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The Ebola Wars: The best article I’ve seen yet

The New Yorker has the best article I have read yet on the Ebola outbreak. Finally we get human story and details of how this outbreak started and spread, along with the outstanding heroic efforts of those on the front line. The article has details on everything, the genetics, the virology, the story of escalating fear as health workers started to get infected, and the hard decisions.

Who would get doses of ZMAPP, and which other experimental therapies would be tried?  ZMAPP is the genetically engineered copy of antibodies against Ebola, and it does appear to be useful, even though it has not been properly tested. Kent Brantly, the US doctor who contracted Ebola, improved within hours of receiving ZMAPP. His recovery was so fast his medical staff wondered if it were possible, but his colleague Nancy Writebol did not show the same progress.

Know thy enemy: only six proteins and one line of code, yet so incredibly deadly. The virus is not one virus, but a swarm of particles — an evolving population.

Since Ebola makes errors as it replicates, each genome was like a hand-copied text, and detectable differences would emerge among the genomes; there isn’t just one “strain” of the virus. Ebola is not a thing but a swarm. It is a vast population of particles, different from one another, each particle competing with the others for a chance to get inside a cell and copy itself. The swarm’s genetic code shifts in response to the changing environment.

As far as the the current news goes, I am heartened that so far there are no new cases spread from the two Texas Nurses. That is a good sign. Their contacts are not out of quarantine yet, but the peak incubation period is 6 -12 days.  Amber Vinson flew on Oct 10 and 13.

The simple particle of information and the devastating medical progression:

The virus is extremely infectious. Experiments suggest that if one particle of Ebola enters a person’s bloodstream it can cause a fatal infection. This may explain why many of the medical workers who came down with Ebola couldn’t remember making any mistakes that might have exposed them. One common route of entry is thought to be the wet membrane on the inner surface of the eyelid, which a person might touch with a contaminated fingertip. The virus is believed to be transmitted, in particular, through contact with sweat and blood, which contain high concentrations of Ebola particles. People with Ebola sweat profusely, and in some instances they have internal hemorrhages, along with effusions of vomit and diarrhea containing blood.

Despite its ferocity in humans, Ebola is a life-form of mysterious simplicity. A particle of Ebola is made of only six structural proteins, locked together to become an object that resembles a strand of cooked spaghetti. An Ebola particle is only around eighty nanometres wide and a thousand nanometres long. If it were the size of a piece of spaghetti, then a human hair would be about twelve feet in diameter and would resemble the trunk of a giant redwood tree.

Once an Ebola particle enters the bloodstream, it drifts until it sticks to a cell. The particle is pulled inside the cell, where it takes control of the cell’s machinery and causes the cell to start making copies of it. Most viruses use the cells of specific tissues to copy themselves. For example, many cold viruses replicate in the sinuses and the throat. Ebola attacks many of the tissues of the body at once, except for the skeletal muscles and the bones. It has a special affinity for the cells lining the blood vessels, particularly in the liver. After about eighteen hours, the infected cell is releasing thousands of new Ebola particles, which sprout from the cell in threads, until the cell has the appearance of a ball of tangled yarn. The particles detach and are carried through the bloodstream, and begin attaching themselves to more cells, everywhere in the body. The infected cells begin spewing out vast numbers of Ebola particles, which infect more cells, until the virus reaches a crescendo of amplification. The infected cells die, which leads to the destruction of tissues throughout the body. This may account for the extreme pain that Ebola victims experience. Multiple organs fail, and the patient goes into a sudden, steep decline that ends in death. In a fatal case, a droplet of blood the size of the “o” in this text could easily contain a hundred million particles of Ebola virus.

The end stage decline can start suddenly:

Around seven o’clock that evening, Plyler went to Brantly’s house to see how he was doing. When he looked in the window, he was stunned. Brantly had abruptly gone into the end-stage decline. His eyes were sunken, his face was a gray mask, and he was breathing in irregular gasps. “A clinician knows the look,” Plyler told me later. “He was dying.” Brantly, a clinician himself, realized that he was on the verge of a breathing arrest. With no ventilators at the hospital, he wouldn’t make it through the night.

Plyler made a decision. “Kent, I’m going to give you the antibodies.”

One promising treatment — ZMapp seems to work, but not in all people

The plan was to drip the first dose into him very slowly, so that the antibodies wouldn’t send him into shock. Plyler stayed by the window and prayed with Brantly. After less than an hour, Brantly began to shake violently, a condition called rigors. It occurs in people who are near death from an overwhelming bacterial infection. Plyler had a different feeling about these rigors. “That’s just the antibodies kicking the virus’s butt,” he told Brantly through the window. Three hours later, Lisa Hensley got a text from Lance Plyler: “Kent is about halfway into the first dose. Honestly he looks distinctly better already. Is that possible?” Hensley texted back to say that monkeys on the brink of death had shown improvement within hours.

Brantly also received blood from a survivor — (I think) from an American virologist named Lisa Hensley who contracted Ebola years before in a lab accident. She still works with Ebola. She was the one who advised Brantly on all his options:

She couldn’t tell him what to do. “These are all very personal decisions,” she said. Then she told him that she had been exposed to Ebola, sixteen years earlier. At the age of twenty-six, working in a spacesuit with liquids full of Ebola particles, she had cut her finger with scissors, which had gone through two layers of gloves. The only experimental treatment at that time was a horse serum made by the Russians; this could kill her, and she had decided not to use it unless she was certain that she had contracted Ebola.

One of the heroes of this story is Humarr Khan, he was viewed as a national hero in Sierra Leone. Only 30 years old, but already a doctor who had stepped up to treat the untreatable, feared Lassa fever. He worked the Ebola ward, and kept working when other staff fled in fear:

‘Khan worked long hours in the Ebola wards, trying to reassure patients. Then one of the nurses got sick with Ebola and died. She hadn’t even been working in the Ebola ward. The virus particles were invisible, and there were astronomical numbers of them in the wards; they were all over the floor and all over the patients.

Daniel Bausch, an American Ebola doctor who had been helping at Kenema, and his colleagues recently wrote that Khan had remarked, “I am afraid for my life, I must say. . . . Health workers are prone to the disease, because we are the first port of call for somebody who is sickened.” They also quoted Khan’s sister Isatta as saying, “I told him not to go in there, but he said, ‘If I refuse to treat them, who would treat me?’ ” Perhaps Khan was thinking of his predecessor Dr. Conteh, dying in his own ward.

He told her, “I have to do everything I can to help these people,” and then he would put on his gear and go back into the Ebola wards. Khan was a general in a battle where many of his troops were dead or fleeing.

Humarr Khan did contract Ebola in late July, and moved himself to a different hospital where there were Ebola experts because ” he didn’t want his staff to see him develop symptoms and he felt that his presence would further demoralize them.” Doctors treating him put a worldwide call out for help, and agonized for three days whether to give him ZMapp, but decided against it, because it was so experimental (it had not been used on Brantly or Writebol yet) and there was no intensive care unit in the hospital he was treated in. Tragically he did not survive. I don’t know if someone tried to give him blood from a survivor.

Could it go properly airborne? Unlikely, but it could still evolve to be so much worse than it is.

As I mentioned, there is a spectrum of “airborne” transmission, and Ebola is possibly at the very lowest end of that spectrum. It is unlikely to ever be spread like Influenza is but that does not mean it can’t change in ways that make it far more contagious. Almost all viruses evolve to be more easily spread, and usually that means with a lower mortality. But with a 70% fatality rate, there is so much potential for the virus to be half as deadly, but twice as infectious, and therein lies a nightmare of epic proportions. When Preston refers to “airborne” he is referring to the higher end of the spectrum. He found a expert with a different way of explaining the conundrum.

The question often asked is whether Ebola could evolve to spread through the air in dried particles, entering the body along a pathway into the lungs. Eric Lander, the head of the Broad Institute, thinks that this is the wrong question to ask. Lander is tall, with a square face and a mustache, and he speaks rapidly and with conviction. “That’s like asking the question ‘Can zebras become airborne,’ ” he said. In order to become fully airborne, Ebola virus particles would need to be able to survive in a dehydrated state on tiny dust motes that remain suspended in the air and then be able to penetrate cells in the lining of the lungs. Lander thinks that Ebola is very unlikely to develop these abilities. “That would be like saying that a virus that has evolved to have a certain life style, spreading through direct contact, can evolve all of a sudden to have a totally different life style, spreading in dried form through the air. A better question would be ‘Can zebras learn to run faster?’ ”

There are many ways by which Ebola could become more contagious even without becoming airborne, Lander said. For example, it could become less virulent in humans, causing a milder disease and killing maybe twenty per cent of its victims instead of fifty per cent. This could leave more of them sick rather than dead, and perhaps sick for longer. That might be good for Ebola, since the host would live longer and could start even more chains of infection.

Richard Preston has done excellent work and a lot of research to put this together in the New Yorker. It is a long feature article with so much more detail than I have seen elsewhere. I found it fascinating.

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