Magic in the Matrix
When Alan Spievack arrived at Professor Maxwell Elliott Power's office in the spring of 1952, he wasn't sure what to expect. Power began by looking over his glasses at the freshman from
"He asked me a series of questions clearly designed to see if I had cheated," remembers Spievack, who graduated cum laude in 1955.
When Power determined that Spievack wasn't dishonest, just uncommonly smart, he strongly suggested that he pursue honors in biology. Then, about a week later, Power summoned him to his office again. This time he loaded Spievack up with gear and they headed to the
"He set up a private tutorial for me," Spievack says. "He showed me how to use a microscope, how to make tissue slides, how to use lab equipment and conduct experiments."
In high school, Spievack had tried to create a perpetual motion machine. Clearly, research and experimentation appealed to him, and he quickly got so engrossed in the regeneration project that he didn't want it to end when the summer break arrived. Neither did Power. So they packed up all the equipment, including the salamanders, and relocated to Spievack's family home in
Spievack's collaboration with Power was cut short when the professor died in 1954. Spievack was "devastated" by the loss of his mentor, but he was not about to abandon the interest in regeneration that Power had sparked on the Kenyon campus.
He won a Fulbright Scholarship to
"People used to think it was Buck Rogers science to talk about regenerating tissues," Scott Bruder recently told the Wall Street Journal. He is vice president of Regenerative Therapeutics, one of several companies using regenerative technologies to provide medical treatment. "This is the new wave."
After Kenyon and medical school, Spievack finished his training in general surgery at
"I flunked freshman algebra," he says. "I felt good about that because Albert Einstein did the same thing."
The years sped by, and Spievack was consumed with his medical practice, but he never lost interest in regenerative medicine. He continued to conduct research in the field, and in 1992 he worked with a small
Over the next few months, Badylak discovered something amazing. Not only was the section of small intestine functioning properly, it was actually morphing into something very close to an aorta, with little, if any, scar tissue forming. In a 2007 Esquire magazine profile, Michael Rosenwald wrote that Badylak "had accidentally performed the biological equivalent of a magician turning a handkerchief into a dove. But this was not illusion."
"We've been spending the last twenty years trying to understand how that happened," Badylak told the Wall Street Journal.
The key to this biological magic is something called an extracellular matrix. It's the material that links cells to one another as they divide, grow, and become tissue and body parts. That's why it's often referred to as cellular scaffolding.
Badylak's research pointed to a form of extracellular matrix called the submucosa found in the intestines, bladders, liver, and other organs of all animals. To test his theories, he inserted the submucosa into the injured organs of other dogs and got the same result - regrowth and healing without scarring or even infection.
Unlike salamanders and starfish, humans (and most other complex life forms) don't kick into regeneration mode when they are severely injured. It's all about survival, so scar tissue forms instead. And scar tissue simply doesn't function as well as normal tissue.
That's not the case, however, in the womb, where humans can quickly develop and grow new parts, as well as recover from fetal surgery. This ability begins fading approximately three to four months into gestation, about the time the immune system begins to take over. Badylak says children can still regrow fingertips up until the age of two.
In a sense, the extracellular matrix fools the cells into thinking they're in the womb again. The cells begin to combine and they are soon aided by stem cells from the body's own supply in bone marrow and elsewhere. These stem cells are not as useful as embryonic stem cells, but they still play an important role in regeneration.
Badylak's work dealt with the fundamental questions that had intrigued Spievack since his Kenyon days when he was living in Beta Theta Pi housing.
"If you could do something as an embryo, why couldn't you do it again?" Spievack asks. "Or maybe even a third or a fourth time. You basically want to turn off the scar tissue mechanism and turn on the embryology. That's what interested me about regenerative medicine."
And Spievack was definitely interested in what Badylak had to say in
"I sat there as this talk was going on and I noticed I was getting closer and closer to the edge of my seat until I was about to fall off," Spievack remembers. "This guy had done it. He figured out that all species--birds, fish, mammals--can regrow themselves more than once."
The pair connected after the lecture and became friends and unofficial collaborators. Badylak, who is now a researcher at the
Since 2000, collaboration between Badylak and Spievack has resulted in their obtaining ten National Institutes of Health research grants under the Small Business Innovative Research Program, totaling more than $3 million. These grants have resulted in publications demonstrating the regeneration of the larynx, vocal cords, esophagus (soon to be tested in humans), urinary bladder, all the components of the muscular skeletal system, and many other tissues. Spievack presently holds nineteen medical-device patents. Studies with the United States Army hope to advance the trauma applications of this regenerative technology.
While Alan settled in
He went to the emergency room for treatment and scheduled an appointment with a surgeon, who recommended a graft using skin from his thigh or forearm. Lee had his doubts about the treatment, so he called his brother from his car in the hospital parking lot. Alan told him there was no need for him to be injured twice.
So Lee canceled the appointment, and Alan sent him a vial of matrix powder, which resembled grated parmesan cheese. He applied the powder to his finger as Alan instructed. In four weeks, the wound was closed. In four months, the finger had grown back to normal size. In the winter, Lee noticed that while his other fingers chapped in the cold, the regenerated finger did not. He also has to trim the fast-growing nail on his middle finger every couple of days.
"The fingertip is only two years old now, but the rest of me is sixty-nine," Lee says. "I never had any inkling that it would not work. I've always had that kind of confidence in Alan."
There's no doubt that Lee Spievack's story is encouraging, if not amazing, and that regenerative medicine is being used to speed the recovery of patients with a variety of injuries all over the world. The military is funding studies right now to determine if regenerative medicine can help soldiers injured in combat. But the reality is that doctors and scientists are really just beginning to fully explore this field.
"We are very uninformed about how all this works," Badylak recently told the Associated Press. "There's a lot more that we don't know than we do know."
Alan Spievack played a big role getting the field of regnerative medicine to this exciting juncture, a role that began when he aced an exam in Professor Power's anatomy class at Kenyon. It's fitting that Spievack was the first recipient of the Maxwell E. Power Prize in Biology, awarded on Honors Day in 1955. Despite all that he's accomplished, Spievack is still wondering what's next.
"There's a question that haunts me," he says. "What's on the next page?"
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