Back joints with a normal range of flexibility hold a unique place in the body's architecture: They give us strength, power and stride. But back joints with damaged discs hold a unique capacity for crippling pain -- the price we pay for walking upright, playing sports, lifting heavy objects and, sad to say, simply living into middle age.

"Our backs just aren't designed to last a lifetime," says Jeffrey Lotz, director of UCSF's Orthopedic Bioengineering Laboratory and a professor in the department of orthopedic surgery. "A lot of damage accumulates by the time we reach 45." Indeed, as in so many other anatomical and organ systems, evolution has frontloaded us for youth. Consider this: the 23 intervertebral discs, over which so much ink and agony have been spread, separate our 24 spinal vertebrae, preventing what is essentially a bony structure (with its accompanying column of nerves) from settling into a straitjacket. Think about a golf swing or a swimmer's turn; these are impossible feats without such a remarkable innovation.

Special function requires special construction and, true to form, the disc is distinctive among bodily organs. For one, it is composed of three tissues, two of which are fibrous and spongy. The third more closely resembles cartilage. The tissues, which live in an environment that is 80 percent water, also contain multiple cell types, which because there is no blood supply, must obtain nutrients through diffusion from the nearby bone. It is an efficient system, but not an error-free one. Discs degenerate with normal wear and tear, losing stiffness at first, only to reverse course and become more rigid with age. No wonder that lower back pain has become a chronic condition among so many and treatments to prevent or ameliorate it, such an enormous health care enterprise. (See "Back Up," page 44.)

Yet, as Lotz and his fellow bioengineers were forced to admit less than a decade ago, they knew little about why degeneration begins and even less about how it proceeds. And even more puzzling, they could not predict if damaged discs would always be painful. It turns out that they are not. "We suspected that there was a combination of mechanical and biological events, but we weren't sure." Analysis of surgically removed discs (the result of a discectomy) as well as pressure tests on cadaver spines provided data on how spinal loads are distributed and the first real insight into back damage; cracks and breaks in the bone are the main culprits in degenerative disc disease. But the process of degeneration itself remained a mystery.

Thanks to the work of Lotz and his colleagues in the bioengineering laboratory, some of the mystery has now been solved. The key clues emerged from a series of pioneering experiments on mice tails, which mimic our disc system in its robust and pliant youth. In short, Lotz inserted pins into the tails of mice. The pins compressed the discs, allowing the scientists to study the impact of these compression forces on cellular as well as bone structure. What they learned was surprising.

Explains Lotz, "While a strong force did not break the bone or make the disc burst, the compression did make the cells of the disc change their elongated shape." This might seem logical, even innocuous, given the squishing effects of compression. What was unexpected were the consequences. "The change in shape makes the cells die." And since the cells at the center of the disc are the most vulnerable to damage (remember, there is no blood supply) and critical to the resilience of the spongy structure, cell death means disc trouble.

Still, knowing that the cells died did not explain the pain so often associated with degenerative disc disease, or the lack of it. In some cases, of course, a distended disc impinges upon the nerve column. Pain is the result of physical intrusion. But Lotz and his colleagues suspect that another factor -- an inflammatory substance released by distressed disc cells -- may also be to blame. They now are testing their theory in a mouse model.

The goal as always is to stabilize and neutralize the problem. To that end, Lotz is testing various methods -- heat being one example -- to evaluate their effectiveness. At the same time, he is examining the merits of his own "biomaterial nuclear implant" (to replace the nucleus of the disc), which can be injected into an inflatable sac inserted through a tiny hole in the spinal ligament.

As knowledge builds, the hope is that bioengineers will learn enough to, if not prevent, at least forestall disc degeneration. And as plans proceed for the bioengineering laboratory to become part of UCSF's recently planned bioengineering department that will exist within the Institute of Quantitative Biology (QB3) at UCSF Mission Bay, Lotz dreams even bigger. He would like to reverse existing damage. "We know that degeneration is the result of compression forces. We know that collagen cells prefer to be elongated, that when they are squished, they likely release an inflammatory substance before they die. We need to figure out how to interrupt this process." Easier said than done, of course, one reason why Lotz has a single recommendation in the meantime: "Stretch."