
This Silver Age of hepatitis research came at a time of extremely simple scientific methods, when compared with those of the more recent “Golden Age” of the 1990s. Dr. William
C. DeVries, in an oral history interview with St. Andrew’s Episcopal School student Emily
Fiuzat, remarked upon the time as one of very basic scientific technology. Dr. DeVries, a member of the first heart-transplant team, declared, “…if you got sick at that time, you go to your doctor and he put a stethoscope on your chest and listened to your heart and then he would order a chest x-ray…and so we were very, very elemental at that time” (DeVries 26). The simplicity of the technology at that time certainly limited the doctors’ approach to treating hepatitis; there was very little they could do, especially in a time with very little knowledge of the disease. Thus, scientists of the Golden Age of hepatitis research were essential in the effort against hepatitis.
At the time of Blumberg’s experiments and hepatitis discoveries, the media, especially newspapers, brought hepatitis cases to the public’s attention. A Washington Post, Times article about the environment in 1965 identified hepatitis as one of the threats induced by water pollution (AP “White House”). At this time, more and more people were becoming concerned about the health risks of industry and mechanical transportation. This topic of hepatitis- contaminated drinking water also appeared in the same year in the New York Times (Hill 30). In addition to these concerns, in a 1965 edition of the New York Times, Dr. Luther L. Terry,
Surgeon General of the United States at that time, announced goals to eliminate certain devastating diseases, including hepatitis; he hoped to find “new weapons to curb” these diseases in the following twenty years (AP “Terry”). Finally, in a 1984 edition of the New York Times,
Laurence Altman declared hepatitis a “widespread threat” in the United States as the epidemic took hold of American society and several kinds of hepatitis were identified (Altman C1). These reactions demonstrated the United States’ attempt to identify and conquer the disease-related problems of the time.
Hepatitis research reached its Golden Age, an appellation by Dr. Robert Purcell, in 1964, following Saul Krugman’s experiment for HAV and HBV (Purcell 957). In 1964, Baruch
Blumberg stumbled upon the Australia antigen7 as he studied serum proteins (Berkman 43).
Harvey Alter, working at NIH at the time, described the discovery as a “monument to non- directed medical research and as a tribute to investigative perseverance” (Purcell 957). Many scientists of the time encouraged undirected research, scorning those who let others determine
7 The Australia Antigen, or Au antigen, is present only with HBV, and is a key to diagnosing HBV; Dr. Baruch Blumberg was the first to use it in 1966 (Everson 11). the path of their work. The Australia antigen, Blumberg found, had an association with viral hepatitis. Kazuo Okochi of Tokyo, Japan, as well as Alfred Prince, David Gocke, and Paul
Holland in a separate study, recognized that the Australia antigen was a key to diagnosing, and therefore preventing, hepatitis B. The Australia antigen was named the hepatitis B surface antigen, or HBsAg, and scientists diligently worked to find an HBV vaccine (Purcell 957).
In the early 1970s, scientists James Maynard and Dr. Robert H. Purcell successfully transferred the hepatitis B virus to chimpanzees, taking themselves one step further in the research process (Purcell 956). Transfusion-related HBV was a large issue at that time, and the risk was very great that a large percentage of recipients of blood transfusions would also receive
HBV in their blood transfusions. The fear that surrounded this topic made it essential for the scientists, including Dr. Robert Purcell, Robert Chanock, Paul Holland, and Harvey Alter, to use the HBsAg to test blood donors for HBV. As a result, from 1970 to 1972, the American blood banks extended HBV testing to counter the trepidation that accompanied this risk. In addition, the industry removed business blood donors, which Dr. Robert Purcell believes may have helped more blood recipients (Purcell 957).
Finally, as a result of extensive research, John Gerin, Maurice Hilleman’s colleagues, and
Baruch Blumberg’s colleagues invented the first HBV vaccine in 1981. Wolf Szmuness and
Cladd Stevens conducted the experimental trials in homosexual men in New York City, finding the vaccine a success. Dr. Robert Purcell described the testing as “a classic in its planning and execution,” to be imitated if possible for its efficiency and success (Purcell 962). Scientists replaced this plasma-derived vaccine with the first recombinant vaccine8 in the world (Purcell
962). The recombinant vaccine, created with recombinant technology from William Rutter of
8 Scientists now prefer the recombinant vaccine, as it does not have a risk of blood tainted with other diseases (Gallagher 36). the University of California in 1977, allowed scientists to produce the vaccine in large amounts without any risk (Gallagher 36). This chapter of Hepatitis B research provided a relief from the fear and mystery surrounding the virus. Now, children in the United States are vaccinated at a very young age, lowering the risk significantly. In addition, with the HBV vaccine, the risks of
HDV were lowered; fewer cases of HBV produced a lower potential for HDV.
Shortly after the discovery of the Australia antigen and the beginning of intensive HBV research, Friedrich Deinhardt successfully transmitted viral hepatitis to marmoset monkeys. This accomplishment in 1967 allowed scientists to proceed with experiments and tests on non-human patients (Purcell 956). In 1973, scientist Stephen Feinstone of the NIH used Albert Kapikian’s electron microscopy9 to find viral hepatitis in feces; he named it the hepatitis A virus, or HAV
(Anchord 35). Research finally commenced after several false starts; Thomas Chalmers of the
NIH reportedly remarked, “Well, I see that the hepatitis A virus has been identified…again”
(Purcell 957). In 1975, Jules Deinstag and James Maynard transferred the HAV to chimpanzees for further testing, demonstrating the developments of modern science (Purcell 956). Scientists were able to use different animals, similar to humans, in their pursuit of a vaccine and various treatments for the hepatitis A virus.
The last large hepatitis epidemic struck the world in 1989, but there have been many cases since. The absence of a severe epidemic did not signify the end of the disease. Officials estimated about 125,000 new reports of HAV each year following 1989 (Berkman 6). Following the 1989 epidemic, Philip Provost, Maurice Hilleman, and William Miller initiated serological10 procedures and the isolation of HAV; their work was vital to the progress of vaccine
9 Albert Kapikian learned immune electron microscopy with June Almeida of the Royal Postgraduate Medical School in London. He used it to find the Norwalk agent (the most common cause of epidemic diarrhea in adults), and taught Stephen Feinstone of the NIH (Purcell 958). 10 Serology is the study of blood serum in response to introduced substances in regard to the immune system. development (Purcell 958). As with the polio vaccines, the first HAV vaccines, although only available in Europe by 1993, were killed-virus vaccines; scientists such as Dr. Robert Purcell believed that live-virus vaccines would succeed them (Purcell 962). Maurice Hilleman finally developed the first HAV vaccine in 1996, to be followed by several others (Gallagher 29).
Hepatitis C, hepatitis D, and hepatitis E all had minimal development in the “Golden
Age” of hepatitis research. In 1978, Harvey Alter, Edward Tabor, Blaine Hollinger, and Alfred
Prince transferred HCV to chimpanzees (Purcell 956). In the mid-1970s, Mario Rizzetto of
Turin, Italy, used immunofluorescence microscopy to find the HDV antigen in patients with
HBV (Purcell 958). In 1980, scientists transmitted HDV to chimpanzees, allowing for supplementary research, including the discovery that HDV is the only transmissible virus in the animal kingdom (Purcell 959). In addition, Mikhail Balayon transferred HEV to cynomolgus monkeys in 1983 (Gallagher 39). These animal virus transfers are the potential for the discovery of HCV, HDV, and HEV vaccines, just as similar transmissions helped produce the HAV and
HBV vaccines.
Scientists invented several treatments for patients with hepatitis. Most treatments are in the form of an interferon, or a protein that works to bolster the efforts of the immune system.
Harry Greenberg discovered the efficacy of leukocyte interferon, an antiviral agent, in 1976 for use in therapy for hepatitis patients. Scientists at the NIH used an interferon inducer in chimpanzees, and Jay Hoofnagle initiated recombinant interferons in the same year. Referring to the interferon treatment for hepatitis, Dr. Robert H. Purcell of the NIH declared, “Only a proportion of [hepatitis] patients respond favorably, and there remains a need for more universally applicable, less expensive therapies for these chronic diseases” (Purcell 962).
This research on hepatitis and its epidemics prompted debates about safety in public food. Government regulation was a topic of debate for many who feared a hepatitis epidemic. On
November 19, 1997, Caroline Smith DeWaal remarked to the National Press Club that the need for regulation was great; diseases such as hepatitis A were found in school lunches, producing a
HAV endemic in a Michigan school district. Thus, the discussions on hepatitis prevention even prompted hopes for a better federal regulation of food in the U.S. (DeWaal 150-154).
The study of epidemics such as the Black Death, poliomyelitis, and hepatitis was very simple in those times of panic. Many people recorded history in the form of songs; these songs outlasted the original epidemics and told of the lack of knowledge and of the prevalence of the disease in daily lives. The popular rhyme, “ring-a-ring o’ roses” was simply a reference to the sickness and eventual death from the Bubonic Plague of the fourteenth century (Ryan 121).
Others, such as historian Giovanni Boaccaccio described the rumors of causes of the Black
Death, giving each as truth, as nothing could be known for certain (Giblin 18). Angolo di Tura, also of the fourteenth century, insisted that the end of the world was near (Giblin 20). The very names of the epidemics, such as the ominous “Black Death” or the inaccurate “infantile paralysis” and “yellow jaundice” tell of the wish to identify and destroy the terrifying diseases in the face of dramatized emergencies. In addition, scientists of the twentieth century, such as Dr.
Robert Purcell, told of the uncertainty that marked the period of study, as in the misidentifications of HAV. Modern historians, including David Oshinsky, isolated cultural changes, like the new consumerism through philanthropy (Oshinsky 5). Assigning epidemics to
God’s wrath or other spiritual problems was common in the Middle Ages, but in more modern times, historians turned the blame to the common modern troubles of pollution or industry.
Throughout these histories, uncertainty was prevalent; there was very little knowledge or science to aid victims or doctors. However, few hesitated to expand upon the fear and mystery surrounding their topics.
In all of the research of various plagues, and especially of the hepatitis epidemic, the common goal was to end the fear and suffering of the victims of each disease. Scientists struggled to find three vital factors of each disease: the cause, the cure, and prevention. These three are of the past, present, and future, and the scientists work with each to eradicate the epidemics that plague humanity. In order to defeat the epidemics of today, scientists must look to the past, to find the evidence of the disease in the past and the solutions of other epidemics.
Therefore, the epidemiology of the Black Death, polio, and hepatitis will lead to a safer world for the future, without the fear and mystery of the epidemics of today. These diseases are not entirely eradicated in the world today. The fight continues between science and infection. Interview Transcription
Interviewee/Narrator: Dr. Robert H. Purcell Interviewer: Lauren Heywood Location: Dr. Purcell’s office at the National Institute of Health, Bethesda, MD Date: December 23, 2008
Lauren Heywood: This is Lauren Heywood, and I am interviewing Dr. Robert Purcell as part of the American Century Oral History Project. The interview took place on December 23rd, 2008 at
NIH. Can you describe your family as you were growing up?
Robert Purcell: Yes. I was one of three children; I was the middle of three children. My parents were both schoolteachers. I was born in Iowa, and my family moved to Dallas, Texas, when I was six months old, so I am barely an Iowan. My father actually was a coach and science teacher in Iowa, and my mother was a housewife at the time. Later in life, she took up teaching, and she taught English, in fact she taught me English in high school. My father taught at a different school, so I didn’t have him in any classes. After living in Dallas until I was nine years old, my family then moved to rural Oklahoma, and that’s where I spent the rest of my time until I finished college.
LH: How did you spend your free time when you were a child?
RP: Doing all the things that children do, particularly in rural Oklahoma: playing football in the front yard, or going on hikes, walking, seeing things. I spent a lot of time outside; I like nature, a lot. Those were the main things I did.
LH: When did you first hear about hepatitis? Can you remember your first…? RP: Let me just go back and – take things kind of in perspective and in chronological order. I first became interested in science when my older brother was in science courses at college, came home for one of his visits and just showed me some simple chemistry experiments that I found absolutely exciting things, just simple things, like change of physical state of matter, and that was the first, I think. He also brought home a copy, an old copy, of Scientific American. I don’t know if you’ve ever seen that magazine, Scientific American.
LH: (shakes head)
RP: It’s sort of a science for the layperson, and it describes new scientific discoveries and trends and such, and ways that people can understand it, people who are not scientifically trained, and I found that absolutely amazing, so that was my first recognition that, gee, I really liked science; I hadn’t thought about it before that. And then when I went to a local junior college that was really only about 18 miles from where I lived in rural Oklahoma, and I had the great blessing of having a very good science teacher because the high school I went to was really, really mediocre in terms of most things, but particularly in science. It really did not have good science or math: no physics, no chemistry, no foreign language, and so I had a lot of catching up to do, and at junior college I had a chance to do that. My chemistry professor, he was of Mexican descent, and he was just one of those people who lights a fire under students, and so, it actually was the reason I majored in chemistry, it was because of him. After junior college I went to Oklahoma
State University; I took my last two years there, and continued my major, and I had people who sort of changed my life there also. Another person in the junior college had looked at my records and knew that I was doing well, and asked if I’d ever considered medicine as a career, and I never had considered that before, so I thought about that, and eventually decided. I went to a big decision over whether to get a Ph.D. or an M.D. degree in graduate school, and I decided for an
M.D. degree, and so I took pre-med courses, many of which were scientific courses also, and then I started medical school at Baylor College of Medicine in Houston, which I liked a lot, and then I was influenced there by another person who was my – I got involved in a masters program in biochemistry – this was before they had M.D.-Ph.D. combined programs, which they now have in many medical schools, so this was sort of a first attempt to get more scientific training to physicians, and I liked that a lot. Then I ended up transferring to Duke Medical School, where I finished my medical career, but I have a biochemistry masters degree from Baylor, so that sort of mixed up things.
LH: Why did you transfer to Duke?
RP: Actually, it was because of an affair of the heart. The person I had a relationship with was in North Carolina, Durham, North Carolina, and I was in Houston, and so that’s the main reason
I went.
LH: Another St. Andrew’s student interviewed Dr. William C. DeVries of the artificial heart transplant, and he discussed the primitive nature of medical technology in the 1960s. Was there any overlap in the difficulties that you and he ran into?
RP: Yes. We’ve learned an enormous amount, actually before the 1960s, and an enormous, enormous amount since the 1960s. The 1960s, really beginning in the 1950s, was when, in virology, you could begin to use cell cultures to isolate viruses. Before that, you could really only work with viruses generally in animals, where you could tell that they were infected by the disease, and eventually by the fact that they made antibody to a particular agent, but with the ability to grow cells in flasks and culture…it was possible then to look for more viruses, and it was a huge bunch of viruses that were discovered over that period of time…1950s, 1960s. The person who was the lab chief when I first came here found many, many of these viruses; he was just at the right time in the right place, and so, some of the viruses that are still worked on in this laboratory were ones that he discovered at that time. At that time, also, in the 1960s, it was interesting you mentioned heart technology. I first really thought about, it wasn’t the first time I heard about hepatitis, but the first time I thought about it much was in the early 1960s when Bob
Chanok, who was the lab chief here at the time, wanted to expand the studies that were going on in this laboratory, Laboratory of Infectious Diseases, and one of the things he wanted to study was viral hepatitis, and so I often tell the story. I was the newest person here; I was here as an epidemic intelligence officer from the CDC assigned here. So he (laughs), I just remember, he went down the hall, trying to find somebody to convince them to work on viral hepatitis, and they all had other projects they were working on; I could hear (laughs) I could hear him coming down – each person telling him, no, I’m too busy, I have other things to do. I was the last person in line, and the little person on the totem pole, so I agreed to work on it, so we set up a study of viral hepatitis in people who were undergoing heart surgery here at the NIH, ’cause this was the early days of heart surgery, and the technology was such that it was a pretty high mortality.
People who were undergoing, for instance, a valve replacement received an average of 18 units of blood, so a huge amount of blood. Now, now they don’t receive any blood, generally. LH: Oh, really?
RP: They either obtain blood from them before the surgery, which they then will re-transfuse into them during the surgery, or the technique is so good now that they don’t lose that much blood. But, receiving that much blood meant that they were exposed potentially to a lot of people who might be chronically infected with hepatitis.
LH: Right.
RP: We knew nothing about viral hepatitis at the time, or virtually nothing. So, what we decided to do was to follow patients who were undergoing heart surgery, and to obtain blood samples from them before surgery, and then at intervals for six months, and then generally annually after that, just to see what the incidence of transfusion-associated hepatitis was, and it was absolutely frightening. Of those people who got commercial blood, blood where people had sold their blood, a half of the patients came down with viral hepatitis. That started another study that we did in collaboration with the blood bank, which was to look at just how dangerous commercial blood was, and what we found in the subsequent study was that no one who got volunteer blood, in that particular study, got hepatitis at all, whereas, again, about 50 percent of those who got commercial blood developed hepatitis. So that, and other studies like it, led to changes in how blood banks operated. They quit buying blood and encouraged people to donate.
LH: Wow. Were there any other kinds of innovations in medical technology that brought on that kind of a discovery into hepatitis, like how the heart transplant and heart operations really brought people’s eyes open to how important hepatitis research was? (pauses) Was there any other kind of an operation?
RP: Yeah. There were breakthroughs at the time, partly based on the clinical samples that were collected from heart surgery patients and our study and other studies elsewhere, because you knew which patients had developed hepatitis because of certain laboratory tests that you can do to show that there’s damage to the liver, called ALT and AST tests. They measure serum levels of enzymes that come from the liver, and when liver cells are damaged, those spill out into the circulation so you can measure it. It’s a very nice marker of hepatitis. Actually, I can just show you a thing right here (indicates three graphs from his desk) this blue represents ALT, Alanine
Aminotransferase, levels in the serum, and when they go up like this, it means that there’s hepatitis, and so, in this in particular (taps graph)…now this happens to be in a chimpanzee and not in a patient, but the same thing is true. It peaked right here (indicating the graph again), and then came back down. Later, the same is true here. Much lower levels here, a much milder infection in that particular one (returns sheet to corner of desk). So, with those kinds of tests, you knew that this person, if this were a person, had hepatitis. So then you could take a sample taken before transfusion, and a subsequent sample, and see if you can measure antibodies to something.
LH: Oh, yeah.
RP: You try to figure out what. At this time, there were no markers; back in the 1960s, there were no markers for any hepatitis virus. It was thought that there were two viruses because one seemed to be short-termed and sort of limited, and the other one seemed to be longer and more severe, and the first one seemed to be associated with fecal-oral transmission, and the second one seemed to be transmitted by blood, so the ways to test antibodies were also becoming more sensitive at that time. So, over a series of two or three or four years, tests for, for instance, hepatitis B, which is serum hepatitis, which is the one at the time thought to be the only one that was transmitted by blood, got more and more sensitive, and so it was possible to detect more and more of those cases. But, what we found was that most of the cases, two-thirds of the cases, were not hepatitis B, and so we didn’t really know what they were. Everyone thought, “It must be hepatitis A; it’s the only other hepatitis we know about,” but another of the technologies which came along, which impinged on this, was one called immune electron microscopy. This is a technique where, first of all, you can use an electron microscope to see the virus, for instance in the feces or in the serum, but then, if you mix a sample that contains the virus or the sample that contains antibody to that virus, they form complexes, and you can see those complexes in the electron microscope also. So, if you take a serum before exposure and mix it with the virus, and you don’t see any complexes, and you take a sample taken during convalescence and mix it with that virus, then you see complexes, antigen-antibody complexes, then that’s a very good sign that that virus infected that individual, because the individual developed what we call a syro- conversion, a development of antibody. So, Al Kapikian, who was just down the hall, one of my colleagues here for 45 years, almost 45 years, went to England to learn immune electron microscopy, which was a fairly new technique at the time, and when he came back, one of the things he did was apply this to acute gastroenteritis, you know sort of winter vomiting disease or stomach flu it’s called, and what he found, eventually, was a virus that people with this disease were infected with, and they developed antibody to that virus, and that was how he could relate that virus found in their feces to their disease. That was exciting; that was the first gastroenteritis virus that was ever discovered. So, we were faced with the dilemma of having hepatitis in people receiving blood. At that time there was not a test for hepatitis A, so we said, “Let’s see if we can apply that same technique to look for the hepatitis A virus.” So over some period of time, Steve Feinstone, he was a post-doc of mine at the time, learned the technique from Al, applied it to various samples that we got from people who had what appeared to be hepatitis A, that kind of viral hepatitis, and eventually found the virus in the feces, and then showed that these people developed antibody. This was the first test for hepatitis A. So, when we had these heart surgery patients who had hepatitis, we (?said?), let’s just see if they developed antibody to hepatitis A, and the short answer is, they did not. Some had been infected previously with hepatitis A virus; they did not have a rise in antibody. Others had not been, and they didn’t develop antibodies, so there was a third hepatitis virus, which we called non-A-non-B, thinking that we would have a test for it very quickly, but we didn’t for a very long time. (laughs) So that was the third hepatitis virus, but that was discovered because of the development of new and sensitive assays and tests. We and others went on to make more sensitive tests for antibody to hepatitis A, but it wasn’t until 1989 that we really had a test for non-A-non-B hepatitis. That was when the virus was cloned and sequenced by Michael Houghton at Chiron Corporation in
California, and his ability to do that was really based on several other things: clinical samples from people who had studied this kind of hepatitis previously and materials from chimpanzees that had been infected with this kind of a virus. Non-human primates are really about the only animals that are susceptible to the human hepatitis viruses, and the chimpanzee is the only animal that’s susceptible to three of the viruses, so they’ve been extremely important and extremely useful in studying viral hepatitis over the years, and fortunately they don’t get sick from it – but we can measure all of these kinds of things that we have on this chart (pulls chart from box again) here, and study the infection in the chimp, and so plasma from an infected chimpanzee was the material that Michael Houghton used for cloning and sequencing the hepatitis C virus, and it took a very large amount, at least a liter of the chimp plasma, worked on over years and years and years to finally get the clone, the right clone, from the virus, and that opened up that whole field, so once the genome of that virus have been cloned and sequenced, there are ways of telling what part of that genome encodes proteins, and you can express those proteins in an E. Coli expressions system for instance, and then you can look and see where the patients who had this kind of hepatitis developed antibody that was measurable using those proteins as a source of antigen. That was what was done, so the really exciting thing about all of this in terms of transfusion-associated hepatitis is that from a disease that infected, if you got commercial blood, up to fifty percent of blood recipients, we’ve gone to the point where fewer than one in, I guess it’s a million or two million recipients of blood now develop hepatitis. It almost never happens, and that’s a tremendous advance. It’s really good. It’s exciting!
LH: Yes! When you were working with a bunch of these people that you mentioned, was there any tie that was formed between all the scientists working on the hepatitis research as it developed?
RP: Oh, yes. Some of my best friends were the people who I’ve worked with for forty-five years now. Some are here at NIH, some are elsewhere, some have retired by now, but our paths crossed numerous times over the years. We’ve worked, sometimes in the same areas, other times in different areas, where information from these studies have been useful for these studies, so yeah, there’s a real camaraderie, I think, particularly among hepatitis people. It’s been a group of really wonderful people.
LH: Why do you think it’s particularly among hepatitis people?
RP: I don’t know. My earliest work, my first scientific work in virology, was on cancer viruses.
At that time, there weren’t any recognized human cancer viruses, so principally cancer viruses of animals. The first one I worked on was one that’s called Amyotrophic, no, I’m sorry…it’s a chicken virus anyway, that causes a disease in chickens, and I worked on this while I was at
Duke, basically at night (laughs), at night in my spare time, and I got to know a lot of the people working in cancer virology, and they were actually a different sort of set of people (laughs).
They were a pretty aggressive group, and it was a real pleasure to work with the hepatitis people.
They just seemed to be a different type of person. So that’s the reason I made that comment.
LH: Was there any time when your research was unusually impacted by current events, non- scientific events?
RP: I’m eating the goodies right now, so I might (laughs) not be as easy to understand. (referring to cake delivered before the interview) One recurring problem is the ability to use animals in research. This is always a controversial subject, and many people feel very strongly against the use of animals, but in fact, it would be very difficult to have made many of the advances that have been made, not just in virology, certainly in infectious diseases in general, but in many, many fields of science and medicine, without the ability to use animals, so from time to time this has been a potential problem, only we’ve always been able to do this. We always are very sensitive to the needs of the animals and to the fact that we’re not harming them, but we really do need to use them, and so that has been one area of controversy. Occasionally, funds become tight. They’re tight now because the whole world is having financial problems, and money will be tight for the next several years for research purposes. (pauses) Those are the main things, I think. Sometimes just having to wait for science to move forward the next step to provide you with the tool you need to ask and answer the next question, that’s always a problem. We can do things now that we couldn’t dream of doing twenty or thirty years ago, even five years ago. It’s just amazing.
LH: Can you give an example of some of that?
RP: Sure. Let me begin by saying that my first research paper, which was in a library course at
Oklahoma State University on how to use the library…that first report was on a paper that had just come out, which was sort of…it was interesting, but it was like a two page paper and it was by Watson and Crick, and it was the first discovery (laughs) of the importance of nucleic acid and the structure of the DNA molecule. From that inauspicious start has come the whole field of molecular biology, really based on that first observation within many, many ones after that. It was only a few years ago, not very many years ago, where determining the sequence of something was a major job, and the nucleic acid sequence of something was a horrendous job. It was very expensive, it took a long time, the techniques were not terribly good, and it was just in the very few past years that you could sequence the genome, of a virus for instance fairly quickly. Now that technology has reached the point where you can sequence everything in, let’s say a homogenated tissue, put it all together into a united sequence, and maybe identify a needle in a haystack in there, the sequence of something else. That’s a technique we’re going to be using in the immediate future, because we have several viruses that we know are there, but we don’t have a sequence for, and we need the sequence to see how they fit into the scheme of things. That’s very exciting. You can sequence the whole human genome very quickly now with these procedures, and it will put it all together. We’re doing a lot of work with microray analysis. This is a technique that’s only been available for a few years, and it’s based upon the same chip technology that’s used for electronics and information technology. A huge amount of information goes onto one little chip, and with that, now, the entire human genome is represented on that chip. We’re looking at a lot of our samples that we collected from our studies in chimpanzees over the last 30 years where we took biopsies from the chimps, liver biopsies, and we took them at the time, with a test called immuno-florescence, to look for viral antigens in the liver cells. But we had leftover materials from that, and we found that we could use those pieces of liver biopsy to do microray analyses, so over the past two or three years, we’ve been looking at these serial biopsies from the chimpanzees by microray analysis and by looking at all of the changes that have occurred in the chimp, not so much in the genome, but expressed genes in response to the viral infection. Because we worked with all five of the human hepatitis viruses over the years, we have materials like that from the chimps, so that we can look at all five of the viruses. Now we’re making comparative pathogenesis studies to see what this virus does in the chimp that this one doesn’t do and vice versa. Since we’ve used the same chimps for different viruses in some cases, we can see where there are differences related to the chimp, whether there are genetic differences that make this chimp, for instance, respond with a more severe infection than this one. We’re spending a lot of time and effort doing that right now. We’ve kind of quantified how the chimp responds. The chimp genome is virtually identical to the human genome, they’re about 99 percent identical, so you can use the microray chip that’s designed for human studies with the chimp. We’re also looking to see how the chimp, and by extension the human, responds to these infections, which genes are up-regulated and which are not. In terms of the immune response, you can group them into two categories: what we call innate immune response genes; these are ones that respond to an infection, regardless of what the infection is, and it’s sort of like a whole bunch of genes are up-regulated in response to an infection, and these have to do with responses to interferon, and it involves a number of things called toe-like receptors that cells have that tell the cell that it’s been exposed to something it doesn’t want to be exposed to, such as a foreign nucleic acid, either RNA or DNA, or bacterial components that are not part of the human genome. Their alarms are set off, and a whole bunch of cellular proteins, first cellular messenger RNAs are up-regulated, and then (?these cause the?) synthesis of proteins which then fight these infections, so you can measure those things, you can quantify them. Some viruses have ways of getting past the host’s immune response; they can down- regulate or disarm a part of the host’s immune response, and you can look at those things. But we have had a lot of samples in which we could not identify what hepatitis virus was there; it didn’t seem to be any of the five that we have tests for. We’ve tried to transmit those to chimps over the years also. Now we’re going back and looking at those, and I think we probably have evidence for another hepatitis virus, based upon being able to use microray as kind of a diagnostic test where the chimp will respond to the infection, even though we don’t know what the infection is, but there are markers that say, something’s going on here. Then we can begin to try to find what that is, and go through all of these other things we’ve done before to identify diseases.
LH: Wow.
RP: So there are still things to do.
LH: When you first started hepatitis research, can you describe a typical day in the research lab?
RP: I was younger then, so I spent a lot more time, a lot more time, in the laboratory than I do now, but because it was during the era of tissue cultures, a lot of what we were doing was involved with tissue cultures, my first work here was not with hepatitis. It was actually with respiratory viruses, and since I was an Epidemic Intelligence Officer sent from the CDC, I was supposed to be good at, though I guess I wasn’t necessarily (laughs), was epidemiology and doing clinical trials and epidemiologic clinical trials. So, what some of my first roles were here was to do vaccine efficacy trials. Bob Chanok, who was the lab chief then, had developed a vaccine against certain types of adenoid viruses that were a big problem in the military. At the main military bases, there would be epidemics of pneumonia, with some deaths of military recruits, so he had developed this vaccine, which was a very interesting concept. Adenoid viruses infect the respiratory tract and the intestinal tract. What he found was that if you bypass the respiratory tract, and affect just the intestinal tract, you get a silent infection in which you develop immunity but no disease. What was happening in these military recruit camps was that this virus was being coughed out, and people were transmitting it by respiratory route to the people around them and they were getting sick, so what he decided to do was to put the live virus in a capsule that was then empirically coated so it wouldn’t dissolve, like a regular gelatin capsule. It wouldn’t dissolve until it got to the intestinal tract, the upper GI tract. Then it dissolved and the virus infected the intestinal tract and caused immunity, but for reasons that are still not clear, never spread, never got back into a respiratory cycle. Basically it wiped out this kind of a disease in military recruits. It was a great step forward. It never worked for the other adenoid viruses very much, which were primarily infections of children and young adults in the general population, but it certainly worked in the military. Just another part of that story, several years ago…this is how silly reasoning gets institutionalized sometimes…one of the younger secretaries for defense in the military decided that there was no respiratory disease in military recruits anymore, so why waste time and money on this vaccine. They just discontinued the program, and not surprisingly, a year or two later, they began having epidemics, actually with deaths of recruits. It’s taken about ten years to get that program back on line, because the company that was making the vaccine just got rid of the stuff; they no longer had any use for it, so it’s taken a long, long time. Stupid decisions.
LH: Which events in the history of hepatitis research and the world at large were surrounding the beginning of your career in hepatitis research?
RP: As I mentioned, no one knew very much about hepatitis at the time. Some progress was beginning to be made, at the time principally with studies in human volunteers. At the time, it wasn’t appreciated how serious viral hepatitis could be, so studies were carried out. One set of studies…and this was in the 1950s…was carried out by what was called the Division of
Biological Standards, the DBS. At the time, that was part of the NIH, and some of the senior clinical scientists there initiated volunteer studies. I think they were in prisoner volunteers. Now this is something now considered to be highly unethical, to do clinical studies in prisoners, who really are a captive audience. But, they were done, and in fact, other studies were also done by someone else in homes for the mentally retarded, on Staton Island, called the Willowbrook
School. I knew the person who did it; he was a fine individual and never considered himself unethical. Those studies also were not considered to be totally unethical, that you can’t do the studies in the mentally retarded. You can do studies in children if their parents agree or if they have a guardian who can make rational decisions for them. In fact, some studies have to be done in infants and children, because those are the ones who are infected, so if you’re going to test a vaccine, eventually you have to test it in those. But, the studies at Willowbrook were very important because they were the first to confirm that there actually were two hepatitis viruses.
One patient, whose initials were MS, was actually infected with materials from other patients, and then he was given another inoculum later, he or she, I don’t know which it was, and developed hepatitis again, and so that was the first evidence that there were two hepatitis viruses and one did not protect against the other. Then, if you re-challenged children who got the first one, they didn’t get that one again. If you re-challenged ones who got the second one, they didn’t get that one again either. These were called MS-1 and MS-2 for the first and the second infections in the patient MS. Those clinical materials collected from those children, serum samples from earlier on when they were taken, became very important as reagents for characterizing these viruses in other laboratories including in ours. You had paired sera as we talked about earlier, before infection and after infection. You could say, okay, this virus I have here is the same one that this person got; this is hepatitis A, this is hepatitis B. Interestingly, hepatitis C never occurred at Willowbrook. The other two occurred there, I would say, endemically. Everybody there got them, because with children who have mental disabilities, hygiene is not what it should be, and so essentially, they all got both of the viruses there. Saul
Krugman’s hypothesis was: okay, they all got hepatitis; why don’t we try to learn something from it? When they come in, we’ll get permission from their parents to put them in a hepatitis study; we’ll give them the material in a controlled way, so that we can try to understand what’s going on and, eventually, help them and prevent hepatitis. And that was what was done, and those actually became very important reagents. So, that was going on at the time, that was important. We were just beginning to learn things about hepatitis, and then, just about that time, what really kind of opened the field up was a study done by Baruch “Bary” Blumberg, who was here at NIH at the time; it was sort of like he was a fellow. He was really interested in genetic differences among different people in different populations, so he was looking for these kind of genetic differences and his hypothesis was that people who might have different proteins…these were serum protein differences that were really from genetic ones. Someone who gets a whole lot of blood…it’s been transfused a lot would probably have seen those proteins…and might have developed antibodies to them. So he took sera principally from hemophiliacs, who had to get blood transfusions at frequent intervals, to use as a source of antibody. Then he just looked at sera from people from all over the world, from different populations, and he found one day… he did this with a test called augri gel diffusion, where you make a thin layer of agar, kind of like gelatin on a plate on a slide, and punch two holes in it, and you put something that you think might have the antibody in it in this hole, and you put something you think might have antigen in this hole, and then they diffuse out into the agarose, or the gelatin-like stuff. Where the two come in contact with each other, they form a precipitate line, they form a complex which precipitates. You can see this line in the gel. It’s not a sensitive test, but it’s a specific test, and at the time, it was one of the best tests available. So, he did that with serum from the hemophiliac as a source of antibody and serum from some Australian aboriginates in this one, and he got very strong lines. So he said: it looks like a new antigen, and it might be interesting.
A fellow who was here for as a two year fellow, like I was kind of here as a two year fellow, was
Harvey Alter at the time, who was working in the blood bank. So, he was working with Bary
Blumberg, and he got interested in that, and they worked on it. Bary originally thought that this was a genetic thing, but eventually, due to the work of a lot of different people, it became clear that this was not a genetic thing, this was probably an infectious thing. By a number of different tests it was possible to show that the antigen was very common in children from home for the mentally retarded, among hemophiliacs, among certain populations in developing countries, particularly Africa and Asia, and what it turned out to be was the envelope portion of the hepatitis B virus. Blumberg called this the Australia antigen; that’s what it was called for a long time because it came from an Australian aboriginate, and he was probably the last person on
Earth to realize what the significance of this was. For years he thought it was a strange kind of thing that was half genetic and half transmissible. In fact, he won the Nobel Prize for that concept. (laughs) But then it turned out that this was part of the hepatitis B virus, so once that antigen was found, that then opened up all kind of possibilities. You could use it to look for antibody in other populations, and then, when it became pretty much clear what it was, you could begin thinking about, might this be able to be used as a vaccine? So actually John Gerin and I purified some of that material and…by then we had known that chimpanzees were susceptible to hepatitis B virus…immunized them with that material and challenged them with the live virus and showed that they were protected. That was the first hepatitis B vaccine. Those were kind of some of those things that…but we’ll never get to your questions, so…
LH: Oh, that’s fine. (both laugh) I read your 1993 essay on the discovery of hepatitis viruses, and you wrote about the Silver Age and the Golden Age of hepatitis research. Can you expand upon how your research was different from that of the Silver Age?
RP: The difference between the two was we began to have specific tests in the Golden Age, so that we could identify hepatitis, first hepatitis B virus and say serologically, this is hepatitis B virus, this person has had it, this person has not had it. Then we could say, here’s somebody with, what then was called infectious hepatitis virus, then hepatitis A virus. Here’s somebody with hepatitis. This individual did not develop antibody to Australia antigen, divided by the components of the hepatitis B virus; this is indeed a different virus. How can we identify it, and by immune electron microscopy it was possible to do that, so now we had two viruses that could be specifically identified. Then there was the non-A-non-B hepatitis virus. That, as I said, took until 1989 before there were tests to specifically identify that. We were fortunate to work with some other people, principally from Italy, who discovered sort of again by accident, another virus, which turned out to be hepatitis D virus, or the Delta agent. Now you had specific assays for four different viruses. There were epidemics, water-borne epidemics, in India, which everyone thought was probably hepatitis A because at the time they occurred, 1956 for instance, there was no other virus known to be transmissible by those means. There were no tests either, but the fact that there were these big epidemics occurring among older children and young adults, while at the same time we’d been able to show with very sensitive serologic techniques that in that kind of population everybody had already been exposed to hepatitis A by age five years, and as far as we could determine, there was life-long immunity to hepatitis A. There must be another virus, so we began working on that one. Then it was not until 1983 that Mikhail
Balayan in Russia infected himself and could show that there were virus-like particles in his feces, that he developed antibody to those…he didn’t have them to begin with…he did have them in the convalescent phase. He had been infected with the hepatitis A virus previously, as almost everybody in Russia had, and he did not have a change in antibody level to hepatitis A, so he knew it was different from hepatitis A. He also transmitted it to cynomologous monkeys, which are kind of like research monkeys, and so he also developed an animal analysis system.
LH: Wow. How do you feel, knowing that you are influential in saving lives?
RP: It’s a wonderful feeling, is what it is! (laughs) It’s the kind of job where you __ yourself because you’re able to do it. We’re rewarded for it, and there’s a tremendous feeling of satisfaction to do it. What’s happening…we have vaccines for hepatitis A, hepatitis B, hepatitis
D, and hepatitis E. Now the vaccine for hepatitis A has been licensed for a number of years; several companies make it. The one for hepatitis B has been licensed for even longer, and it protects against hepatitis D also, because hepatitis D virus is defective. We’ve just developed the one to hepatitis E recently. The A and B vaccines are marketed and have been for many years, whereas the hepatitis E vaccine is not yet marketed, and we’re trying to get companies to do that, because it’s still a major problem in Africa and Asia. And hepatitis C, we do not, and it’s kind of like human immunodeficiency virus; it’s a very difficult virus and we’re probably not going to have a vaccine for a while with that one. Having said that, we know that hepatitis B infections are diminishing worldwide where the vaccine is used. The same is true with hepatitis
A infections and will happen for hepatitis E if we have the vaccine out there. That has ramifications because in Asia and Africa, where most of the hepatitis B infections occur, infection occurs in infancy and early childhood, where most of the infections go on to chronicity, they cause a life-long infection, and eventually cause chronic hepatitis, liver fibrosis, cirrhosis, and liver cancer. So both hepatitis B and C are cancer viruses as well as hepatitis viruses. We already know, in some countries like Taiwan, not only the incidence of viral hepatitis has gone down since they started a massive vaccination program, the incidence of liver cancer has gone down. So that’s really exciting, to be able to prevent that. Now, having said that, there are still about 350 million people in the world chronically infected with hepatitis B, about 170 million chronically infected with hepatitis C, about 15 million chronically infected with hepatitis D, so that adds up to about a half a billion of the world’s population, in fact with one or more of those viruses, many of whom will die as a result of that infection, so it would be great to have ways, not only to prevent future infections, but to treat those who have them now. So that’s another area where there’s a lot of research going on. (pauses) Don’t forget to eat your panettone.
(indicates cake)
LH: Right! (both laugh) It’s very good. David McCullough described the influenza epidemic of
1918, saying, “It would be as if today, with our present population, more than 1.4 million people were to die in a sudden outbreak for which there was no explanation and no known cure.”
Although he was not speaking of hepatitis, how would you classify hepatitis when compared to the major epidemics of history? RP: Hepatitis viruses cause epidemics, but not the kind of epidemics that respiratory viruses, for instance, cause, or other viruses such as smallpox, which also is spread by the respiratory route.
With hepatitis A and with hepatitis E, you can have water-borne epidemics that can involve hundreds of thousands of people, but it’s not the same order of magnitude as, for instance, the pandemic flu. I’ll just tell you a little aside: the person who has recovered that influenza virus from the pandemic of 1918 is here in this laboratory; his name is Jeff Taubenberger. He did that while he was at the armed forces institute of pathology, down the road a way, using these fabulously sensitive and exotic techniques that are now available. You could get the nucleic acid out from lung tissue from fatal cases of that kind of influenza that were stored from autopsies that were done at the time, and they have gotten the whole sequence. They have been able to put it together into an infectious virus, and it’s now being studied in laboratories where there’s a very high security level so it doesn’t get out to try to find out why it was so much worse than other influenza viruses. They don’t really completely know yet, but they’re making advances on that.
What we have is kind of an on-going semi-epidemic of viral hepatitis worldwide that causes huge amounts of disease and problems, but it’s on going all the time. It’s not one of these like the influenza epidemic. The interesting thing about that influenza epidemic was, if you look at life expectancy charts over the past century or century and a half, you see a regularly increasing life expectancy as things have gotten better for everybody, with the exception of that one point in time in 1918 where life expectancy dropped precipitously because so many people died at that time.
LH: Wow. In the 14th century, historian Giovanni Boaccaccio explained the bubonic plagues as
God’s judgment upon the world. In the polio epidemic, David Oshinsky identified a new philanthropic consumerism, like the March of Dimes, in the crusade against the disease. How do you think the public view of hepatitis, as another type of widespread disease, has evolved?
RP: Somewhat in the same way. Many people are less aware of the impact of viral hepatitis than they were, for instance, of the epidemic of polio. Polio was very interesting because, in some ways, the epidemiology has been very much like hepatitis A virus epidemiology. It’s a virus that has infected everybody in infancy in developing countries, and for the most part, it doesn’t cause the disease, or at least not in everybody, when infections occur at that age.
Hepatitis A virus is like that also; it infected nearly everybody in developing countries, but when the infection occurred in the very young, they basically didn’t get sick, or they didn’t get very sick, or they didn’t get sick really from it. Polio is a little bit worse because, even in very young children, a portion of those will develop paralysis which, of course, is life-long for them. But most polio virus infections in the very young are what we say sub-clinically occurring…nobody knows they occur…so it’s infecting everybody at a very young age, hepatitis A virus and polio like that. So what really caused the epidemic of polio in the United States, and in other industrialized countries, was better hygiene leading to people not getting infected in infancy, but getting infected as older children and young adults, where most cases led to paralysis or death.
The same is true for the hepatitis A virus, where one out of every two adults will be a clinical disease with hepatitis A, whereas in infancy almost none of them are. So what you saw with polio virus in the 1920s, ’30s, ’40s, in the United States was an increasing epidemic just because people were getting infected at an older age. We’re beginning to see that with hepatitis A; we still have it with hepatitis A in the United States also. You’re seeing it now in countries like
India, particularly in urban areas where better-educated and more wealthy people live. They’re not getting exposed in infancy; now they’re getting exposed at an older age, so there’s more hepatitis A. Countries like India will have to address the issue of universal vaccination against hepatitis A. They don’t use it now because they still have a natural vaccination by children getting infected at an early, early age. But those are kind of unexpected things that happen when you try to make life better, increase the public health level, and such.
LH: Right. In your opinion, what’s the overall impact of your research? (pauses) So, if we look back in a hundred years, what are they going to think about your research?
RP: Rather than my research, I would say, all of my peers. This cohort, this generation of people who worked on viral hepatitis collectively made a huge number of changes, and I think it will be looked upon very favorably. One of the things I tell people is, we talk about mankind’s great contributions, the things they’ve done, the cathedrals they’ve built, the this and the that that they’ve done, but one of the greatest is the conquest of smallpox. It’s unbelievable how important this has been to society, and yet most people don’t even think about it. It’s the complete eradication of one of the world’s worst diseases; it was in the same category as the black plague, and the bubonic plague, and other similar diseases, and it may be the only virus to be completely eradicated, but it’s been an enormous thing. While we haven’t eradicated the hepatitis viruses, we have basically eradicated transfusion-related hepatitis viruses.
Hemophiliacs don’t get sick and die of their hepatitis except for those who were infected before the blood was made safe. Millions of people won’t die of liver cancer because of this, or of hepatitis. I’ll tell you a personal story: I’ve worked on viral hepatitis for many, many years, and about ten years ago, my sister-in-law, from my older brother who I spoke of before, was having trouble with a fungus infection of her toenails was what really started it, and the drug that she used to treat that can affect the liver. So they would routinely take liver tests to make sure that the liver was okay, and it turned out her liver wasn’t okay. She had elevated ALT levels, and they followed up on that and they found that she was chronically infected with hepatitis C virus, probably from a transfusion that she had gotten twenty years ago. And that’s kind of a characteristic thing now; people never knew that they had a hepatitis C virus infection until twenty or thirty years later when, for reasons that are unclear but may have to do with the immune system not being able to cope with things as well, the infection gets worse. They develop chronic hepatitis, they develop cirrhosis, and they may develop liver cancer. She didn’t have liver cancer, but she had developed cirrhosis and a failing liver. Actually, she died about three years ago now from her hepatitis C, so these things can be very close to home. So those things we won’t see anymore, after this generation of people, except for drug addicts, who are now the principal people in the United States who get hepatitis C, from sharing needles. We won’t see that anymore, so it’s been really a tremendous, tremendous change. (pauses) So I hope they’ll look favorably on us in a hundred years. (both laugh) I think they will.
LH: And finally, what are your hopes for the future of hepatitis research?
RP: The biggest hope is that we can develop a vaccine and better treatments for hepatitis C. The treatment of choice now is interferon plus another drug and antiviral that’s usually given with it.
But the most common genotypes of hepatitis C virus are resistant to those drugs, so there’s a need for better drugs. Among those who have the most common types of hepatitis C virus infection, only about fifty percent can be cured with this treatment, so there needs to be better treatment. People are working on anti-virals that attack different parts of the virus; it’s protease, it’s polymerase, a gene and other parts of it, as has been done with HIV in the past. We don’t have a vaccine for HIV, probably won’t for a long time, but we have very good antiviral treatments. They’re expensive, but they can keep people alive for years, and they can lead essentially a normal life for years if they take the antiviral treatments. The hope is for people with chronic hepatitis C virus, eventually we can develop those anti-virals for that too.
Treatment for chronic hepatitis B is not all that good, but there are treatments that keep people basically stabilized for years. So I’d like to see a vaccine for hepatitis C, I’d like to see better anti-viral treatments for chronic hepatitis, viral hepatitis of all types, I’d like to see whether we have another hepatitis virus and if so how important it is and if we could do something about it.
Epidemiology suggests that there’s at least one more hepatitis virus that may account for maybe the second most important cause of viral hepatitis in most of Asia and may be behind hepatitis E in adults. It might be the third or fourth most important one in the Middle East and much of
Africa, so as hepatitis A and B come under control in those regions, this other putative virus will become increasingly more important over time. So, I’d like to see if there is another one there. I think we actually have it, and if we can do something about it…By then it’ll be time for me to retire. (smiles)
LH: (laughs) Is there anything I failed to ask you that you think is important for me to know to understand hepatitis research?
RP: No, I would just add probably that these viruses are very difficult to work with, more difficult to work with than a lot of other viruses because…I talked about the Golden Age of tissue culture research, where a lot of viruses were discovered, a lot of viruses are studied routinely now in cell cultures that support their growth. You can tell whether the virus is there because it kills the cell, and there are all kinds of assays that you can use for that. Many of the viruses are transmissible to small laboratory animals like mice or guinea pigs or hamsters or rabbits or something of that sort, so for the most part, the hepatitis viruses don’t grow in cell culture. Hepatitis A virus does, but only with great difficulty, and it took years to isolate that virus in cell culture. Certain strains grow well enough in cell culture that that’s the source of the hepatitis A vaccine: viruses grown in cell culture and then inactivated with hormone, and that becomes the vaccine. Among the other four viruses, hepatitis B virus doesn’t grow at all in cell culture still. Hepatitis C virus: there’s one strain that grows in certain cell cultures, limited cell cultures. Hepatitis E virus: Dr. Emerson here down the hall has isolated hepatitis E virus in cell culture, but again, only a few types of cells and only a small number of strains, and it grows very, very poorly. So, you don’t have tissue culture systems basically for most of these viruses.
They don’t grow in common laboratory animals, as I mentioned previously; for the most part, non-human primates are the only susceptible species, and for three of them, the chimp is the only susceptible species. So, they’re really hard to work with. You have to do molecular things with them. You have to try to clone them and express the antigens. Many of the characterizations of the virus and the virus genome have come from putting together a full-length genome of the virus, and then, since you don’t have a…what you normally do with a virus, with a cell culture you do what’s called transfecting: you put the nucleic acid, even without its protein coat, into the cell, and it will initiate infection and then produce the viruses. So you can modify that genome, change things, take parts out, and then put it in the cell culture and see if it still grows. You can learn a lot about the different parts of it. You can’t do that with the hepatitis viruses. You can do transfections, but you have to do them in the animal, so we do what’s called percutaneous
(which means through the skin) intrahepatic (which means inoculating right into the liver)… these genomes to see whether they’re infectious. So then you make a little change in one, then you may have to do a percutaneous intrahepatic transfection to see if it’s still infectious. These are very difficult ways to do things. We’ve got a lot of information that way, but it would be much easier if we could just do it in cell culture. So, it’s a very difficult thing to work with.
HIV, for instance, grows well in cell culture; you can do a lot with that. Haven’t been able to make a vaccine to it, but at least you can do a lot of characterization. We can’t do that here, so it’s tough.
LH: Is there anything that you particularly wanted to talk about that we didn’t get to?
RP: Tell me a little about yourself and how things are going for you, and if you enjoy this sort of thing?
LH: Yeah, I’m kind of interested in going into some type of research science. I’m not sure what.
I had a great Chem teacher last year, and I really liked biology in 9th grade, so just tentatively, that’s kind of what I’m interested in.
RP: It’s important to have a really good teacher, isn’t it?
LH: Yes! Makes all the difference. RP: It really, really does. It can really spark an interest.
LH: Yes. (pauses) I’m going to turn this off.
RP: Okay. Time Indexing Recording Log
Interviewer: Lauren Heywood
Interviewee: Dr. Robert H. Purcell
Date of Interview: December 23, 2008
Location of Interview: Dr. Purcell’s Office at the National Institute of Health, Bethesda, MD
Recording Format: Audio: CD
Minute Mark Topics presented in order of discussion in interview _
0:00 Introduction/Childhood
5:00 University Education/Professors
10:00 Blood Transfusions Transmitting Hepatitis
15:00 Immune Electron Microscopy
20:00 Ties Among Hepatitis Researchers
25:00 Developing Technology
30:00 Identifying Hepatitis Viruses with Chimpanzees
35:00 Studies in Human Volunteers
40:00 Testing for Antibodies and Antigen
45:00 Having Four Different Assays: Different Epidemics
50:00 Hepatitis as an Epidemic
55:00 Causes of Polio Infection
60:00 Hoping to Develop a Vaccine and Better Treatments for Hepatitis C
65:00 Difficulties of Researching Hepatitis Interview Analysis
Dr. Robert Purcell, a vital member of the team of scientists working to end the devastating progression of viral hepatitis, worked for years to find treatment and cures for the many variations of hepatitis before doctors diagnosed his own sister-in-law with chronic hepatitis
C. She later died of hepatitis C, with complications of cirrhosis and liver failure. He merely said, “These things can be very close to home,” voicing his own hope that, due his own work and that of his colleagues, things are very different now (Purcell qtd. in Heywood 49). Advanced technology and increased awareness, largely resulting from Dr. Purcell’s work, have led to immense improvements in diagnosing and treating various types of hepatitis. In this oral history interview, Dr. Purcell explained the long and complex journey to victory over hepatitis that remains unfinished to this day, but not without the hope of success. His valuable comments in the interview will allow many to vicariously experience and understand the complexities and necessity of medical research. This oral history, although it is not a complete history of the time, is a necessary supplement to the impersonal history that many already learn. This process, subject to imperfections of memory and limitations of one man’s personal experience, portrays the interviewee’s own life, unaltered by other views, and allows the reader to understand the biases and emotions of that time. Through explanations of his own experiences, Dr. Purcell’s oral history interview reinforced the common knowledge of the difficulty of research and technology of the past, but it challenges the accepted value of public participation in the research of epidemics.
In the interview, Dr. Purcell explained his work as vital and compelling, with the ever- present and noble aspiration to saving lives. He first discovered an interest in science when his older brother brought home a copy of Scientific American, a science magazine for the layperson. Following a weak education at his local high school, he decided that he “had a lot of catching up to do;” he proceeded to attend junior college, where he renewed his interest in science from a fascinating chemistry professor (Purcell qtd. in Heywood 25). Following an educational career at Oklahoma State University and Baylor and Duke Medical Schools, Dr. Purcell became an
Epidemic Intelligence Officer stationed at the National Institute of Health. As a lower position in the science hierarchy, the lab chief assigned him to the new study of hepatitis. He averred that the scientists “knew nothing about viral hepatitis at the time” (Purcell qtd. in Heywood 28). New technology in liver tests and hepatitis diagnoses brought about more and more discoveries, such as Baruch Blumberg’s accidental discovery of the Australia Antigen. These discoveries, according to Dr. Purcell, mean, “millions of people won’t die of liver cancer…or of hepatitis”
(Purcell qtd. in Heywood 48-49). In a startling statement, Dr. Purcell announced the suspected existence of yet another hepatitis virus, discovered with much of the new technology of the
“Golden,” or modern, age of hepatitis research. Finally, he identified hepatitis as a definite cause of epidemics throughout the world, especially in underdeveloped countries. Combined, these varied discoveries and identifications allowed Dr. Purcell and his colleagues to treat and cure many hepatitis patients.
In addition to his work in hepatitis research, Dr. Purcell made several comments on his personal interactions in hepatitis research. He observed that he valued the relationships he made with the scientists studying hepatitis very highly, especially when contrasted with the
“aggressive group” in cancer virology (Purcell qtd. in Heywood 34). Throughout the interview,
Dr. Purcell emphasized the significance and necessity of animal testing, despite the frequent protests and opposition to the practice. Dr. Purcell assured his audience of scientists’ sensitivity to the animals, but he also insisted, “We really do need to use them” (Purcell qtd. in Heywood 36). In addition, he addressed the use of prisoners and retarded children for hepatitis testing, saying that “some studies have to be done in infants and children” due to infections in those groups (Purcell qtd. in Heywood 40). In conclusion, Dr. Purcell, in speaking of his role in saving lives, declared, “There’s a tremendous feeling of satisfaction to do it” (Purcell qtd. in Heywood
44).
In his interview, Dr. Purcell confirmed the difficulty of research with the primitive scientific technology of the 1960s that artificial heart expert Dr. William C. DeVries described in an earlier oral history interview. Many of the difficulties that both of these experts spoke of were in reference to new medical technology that, while attempting to perform surgery for one medical problem, introduced an additional disease, such as hepatitis, in a routine blood transfusion. These complications often transformed many life-saving surgeries into weeks of doubt, fear, and often sickness. In addition, research capabilities were quite limited; new techniques that revolutionized the field of research, such as immune electron microscopy and microray analysis, only became widely used after the 1960s. In speaking of this period of medical history, Dr. DeVries declared, “We were very, very elemental at that time” (DeVries
26). He expanded on the elemental processes that limited doctors’ abilities to treat or cure their patients at that time, emphasizing the difference between the present and the past in medical technology. The mere lack of understanding that surrounded complex and dangerous diseases complicated even routine surgeries. Dr. Purcell confirmed the limiting effects of these primitive developments, saying that “back in the 1960s, there were no markers for any hepatitis virus”
(Purcell qtd. in Heywood 31). There were only two known hepatitis viruses at the time and no advanced techniques for diagnosis or treatment. This restricted both doctors and scientists as they sought to identify, treat, and cure the virus that plagued so many people. Through this deduction, Dr. Purcell supported the common idea that primitive technology restrained the medical treatment and research of the 1960s, putting many lives into jeopardy. These limitations impacted various fields of science and medicine in the 1960s in America, despite differences in purpose or technique. Therefore, Dr. Purcell’s oral history endorses the concept of an inadequate medical ability in the 1960s suggested by Dr. William C. Devries.
Dr. Purcell challenged the public’s awareness of the epidemic of hepatitis, in contrast with historian David Oshinsky’s concept of modern philanthropic consumerism. Throughout history, the impact of the public on medical research and treatments was tremendous. Common citizens in the time of the bubonic plague created an elevated level of fear, generating panic and a rapid spread of the disease. In the United States, citizens of the early 20th century united to solve the major medical issues of the time, such as in the March of Dimes during the polio epidemic. In referring to the National Foundation in that terrifying American polio epidemic, historian David Oshinsky identified a novel idea: “a new model for giving in modern America, the concept of philanthropy as consumerism, with donors promised the ultimate personal reward: protection against the disease” (Oshinsky 5). Oshinsky viewed these citizens, who gave what they could to fund the race for the cure and elimination of the polio virus, as a wonderful influence on research. These people, according to Oshinsky, created a change in the swiftly growing consumer culture of America in which everyone knew about and together eliminated threatening epidemics, creating modern heroes out of research scientists. However, Dr. Robert
Purcell illustrated a modern and opposing idea of the public’s role in research and cures for diseases. He openly addressed the controversy surrounding the practice of conducting studies in testing animals and in human volunteers. Defending the use of these testing subjects, Dr. Purcell acknowledged, “This is something now considered to be highly unethical…I knew the person who did it; he was a fine individual and never considered himself unethical” (Purcell qtd. in
Heywood 40). These contemporary challenges to research science introduced a different understanding of the public’s role in research; no longer idolizing scientists, it proceeded to find fault with their methods. This public disapproval has endangered the research possibilities for scientists and removed much public support and motivation for research science. Thus, Dr.
Purcell’s interview called David Oshinsky’s representation of the public’s contributions to philanthropy as consumerism into question and introduced a new concept of endangered research science.
Throughout the interview process, I learned of the difficulties and excitements of research science. There is truly a large society in the world of research science of which few outsiders know in the world; I feel privileged to have become one of the few. I am also quite interested to witness the excitement of each new discovery in research science through an oral history, and I was surprised by the suspense and thrill of hearing the dramatic story of one man’s contribution to our society. Finally, no book can give the same pleasure as Dr. Purcell gave when he described the amazing advances he and his colleagues have made in hepatitis; he explained, “From a disease that infected, if you got commercial blood, up to 50% of blood recipients, we’ve gone to the point where fewer than one in…two million recipients of blood now develop hepatitis” (Purcell qtd. in Heywood 33). Appendices: Appendix I.
Q uickTimeª and a TIFF (Uncompressed) decompressor are needed to see this picture. Appendix I. (cont.) Appendix I. (cont.) Appendix I. (cont.) Appendix II. Appendix II. (cont.) Works Consulted
Altman, Lawrence K. "Mysterious Form of Hepatitis Seen as Widespread Threat." New York
Times 28 Aug. 1984: C1+C9. JSTOR. 9 Dec. 2008
Altman, Lawrence K. “Use of Commercial Blood Donors Increases.” New York Times 5 Sep.
1970: 1+12. New York Times. 13 Feb. 2009 ?res=F10B1FF9345A16768FDDAC0894D1405B808BF1D3>. Anchord, James L. Understanding Hepatitis. Jackson: University Press of Mississippi, 2002. Associated Press (AP). “Terry Predicts End Of 9 Diseases by ’85 And New Advances.” New York Times 10 Feb. 1965: 20. JSTOR. 9 Dec. 2008 Associated Press (AP). “Text of White House Message on Guarding U.S. Beauty.” Washington Post, Times 9 Feb. 1965: A8. JSTOR. 9 Dec. 2008 Berkman, Alan, and Nicholas Bakalar. Hepatitis A to G. New York: Warner Books, Inc., 2000. DeSalle, Rob, ed. Epidemic: The World of Infectious Disease. New York: New York Press, 1999. DeVries, William C. "A Heart Unbreakable: The Jarvik-7 Artificial Heart Implants." Interview with Emily Fiuzat. Oral History. Dept. home page. 2007. St. Andrew's Episcopal School. 14 Dec. 2008 DeWaal, Caroline Smith. "Increased Government Regulation is Necessary to Prevent Food- Borne Illnesses." Epidemics: Opposing Viewpoints. Proc. of National Press Club November 19, 1997. Ed. William Dudley. San Diego: Greenhaven Press, 1999. 150-154. Everson, Gregory T. and Hedy Weinburg. Living with Hepatitis B. New York: Hatherleigh Press, 2002. Gallagher, Aileen. Hepatitis. New York: The Rosen Publishing Group, Inc., 2005. Giblin, James. When Plague Strikes: The Black Death, Smallpox, AIDS. New York: HarperCollins Publishers, 1995. Grady, Sean M., and John Tabak. Biohazards: Humanity’s Battle with Infectious Disease. New York: Facts on File, Inc., 2006. “Hepatitis E: The Story of the Hepatitis E Vaccine.” National Institute of Allergy and Infectious Diseases. 2007. National Institutes of Health. 14 Feb. 2009 Hill, Gladwin. “Scientists Seek to Perfect Separation of Sewage and Water.” New York Times 1 Mar. 1965: 30. JSTOR. 9 Dec. 2008 McCullough, David. Foreword. Influenza: 1918. By Lynette Iezzoni. New York: T.V. Books, 1999. 7-8. Oshinsky, David M. Polio: An American Story. New York: Oxford University Press, 2005. Purcell, Robert Harry. Oral History Interview. 23 Dec. 2008. Purcell, Robert H. "The Discovery of the Hepatitis Viruses." Gastroenterology 104 (1993): 955- 963. Ryan, Frank. Virus X: Tracking the New Killer Plagues Out of the Present and into the Future. Boston: Little, Brown and Company, 1997. Worman, Howard J. The Liver Disorders and Hepatitis Sourcebook. New York: McGraw Hill, 2006.