Science Masters Killer Viruses, Debates Their Disposal : Medicine: Smallpox has been conquered by vaccine. A few frozen viral samples are all that’s left on earth. Should they be preserved or destroyed?
Here, in the bland buildings of the Centers for Disease Control and Prevention, is a murderers’ row of hundreds of killer viruses, guilty of uncounted millions of human deaths over the ages. They languish in deep frozen sleep.
But they pose a dilemma.
What should science do with a killer virus when it has been rendered helpless? Some call for its execution. The instant culprit is smallpox, but there are others condemned to Death Row.
Together, these tiny threadlike strands have ravaged the human race from time unremembered, stifled human progress more than all the wars humans have waged upon each other.
In the viral kitchens of CDC one need only add living cells, water and oxygen to the dried and frozen viruses to re-create their ancient lethal brews. The value of this catalogue of viruses is not questioned. In the recent outbreak of a mystery disease in the southwestern United States, the guilty agent was tracked down, even though it was not considered one of the prime suspects, through the viral archives of CDC.
One of the viruses on store here is what many consider the most lethal known to man.
It is the Zairean strain of the Ebola virus, fetched from the sick and dying of Central Africa. It is still active in the wild; it can kill in days and spread faster than a California wildfire. The value of keeping the captive virus is not in question.
The value of captive smallpox virus is. The World Health Organization proclaims the disease eradicated from the earth and calls for destroying the virus.
The few remaining samples are carefully stored in deep freezes at this center and in Moscow.
Scientists hope to decide their fate by this spring.
Smallpox is the first killer virus to reach the status of dispensable.
Polio is approaching that point. It has been wiped out in the Western Hemisphere and faces the same fate elsewhere on earth before the century is out.
Smallpox poses a unique predicament. Incinerate it, or keep it against an unforeseen recurrence, for further study, or just as a reminder of the unkind side of Mother Nature. The ethics may be easier with nuclear warheads and poison gases.
Viruses are tougher. In 1967 when the World Health Assembly resolved to wipe out smallpox with the use of an effective vaccine and concentrated public health measures, more than 40 countries were still fighting the disease within their borders. Ten years later the last natural case was recorded in Somalia.
In the waning months of the disease, there was a $1,000 reward posted for information leading to any case of the disease. Humankind is the only natural reservoir for the variola virus which causes smallpox. Likewise, polio.
But even on the ropes, variola, transmitted mostly through the air, is an insidious enemy. Dr. Brian Mahy, director of the division of viral and rickettsial diseases at CDC, outlined some slip-ups along the way.
“In 1973, a vaccinated woman who had observed egg inoculation with variola virus at the London School of Hygiene became ill, and before her smallpox was correctly diagnosed she infected another patient at the hospital. Two persons who visited the secondary case subsequently contracted smallpox and died.
“A worse tragedy occurred in 1978 at Birmingham University (a year after the virus was adjudged eradicated in the wild) where a 40-year-old photographer became infected with the Abid strain of variola virus that had apparently leaked through a service duct from a laboratory where experimental research on the virus was being carried out. Filled with remorse, the poxvirologist who was head of the laboratory took his own life a few days before the photographer herself died of smallpox.
“Although vaccination of persons believed to be at risk successfully contained a potential outbreak of the disease, the photographer’s 70-year-old mother also became infected, even though she had been previously vaccinated. She was the last person to replicate variola virus, and fortunately she survived.”
Dr. Mahy, who has encouraged debate on the question of smallpox destruction, has himself voted for it.
In sum, the argument is that the agent is too deadly to be tolerated and once the genetic sequence of the virus is documented there is no further need for it.
Prof. Colin Howard, head of pathology and infectious diseases at the Royal Veterinary College, London, said there is still much work to be done. Not all of variola’s secrets are known.
He asks what Edward Jenner, the 18th-Century English physician who discovered the original smallpox vaccine, would say. “I am sure Jenner’s natural curiosity would have exceeded his desire to accede to popular opinion.”
Besides, if danger is measured by virulence alone, then what of other more virulent viruses? “Are we to destroy stocks of all pathogens once they are eliminated?” Howard asks.
Even when the smallpox genetics are completely known, it will be very difficult to synthesize the virus again, so once gone, all gone.
Scientists know the genetics of the maverick that is the Ebola virus. It kills 88% of the people it infects, as opposed to 40% in the most severe outbreaks of smallpox.
The difference is science has a very effective vaccine against smallpox. “In the case of a virus like Ebola,” said Mahy, “we have absolutely no vaccine, no treatment. . . . We don’t know where it comes from. Despite an enormous amount of investigation, it’s never been determined where this virus resides. Fortunately or unfortunately, it’s a virus that has only occurred in a couple of isolated epidemics.”
Scientists here have shown in laboratory work that the virus is “absolutely lethal” to non-human primates, but nothing else is sure except that 274 people died out of just over 300 infected in one outbreak in the late 1970s in Zaire.
The Ebola work is curtailed, said Mahy, because of the crisis in the southwest, in which CDC scientists in the Special Pathogens Division were able to pin to a most unlikely virus.
Special Pathogens deals with all sorts of organisms which require the most stringent laboratory safety procedures, and this crosses all types of viruses.
It studies a flock of viruses besides Ebola which kills in four or five days but may appear to be quicker--two days from the onset of symptoms. It also studies the Lhasa virus which kills up to 50% of those hospitalized within 14 days.
In 1990 there was a Lhasa fever case in Chicago, when a man came home to his father’s funeral, became sick and died within 48 hours, but not before his mother and sister were infected and also died. Isolation was the only weapon public health doctors had to confine the disease.
But the major mandate at CDC is to be the barrier between the world’s killing stock and the U.S. citizen.
Viruses are known tricksters. The influenza viruses, for instance, are in constant change.
And last spring nobody knew what it was that began striking down people in the American Southwest until CDC went back to its biological laboratory and sent its detectives into the wild.
It became “an interesting opportunity,” said Dr, Thomas Ksiazek, chief of diagnostics for Special Pathogens. “This could be held up as an example of how modern science can be brought to bear in a rapid way on what appears to be a new problem.
Cases didn’t appear until early to mid-May when the state health department in New Mexico was notified.
They looked in vain for a match with standard respiratory pathogens known to attack the lower respiratory tract.
CDC was called in by May 23.
Epidemiologists were sent to New Mexico to document the pattern of the disease. How many cases were there? When? Where? Were they all of one particular form? They used statistical techniques to try to pinpoint the most likely causes of the disease.
When biological samples became available, they were sent to Atlanta where specialists in all the pathogens were alerted.
Around the Memorial Day weekend, Special Pathogens began dividing up the specimens between scientists schooled in bacterial diseases, rickettsial diseases, viral diseases, parasitic diseases and possible environmental contaminants.
No one knew what they were looking for, least of all the virologists. There were 25 or 30 probabilities, hundreds of possibilities.
“Quite frankly the Hanta virus was the furthest thing from our minds,” said Tsiazek.
Dr. Tsiazek and Dr. Pierre Rollin, a French physician working as chief of the pathogenesis section, sifted through about 40 specimens on a weekend and found antibodies to the Hanta virus in about a third.
“This was the first indication that we might be close,” said Rollin.
The Hanta viruses came to U.S. attention during the Korean War, when up to 3,000 United Nations troops were stricken. Early the virus claimed 15 out of 100 of its victims, although as doctors came to know it better the mortality rate went down to 5% or 6%. Since, it has been found around the globe from China to Scandinavia and the major port cities of the United States.
Knowing that Hanta viruses were carried by rodent feces, two scientists drew traps from the CDC stores and went to the scene. From the specimens they shipped back to Atlanta it looked like the deer mouse was carrying a Hanta virus.
Still, the known forms of Hanta killed by acute renal failure. The New Mexico agent killed by respiratory failure. The Special Pathogens branch needed more proof.
That fell to Dr. Stuart Nichol, who began a detailed probe.
He used genetic detection techniques on autopsy materials and rodent feces, pulling up genetic pieces, sequencing them for comparison. They were the same as the virus in humans.
“So now we knew we were dealing with a newly recognized virus and a newly recognized disease,” Nichol said. The difference was that the old virus destroyed the capillaries in the kidney, and the new one attacks the capillaries in the lungs, drowning its victims in their own fluids.
“It took one to two weeks to get really conclusive evidence from serology and from genetic approaches,” said Tsiazek. “In the old days, without all the modern technology, it would take months or years to identify the etiologic agent in a newly emerged disease. And yet here we were in a matter of days actually with an agent nobody suspected.”
Most viral detective work never ends. Influenza is a case in point. In World War I influenza killed almost as many people, give or take a few million, as died in World War II, the world’s bloodiest war. That virus and its sisters and brothers haunt the Earth today.
It is a virus with an incredible ability to change form and dodge the vaccines prepared against it.
There is a widespread reservoir of the disease, not the least of which are the ducks and pigs of China where the virus is alive and well.
“Viruses are not in themselves replicating organisms,” said Tsiazek. “They are the ultimate parasite. They require a living animal cell that is of the right type to provide all of the machinery to replicate their genetic message. If you remove them from that environment where they don’t have living cells, you must keep them very very cold or by some other means, like freeze-drying, remove all of the water and oxygen so that no chemistry is going on.”
Consequently, there is a large library of flu viruses at CDC, and because of a virus’ ability to mutate or reassort itself, the library grows every year. The main flus on file are the Swine flu, the Hong Kong flu and Influenza B. On the basis of reports from the field, the CDC prepares a new formula for its vaccine of the year. There is a worldwide reporting system for influenza.
Meantime, the scientists at CDC keep up their relentless search for answers to hepatitis, HIV, herpes, the more well-known viral entities, as well as the nature of parasitism and infection.
Dr. Joseph McDade, associate director for Laboratory Sciences, said nature’s really successful parasites are very clever. Some, like malaria, that cause persistent infections in people, mutate and change even while in the body. The body develops resistance to the first invader but misses the mutants that follow.
“You have to think about it as a universe. These microorganisms have been with us hundreds of thousands of years. As long as there have been people and primates they have been there. And they know how to make a living and live well. What they try to do actually is live at the expense of their host without killing him. So that disease and especially fatal disease is a failure of the microorganism because it is killing its host.”
