Feb 13, 2015

Virus Hunter: A Biography from American Medical History


On Wednesday evening, about 10 members of the History Book Club met at the Kensington Row Bookshop to discuss Virus Hunter: Thirty Years of Battling Hot Viruses Around the World by C. J. Peters and Mark Olshaker. Dr. Peters is the virus hunter of the title and Mark Olshanker is a professional writer.

The interest of the club was triggered by the Ebola epidemic in West Africa; Dr. Peters is a world expert on that disease, and was the man in charge of the effort to contain an Ebola epidemic in monkeys that occurred in Reston, Virginia in 1989.
We owe special thanks to Eli and Al, the owners of the bookshop. The shop was closed this week, but opened Wednesday evening especially so that the book clubs could meet as regularly scheduled.
The meeting began with an unusually long discussion of possible future books to be read and discussed. These are all described with links to obtain more detailed information on the club's blog. There was special interest in two topics:
  • California history, since we had not read about that state in the past and its history is quite different than that of other regions of the USA. We were especially interested in Father Junipero Serra, a founding father of the state who is to be formally declared a saint during the visit to the United States by Pope Francis in September. (This will be the first such ceremony ever conducted in the United States, and is likely to be a topic of conversation and debate.)
  • The history of the United States as a sea power in the 19th century. It has been suggested that the oceans were an important frontier for Americans before the opening of western lands. Again, this is a topic that the club has not explored in the past, but is one quite important to the nation's commercial, military and scientific history.
Bolivian Hemorrhagic Fever

A member who had been a health planner began this portion of the discussion when he described having been asked to identify a consultant to the USAID mission in Bolivia many years ago. The consultant was to lead an assessment of that country's health sector. The purpose of the assessment was to form the basis for a consideration of a possible health sector development loan. Our member was asked to find a U.S. citizen who was a medical doctor, with a post doctoral public health degree, strong writing and public speaking skills in English, fluent Spanish, who had worked in Bolivia, and who if possible spoke either Aymara or Quechua. After a week of work three qualified candidates were identified. There was an aside at this point on the huge personnel resources of this country, where such requirements can be routinely fulfilled. Dr. Robert Lebow was selected for the job. 

What makes that anecdote relevant is that Dr. Lebow also appears importantly in our book. Dr. Lebow had been a Peace Corps physician assigned to Bolivia, and he learned of several cases of hemorrhagic fever that had occurred in Cochabama. Viral hemorrhagic fevers had been of interest to the international health community since they had been discovered in Korea during the Korean War, where they had been a threat to American troops. An Argentinian Hemorrhagic Fever had attracted further notice, especially because it proved highly contagious and highly lethal; one team sent to investigate an outbreak had had every member infected and killed by the disease. Lebow recognized that the outbreak in the middle altitude of Bolivia was unlikely to have come from the same rodent reservoir as that in lowland Argentina. He called for help from the NIH Middle America Research Unit (MARU) in Panama; MARU sent Dr. C. J. Peters to do an epidemiological investigation of the outbreak.

Dr. Peters had exceptional training. An outstanding record as an undergraduate led to medical school at Johns Hopkins University (one of the best in the world), After internship he did a residency in immunology, and then worked as an NIH virologist at the MARU under one of the world's experts for some five years. If you think about it, this was about a decade and a half of higher education and specialized training preparing him for the work he was to do during the rest of a long career.

A Bolivian physician friend of Bob LeBow's had agreed to do an autopsy on one of the victims of the outbreak. Tragically, an accident had occurred during the autopsy, and the man was infected and came down with the disease.

At that point in the discussion, our health planner intervened to describe a visit to a hospital in Cochabama that he had made with an official of the Bolivian Ministry of Health. Several anecdotes served to make it clear to other club members that such a hospital could not adequately care for the man suffering from hemorrhagic fever, nor indeed could it protect its own staff from being infected were they to provide such care.

Lebow and Peters agreed that they would care for the man themselves. That meant rotating 12 hour shifts, each working alone under conditions of considerable personal risk. They did so until the patient died. These two men were physicians who cared deeply for their patients, not just public health officers or scientists, and they had put their own lives at risk. We club members considered them to be heroes.

One of the club members who had read this section of the book late in the evening while in bed reported that she had been so disturbed by the described events that she had needed to put the book down, get up, and watch television for an hour to regain her composure.

Virus Hunters

We discussed the small cadre of highly trained and skilled men who go to the ends of the earth, to the most dangerous of places dealing with the most dangerous diseases to find new threats to mankind and to learn how to deal with them. C. J. Peters is prototypical, but there are others.

A member briefly described the work of Dr, Robert Shope, a Virologist who was on the faculty at Yale for decades and eventually went to a university in Texas. "He helped discover hundreds of viruses, conducting investigations in Malaysia as an Army medical officer and in Brazil for the Rockefeller Foundation. At Yale, he led or participated in investigations of Rift Valley fever, Lassa fever, Venezuelan hemorrhagic fever and other diseases......Dr. Shope also built the World Reference Center for Emerging Viruses and Arboviruses, a collection of some 5,000 samples."

A reference center is an important tool, helping virologists identify the viruses that they isolate from human patients or animals. Such collections also help illuminate the genetic relationships among viruses. Discovering that a new virus is genetically related to known viruses can suggest how contagious it may be, how it is transmitted, how lethal it may be, and even how to deal with it.

Dr. Shope was also one of the editors of a major report issued by the National Academies of Science, Emerging Infections: Microbial Threats to Health in the United States (1992). The Spanish Flu that was associated with World War I was such an emergent disease; it killed 50 million to 100 million people world wide. The HIV/AIDS epidemic is from another emergent virus, and its slow-motion epidemic appears comparably lethal to mankind.

One of the points made in our group is that viruses mutate, and the strains of a virus newly arrived in humans may evolve quickly; it is possible for emergent diseases to become more contagious, more deadly, or both. Such mutation has been one of the threats of the Ebola virus. It is an RNA virus, likely to mutate more often than DNA viruses. The more people that are infected, the more opportunities for the evolution of more dangerous strains of the virus. The current epidemic which for the first time infected more than a handful of people, thus threatened to be the site for evolution of an even worse Ebola disease agent that the current strain.

The point of Emerging Infections was that a global epidemiological surveillance system that was capable of quickly detecting an emerging infection and limiting its spread is of direct value to the United States as well as to all other countries. Some advances have been made in achieving such a system (SARS was mentioned), but it has not yet come near to perfection.

Virus hunters like Drs. Peters and Shope are the first line of defense against emerging viral diseases. There are not many of them, but we were surprised that there were any at all. They are very highly trained, they risk their lives in their work, they travel to the ends of the earth often living in the roughest circumstances, they work in evil locations such as bat caves and infectious disease wards, they must sometimes wear uncomfortable protective gear, and they are paid only modest government salaries. A member who had been a school counselor told us that he had regularly been surprised by students choosing careers that to the outsider seemed most unattractive.

The Reston Ebola Outbreak

Reston Virus

Ebola broke out in 1989 in a facility being used to quarantine monkeys in Reston Virginai. It was caused by a filovirus similar to the species of Ebola that cause human disease, but apparently several humans who handled monkeys were infected but did not become sick. It was not the same Ebola species that has ravaged African nations. Initially it was thought to be more dangerous to humans than it eventually proved to be and there was great anxiety among those dealing with the disease.

We were struck by the good fortune that the outbreak occurred near Ft. Detrick in Maryland. Dr. Peters was assigned there, and the Army's research facility there had one of the only staffs in the nation capable of dealing with an Ebola virus outbreak. It also had unique physical facilities needed to deal with the outbreak.

One member of our team noted that accidents seem to happen more frequently than one might expect among people handling such dangerous disease agents. A member recalled a (long ago) job as a bartender, noting that cuts were common in that job, even though everyone knew that handling broken glass was a common hazard of the work. Another member, one who had once worked in a military blood bank, added that he too had found accidents there more common than one would expect.

The situation in research involving disease agents is getting safer. Today there are four levels of research laboratories defined, and the U.S. does not fund research unless it is to be conducted in a lab with a sufficient safety rating to assure the security of the research.

In 1989 there was only one level 4 lab in the country, but fortunately it was in Ft. Detrick. That is the level designed to deal with highly contagious, potentially lethal disease agents for which there are no known treatments. That is what is still appropriate for handling the Ebola virus.

We discussed the fact that the thicket of regulations designed to protect the public from health risks also creates barriers to the conduct of the biomedical research that might really protect the public. Virus Hunter is especially good at explaining how this phenomenon worked in the Reston Ebola outbreak. There were different regulations in Virginia and Maryland. There were different federal regulations for use of non-human primates in medical research and for quarantine of imported animals. The federal Center for Disease Control had to be involved as there was a national threat to public health. The Department of Defense had its own regulations. Dr. Peters and his collaborators had to deal with them all and with the officers each employed to enforce its specific regulations.

Some members of our club found it shocking that the ultimate control of the outbreak was achieved by killing all of the hundreds of monkeys in the facility -- healthy as well as sick. This was a terrible job! Monkeys are smart and quickly realized that they were in danger; they are tough and fought for their lives. Many of the cages in the facility (which was a quarantine facility, not a research facility) did not allow immobilization of the monkeys. The people were working in protective suits that were hot, uncomfortable, and limited their mobility. The workers feared that if bitten they might come down with a potential fatal disease. Even disposal of the bodies created problems -- were they potential sources of lethal human infection?

That led us into a discussion of the complexity of rules for the ethical treatment of animals involved in research. For example, there are different rules for treatment of laboratory animals than for livestock, and still different rules for wild animals. The rules for treatment of non-human primates recognize that they are intelligent and much like humans.

That part of the discussion was ended with an unanswerable comment: We thought of a researcher carefully assuring that the cows involved in his research (research funded by the Department of Agriculture, with protocols approved by his university) are treated humanely. Would he then go out and enjoying a steak dinner?

Where Are They Now?

Dr. Robert Lebow continued for many years to consult in the field of international health, but his main interest became a community health service he created in Idaho. He built it into "a $9.3 million a year operation, treating more than 18,000 patients in 10 locations.....(I)n 1998 and 1999 he was (also) president of Physicians for a National Health Program." He published a book, Health Care Meltdown: Confronting the Myths and Fixing our Ailing System. Tragically, he was disabled by an accident riding his bicycle to work in 2003, and died that same year.

Dr. Robert Shope suffered a major pulmonary disease of unknown origin; he died in 2004 as a result of complications from a lung transplant carried out to treat that disease.

Dr. C. J. Peters is still active, and is one of the experts called upon to help deal with the current Ebola epidemic.

Measles

The current outbreak of measles in the United States (after it had been eradicated following the 1971 introduction of the measles-mumps-rubella - MMR - vaccine) led us to a disbelieving discussion. We wondered how highly educated people were denying their children immunization, based apparently on a discredited article published years ago. There has even been a report of a "measles party" -- parents of a child who had contracted measles invited their friends who had children who had not been immunized to bring them so that they too could contract the disease; these parents apparently preferred to immunize their kids by giving them the dangerous disease rather than the safe vaccine. It was pointed out that in 2012, there were some 150,000 deaths from measles in the world, since mass immunization has not been possible in many parts of Asia and Africa.

A member pointed out that German measles (also known as rubella) was a real danger to pregnant women, causing many unwanted abortions prior to the general availability of rubella immunization.

Another member reported having contracted mumps as an adult prior to the availability of the MMR vaccine. He wound up hospitalized with a dangerous complication. Mumps too is a dangerous disease.

That member who had suffered an attack of shingles strongly recommend adult immunization against shingles. It was noted that the vaccine does not offer 100 percent protection and that shingles may recur, but reduction of the likelihood of an attack is still worthwhile. However, another member mentioned that she had a chronic medical condition that precluded her taking the vaccine.

The bottom line of this portion of the discussion was that while vaccines are generally safe, some vaccines are dangerous for some people. While vaccines are one of the most important advances in public health, one should always consult with one's physician before being vaccinated. One should not follow medical advice about so important a matter from untrained people.

Ebola in West Africa


We concluded the discussion with a review of the current information about the Ebola epidemic in three African countries -- Guinea, Liberia and Sierra Leone. There have been nearly 23,000 reported cases, of which nearly 13,000 have been confirmed by laboratory tests. There have been more than 9000 deaths.

While at one time there were 1000 or more new cases being reported a week, in January 100 cases or less were being reported per week. That reduction has led to a change in the response strategy. Now emphasis must be placed on maintaining the effort, identifying every contact, quarantining contacts when possible, isolating the infected and eliminating every last case.

We discussed why the incidence had fallen off. In part this was because community behavior had changed, and people were avoiding the contacts that earlier had led to the high contagion rate. In part the change in behavior was due to the impact of public health messages, in part to people spontaneously choosing to avoid Ebola victims, and in part it was due to the officials sending burial teams in protective gear to bury the Ebola dead rather than leaving that task to family and community members.

During this epidemic, it was learned that people sick with Ebola hemorrhagic fever were more likely to infect others later rather than earlier in the course of the disease. Early case identification and hospitalization therefore seems to have had a significant benefit in reducing the spread of the disease.

We noted that people who recovered from Ebola had gained an immunity, and young recovered people were playing an important role in caring for the many Ebola orphans -- children who are sometimes shunned by relatives who might otherwise care for them but fear that they may still carry the disease.

The U.S. troops who had played an important role in building facilities to help the countries deal with the epidemic are now largely back in the United States. The USA is still supporting some 10,000 people in West Africa working to end the epidemic, most of them Africans. There are more than 200 U.S. Center for Disease Control staff there contributing to the epidemiological efforts.

The world still has few remedies to help a patient survive Ebola hemorrhagic fever. A member brought in an article from the Washington Post that described the difficulties of testing new treatments that have emerged for the disease; there is only a waning numbers of patients on whom to do the tests. She also brought in an article from the same source that described three potential vaccines, two of which have entered testing; the completion of those trials is also questioned.

Final Comments

Looking back, the discussion  was wide ranging, focusing on topic about which we would like to know more. These topics ranged from the history of the parts of the United States with Hispanic backgrounds, to the role of Americans at sea, to the fall of the Ottoman Empire and how its division influences the region today, and indeed to medical history.

The Book Club has not focused on American medical history in any depth in the past, and this week we focused on one story from that history, especially as seen through the biography of one man, C. J. Peters. It is the story of the scientifically trained experts who contribute to our knowledge of infectious diseases.

Many historians of medicine believe that a century ago a visit to a doctor was more likely to result in harm to the patient than medical benefit. That century has seen unprecedented advances in medicine and a corresponding dramatic increase in life expectancy in the USA. Much of the improvement has been achieved through the prevention and treatment of communicable diseases -- notably the development of vaccines, antibiotics and antivirals (as well as other drugs treat some communicable diseases).

On the other hand, the 20th century saw the Spanish flu and HIV/AIDS pandemics and many epidemics. Moreover, the benefits of modern medicine have still not fully penetrated to the ends of the earth. Experts believe that new disease agents will emerge, probably in these under-served areas, with the potential to cause new pandemics.

The virus hunters have been in the vanguard of the public health movements. They remain the front line defense against emerging viral diseases. They are a special breed, often heroic. The History Book Club members present enjoyed beginning to learn about these heroes and their work.

Below are President Obama's recent speech on American leadership in the Ebola response (which was distributed via the club blog) and two posts related to the book by one of our members on his own blog.




Previous blog posts:

11 comments:

  1. Thinking back on the discussion of Virus Hunter, it occurs to me that we might have brought our historical perspective more to bear on the topic. Here are a couple of ideas:

    1. There had been more than 20 Ebola outbreaks recorded in the past, but each had very few cases. This Ebola epidemic has had nearly 23,000 and counting. Why the difference?

    The population of Africa has been growing and people there have been migrating to cities in large numbers. This is the first outbreak that occurred in the resulting densely populated areas rather than sparsely populated rural areas. Thus the likely number of people that could be newly infected by each Ebola victim increased.

    On the other hand, traditional behavior caring for the sick and dealing with death persisted in the more urbanized population. Care givers were exposed to the disease, as were those preparing the dead for burial.

    Urban poverty was clearly implicated. People lived close together in urban slums, housed in shacks with no running water nor connection to sewerage, often sleeping several to a bed. There were few doctors or hospitals, and the poor had little access to those that existed.

    There was little trust of the government -- not unreasonable after civil war and corruption.

    In short, "a perfect storm" of conditions favoring an epidemic.

    2. The 20th century has seen great advances science and technology. How have they affected the approaches to the current Ebola epidemic?

    Lets go back to 1950. At that time Ebola was unknown to science. The public was just beginning to differentiate between bacterial diseases for which there were already some antibiotics and hope for others that could cure other bacterial diseases versus viruses for which there were no curative antiviral drugs but in some cases safe and effective vaccines.

    The field of molecular biology, and the interrelated roles of DNA, RNA and proteins in cell biology has only been developed since the 1950s. Since 1950, a great deal has been learned about the nature of viruses, how they cause disease (at the cellular level) and the immune response that can eliminate viruses from the body. Some antiviral drugs have been put into use for other diseases. Biotechnology has led to new ways to create vaccines and new kinds of tests to diagnose viral infections.

    Currently there are three experimental Ebola vaccines, each made by a process that could not have been understood in 1950. So too, there are several antiviral drugs being tested for use against Ebola; they function in ways that would not have been understood in 1950. One prospective drug potentially useful against Ebola virus is produced in genetically engineered tobacco plants, something that might not even have been imagined then. The tests used in laboratories -- that have relatively quickly confirmed some 13,000 cases of Ebola infection -- use techniques that had not been invented in 1950.

    Advances in transportation and communication technology since 1950 made it possible to mobilize a global response to the epidemic, moving thousands of people to the countries affected as well as tons of equipment. Computers are being used to analyze cell phone records to map the epidemic. Indeed, telecommunications advances and even radio and television technologies new to Africa since 1950 are being used by those responding to the epidemic.

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  2. Norm wrote on our listserve:

    "There may have been another contributing factor as well. In 1972 I was sent to Liberia to start a rural health program in Lofa County, the impoverished northernmost part of Liberia – in the section where Liberia, Sierra Leone and Guinea meet. All went well, and I met with President William Tolbert to resolve the last barrier, start a training program and other details. We had an ambulance in place before I even started home for final approval by AID. But it wasn’t operational for long. A few years later a Krahn enlisted man murdered Tolbert, made himself a general, and launched one of the most incompetent governments ever. He was followed by Charles Taylor, a mass murderer in both Liberia and Sierra Leone, and somewhere in this mischief the Lofa County health project evaporated. It had been located in the exact spot where the Ebola virus entered Liberia, very close to its origin in Guinea. If it had survived, it might have been of help in containing the virus and in alerting JFK Hospital in Monrovia, with which it was linked. But by the time the virus struck, there was pandemonium and no remaining health facilities there. It held a populace that was not only impoverished but also in a battle zone where no public resources of any sort existed."

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  3. "From the mid-1970s to the mid-1980s, Bolivia made slow but steady progress in improving the health conditions of its population. Life expectancy rose from forty-seven years in 1975 to nearly fifty-one years in 1985. During the same period, the mortality rate dropped from 18.4 to 15.9 per 1,000 population, while the infant mortality rate dropped from 147.3 to 124.4 per 1,000 live births." http://www.country-data.com/cgi-bin/query/r-1579.html

    The figure of one out of six to eight babies dying before reaching the age of one is perhaps more favorable that it should have been. As I recall the definition at the time of a live birth involved both survival for 24 hours and not born with major birth defects. U.S. life expectancy at birth (not the highest in the world) is currently 78.74 years. Health conditions and health services in Bolivia at the time Drs. Lebow and Peters worked there were not good!

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  4. Fast diagnostic test for Ebola approved. "The so-called ReEBOV Antigen Rapid Test involves putting a drop of blood on a small paper strip and waiting 15 minutes for a reaction in a test tube. It is able to correctly identify about 92 percent of Ebola infected patients and 85 percent of those not infected with the virus, the WHO said." http://www.huffingtonpost.com/2015/02/20/who-approves-breakthrough_n_6719770.html

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  5. An article in the current issue of The Economist indicates that the rate of finding new cases of Ebola in West Africa is higher in February than it was in January. Moreover, many new cases are not in contacts of known cases that were being followed, suggesting that there are undetected cases unknown to public health officials. The article also suggests that with the rainy season coming soon, case finding and contact tracing is going to become more difficult. Thus it might be even more difficult than previously thought to "get to zero". I would hate to see Ebola become endemic in West Africa, available to trigger new epidemics there and elsewhere.

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  6. An article in The Economist notes that the Ebola epidemic in West Africa is almost contained after it "has infected some 25,000 people and killed more than 10,000 of them—almost all in Guinea, Liberia and Sierra Leone." The article goes on to emphasize that the world needs greater protection against the emergence of major epidemics and pandemics: "Unfortunately, only 64 of the 194 members of the World Health Organisation (WHO) have surveillance procedures, laboratories and data-management capabilities good enough to fulfil their obligations under an agreement known as the International Health Regulations. This, though, is changing. In Africa, Ethiopia, Rwanda and Uganda have sharpened up. So has Vietnam. America is now helping 30 other countries, including the three affected by Ebola, to follow suit while, at the same time, improving their networks of clinics. Groups of neighbours are also coming together to form regional surveillance networks that can follow outbreaks across borders. Researchers in Cambodia, China, Indonesia, Laos, Thailand and Vietnam, for example, have formed what they call the Asian Partnership on Emerging Infectious Diseases Research."

    http://www.economist.com/news/science-and-technology/21646714-ebola-epidemic-draws-gradually-its-close-how-should-world-arm

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  7. The Frontline TV series aired a program on public television on the Ebola epidemic in West Africa. It made the point that the countries involved and the international public health community were not prepared to deal with a major outbreak of Ebola (even though such an outbreak had been predicted in Africa for many years). It also suggests that in Liberia (where we may hope that the epidemic has been stopped), it was changes in the public behavior that ended the epidemic. I fear that even with this warning, the world has not yet developed an adequate system to respond to the threat of epidemics of emerging diseases.

    Few Americans are able to understand how desperately bad living conditions and health services are in large parts of Africa -- areas with hundreds of millions of inhabitants. I worked in Latin America as a health planner many years ago, and although Latina American conditions are better than those in Africa, I have some idea of the desperation faced by people in Africa when confronted by Ebola. For most in developed countries, this TV program will be hard to watch, but it should be mandatory viewing.

    http://www.pbs.org/wgbh/pages/frontline/health-science-technology/outbreak/could-officials-stopped-ebola-outbreak-sooner/

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  8. The good news is that the Ebola epidemic appears to have ended in Liberia and new cases are way down in Sierra Leon and Guinea. There is also bad news. It appears that men may be able to transmit Ebola virus in semen for much longer than previously thought. Moreover, many long term dangers are appearing in those who appear to have recovered from the acute phase of the Ebola infection, including eye infections that can lead to blindness.

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  9. The good news is that the Ebola epidemic appears to have ended in Liberia and new cases are way down in Sierra Leon and Guinea. There is also bad news. It appears that men may be able to transmit Ebola virus in semen for much longer than previously thought. Moreover, many long term dangers are appearing in those who appear to have recovered from the acute phase of the Ebola infection, including eye infections that can lead to blindness.

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  10. Ebola situation report - September 2015

    There were 3 confirmed cases of Ebola virus disease (EVD) reported in the week to 30 August: 2 in Guinea and 1 in Sierra Leone. The case in Sierra Leone is the first in the country for over 2 weeks. Overall case incidence has remained stable at 3 confirmed cases per week for 5 consecutive weeks. In addition, the number of contacts under observation continues to fall, from approximately 600 on 23 August to approximately 450 on 30 August. Of those, over 400 are located in Guinea. All 48 contacts under follow-up in Sierra Leone are associated with the most recently reported case from the western district of Kambia, which borders Guinea.

    http://zunia.org/post/ebola-situation-report-september-2015

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