8

Tania Can’t See It

Henry was even paler, his pronouncements more clipped.

Were they wasting their time?

Tania first met Kai when he was ten years old. Henry and Kamila had invited their colleagues from the university over for dinner. They ate duck and looked out over Lake Geneva, and the conversation sparkled like the champagne in their glasses. Everyone had brought their partner. Tania was with her boyfriend. A PhD student, she was the youngest in the group. She had been working for Henry for two years. He had never mentioned Kai.

The ten-year-old was slender and lovable, she recalls, and anything but quiet. He knew how to draw attention to himself. He wandered around and started a conversation with everyone, about bowling and swimming, about himself and his family. It was a pleasure to listen to him. What a bright boy, she said to herself. On the way home, she was surprised to hear her boyfriend say:

“Now, that’s a weird kid.”

“Weird?” Tania replied. “He’s just a child.”

“No, no,” her boyfriend said. “Something isn’t right there.”

Tania didn’t give it any more thought. On Monday, back in the lab, she thanked Henry for the lovely evening; she had already forgotten her boyfriend’s comment. Henry didn’t follow up either. He was never one to chat about his son’s autism.

In retrospect, Tania is glad she didn’t know. The doctoral student has since become a professor who now works in Basel. “If I had known, the pressure would have been too great,” she says. Perhaps she would have rejected the job, turning down the man who showers her with praise until this day. “Henry isn’t everyone’s buddy, but he impresses me a lot. Every time I run into him, even for only five minutes, I’m once again astounded how smart he is.” Henry should consider himself lucky that Tania took the position, for she would give his research a decisive push.

Tania had no idea what awaited her when she stepped into the dean’s office. She was one of the smartest students in the country, had won prizes in chemistry and quantum physics, but her dissertation topic wasn’t satisfying to her. She told the dean she wanted to transfer. Didn’t the EPFL have a new science department? Might there be something for her there? “Well, yes,” the dean said, nodding his head, he might have something for her. The university was expecting a remarkable professor. Neuroscientist Henry Markram—she had surely heard of him—had been courted by the world’s best universities but ended up choosing their institute. Markram had big plans and could certainly use a gifted person like her. Could she imagine transferring to neuroscience? He knew she was a chemist, but wasn’t the brain mostly chemistry, anyway? Her prize in physics had proven her versatility.

The dean gave her Henry’s telephone number, said she could say he referred her, and soon she was sitting across from the new star professor. Five minutes into their conversation, she thought: This is what I want to do.

Henry didn’t even look at her résumé. “When can you start?”

Two months later, she was sitting in one of the best labs in the world, surrounded by vials and test tubes, centrifuges and microscopes, the best computers and tools. Henry told her that he wanted to go further than any autism researcher before him. This meant not only measuring brainwaves and counting neurons but delving as deeply as possible into the cells and understanding how they communicate. Through this precision work, he wanted to get to the bottom of Merzenich’s thesis and closely study the faulty inhibitory neurons.

She would be responsible for creating an animal model—breeding autistic rats. He had already done the groundwork. Mercury, alcohol, and the drug thalidomide didn’t seem to do the trick. But there was this epilepsy medication. She could take a look at it and feel free to make recommendations of her own. Tania took off to the library and pored through the relevant books. She went to the database, scrolled through the right pages, and eventually came upon a frightening study. Some people who suffered from epilepsy had been prescribed a medication called Depakote, which contained an agent called valproic acid (VPA) that seemed to do a good job alleviating seizures. In pregnant women, however, it had proven to have horrific side effects, one of them being that nine in every hundred newborns developed autism.

Many years later, in 2017, France would establish a fund to compensate women who had been prescribed the drug during pregnancy.

Scientists had since discovered that VPA also caused autism in rats, which closely resembled the human disorder, causing reclusiveness and phobias. To induce the disorder, one needed to administer the medication to the animal on the twelfth day of pregnancy, when the neural tube closes. Tania rushed into Henry’s office: “I’ve got it!”

The work began. Tania had her difficulties with the patch clamp, the method of measuring a cell’s electrical currents that had earned Henry’s mentor Bert Sakmann and his colleague Erwin Neher the Nobel Prize. It required great skill. She had to work with a tiny artificial hand, a micromanipulator, which translates crude human movements into fine mechanical ones.

She took one of the rat brains, which lay there like a loaf of bread, and started cutting razor-thin slices off it, 0.3 millimeters that contained a million neurons. She submerged the slice in oxygenated brain fluid to prevent it from dying and then used a glass micropipette to stab into the brain cell—into the inhibitory neuron. The procedure calls to mind images of artificial insemination, when the sperm is inserted into the egg, but the brain cell is a hundred times smaller. A tiny flake hung on the end of the pipette, a membrane patch. With tiny hand movements and big physics, you could use it to measure the cell’s electric currents, monitor how it fires when exposed to stimuli. In the lab, electrical impulses provided this stimulation, rather than, say, a dancing cobra. If the cells proved to be talking to each other less, this would bolster Henry’s thesis. Perhaps a medication could be developed to remedy the flaw. It was important research: Tania was inspired by the task. Now this was a dissertation topic!

Working on a cell is an achievement all by itself. Scientists spend whole workdays “hunting them,” trying to “catch” a single one at the right angle. Henry, on the other hand, had developed a technique and a certain dexterity that allowed him to measure up to twelve cells at once. This allowed him to monitor not just the activity of one cell but the communication between several. He could see whether one cell was talking to other cells and if the other ones could hear it.

Henry taught Tania the technique and their work progressed. She cut slices; adjusted the microscope, an inverted one that looks up from below; spent hours adjusting the micromanipulator; and stabbed into the cell, measured its currents, and compared the numbers to old studies. It seemed almost jinxed: the values suggested nothing unusual. Measurement after measurement, cell after cell, everything appeared normal; the inhibitory neurons were doing their job. Meanwhile, in the cerebral cortex, where the higher cognitive functions are located, the cells responded more intensely than usual. This was the exact opposite of what they had predicted. Weird: an autistic brain that overreacts. What on earth was going on?

Henry kept looking over her shoulder. Were the measurements correct? Had they made a mistake? Was the gauging station programmed correctly? Had she used a vibration isolator? Was the Faraday cage correctly arranged, blocking off outside currents and friction that could skew the results? Was Tania having trouble with the subtle handiwork of the patch clamp?

Tania’s anxiety swelled as the months passed. The dean awaited her dissertation, while Henry’s looks grew more concerned. She had nothing to show either of them. High-flying Tania was stuck. “Look for another topic,” her lab advisor, Gilli, suggested. “Nothing will come of this.”

Henry, her mentor, showed his face less and less. When he did, he was even paler, his pronouncements more clipped. Why should he waste more time on these rats! Did they need another animal model? Another thesis? Another PhD student? What could he change? Things couldn’t go on this way. Henry had lost four years to these inhibitory cells. He had blown his first research grant on them in Israel, frittered away two years of research in Lausanne, and he had precisely nothing to show for it. Four damn years had passed since Kai had petted that damn cobra, since Henry had sworn to dedicate his knowledge to something useful. In those four years, he had made no progress whatsoever. In the meantime, Kai had regressed considerably. Henry found it harder than ever to reach him in his world.