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Zi Wang Thought He'd Cracked the Toxo Parasite. Then He Made His Breakthrough Disappear 

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While spending most his waking hours in the lab, Wang used his little free time build his skills as a professional magician. - DANNY WICENTOWSKI
  • DANNY WICENTOWSKI
  • While spending most his waking hours in the lab, Wang used his little free time build his skills as a professional magician.

Wang and Sibley started publishing their early results on the dopamine hypothesis in 2015. The Johns Hopkins lab published its results this year in Behavioral Brain Research.

To Sibley and Wang, these studies appeared to be the nails in the coffin of the dopamine theory. The results rocked the Toxo scientific community, forcing researchers — particularly those investigating ties between Toxo and mental illness — to consider alternative mechanisms to dopamine.

Wang certainly isn't the first graduate student to blunder into a theory and wind up staring at its wreckage. But it still leaves researchers with no choice but to start back at the beginning.

"We don't have good candidate for a simple explanation that would replace the dopamine idea," Sibley acknowledges.

The truth is, Toxo's behavior lends itself to a vast number of branching hypotheses and interpretations, and the bug's presence in billions of people means that it can be shown to correlate with any number of things. Could Toxo really be behind schizophrenia? Or depression? Or implicated in untold millions of car accidents? Could it really be manipulating the type of watch you wear?

Maybe, says Sibley. Maybe not.

"On one level it sounds crazy, but there might be something to it. It does cause chronic infection in the brain. It could alter behavior and maybe it makes you less fearful and you step in front of a bus."

What Sibley is certain of, however, is that scientists will continue to perform association studies that draw correlations between Toxo and human behavior, especially psychiatric illness.

"The thing is," he adds, "is that we don't really have a way to alter those outcomes, even if they're true."

Without dopamine, a cogent, simple theory of cause and effect, scientists are left stumbling, searching for a new light to illuminate Toxo's darkness.

Like any good magician, Wang doesn't reveal the secrets behind his tricks. The day after his gig at the benefit gala, Wang shuffles a deck of cards onto a table at a Soulard cafe. Late-morning sunlight streams onto the succession of numbered cards and tranquil royal faces, and the pieces of painted cardboard seem to glow.

"The secrets of magic are ugly," Wang says, squaring the deck in his hands. "They're not entertaining and they're not enjoyable. They're pretty much universally disappointing."

Still, on the condition that the details of his specific methods remained concealed in publication, Wang runs through one of his tricks for a reporter, spelling out each step, each misdirection, each sleight of hand.

He's right about the disappointment, of course. The trick creates, in Wang's words, "impossible suggestions" of movement and space. To a normal audience, it is a captivating wonder that looks like, well, magic — especially when Wang rattles off several variations of the impossible in a manner of seconds.

In fact, the trick is built on several verbal lies, tactical use of body language and blazing-fast hand speed. Wang has spent years training to accomplish more in a half second with one hand than most people could do with five minutes. Even if you know what he's doing, his movements are hard to track.

Visually, the card is resting in your hand. You can feel the glossy surface pressed between your fingers. You can see it entering into a deck at a particular point, and moments later it's in an impossible location on the other side of the table, in a different deck of cards entirely.

Of course, the real magic is happening in Wang's hands, too fast for the eye to detect.

It takes four demonstrations — the final attempt done at quarter-speed — for this slow reporter to finally wrap his head around the mechanism behind the "magic." In a moment, the truth is obvious, and it is a definite let-down. It leaves a sudden stabbing embarrassment. You feel dumb for missing it before.

Wang tries to be reassuring, but he knows, in a way, what it's like. The death of his dopamine hypothesis was crushing. It forced him to wrestle with years of built-up expectation.

Over seven years working towards his Ph.D, Wang had imagined how this breakthrough could make his work famous. He could see the headlines in his mind. "Parasite Turns Rats Crazy: Here's How It Does It."

"I never wanted anything more," Wang says. He's put his cards away. He notes that a Toxo lab in England, which was behind the widely cited 2009 study supporting the dopamine theory, published a 749-word critique of Wang's journal article, alleging his experiment showed methodological and technical flaws. Wang and Sibley responded with a 1,716-word rebuttal.

Other labs are still actively investigating Toxo's link to schizophrenia, and some scientists continue to find interesting links in the parasite's spread to humans. Going forward, though, Wang (and Sibley) consider dopamine a broken hypothesis.

"The stack of evidence has piled up to suggest that whole dopamine idea is wrong, it's pretty high," Wang says bluntly. "It's pretty robust. I wouldn't expect good results at continuing to hammer at it."

Still, it's not like Wang's research produced nothing. As detailed in a 2017 study published in the journal PLOS Pathogens by Wang and colleagues at the U.S. Department of Agriculture, the work on dopamine uncovered something new about H1 that didn't have anything to do with dopamine. Instead, USDA scientists found that H1 actually supplies key materials for building the protective shell around Toxo spores during the reproductive stage inside cats.

When H1 is sliced out of Toxo, the spores are left vulnerable. Without the protection of a sufficiently thick shell, the parasite isn't viable outside the cat.

"It turns that [H1] is not just a precursor to dopamine, it's also a precursor to a lot of structural proteins," Wang explains. "It's probably a precursor of the outer shell that the parasites use to go dormant and form a spore and survive in the environment."

It's not a world-shattering discovery, but it's one in line with the steady, drip-by-drip process of research that's traditionally come out of the Sibley Lab. And there's possible relevance for a future treatment: If the parasite's reproductive cycle can be disrupted, it could stop Toxo's spread.

Asking Wang — or any scientist — to broadly speculate about their work is usually a tricky proposition. At some point, the conversation crosses a line into story and myth, and that's how you get experiments framed around belief and assumption. The story of Toxoplasma is still being written, and, sometimes, erased.

The future of the research continues, in the Sibley Lab and in similar labs across the world. And the tiny parasite continues to be one of the most successful parasites on Earth, reproducing, forming spores and spreading to more hosts. What it's doing in the majority of its human hosts, we still don't know.

Those discoveries could lie years or decades in the future, and it shouldn't be a surprise when new, promising hypotheses arise claiming to unlock the parasite's secrets. Wang has seen Toxo's tricks up close, and he knows how seductive a single, perfect answer can be.

"We all want to see the world the way we believe it to be. It's just human," he muses. "We're so much better at identifying evidence that confirms things we believe already."

For now, Wang — who earned his Ph.D. in 2017 — splits his time between his lab and his magic. During the workday, he investigates and catalogues the physical properties of the world, while on the nights and weekends he gives every appearance of violating the laws of physics with a stack of painted cardboard paper. Every week, Wang the Mentalist leaves a new audience gasping at tricks that they know, deep down, can't be real.

Wang has embraced this life of performative deception, and with it attention and applause. Still, the mystery of Toxoplasma is never far from his mind. The question remains: What is Toxo really doing in the human brain?

It's not for Wang to answer. The next round of discoveries will fall to some other researcher. A scientist with some other beautiful theory. Next time, if they watch closely, they just might glimpse the blur of the parasite's hands.

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