Dr. Frederick A. Murphy Talks about the Ebola Virus
An Interview by Sean Henahan, Access Excellence
The book "The Hot Zone" and the film "Outbreak" have seized
the public's imagination and brought into focus many issues
regarding the very real threats posed by new and emerging
diseases. In this interview we talk with
Frederick A. Murphy,
D.V.M., Ph.D., Dean of School of Veterinary Medicine, UC Davis.
At the time of the 'Reston incident', Dr. Murphy was the director
of the National Center for Infectious Diseases at the CDC in
Atlanta. Dr. Murphy is considered one of the world authorities on
viruses. He was the first one to look at Ebola virus
'face-to-face' in the electron microscope. Dr. Murphy appears in
"The Hot Zone" and his now famous photo of the Ebola virus
appears in the film "Outbreak".
Dr. Murphy has also provided an extensive
three excellent electron micrographs to accompany this interview.
Q: The book "The Hot Zone" and more recently the film "Outbreak" have brought public attention to the reality of emerging viruses
and potentially disastrous epidemics. It can be difficult to
tell fact from fiction with these kind of sources. I'd like to
ask some questions gathered from high school science teachers and
students all over the country to clarify some of the issues
raised by this book and this movie.
A: The public response to the book and the film has been phenomenal. Half of the posts for a virology conference on the
Internet I look at are about the Ebola virus. I myself have had
innumerable calls from the press and other media people. By the
way, I want to say hello to the Access Excellence people and say
I had a great time down at Genentech last summer when I spoke on
the subject of new and emerging diseases.
Q: Please explain how Ebola and the other filoviruses are classified and how they are related to other known viruses?
A: The viruses are classified in the family 'Filoviridae', with one genus, 'Filovirus'. There are four known viruses. We have
Marburg virus and three Ebola viruses: Zaire, Sudan and Reston.
Marburg and Ebola are distinguished by their length when
purified. In the unpurified state you get all different lengths
of these worm-like virions. When they are purified, the
infectivity is associated with a particular particle length,
which is slightly different between the Marburg and Ebola, but
all of the Ebola viruses are the same length.
Q: Considering how similar the Ebola viruses are, how are they differentiated?
A: They are very close. First of all, there is a very small serologic difference among the Ebola viruses which can help
distinguish them. Second, there are sequence differences which
can be determined using the tools of molecular biology.
Q: What have we learned about the Ebola genome, and what remains to be learned?
A: Ebola Zaire has been completely sequenced and Ebola Reston is nearly completed. The gene order of these viruses reaffirms their
independence as a family. Also, some ancient conserved sequences
along with the gene order, i.e. the layout of the genes along the
RNA molecule, put the family 'Filoviridae' into an order, the
only order in virology, 'Mononegavirales' This emphasizes the
ancient phylogenetic connection between three families-
'Filoviridae', 'Paramyxoviridae' (measles, mumps) and
'Rhabdoviridae' (rabies). There is no connection with HIV.
Q: Let's talk about the pathogenicity of Ebola. How does Ebola virus infect humans?
A: In Zaire and Sudan, Ebola virus was spread by close contact
and dirty needles. The center of the epidemic in Zaire involved a
missionary hospital where needles and syringes were re-used
without sterilization. Most of the staff of that hospital got
sick and died. There were secondary cases involving people taking
care of sick people or preparing bodies for burial, but the virus
essentially shut down after that epidemic peaked.
There is something of a misconception that Ebola virus can infect
just about any cell. In fact, the virus has a very specific
tropism for liver cells and cells of the reticuloendothelial
system, e.g. macrophages. Massive destruction of the liver is a
hallmark feature of Ebola Zaire, Ebola Sudan, and Ebola Reston
(the latter in monkeys only).
Q: Ebola Zaire is said to kill nine of ten people infected. What about the surviving one person? Is anything known about natural
resistance to this virus?
A: Starting with Marburg in 1967, there was one fellow who tested positive for the virus 30 days post-infection. In fact the virus
was detected in his semen, and there was a case of sexual
transmission in that circumstance. Another patient had virus in
the vitreous of his eye for more than 30 days. But eventually the
virus died out within these people without killing them. Ebola
too is not persistently carried in the blood and appears to be
self limiting in the surviving patient.
Q: Given that there are some signs of natural immunity to Marburg
and Ebola Zaire, and that the monkey workers were not killed
after exposure to Ebola Reston, does this give us any possible
approaches to vaccine development? Both the measles and rubella
vaccines were based on attenuated viruses.
A: No, I don't think so. I don't think we would know how to select a stable, safe attenuated virus. The kind of research
needed to develop a modified live virus vaccine simply could not
be done given the scope of the problem. That is, you only have a
few people working in labs who would need to be vaccinated, and
you might want a vaccine stockpile in the event of an epidemic,
but these are not the scale of circumstances where we could
afford to develop a vaccine. A killed vaccine is much simpler to
develop, but so far this has not worked with Ebola virus.
Q: On Oct 13, 1976 you prepared a specimen from an African patient with hemorrhagic fever and suddenly realized it might be
deadly serious. Can you tell us what you were thinking at that
A: When I put the specimen in the electron microscope, I was sure it was Marburg. I had worked on Marburg in 1967 and 1968 and had
done a project on experimental Marburg infection in monkeys. The
specimen had come back from Zaire to the CDC in Atlanta in less
than optimal condition, with the tubes in the box broken. Anyone
else would have taken a look and put the whole box in the
autoclave, but Dr. Patricia Webb, wearing gloves, gown and mask,
squeezed a few drops of fluid out of the cotton surrounding the
broken tubes. That was the material the virus was isolated from.
It was placed in tissue culture (monkey kidney cells) for a
couple of days then I got a drop of the tissue culture fluid and
prepared a specimen for the electron microscope. When I saw what
I was sure was Marburg, I shut the electron microscope down and
went back to the room in which I had prepared the specimen. This
was in the days when hoods were a lot more primitive. I "cloroxed
the hell" out of the place where I had done the preparation and
carried my discard pan with gown and gloves etc. to the autoclave
and ran it. Then I went back to the microscope and called Karl
Johnson and Patricia Webb to take a look. I shot a cassette of
pictures and with wet negatives, not good for the enlarger and I
made prints which were available within minutes. I carried these
dripping prints to the office of the Director of the CDC. It was
Q: Then later when Fort Detrick called and said they thought they had found Ebola in Virginia, what was your reaction?
A: The way it is stated in "The Hot Zone", General Russell suggested I didn't believe him. In fact, I took it very
seriously. General Russell himself had enough experience to
recognize Ebola when he saw it. With Marburg 67, it was monkeys
that brought the virus to Europe. In 1976 we had no idea where
the virus came from, so when he said he had Ebola in monkeys I
sure believed him. We went to Fort Detrick the next day.
Q: There are a number of issues concerning the response to an epidemic raised by both "The Hot Zone" and "Outbreak". How well
did these describe the interaction of the various agencies?
A: The movie Outbreak created some false impressions. The law in our country gives the responsibility for epidemic management to
state health departments, with these agencies calling the CDC
when they need help. CDC has no authority to go into a state
except by invitation. The Army could be called in by a state
health department, but to my knowledge this never has happened.
In the Reston incident, the Virginia Health department and the
CDC took over the human health side of the episode and the Army,
at the request of the monkey import company, took over the animal
side. It turned out after lots of surveillance of animal
caretakers and their families that there was no human disease,
but there was plenty of monkey disease. The Army's role involved
depopulating the monkey colony. So the movie Outbreak, where the
Army takes over, is rather fictional.
Q: Has the Reston incident changed the way monkeys are imported and housed?
A: There were a series of CDC investigations after the Reston episode. There was also a complete embargo on the importation of
monkeys for about a year. The CDC then relicensed importers,
denying licenses to those that did not have proper facilities and
staff training. So I would say there has been significant
improvement in this area. Countries that used to export monkeys
are also getting out of that business. primarily for species
The use of captive bred monkeys is absolutely the trend. The goal
is for complete reliance on domestic breeding. We have to stretch
the definition a bit, since there is a huge captive breeding
colony on a small Caribbean island.
Q: Did anyone every figure out how an African Ebola virus ended up in a monkey from the Philippines?
A: No. That's a very good question. We still have no idea where Ebola lives in nature. It was not possible to do field studies in
the Philippines because of a civil war going on in the area the
monkeys came from. Some studies in Africa tried to trace Marburg
and Ebola, but nothing has ever been found.
Q: Are budget cuts affecting the ability of the CDC and other agencies to respond to epidemic outbreaks?
A: Yes. The Army program at USAMRID has been cut quite a bit. Over the past few years the CDC's programs for dealing with
infectious diseases have been nibbled to death by inflation. The
budgets are the same in today's dollars as they were 12 years
ago. In effect these programs have lost half of their purchasing
power, while at the same we've seen an explosion in AIDS and
other infectious diseases.
Q: Such as Hantavirus?
A: Yes, hantavirus is a good example. The same people from CDC and the Army who worked on the new Hantavirus outbreak
previously worked on Ebola. It is a small, wonderful group of
dedicated people. They really have had their budgets whacked. And
then with the emergence of one disease problem after another,
this has really stretched them beyond the breaking point.
Q: Can you give us an update on the Hantavirus situation?
A: It is amazing how quickly the virus was characterized after the first outbreak in the Four Corners area. The virus is
transmitted by breathing dried dust that contains the virus (from
the dried feces, urine and saliva of the mouse vector,
'Peromyscus maniculatus'). The virus could not be grown, so
everything was done by molecular biological means. The first clue
came with the observation of some cross serology with known
hantaviruses. Everything else was done by PCR and partial
sequencing. Six months later they were able to make an isolate.
Since then four different variants of the virus have been
isolated from more than 100 people. It still has a mortality rate
above 50% and has been seen from California to the East Coast and
Florida. It is incredible that this set of variant viruses was
present all along and no one knew it. Although we know the
vector, we also know that controlling this vector, mice, is
We have a similar problem now in California, with all the rains.
The mosquitoes that carry Western equine encephalitis and St.
Louis encephalitis are resistant to virtually every licensed
insecticide. We could have a re-emergence of these virus diseases
The most important mosquito-born disease in the world today is
dengue. This disease is emerging now in all the big cities of the
Caribbean and tropical and sub-tropical America. If you get lots
of dengue and multiple serotypes in an area, you get dengue
hemorrhagic fever. Uncomplicated dengue infection, called
breakbone fever, is like influenza, with all people recovering.
But dengue hemorrhagic fever, usually seen in children, is
deadly. Symptoms include fever, shock, hemorrhaging from the nose
and mouth, respiratory distress and, in some cases, death.
Q: Back to the CDC. What do public health agencies need in order to fight epidemics?
A: The things they need are hard to come by. The National Academy of Sciences, the Institute of Medicine and the CDC have published
plans on what is needed to control new and emerging diseases
better. The plans focuses on better surveillance, better
laboratory diagnostics, better communication and better
education. The plans are very good, but the timing is terrible,
since budgets are so tight, and from what I read in the papers,
budgets will get much worse.
Q: There have been complaints at the vast inaccuracies and dubious details in the film Outbreak. What did you think of this
A: I did see the movie. In fact, in return for the use of the electron micrographs of the virus, Warner Bros. gave us tickets
to the premiere in Sacramento. I thought the early scenes in the
biosafety level 1,2,3, and 4 labs looked pretty accurate. After
that it became fictional, and I enjoyed it as fiction. We know a
virus can't kill someone in an hour. The making of the antisera
in a day was ludicrous. I think all bug movies have a problem,
since once they unleash the bug, there is the problem of
resolving the crisis. Like in the film, 'The Andromeda Strain',
the only way to resolve the story was to have the bug mutate to
become harmless. The real world is not so simple. Fourteen years
into the AIDS epidemic and we still don't have a vaccine or
Q: The CDC is one of two places in the world with remaining specimens of smallpox virus. Both the CDC specimens and the Russian specimens were scheduled for destruction, but have gained a reprieve. Should they be saved?
A: The collections of smallpox specimens at these places are fairly large. CDC has about 500 strains of the virus. It is highly contained in a freezer that is never opened. The WHO also visited the Russian facility and certified its safety.
I was originally in favor of the destruction of these specimens. This was for political reasons, rather than scientific ones. I thought the publicity surrounding its destruction would remind people that we had done something very good. However, within the last two years several different strains of the smallpox virus have been completely sequenced. Some really interesting genes have been found, which may contribute to the understanding of the current consensus is that these kinds of genes must be preserved and studied.
Q: Last question. Any advice for some one considering a career in virology?
A: There are several kinds of virologists. One kind of virologist is a molecular biologist who studies the nature of the virus and how it works. That is the world of molecular biology and cell biology. Virology is also an infectious disease science in the hands of physicians and veterinarians who take specialty training. Virology also interfaces with other areas of biology that have to do with how viruses are transmitted, such as entomology and mammology. The field of virology also includes the whole world of public health and preventive medicine.
The starting point for anyone interested in virology is the undergraduate biology major. Then there is a fork in the road at which the person chooses to seek a degree from a medical school
or veterinary school or to enter a Ph.D program in virology per se. Either way you go, I can say "it's a wonderful life".
More information about emerging diseases and
viruses can be found in Access Excellence
Science Update: Ebola Infection Reported
Dr. Don Francis Talks to Teachers About the Ebola Outbreak
and at the following Web sites
HIV/AIDS (Centers for Disease Control and Prevention)
HIV/AIDS (World Health Organization)
Online Tutorial: Viral Replication
HIV/AIDS Resources (Warts Information Center)
Interview: June 1995. Links updated: 2 August 2009