Foreword

I left the hospital one evening and walked through a narrow passageway toward the parking garage. A large trash dumpster was blocking my path. As I squeezed by, I looked inside the dumpster and saw, to my astonishment, hundreds of old medical textbooks. I telephoned the hospital librarian at home to inquire about this mysterious and troubling disposal and was informed that “there is simply no room in the library for old textbooks, and besides, they are hopelessly out of date.” “But they’re textbooks!” I exclaimed. “If you want them, you may take them,” she said. “They are going to the dumps.”

A textbook is a fossil of knowledge, and it is important not to be mesmerized by the apparent certainty of the knowledge it contains. Some of that knowledge will eventually be proven wrong, and much of the rest will appear quaint, if not downright foolish, over time. An old textbook is a subtle reminder that today’s textbooks, although seemingly fresh and new, will eventually become relics of the past.

If much of the knowledge within a textbook will eventually become obsolete, does that mean we should not bother learning it? No indeed. As Banquo, one of the generals of the King’s armies, said in Act I of Shakespeare’s Macbeth, “If you can look into the seeds of time, and say which grain will grow and which will not, speak.” If every student of science and medicine who read a textbook at the turn of the last century had been content with the knowledge it contained, we would not now have a polio vaccine, total joint replacement, antibiotics, recombinant growth hormone, bone morphogenetic protein, or the promise of stem cell therapy and gene therapy—treatments that have revolutionized the field of musculoskelatal medicine.

Textbooks, clearly, are not the last word.

The first textbook of musculoskeletal medicine, one might say, was written by Nicolas Andry in 1740. Nicolas Andry was born in Lyon, France, and became a professor of theology. At the age of 32, he left the clergy to study medicine. He became Professor of Medicine and eventually Dean of the Faculty of Medicine in Paris. As Dean, he launched a vitriolic attack on barber surgeons, and through that farsighted but unpopular move, lost the Deanship.

Andry died at the age of 84. It was a project taken up in his 83rd year that left an indelible mark on the history of medicine. He wrote, in that last year of his life, a book, the title of which, Orthopaedia is engraved in our vocabulary. “As to the title,” he wrote, “I have formed it of two Greek works, orthos which signifies straight, free from deformity, and paedios, a child. Out of these two words, I have compounded that of orthopaedia to express in one term the design I propose, which is to teach the different method of preventing and correcting the deformities of children.” Thus, in the very title and opening paragraphs of his prophetic little textbook, he planted a seed for the future. From that seed, a crooked little tree of great fame has grown, as we shall see.

Many of the treatments that Andry proposed were, in fact, weak and devoid of value. But the book offers much more. In the middle, we find a simple drawing that is so charming and advanced, so far reaching, that we can forgive the author of any transgression on our language or our thought.

On the basis of one illustration, that of a charming crooked little tree, our knowledge takes root and our imagination soars. Andry uses the metaphor of a crooked little tree to illustrate a critical point. He writes: “The same method must be used for recovering the shape of the leg, as is used for making straight the crooked trunk of a young tree.” With those words, he set the world of science and medicine on a search for a more profound understanding of how physical factors affect living systems.

By the mid-1800s, many scientists and physicians had written on the relationship between bone morphology and applied load. In 1892, the physician Julius Wolff of Berlin, wrote a treatise entitled The Law of Bone Transformation. Wolff summarized 30 years of experiments and proposed a new theory that described how every change in the function of a bone is followed by certain definite changes in morphology. Wolff’s work was so immediately popular that by the time of his death in 1902, the scientific community referred to the effect of load on bone mass as Wolff’s law. The architect, Lewis Sullivan, familiar with Wolff’s work, adopted this principle in his famous theorem: “Form follows function.”

Theories abound on the biological effects of physical stimuli—positing roles for prostaglandins, electricity, calmodulin, integrins, and more. But the transduction of a mechanical signal to a biological message remains a mystery even today.

A little more than a decade ago, the scientific world gained a fugitive glimpse of how a physical strain is converted into a molecular response. The article appeared in the journal Cell with a cover caption reading, “Plant Growth Response To Touch.” In the accompanying article, the authors described how touch induces the expression of four calmodulin-related genes in plants. This work suggested that calcium ions in calmodulin were involved in the transduction of mechanical signals and provided some of the first clues at the molecular level of how a complex living organism responds to a mechanical stimulus in its environment.

The opportunities provided by our molecular tools will undoubtedly allow us to decipher the puzzle further. We are certain to gain a better understanding of the factors controlling bone morphology: the genetic program, the humoral factors, the applied load, and most importantly, the complex molecular signaling pathways that provide the integration. When we do, we may be able to accomplish what Nicolas Andry envisioned in the preface to his famous little book a quarter of a millennium ago: the art of correcting and preventing the deformities in children.

Leaving Andry, a brief stop in time takes us back about 2,000 years, to the Isle of Cos in ancient Greece. There, we find Hippocrates, the Father of Medicine, remembered today for his Oath, but an accomplished scholar of musculoskeletal conditions as well. His method of reducing shoulder dislocations is still employed today. From our visit with Hippocrates, we take a major leap back to a time about 20,000 years ago. We find ourselves staring at the brilliant white calcite walls of the Hall of Bulls in a cave in South-central France near the present day village of Lascaux. There, on a grand scale, a Paleolithic artist painted images of the animals that he or she knew. Among the images is a depiction of an early human figure in what one might imagine to be a supremely traumatic context. So, when did musculoskeletal medicine begin?

Our next stop back in time requires a truly giant leap—65 millions years. For a moment, imagine yourself on the plains of what is now South Dakota with a very old creature by the name of Sue. Sue has sustained an open fracture of her left fibula and many closed fractures of the right ribs in a terrible accident. Sue is a dinosaur, and not just any dinosaur, but one of the largest Tyrannosaurus rex dinosaurs to have ever lived. Sue has osteomyelitis of the left fibula and multiple healing fractures of the right ribs.

In reality, Sue stands motionless before us in the Field Museum of Natural History in Chicago, on the same continent where she roamed 65 million years ago. What tickles us is that long ago, Sue knew how to heal a fracture, and her body knew how to react to a bone infection. The scars of her skeleton are a testimonial to that undeniable fact. Here we are, the beneficiaries of the most advanced educational systems that have ever existed on the planet, and we still do not know exactly how fractures heal or how the body fights a bone infection! But Sue knew because she did it!

Science is a recent invention of human beings, a method of inquiry that provides a structured discipline to our curiosity. Science can answer questions, but it cannot ask them. As students of medicine, questions may occur to us in the clinic today (or in a virtual clinic from 65 million years ago that we can visit tomorrow in a museum courtyard in Chicago). As William Osler, the famous nineteenth century physician said, “Clinics are laboratories, laboratories of the highest order.”

The clinic—the laboratory of the highest order— will be where you can learn things that assuredly will pass the test of time: the skills of physical diagnosis. The importance of physical diagnosis was best exemplified at a high-powered scientific conference that I attended several years ago on the molecular genetics of the skeleton. A young molecular biologist, who had been working on the developmental biology of the skeleton, dazzled the audience with her beautiful work on a genetically engineered mouse in which she had successfully deleted both alleles of a gene not previously known to be involved in the formation or maintenance of the skeleton. The scientist mesmerized the audience with her methods of molecular biology. At the end of the talk, however, all of the questions that followed (not some of them, but all of them) pertained to the clinical findings (or phenotype) of the mouse. None of the questions pertained to the molecular genetics or to the experimental methods. It was as if we were in a mouse clinic and curious mouse doctors were asking questions about the physical examination of the interesting mouse patient.

As we begin to mine the bounties of the human genome, our skills of physical diagnosis will become even more important. They will have to become more important as we struggle to integrate the emerging knowledge of genetic variation into a useful clinical context and as we strive to understand the often subtle and nebulous boundaries of health and disease. So instead of being relegated to obsolescence, like yesterday’s textbooks, our observational and integrative skills of physical diagnosis will likely become even more important over time. As Albert Einstein said, “Concern for man himself and his fate must always form the chief interest of all endeavors. Never forget this in the midst of diagrams and equations.”

Let’s review our travels back in time. Our visit to the apartment of Dr Nicolas Andry let us eavesdrop on the creation of the field of orthopaedics. Our meeting with Hippocrates suggested that there were doctors of musculoskeletal medicine long before Andry. Our encounter with the caveman suggested that musculoskeletal concerns were present at the dawn of human history. Our visit with Sue taught us that reality precedes knowledge. Our lecture at the molecular genetics conference inspired us that the skills of physical diagnosis may become even more relevant over time.

The next story teaches us that one never knows when the future will intrude to question the present or possibly just how unnoticeable the future may be when it first appears.

The time was 30 years ago. The place was a classroom in Baltimore. I was a second-year medical student struggling to learn microbiology. One morning, the professor teaching the course strayed from the outline to tell us about the laboratory experiments he had been conducting on some obscure enzymes in bacteria. He mentioned that these enzymes cleaved the DNA in predictable patterns, and then he used them to cut DNA into predictable pieces. He then showed us a primitive map from another organism using the enzymatic tools that he had isolated from various strains of bacteria. None of the students could see much immediate use for this. After all, we were studying to be physicians to care for patients. What possibly could be the use of some obscure concoction of enzymes that could chop up DNA in a test tube?

Our professor’s comments provoked little interest, and we were all relieved when he got back on track and followed the textbook that he had assigned us to read. There was no reference to the professor’s curious digression on the final exam, and we heard no further mention of his arcane experiments during the remainder of our time in medical school. We all passed the microbiology exam, entered the clinics, and graduated as medical doctors soon thereafter.

Several years later, I turned on the television to listen to the news and saw the face of my microbiology professor prominently displayed. With that, the TV news anchorman announced that the microbiologist had just been awarded the Nobel Prize in medicine. I was truly shocked! For what could he have possibly won the Nobel Prize in medicine? Surely, it was not for teaching a microbiology class to medical students!

The next morning, I bought a newspaper and read the citation of the Nobel Prize Committee about my professor’s work on restriction endonucleases, those curious little enzymes from bacteria that he had told us about years before. Still the importance and implication of the message eluded me.

Fifteen years later, as a medical faculty member, I was having lunch with a medical student and listening to him explain the evolution of molecular biology during the past 2 decades. I knew very little about molecular biology and felt like Rip Van Winkle awaking from a long sleep. One of the highlights that the student mentioned was the discovery of restriction endonucleases and their ability to cleave DNA in predictable patterns. After about 5 minutes of discussion, the lights went on! It became obvious that little could be accomplished in molecular biology without that discovery. Somehow it had bypassed me in medical school, throughout my residency, and throughout my early years of practice. Somehow it had bypassed all of us who sat in the classroom that day in medical school.

But it did not bypass the Nobel Prize Committee or the next generation of medical students.

On that morning in medical school 30 years ago, I had no idea that I was witnessing the birth of a new field of human inquiry—a field that would change the world. It was the one topic in the entire microbiology course that our professor took directly from his lab notebook and brought to the classroom. It was the only topic that he discussed with us in the entire microbiology course that was not in the textbook, and it was one of the only topics that he ever discussed with us that would have any direct or long-lasting importance to our lives and the lives of our patients. It is in the textbooks now. Even more importantly, there are people alive today (who otherwise would not be) because of it.

I leave you with ten untextbook-like thoughts:

1. Clinics are laboratories—laboratories of the highest order.

2. Physical diagnosis skills are timeless. Learn them, practice them, and teach them to others.

3. The greatest discoveries are made not within a field but at the boundaries of a field and within other fields. Step outside and glimpse the future.

4. One never knows when the future will intrude to question the present. When the discussion strays from the text, pay attention.

5. Don’t expect to learn everything, but try hard to learn something. Keep asking questions.

6. If you want to be a top practitioner of musculoskeletal medicine, try first to be a knowledgeable doctor. A broad knowledge of internal medicine, pharmacology, pediatrics, radiology, neurology, epidemiology, genetics, molecular biology, and psychiatry will also be relevant—along with many other fields not mentioned. Likewise, subscribe to a general medical journal and read it.

7. Knowledge alone is not enough. Caring is part of the cure.

8. Learn to communicate and take time to communicate well. When the patient returns home from a visit to your clinic or office, the family will most certainly ask: “What did the doctor say?”

9. There isn’t a condition known to man that surgery can’t make worse.

10. Old textbooks in a dumpster may be a sign of progress.

—Frederick S. Kaplan, MD

Isaac and Rose Nassau Professor of

Orthopaedic Molecular Medicine

University of Pennsylvania School of Medicine

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania