Mano-a-Mano

First documented lethal human to human transmission

First, her chickens died. Then, her niece died, coughing blood as she expired in her mother’s arms.⁴⁷² In 2005, the New England Journal of Medicine reported the first documented case of deadly human-to-human transmission. Until that point, nearly all of the human deaths had “involved people who lived or worked with poultry, poultry meat or eggs in Southeast Asia.”⁴⁷³ While the 11-year-old niece was exposed to sick chickens while living in a village with her aunt, her mother arrived from the Bangkok suburbs to care for her and had no known exposure to chickens, sick or otherwise. The day after the funeral, the mother started to feel sick too, and after severe illness, died. The aunt also fell sick, but recovered.⁴⁷⁴ Both she and her sister tested positive for the same virus that had killed the child.⁴⁷⁵

The report sent shivers down the spine of the scientific and medical community.⁴⁷⁶ In the week following the report, the European science publication New Scientist ran an editorial titled, “Bird Flu Outbreak Could Kill 1.5 Billion People.”⁴⁷⁷ The top UN animal health official spoke of an “enormous sword of Damocles” hanging over the world.⁴⁷⁸ The director of the U.S. Centers for Disease Control and Prevention described it as the number-one health threat in the world and called it a “very ominous situation for the globe.”⁴⁷⁹ Upon hearing the news, a Johns Hopkins University infectious disease specialist said, “I think people were delusionally hoping that it would never be transmitted from person to person and that would save us.”⁴⁸⁰ The head of the World Health Organization in Asia held a press conference. He said: “We at WHO believe that the world is now in the gravest possible danger of a pandemic.”⁴⁸¹

The case compelled Thailand to launch a massive search for other cases of human spread, involving as many as one million volunteers going door-to-door. Thankfully, no further clusters of cases were found.⁴⁸² The virus still has some learning to do. Currently infection requires more than just a sneeze, a handshake, or a breath. So far, all officially suspected human-to-human transmissions have involved “close physical contact that included hugging, kissing, or cuddling the infected individuals to whom they were exposed.”⁴⁸³

H5N1 is a gifted learner. Grasping the mutant swarm concept is critical to understanding how the virus got from strain A to Z+, and how it may get from Z+ to the pandemic strain. One individual may theoretically only be infected by a single virus particle, but one infected cell can start sloppily churning out millions of mutant progeny. H5N1 has a large graduating class. This dynamic mutant swarm breaks out and tries to reinfect other cells. The ones that are best at infecting further human cells are naturally selected to live long and prosper, passing on their genes. Only the strong survive; it’s a mammoth campaign of trial and error.

Out of millions of competing viruses, the ones whose N spikes best worm their way through human mucus, the ones whose H spikes are best at unlocking human cells, the ones with NS1 proteins that best block human interferon—those are the ones that may best survive to make millions more in the next cell. By death, their hosts’ lungs are saturated with more than a billion infectious viral doses per ounce of tissue.⁴⁸⁴ “The clock keeps ticking,” Webster frets. “Every time this virus replicates, it makes mistakes. Sooner or later it will make the mistakes that will allow it to go human-to-human.”⁴⁸⁵

Michael Osterholm, the director of the University of Minnesota’s Center for Infectious Disease Research and Policy, compares H5N1 to a computer hacker. “We’re providing that virus every opportunity. I mean every day, every second, is an evolutionary experiment going on in Asia. You know, it’s like a computer hacker that has a program that will figure out what a nine-digit security code is. If they have enough time and there’s nothing to stop them, they can just run the program until all nine numbers work.”⁴⁸⁶

Senate Majority Leader Bill Frist, M.D., compares H5N1 to a gambler. From the floor of the Senate, Frist explained: “Billions of mutations of the virus are occurring every day. With each mutation, the virus multiplies its odds of becoming transmissible from human to human. It’s like pulling the lever on a Vegas slot machine over and over again. If you pull enough times, the reels will align and hit the jackpot.”⁴⁸⁷

In the end, the virus that wins, the virus that succeeds in making the most copies of itself, is the virus that outperforms the others, passaging through thousands of individual cells to learn how best to infect the human species. It is that virus which gets breathed into the next person’s lungs and the process starts all over so the virus can get even smarter.

Within a single individual, the virus is evolving, adapting, learning. It hits dead ends and tries something new, slowly notching up mutations that may lock into place the ability to effectively survive in, and transmit between, people. Every single person who gets infected presents a risk of spawning the pandemic virus. Describes one virologist, “You’re playing Russian roulette every time you have a human infection.”⁴⁸⁸ One day soon, experts fear, with more and more people becoming infected, the virus will finally figure out the combination—the right combination of mutations to spread not just in one elevator or building, but every building, everywhere, around the globe. One superflu virus. It’s happened before, and experts predict it may soon happen again.