Rudy Tanzi was the first to map Chromosome 21
Tanzi was one of the first to find a gene related to Alzheimer's disease
In his spare time he is a guest keyboard player for Aerosmith
When Aerosmith looked for an organist to play like a “drunken church lady,” they could have taken their pick from hundreds of willing candidates.
But only one was also a Ph.D-wielding expert on how beta amyloid accumulates in the brain. That’s who the band went with for their latest album.
Legendary Aerosmith lead guitarist Joe Perry met keyboard player and pioneering scientist Rudy Tanzi exactly where you’d expect two world famous people from different worlds to meet – on a photo shoot for the men’s fashion magazine GQ.
On the shoot, the two started chatting. Tanzi mentioned he played keyboard, so Perry invited him to jam with the band. The two hit it off so well that since then, the Kennedy Professor of Neuroscience at Harvard has been invited to play with Aerosmith on a number of special occasions. His initial direction, he recalled, was to play like a “drunken church lady.”
“It’s been such fun,” Tanzi said.
But his true life’s work – or at least the job he is most famous for – is what he does as director of the Genetics and Aging Research Unit in the MassGeneral Institute of Neurodegenerative Diseases at Massachusetts General Hospital.
Tanzi is one of the world’s leading authorities on Alzheimer’s disease. Since the mid-1980s, he has been an unstoppable force trying to understand the genetics of the disease that plagues 5.2 million Americans.
As in his musical life, Tanzi is known in the lab for his innovative improvisation and for using an unexpected kind of creative thinking. That’s why he may be the only scientist in the world who credits early-morning bus rides and watching a cheesy ‘80s television show as part of his first big break.
The chromosome 21 guy
Long before Tanzi was named to the Harvard 100 Most Influential Alumni – along with such notables as President Barack Obama and Microsoft co-founder and former CEO Bill Gates – he was just some kid sitting on the back of a bus doing his homework.
It was the early 1980s, and he was living in Providence, Rhode Island. He kept a grueling daily routine: He’d stay up late playing gigs with his rock band, then rise early to catch a bus to make an hour-plus journey to Boston to work in James Gusella’s lab.
Gusella pioneered the use of DNA sequence polymorphisms as genetic markers at his lab at Massachusetts General Hospital. That essentially means Gusella was one of the first scientist to figure out how to map the genes of a disease.
“Jim Gusella and I were just kids in our 20s, trying to figure it all out,” Tanzi said. “Back then, before genetics became a real industry, you had to jerry-rig everything. To take pictures of DNA, I brought in a Polaroid camera my father gave me for my 13th birthday and I’d put it on a ring stand and I took the red acetate we would use from the light show for my band and it put in the lens. I’d take some of the maps from the dermatology labs to light up the DNA. That was the humble beginning of the human genetics revolution.”
On his bus ride, Tanzi would start his complex calculations. He was trying to build a full map of a chromosome to understand the mechanics of Huntington’s disease. “I wanted to get finished fast so I picked the smallest one to map, which is chromosome 21,” he said.
Tanzi says the bus had its regulars with their routines. “They’d be drinking their coffee and get on the bus and say, ‘Hey Rudy, how’s the map going?’ And every day, I’d say, ‘Gettin’ there. We’re gettin’ there.’ ”
There was no computer program to help back then. So Tanzi did all the tedious work by eye and by hand. “I would sit there with these huge family trees on my papers and I would track genetic markers and I would know who had the disease in the family and who didn’t,” Tanzi said.
One night, when he was lying on the red shag carpet back in his Providence apartment, he took out those family trees.
“I’ll never forget I was watching ‘Love Boat,’ ” Tanzi said. “And occasionally I’d look up to see Gopher running around the ship and then look down to write down all the information onto this family tree, then I’d look back up and Gopher was still running around the ship, and then I’d go back to my calculations.
“After just a little while of doing this I thought to myself, ‘My God, this is perfectly lining up. I think we may have found the Huntington’s disease gene.’ I’m not sure if Gopher ever stopped running around that ship, though.”
It turned out his calculations were right. His work earned Tanzi and his project director some renown.
“I was just the hands on the project. It was Guesella’s brain that made this happen, but it was so cool to actually do the work and to experience this kind of ‘aha’ moment for the first time,” Tanzi said. “Plus, for a while I became known as the chromosome 21 guy, at least for a few years.”
Tanzi was hooked, and his knowledge of chromosome 21 would open more doors to his life’s work.
Stealing who you are
“Back then there was so much optimism that we could find human genes that cause disease,” Tanzi said. Working on chromosome 21 led him to study Down syndrome – those with the condition have an extra copy of chromosome 21, along with an increased risk for Alzheimer’s.
“So I said, if I have a map for chromosome 21, maybe there’s an Alzheimer’s gene on this chromosome. So I decided to switch to Alzheimer’s,” Tanzi said. That was around 1983.
“And from there I’ve never turned back.”
At the time, he said, he knew no one with Alzheimer’s. “Sometimes in the lab you do these things like you are solving a puzzle and you don’t experience the human side,” Tanzi said. But only a short time into the work, he got some terrible news.
His beloved paternal grandmother was becoming increasingly confused. It was soon suspected she had Alzheimer’s.
“It’s amazing how as a scientist you become so much more inspired to solve that disease and to work harder and faster by seeing that disease eye to eye, especially in a loved one,” Tanzi said. His grandmother quickly went from being friendly and doting to someone who sat stonefaced, unable to recognize her family.
He says often he will invite families who have relatives struggling with the disease to talk with his students at Harvard.
“What you see is that this disease is really the worst thing you can imagine,” Tanzi said. “Because you spend your whole life – decades and decades – accumulating memories and association, and you develop a personality of who you are based on your experience and memories. And this disease comes in and rips all that right out. So it literally steals who you are from you. There is no other disease that does that. There is nothing worse.”
Spurred on by these examples, he worked with urgency. By 1986, all those long hours in the lab paid off.
“I remember that day,” Tanzi said. “We were looking through this one gene we found, and we said, ‘Wow, this is matching up pretty well. The protein this gene makes looks exactly like the amyloid that we see in Alzheimer’s.’ ” Amyloid is an abnormal protein that starts to build up in the brain in Alzheimer’s cases.
“When we saw this gene, I remember thinking, ‘For the first time since Dr. (Alois) Alzheimer described amyloid in 1906, I think we have finally learned something new about the disease. We now have a gene.’ ”
But his celebration was short-lived, he said. “Little did we know that there were three other groups who’d found the gene over the summer of 1986 and we all published at the same time in February of 1987, but it was still a good moment for us. It meant finally now we have a target for drug discovery.”
How to take ‘shots on goal’
Since then Tanzi and his lab have found several other genes related to Alzheimer’s, and they are starting to get a clearer picture of how the disease works.
His lab is a creative place. He tells his students when they walk in the door that they’ve got to be willing to trust their intuition and to take whatever their pet theory is and try to “bash your hypothesis and see what holds up in the end.”
Even its building is unique – the lab is tucked in an old brick shipping building. From his window, Tanzi can watch the tourists go by in duck boats, taking pictures as they travel along the Mystic River. His office wall is covered with only a small representation of his many awards, and it is dominated by a beautiful black-and-white photo of his then-baby daughter asleep across his arms while he plays the piano.
From this office, he strategizes about the next steps in his race to find a cure. He keeps a big red button on his desk that says “no” when pushed. As a joke, he brings it out when his grad students come in to ask for expensive equipment.
From here, he also makes calls and answers e-mails about his many other projects. There’s the New York Times bestseller, “Superbrain,” that he co-wrote with new-age doctor Deepak Chopra and the successful PBS show that went with it. There are the small pharmaceutical companies he’s co-founded to explore possible Alzheimer’s cures and treatments. There is the work he does as chair of the Cure Alzheimer’s Fund, which aims to fund new studies concerning the disease. And there is the political consulting he has done with the White House, which has set a goal of curing the disease by 2025.
Alzheimer’s has generated a lot of bad news in the past few years. A number of drug trials have failed recently. The handful of drugs that do exist can slow – but not stop – some early symptoms, and even then, only work in less than half the patients. Tanzi, though, believes that with more funding, a cure is possible.
“In general, drug discovery usually takes two or three waves to get there,” Tanzi said. “The first wave already failed. The second wave largely failed, but there is a bit of hope in there. Generally, though, with this third wave that’s coming up in the next few years, I think we’ve learned from our mistakes and I remain optimistic.
“The good news is, largely due to genetics, we know what we need to do. And we have the information that says ‘Here’s how we take the shots on goal.’ ”