Camping Trip Accelerates Bone Research

After completing military service in World War II and then his orthopedic surgery residency in Boston, Marshall Urist returned to his native Illinois and joined the faculty at the University of Chicago. There he partnered with a physiologist, and they focused their laboratory research on bone growth and bone grafting. Urist noted on patients’ X-rays that new bone would not only form immediately around a graft but also at times some distance away, in muscle tissue for instance. He surmised that some chemical messenger must be stimulating local cells to begin producing bone. Thereafter he directed his research to isolate and identify the messenger. In the mid 1950s, Urist moved to Los Angeles and spent the remainder of his career at UCLA.

Urist’s research assistants made regular visits to the slaughter house and returned with hundreds of pounds of beef bones. Under Urist’s guidance they crushed and then processed the bone, first to remove the calcium, and then to tease apart the remaining proteins. Repeating this arduous process again and again, Urist was finally able to reduce a heap of bones to a tiny dot of bone-forming protein in the bottom of a test tube. Injected into even unlikely tissues such as tendon, brain, and fat, these chains of amino acids, known as growth factors, would stimulate the local cells to form bone.

Urist called this growth factor bone morphogenetic protein, and it is known around the world today at BMP. Progress at characterizing and testing the effectiveness of BMP was slow, however, because it existed in only minute quantities and took weeks to isolate and purify. A research fellow unwittingly discovered a shortcut. Up to that point, the isolation steps had been performed at room temperature. Wanting to leave for a weekend camping trip before a batch of bone could be completely processed, the assistant refrigerated the mix and took off. The next week, that batch yielded a far greater quantity of BMP than what they were previously able to harvest.

In due time, Urist, his former fellows, and others characterized the specific chemistry of BMP, which turned out not to be one compound but a family of closely related growth factors, all of which stimulate bone formation. Investigators have been able to coerce bacteria to produce BMP. This form is now commercially available and approved for certain clinical applications. It is particularly useful to hasten the healing of recalcitrant fractures in the leg and to ensure early and complete fusion of spinal segments when treating pain in the low back or neck. For back fusion operations, surgeons now combine specially designed hardware that securely fixes one vertebra to the next with BMP-impregnated cadaver bone graft. These advances have markedly increased the success of this often-risky procedure. I wonder where we would be today if the lab assistant had stayed home that weekend.