Changing the Culture

Harvard's new and innovative stem cell concentration focuses on the humanity behind the research to create classes that are anything but standard.
By Li S. Zhou

Travis Roy was 20 years old when he started at his first college game, sporting number 24 in the red and white of Boston University. In October of 1995, they were facing off against the University of North Dakota. After a lifetime of preparation,  Roy was ready to play Division I hockey.

Since the tender age of three, Roy had been pushing himself on the ice. His dream was to play college hockey, followed by a career in the NHL and even the Olympics. These were lofty goals, but Roy remained optimistic about his abilities. He referred to playing hockey as his “sixth sense,” something that came to him as naturally as sight and sound. Despite also excelling at tennis, soccer, and lacrosse, Roy considered hockey his game.

His drive and talent didn’t go unnoticed. A nationally-ranked athlete, Roy had been heavily recruited during his senior year and won a scholarship to join the BU Terriers, the defending NCAA champions. But a mere 11 seconds after the referee dropped the puck onto the ice, Roy’s career as an athlete was over.

Lee J. Roy watched from the sidelines as his son’s body flew headfirst into the sideboards of the rink, thrown off balance after another player dodged his body check.  Lee knew he’d raised a resilient kid who picked himself up after falling down, but he realized that something was seriously wrong when the same boy who always kept playing made no attempt to get up after this fall. Travis tried to move, but after cracking his fourth and fifth cervical vertebra during the collision, he was paralyzed from the neck down.

His father ran down to the ice from the stands to see his son. “I’m in big trouble,” Travis managed to say. “I can’t feel anything and my neck is hurting...but Dad, I made it.”

Fifteen years have passed since the accident at BU. Through physical therapy, Roy has recovered the ability to use his right arm. Yet he hasn’t allowed his disability to impede an active lifestyle. He travels the country as an inspirational speaker, promoting the potential rather than the limitations of life. In 1997, he wrote “Eleven Seconds,” an autobiography that documents his journey from the tragic moment on the ice to his new, very different life as a quadriplegic. That same year, he started a foundation that funds research on treating spinal cord injuries and supports patients who don’t have the money to cover medical costs. Since then, he has supported stem cell technology, a promising cure for not only spinal cord injuries, but a wide array of problems ranging from cancer to heart disease.

JOURNEY TO THE FOREFRONT

This year, Human Developmental and Regenerative Biology (HDRB) attracted just under 50 sophomores for its inaugural class of concentrators. The emergence of this concentration is the latest in a wider effort by the University to bring stem cell research to the forefront. It began six years ago when Professor Douglas A. Melton, while surveying the field of stem cell research, realized that bringing together some of the best minds in the subject would remove many of the barriers to collaboration. Thus, the Harvard Stem Cell Institute (HSCI) was founded. What began as committee meetings in the Holyoke Center evolved into a comprehensive team of scientists, now established at local research insitutions such as Massachusetts General Hospital and Joslin Diabetes Center.

A few years later, Melton helped form the Stem Cell and Regenerative Biology another angle to studying the life sciences. Classes were offered that focused on the growth of human beings and the role that stem cells could play in helping treat diseases and injuries. It was during this time that talk began of a new concentration.

There was interest from the students in SCRB classes as well as the HSCI researchers who were teaching the SCRB classes. Melton and his colleague Kevin C. Eggan, a recent Biology Ph.D. from MIT, started laying the groundwork. After a proposal submission and several rounds of administrative examination, the HDRB concentration was born—the eighth to be added to a growing number of specialized fields in studying biology.

Melton, now a concentration advisor with Eggan, says one crucial principle guided the decisions when crafting a curriculum that was unique to HDRB. “There was an increasing recognition that students are quite interested in the human being, less interested in just studying model organisms,” he says.

FROM PETRI DISHES TO PATIENTS

Early on in the new fall course SCRB 180: “Repair and Regeneration in the Mammalian Brain,” Travis Roy came to the Biolabs to talk about hockey, his accident, and coping with the aftermath. As one of 250,000 Americans living with spinal cord injuries, Roy told the students that he could someday be treated by developments in the same field studied in the course.

Professor Jeffrey D. Macklis, who co-teaches SCRB 180 with Professor Paola Arlotta has been working for the past 15 years on the development and regeneration of neurons and brain circuitry in mice. He has also received significant grant money from the Travis Roy Foundation for his research (the two have become good friends).

His lab studies the molecular controls over the development of different kinds of neurons—cells that comprise the nervous system, which includes the brain and spinal cord—and figures out how to stimulate the growth of these neurons in the brain with already-present progenitor (“stem”) cells.  In specifically examining motor neurons that connect the brain to the spinal cord, Macklis aims to grow new neurons in damaged or malfunctioning parts of the brain and reactivating the controls and skills those parts once had. But despite their own expertise, Macklis and Arlotta invited Roy as a speaker to demonstrate the human side of stem cell science, while allowing Macklis to derive with the class what cells and circuits are injured and in need of repair.

“Meeting Travis and going through all of his injuries and symptoms basically laid out the whole biology relevant to spinal cord injury and, by analogy, ALS (amyotrophic lateral sclerosis, a disease that attacks the cells in charge of voluntary muscle movement),” says Macklis. “Since there are so many diseases and kinds of neurons, Paola and I used Travis’ practical motivation as a way to say, ‘Let’s study these systems in detail.’”

SCRB 180 also emphasizes the dynamic methods behind the medicine. The teaching style is partially Socratic, and Macklis and Arlotta step away from traditional lectures to encourage student discussion and interpretation of the science. While there are two textbooks, and weekly readings, they are only meant to provide a foundation for individual inquiry.

“The best education for students is not to teach them individual tidbits to remember. I want to be changing the tidbits every six months,” says Macklis. “If we taught them all the tidbits now, they’d be wrong in three years.”

Students filling out course evaluations for the course wrote that “regurgitating” facts was not sufficient and that it was “a thinking class.”

SCRB 167: “What does Human Disease Teach us about Mammalian Biology?”—a 14-person seminar, takes a similar approach by bringing in patients suffering from the conditions covered in the class; one day featured a leukemia survivor and his wife, who discussed his past treatments, his bone marrow transplant, and his battle with “graft--versus-host” disease, in which transplant cells attack the cells of the host body.

“I think it is good for students to see a live person at the end of this. It’s not just in mice,” says Professor Jerome Ritz, who also spoke that day about his research on graft-versus-host disease at the Dana-Farber Cancer Institute.

“We are using disease and patients to illustrate basic features of stem cell biology. I think that’s a very unusual teaching approach for undergraduates,” says Professor George Q. Daley of his course’s structure. “I think it’s going to be particularly effective in the field of stem cells which has so much medical relevance.”

Along with the classroom engagement and exposure to implications in actual treatment, the concentration adds a unique academic requirement: one semester’s worth of research in a lab.

For the new concentrators, this is a large part of the experience they hope to gain by joining HDRB. “You can lecture about the topic as much as you want. Lecturing is not as strong a way of teaching as actually [being] involved with research,” says Edward Daniel ’12.

S. Alison Kraemer ’12 agrees. “You can have as much didactic learning as you want, and you don’t really understand what you’re learning until you apply it,” she says.

Willam J. Anderson, the undergraduate curriculum development manager for HDRB, stresses the benefits of such an “active approach.”

“By being able to do hands-on research...it really allows [students] to obtain ownership over the experiments that they do,” says Anderson. “To look at something that no one else has looked at before, so they’re adding to the process that may be in the future be taught in the classroom.” That kind of change is to be expected in a fast-paced field. According to Melton, any new methods of experimentation could be incorporated in a course within a year or two.

THE “CRÈME DE LA CRÈME”

Although the concentration can only currently boast a group of 15 professors, they are, as Anderson says, “the crème de la crème.”

Professor Amy J. Wagers, for example, announced in late January a discovery she and her lab had made which showed that when exposed to proteins that were usually found in the blood of young mice, the blood of old mice became younger as well. In other words, her research was able to reverse ageing in the cells of old mice, and it suggests that the diseases that occur as a result of old age could be combated with developments in stem cells.

Her colleague Kenneth R. Chien ’73 has devoted his time to examining one of the body’s most important muscles: the heart. Last fall, in a collaboration with K. Kit Parker of the School of Engineering and Applied Sciences, his lab made headlines when it produced a strip of fully-functioning heart muscle from mouse stem cells. The muscle acts just as a normal heart would; it beats, contracts, and it even responds to a pacemaker. The next focus for Chien is in creating a “heart patch,” which could treat people with heart disease by replacing damaged tissue with healthy cells—somewhat like a bandage over a scraped knee, if that bandage were to actually become part of the knee.  Although Chien believes they will have a film of human heart muscle finished by the end of this year, he acknowledges that the process to creating a “patch” is not one that can be rushed.

“It is the beginning,” he says. “Everything starts with a Model T before it can become a Porsche. This is sort of like Orville Wright; if you can get the plane off the ground for about six feet, that’s better than nothing, and from then you work on that and make the next version.”

Inevitably, this research often diffuses into the professors’ teaching. Wagers taught SCRB 190: “Understanding Aging: Degeneration, Regeneration, and the Scientific Search for the Fountain of Youth” in the fall semester while also doing groundbreaking work on an actual “fountain of youth.”

The intersection between lab and classroom even applies to SCRB 10, the department’s introductory course. “We were learning from people who really were out there empirically gathering data,” says Samuel H. Marrs ’12,  an HDRB concentrator. “They were actually doing the work and showing us, or showing us colleague’s work—all contemporary, all 2000 and above. Sometimes we’d even look at things that were 2009, a couple months prior.”

Despite its success so far—the benchmark Q rating for SCRB courses is 4.4, significantly than higher than the 3.9 held by the natural sciences division—HDRB nevertheless struggles as a new and relatively small concentration. Kraemer expressed concern about getting into a lab class for the spring semester, which only had a limited number of spots; other students via Q Guide have mentioned that the courses are enlightening, but unstructured.

While many of the classes are still being fine-tuned after their first runs, the HDRB faculty have pushed to establish strong connections with their concentrators. “They really want to hit the ground running. I like this a lot because they really try to make sure we are taken care of,” says Daniel.

Janelle S. Lambert ‘12 echoes these sentiments: “They are always aiming to get opinions and advice about what they want in the concentration,” she says. “It’s also kind of small right now. I get to know basically everyone.”

To further improve intra-concentration bonding, there have been lunches with professors and talk of a possible trivia night or “Gattaca” screening, followed by a discussion of the plausibility of the technology portrayed in the film. Anderson says that HDRB is trying to become a community.

It is partly due to the efforts of a professor seeking to establish strong connections with his students that convinced Lambert to commit to HDRB. After taking the Freshman Seminar “Blood: From Gory to Glory” with Professor David T. Scadden, co-director of HSCI, she was impressed by the lab work that Scadden showed her class. On one occasion, they were able to watch as a mouse —irradiated to the brink of death was injected with stem cells—two weeks later, they returned to find the same mouse, up and running.

In the end, professors hope to have HDRB concentrators proficient in multiple scientific disciplines and aware of the practical applications of those disciplines. “I believe that graduates in this degree will be better prepared for almost any aspect of the life sciences as it relates to business, technology, medicine, science, engineering, politics, sociology, than perhaps any other scientific discipline,” says Chien. “It encompasses a lot of the features of the complexity of modern science in a modern world.”

A CLEAR LENS

Those studying HDRB have their own aspirations to become doctors, surgeons, researchers, and industry professionals, but Alison Kraemer has a uniquely personal attachment to the work.

At the age of 13, Kraemer was an avid dancer, practicing at a dress rehearsal for an upcoming performance. During a transition in one of her pieces, another larger girl accidentally knocked her down. She suffered from spinal injuries and pain from that fall, and they’ve kept her from dancing ever since. “There’s basically nothing out there that can cure me,” says Kraemer.

After the accident, she devoted herself to other interests such as playing the flute and Model U.N. While on a committee for Model U.N. during her freshman year of high school, she first encountered the idea of stem cells after being assigned the topic of human cloning as a delegate. In later reading Christopher Reeves’ autobiography, she became even more interested in the subject and found the outlet to pursue it when she came to Harvard.

Kraemer worked in Paola Arlotta’s lab on the differentiation of stem cells in the motor neurons of the spine this past summer, and she discovered her passion for a field that would actually matter for her. One day she would like to be able to help people with stem cell technology as a spinal orthopedic surgeon.

“I really want to be an instigator, or at least a participator in research,” she says, “Basically because of my injury, I learned a lot about orthopedics and spinal neurology. I don’t want anyone to suffer like I have or worse.”

Many scientists caution against moving the process too quickly. “This is not going to be easy, and we have to make it very clear that each one of these advances in stem cell biology gets us closer,” says Chien. “We have to distinguish between getting a first down, getting across the 50-yard line, and a Hail Mary pass. These are important steps, but might not necessarily be the touchdown that we’ve been waiting for.”

Kraemer, Roy, and the others out there who stand to regain vital aspects of their lives when these treatments become possible, hope that time will come as soon as it can. These people are the lens that learning in the HDRB concentration is being seen through. While the future advances in the stem cell field may be blurry, the lens itself is clear.

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