“If I were a cartilage cell, what would I like?” Such are the unusual and fruitful musings of Dr. Barbara Boyan, the Price Gilbert, Jr. Chair in Tissue Engineering and the Associate Dean for Research, College of Engineering at the Georgia Institute of Technology.
Dr. Boyan, who also holds an appointment in the Department of Orthopaedics at Emory University, grew up in Canada around a dinner table where discussions centered on intriguing ideas and business. She says, “My parents were both in the business world, but they were not interested in my brother and I following in their footsteps. My father was wise enough to say that regardless of what career I chose, I needed to stay focused on what someone wanted to ‘buy.’ My time in the business arena has only strengthened this idea—when it comes time to turn an idea into a useful product you can’t just turn it into what you think people want. It must be something that people, in this case, surgeons, would actually use. Many times the product may be difficult to put into clinical practice, because, for example, it is the wrong shape or too complicated. I myself have an idea every 20 minutes, but few of them actually turn into products.”
Having to watch a parent’s painful struggle with daily tasks would, over time, solidify Barbara Boyan’s conviction that she would enter the medical field. “I knew from the age of 10 what I wanted to do, ” says Dr. Boyan. “I had my mind set on becoming a teacher and I was determined to cure arthritis. My mother had severe rheumatoid arthritis (RA) and I, thinking in the simplistic manner of a child, decided to undertake something that could help her. As I grew older, I had career conversations with my uncle, an orthopedic surgeon who was very supportive. At that point—and up until the time I entered graduate school in 1970—everyone thought that arthritis was a disease where the joints calcified and froze in place. I thought that if I could figure out how they calcified, then I could figure out how to prevent it.”
Entering Rice University in 1966, Dr. Boyan would become part of a longstanding educational tradition that results in a lifetime of learning and kinship—despite having to maneuver in a man’s world. “Rice was primarily an Engineering, Science, and Technology school which at the time contained few women. It was imperative that I quickly learn how to function in a world dominated by men. As for the academic learning, Rice was organized on the English model of college, meaning that there is a small group structure and that you get to go through all four years with the same people. This has resulted in wonderful, long term relationships—my college classmates and I are still in contact and regularly consult one another.”
Often, mentors see what you can’t. Such was the case with Dr. James W. Campbell, Dr. Boyan’s first mentor at Rice. “Dr. Campbell, a biologist, said, ‘Look, I know you think you want to pursue a Ph.D. in education, but I believe you have a future in science. Stay here in the lab for one year and see what you think.’ I took his advice and he was absolutely right! I was hooked on biological research from day one. Dr. Campbell has always been someone I could rely on, but he was never easy on me. He took a chance on a female at a time when few people were doing so. One of his primary gifts was to teach me how to think about and organize my writing.”
To peer more deeply into calcification, Dr. Boyan undertook a Ph.D. at Rice to explore how the process occurs…and what can go wrong. “I wanted to get an appreciation for how simple organisms calcify. To augment my understanding, in 1975 I did a postdoc in which I looked at the genetics of how bacteria calcify. My program, undertaken at the University of Texas (UT) Health Science Center in Houston, was in the dental school because during that time the majority of the funding for research in bone biology and calcification came from the National Institutes of Dental Research.”
Dr. Boyan continues, “After three years of studying how bacteria calcify I began an independent program looking at growth plate cartilage. One of my mentors was Dr. Barnet Levy, one of the most famous pathologists around. From him I learned to not be afraid to share my ideas and to take chances on seemingly unlikely hypotheses. I was also guided by Dr. James Vogel, a physical chemist who helped by putting me into a lot of situations that allowed me to develop an independent career. He introduced me to people I needed to know, and allowed me to write my own grants.”
While Dr. Boyan, eventually the recipient of a career development award from the National Institutes of Health (NIH), studied mechanisms that controlled calcification, the world outside the lab woke up to new revelations about her mother’s disease. Dr. Boyan: “The wider medical community had just begun to understand that RA was an immune disease…and that the cause was not calcification. By that time, however, I was enamored of calcification and stuck to my goal of finding the defect that caused abnormal deposits.”
The politics of funding then forced Dr. Boyan to pull up her bootstraps. “After finishing my postdoc in 1977 I became an Assistant Professor at the University of Texas Dental Branch in Houston. Fortunately, I was successful at getting grants, although it was a bit of a struggle because President Nixon had cut the majority of research funds. I faced the music, however, and learned to be resourceful. It was obvious that if I really wanted to do this research, I would have to energize the process (and myself) in order to get it done. Nowadays mentors provide so much assistance that students don’t have the opportunity be self-supporting.”
Dr. Boyan found that although she could be self-sufficient, some life situations asked for conciliation. Dr. Boyan: “In 1975 I got married to a lawyer in Houston; six years later he decided he hated law and wanted to work for his father’s construction company in San Antonio. I met with the Dean of the dental school, who essentially said, ‘Well, you have to go live with your husband.’ He phoned the Dean of the UT Health Science Center dental school in San Antonio and in the paternalistic tone of the day, said, ‘I’m sending our young lady to you.’ Despite the fact that I had a substantial amount of grant money I was at the lowest end of the pay scale because of my XX chromosomal configuration. But my salary doubled because I switched to the dental school in San Antonio. And I never had to negotiate…the Dean thought I was worth it.”
Next came new connections and a new look at connective tissue. “For six years I served as Associate Professor in the dental school at UT San Antonio, with a joint appointment in biochemistry. In 1987 I moved into the department of orthopedics in the medical school and undertook a study on how bone forms, how it is calcified and how cartilage contributes to that process. This move was a natural fit, and was supported not only by the Deans of the dental and medical schools, but by two of the most famous names in orthopedics…Drs. Marshall Urist and Melvin Glimcher. At the time there were approximately 50 dental schools in the U.S., whereas there were over 200 medical schools; my mentors wisely saw that there were more opportunities for me at one of the latter institutions.”
Then she would take her knowledge of cell theory, gene theory, and the like…and go to market. Dr. Boyan: “During my time in San Antonio I came to see that I enjoyed working with companies and even began launching companies myself. I liked the goal of taking ideas from biology and creating usable, useful products. Although it was obvious that there were things we could commercialize to help improve people’s lives, I also realized that the NIH way of conducting basic research at the time wasn’t amenable to commercialization. Someone working on an NIH project will learn quite a bit, but you could do that forever and not create a product.”
On the quest for funds, Dr. Boyan learned that NIH had created the Small Business Innovation Research (SBIR) program. And then she met the VCs. “I had lunch with a woman friend who was an accountant and lawyer and said, ‘Here is how we can build a company and get SBIR grants.’ By the end of the meal we had incorporated and had a plan. We purchased our first equipment with personal loans, and then acquired an SBIR grant, one of the first in Texas. I continued with my teaching and research responsibilities when along came an idea that we were able to commercialize without an SBIR.”
Dr. Boyan continues, “We were awarded $7 million in venture funding from a large orthopedic company to produce an implant to stimulate cartilage repair. While originally meant for osteochondral defects, it was actually marketed as a bone graft material. In some instances surgeons take the part of the knee that is non weight bearing and use it as a plug in the part of the knee that is weight bearing, a procedure known as mosaic arthroplasty. The implant is put into the location where the plug was removed so that healing can occur. In developing this product, I wore my biologist hat, thinking, ‘If I were a cartilage cell what would I like?’ In depth discussion with a mechanical engineer also went a long way towards making this a successful product. As a result, I co-founded OsteoBiologics with Dr. Kyriacos Athanasiou, which was then purchased by Smith & Nephew.”
To those small companies that may be planning on commercializing a product, Dr. Boyan advises, “Stay virtual for as long as possible. Eventually, however, it is necessary to move a company out of the university, especially once pivotal preclinical studies begin. It is important to identify a ‘killer application’ and then focus all the company’s efforts on product development for that application. It is difficult for university scientists to do this because they are driven by wanting to know why things happen. This phase of the company is often best driven by an engineering approach, with a product development plan focused on timelines and milestones.”
For years Dr. Boyan could write her own grants…now it was time to write her own ticket. “In 2001 I began serving on an external advisory board at Emory University and Georgia Tech. My assigned mission was to recruit a cell biologist for their Center for the Engineering of Living Tissues, which at that point was mostly engineers and clinicians. For two years I worked to recruit the appropriate person for the position, but in the end, was unsuccessful. I finally told the schools, ‘I will do it myself on a consulting basis, but I don’t want to leave Texas.’”
“Then I received a call from the Dean of the College of Engineering, who said, ‘We need you. We have large donors but they want a biologist on staff. Tell us what you want and we’ll make it happen.’ They honored this agreement every step of the way. As my friends said, this was the last of the great offers.”
On the research front, Dr. Boyan has news for those who think that gender is irrelevant to implant design. “My team and I have studied how cells are influenced by the structural and chemical properties of biomaterials. Recently, we have observed that cells on the surface of orthopedic biomaterials release factors that influence cells in the surrounding bone, including angiogenic factors that can influence the extent of new blood vessel formation. Interestingly, cells from male donors and female donors exhibit small but statistically different responses to these materials, suggesting that we need to consider patient sex in design of implants and in controlling tissue responses after implants are placed.”
Going forward she hopes to “make autologous automatic”. Dr. Boyan: “We are currently focused on developing methods for local delivery of stem cells for treatment of large musculoskeletal injuries. Our goal is to make the intra-operative use of autologous cells routine care for orthopedics.”
Looking outside the skeletal framework, Dr. Boyan sees other opportunities for learning and healing. “Orthopedics needs to consider the contributions of angiogenesis and innervation to bone healing. Without a good blood supply and neuromuscular stimulation, many of the technologies developed for treatment of large bone defects will not succeed clinically. Infection control and inflammation are two other areas that should receive more attention.”
As for young women entering the orthopedic research arena, Dr. Boyan comments, “It is difficult to establish one’s leadership role in a universe that is predominantly male, in part because of style. I found it was necessary to be very organized so that I could get my work done during the day in order to take care of family issues in the evening. This meant I had less time to ‘shoot the breeze’ and no time to exercise. Each person needs to set her priorities with the understanding that she cannot do it all. To be heard by male colleagues and residents, it helps to speak in a lower tone of voice, keep sentences clear and concise, and take nothing personally. The rest will fall into place.”
Such words of confidence also apply to Dr. Boyan’s family life. “My husband and I are now raising three of our grandchildren, all under the age of eight. It is my hope that we will be able to see them grow into healthy, productive adults, and of course, I wouldn’t mind at least one orthopedic surgeon in the bunch…but a geriatrician may be more useful.”
