The For-Life Transplant

You could say that Joseph Leventhal is obsessed. Since he was in medical school in the 1980s, he has been pursuing what he calls “the holy grail” of the organ transplant field: a way to thwart the body’s natural instinct to reject its new part. A kidney transplant, for example, means a lifetime of antirejection drugs that can have such serious side effects as diabetes, high blood pressure, and depression. Worse, the patient will likely require another kidney down the road. “If you’re someone in your 20s or 30s, you’re going to need at least one or two more transplants to have a normal life expectancy,” says Leventhal.

Now the director of kidney and pancreas transplantation for Northwestern Medicine’s Comprehensive Transplant Center, Leventhal has created a procedure that could considerably improve conditions for the 17,000 people a year who receive new kidneys. It involves injecting stem cells from the living donor into the patient, thereby altering the response of the recipient’s immune system. “We are essentially tricking the recipient’s body into seeing the donor organ as part of himself or herself,” Leventhal explains.

The procedure would eliminate the need for post-op drugs and additional transplants. Even more remarkable, the donor wouldn’t have to be a genetic match to the recipient, so virtually anyone could provide the organ.

Initial tests look promising. Twenty-seven patients have received the new kind of transplant since 2009. Of the 19 who have hit the two-year mark, 12 have come off antirejection medication entirely without losing normal kidney function. “A success rate like that for people who are mismatched and unrelated hasn’t been achieved before,” says Leventhal.

Further testing is needed, but Leventhal is hoping the procedure becomes routine by the end of the decade. He’s also working on another way to improve the body’s acceptance of a new organ: by extracting, multiplying, and reinjecting a patient’s own regulatory T cells. If it’s successful, the procedure could work with organs from deceased donors as well—a big step forward.

Leventhal notes it’s been especially gratifying to produce these breakthroughs in Chicago, an often-underestimated city in the realm of scientific research. “The big kids on the block were in Boston and Palo Alto,” he says. “Our work was met with a lot of skepticism and disbelief. People couldn’t believe that we could do this here in Chicago.”

The Prosthesis That Feels

Imagine a prosthetic arm that can be controlled by its wearer’s thoughts. That person—let’s say he’s a quadriplegic—wants to pick up a bottle. Or scratch his chin. Or wave. He simply thinks about doing the task, and—voilà!—the hand performs it in fluid, nearly human-like motions.

Now let’s add a wrinkle, and it’s a doozy: He wants to feel the smoothness of a baby’s cheek.

Scientists led by a team at the University of Chicago are on the verge of making that possible. They are working on a prosthetic arm that not only will be controlled by its wearer’s thoughts but will be able to transmit the sensation of touch back to the wearer.

“This offers the chance to really restore lost function in a patient population whose condition is very devastating,” says the brains behind the invention, Sliman Bensmaia (pronounced SLEE-man bens-MAY-yuh), a neuroscientist and an assistant professor in the Department of Organismal Biology and Anatomy at the U. of C. The sense of touch is crucial. Without it, your hand, prosthetic or not, becomes an ungainly claw. “To use your hand, you need not only to send signals to your muscles to move it, but you also need to get signals back about the consequences of those movements,” Bensmaia explains.

To demonstrate, he shows a video of a woman grabbing a match from a pile of them and deftly striking it against a flint to light it. Easy. Next he plays a video of the same woman performing the same task, but this time several of her fingers have been numbed. She clumsily paws at the pile of matches, knocking them across the table. Finally, she uses a nonnumbed finger to help get a match lit. “Did you see that?” exclaims Bensmaia. “She cheated!”

Bensmaia’s invention—known inelegantly as the modular prosthetic limb—“closes the loop,” as he puts it. It gives users a sense of “embodiment”—the feeling that their prosthesis is part of them. “I’m not claiming that we’re reproducing touch exactly,” Bensmaia cautions. “But we try to produce the kinds of neural activations in those parts of the brain that would be experienced if you had an intact arm.”

Needless to say, the innovation is a godsend for the nearly two million people in America alone who have lost a limb and the roughly 276,000 who are paralyzed. The sense of touch, after all, is core to the human experience. “We touch the people we love, and that’s an important way to communicate,” says Bensmaia. “We hope that by restoring touch, we’ll also be able to restore that aspect. It’s not uncommon for amputees or quadriplegics to yearn to touch someone.”

That Bensmaia would find himself the driving force behind the project seems almost as unlikely as the astounding work itself. With his wide shoulders and athletic build, the 41-year-old looks as if he’d be making tackles on a rugby field rather than calculating algorithms in a lab. A native of Algeria, he was an unremarkable student in cognitive science at the University of Virginia, where his goal was simply to make it as a rock musician. “I’d started with piano but switched to the bass because I thought it was cooler,” he says. (He still plays keyboards in the local funk band FuzZz.)

After graduating in 1995, he ended up in Charleston, South Carolina, “because they had no motorcycle helmet laws and a good music scene.” He spent a year futzing around town, selling encyclopedias and doing odd jobs. Finally, he says, his mother told him, “Look, you’re a total loser. You need to go to graduate school.”

Bensmaia got accepted into the cognitive psychology program at the University of North Carolina, where his adviser, Mark Hollins, was an expert in the field of tactile psychophysics. “He picked me because I knew how to program computers,” Bensmaia says. “If he’d been an expert on language, I might be a psycholinguist now.”

After receiving a master’s and doctorate from the University of North Carolina, Bensmaia headed to Johns Hopkins University’s Zanvyl Krieger Mind/Brain Institute to study neurophysiology. In 2006, he joined Revolutionizing Prosthetics, a program funded by the U.S. military’s Defense Advanced Research Projects Agency to improve arm and hand prostheses. There, one of the program’s leaders suggested Bensmaia work on creating prosthetic limbs that transmit the sense of touch.

Bensmaia’s first response: “I thought it was completely outlandish. I didn’t think it was going to work.” But the more he looked into it, the more he realized it was possible. Whether your arm is gone or, in the case of paralysis, no longer neurally connected, he explains, “the parts of your brain that send signals to it are still there, and so are the parts of your brain that receive signals back from the arm.”

The cochlear implant, used since 1984 by people with severe hearing loss, proved a useful model for how to reestablish the neural connection. The device converts sound to electrical impulses, then sends those signals past damaged parts of the ear to the auditory nerves, allowing the person to hear. Similarly, Bensmaia’s prosthesis would circumvent a missing or paralyzed limb to create the sensation of touch by electrically stimulating the brain.

Earlier prosthetics research had mapped the brain to determine which areas control specific functions. “If the brain was just chaos, we’d be screwed,” Bensmaia says. “But we’ve learned that it has some organization to it. The area that moves the pinkie finger is right by the area that moves the ring finger, and so on.”

Thanks to this mapping, Bensmaia knew which areas of the brain interpreted touch. But would stimulating them electrically produce that same sensation? His first breakthrough came in early 2011 while working with rhesus monkeys. For six months, his team taught them to report, via eye movements, the difference in placement and pressure of pokes to their hands. Then the team replaced those actual touches with electrical stimulation to see if it elicited a similar reaction. “The very first minute we started zapping the monkey’s brain instead of poking its hand, it responded exactly as if we had poked its hand,” Bensmaia says.

The team then repeated the test, only this time poking a robotic hand equipped with sensors that simultaneously stimulated the monkeys’ brains. Again, the monkeys reacted as if their own hands had been touched.

“I was like, ‘Holy shit, man’—those might have been my exact words,” recalls Benamaia. “That was the eureka moment. The results provided a blueprint of how to restore touch.”

Theoretically, the fluidly moving prosthetic hand will eventually enable the user to feel the dimples of an orange peel or the fibers of a beach towel. But since monkeys can’t talk, Bensmaia won’t know for sure until it’s tried on humans. Initial trials with quadriplegics are “imminent,” he says. And if those go well, the broader possibilities are mind-boggling.

“The idea of interfacing the nervous system with machines directly has a lot of other potential applications,” Bensmaia says. “Imagine if you could consult this wealth of information that’s available on the Internet but through a direct neural interface. You have a question and—boom—you get that information immediately, without having to type in some words or read a bunch of stuff. It’s pumped right into your brain. Those are the kind of ridiculously long-term and crazy speculative possibilities that this kind of work affords.”

The Fast-Acting Antidepressant

It seems like some horribly cruel joke. There’s no shortage of medications to help people escape the dark spiral of depression, yet the drugs all come with a catch: They take an agonizingly long time—up to six weeks—to kick in.

But that delay could eventually be a thing of the past. A new compound called GLYX-13 (GLYX is pronounced “glicks”) developed by a Chicago-area scientist is producing results within a mere 24 hours in human testing. Just as notable: The medication has displayed none of the side effects common in antidepressants, such as headaches, nausea, and lowered libido.

So how did such a drug come to be? Its creator, Joseph Moskal, gets almost poetic in answering. “A big part of what it means to be human is to be able to think, learn, remember, forget, get depressed, get excited, be happy, and fall in love,” says the founder and chief scientific officer of the six-year-old Evanston-based biopharmaceutical company Naurex. “They’re all connected, so by looking at how the brain makes and breaks memories and learns, there were keys to how to inhibit things like depression.”

Prozac and other common antidepressants keep levels of serotonin, a crucial brain chemical, high by preventing its reabsorption. GLYX-13 works on a different neurotransmitter, glutamate, which some believe affects depression more directly—hence the quick results. “We’re bringing the whole business of how the brain functions to bear,” says Moskal, who is also a research professor at Northwestern University and serves as director of its Falk Center for Molecular Therapeutics. GLYX-13 allows the levels of glutamate to be fine-tuned—somewhat the way a thermostat “can very, very exquisitely, very precisely, control the room’s temperature.” (Other biotechs are working on developing fast-acting antidepressants—ones that enlist compounds similar to the drug ketamine—but those can cause symptoms of psychosis, according to medical journals.)

Moskal, who hopes to have GLYX-13 on the market within a few years, notes that this application could be just the start when it comes to treating neuropsychiatric disorders. “These receptors have a big role in lots of things that can go wrong,” he says. “People with bipolar disorder, obsessive-compulsive disorder, schizophrenia, posttraumatic stress disorder, and traumatic brain injury could all possibly benefit from the discovery. It’s a very exciting time.”