Autologous Biologics and Molecular Medicine


Autologous Biologics and Molecular Medicine: The clinical translation of cellular and molecular biotechnology to applications in orthopedic surgery from Hippocrates until 2018.


The clinical experience with signaling cell therapies and molecular medicine in orthopedic surgery


Austin Yeargan III MD


Abstract: We had little to go on other than the clinical results from bone marrow stimulating procedures described by previous surgeons and relevant theoretical applications of immunology and stem cell biology when we took a big step in 2006 to modify orthopedic surgical procedures with bone marrow concentrates embedded in activated fibrin and platelet scaffolds. Since that time, the procedures we introduced have changed little, while our understanding of the mechanisms behind the treatments has evolved significantly. This article describes the evolution of signaling cell treatments for orthopedic surgical manifestations of disease and considers future direction for biologic treatments in orthopedic surgery. It is hoped that this work will serve as a knowledge baseline for other physicians interested in developing better options for patients with musculoskeletal disease.

Healing is a natural art

The history of using natural remedies to fight inflammation dates back to at least the time of the ancient Greek physician Hippocrates of Kos. While written descriptions of disease date back to the Shang Dynasty Era (1600-1046 BCE), no clear records concerning Chinese medicine exist until approximately the second century BCE, likely because written language in China did not begin until 1766 BCE. Existing written records focus on acupuncture and moxibustion instead of Chinese herbal remedies. Traditional Chinese medicine (TCM) has not yet been supported by modern science to play a scientific role in musculoskeletal medicine in terms of actually treating disease rather than symptoms. However, proponents in the United States are many and recently, some alternative medicine authors have tried to tie the clinical relief of symptoms in arthritis treatment to the regulation of the same inflammatory signaling pathways that we target using signaling cell concentrating techniques including the well characterized JAK-STAT, NF-kB and MAPK pathways. The vast majority of scientific studies that have shown benefit to acupuncture in the treatment of arthritis attribute adjuvant treatments like exercise as responsible for what others have described as expectation or placebo effects.

In 2007, Zhang et al reported that at least 6.3% of the US population, representing approximately 14.01 million users had tried acupuncture at some point for both complementary and alternative approaches to conventional treatment and to promote general health. Awareness, cost and insurance coverage played larger roles in decision making to pursue acupuncture than effectiveness and safety in the U.S. Population, a trend that is likely to continue.

Hippocrates (460-377 BCE) who is known globally as the “Father of Medicine,” is credited for revolutionizing the practice of medicine and establishing the trajectory for modern medical concepts and techniques. While written descriptions of disease date back to the Shang Dynasty Era (1600-1046 BCE) No clear records concerning Chinese medicine exist until approximately the second century BCE. Prior to the establishment of Hippocratic practices as the gold standard, it was believed that physicians could not heal patients without the aid of a divine intervention from a ‘God’. Modern medicine’s divergence from dependence on the supernatural for healing from disease grew directly from the practices of Hippocrates. The principles of Hippocratic practice include the observation of clinical signs combined with thoughtful scientific consideration, followed by rational conclusion to direct treatment.

Hippocrates was the first to describe the use of the drug salicylic acid, known commonly now as aspirin (Bayer® Corporation, Whippany, New Jersey). Hippocrates described treatment of gravid patients at parturition with salicyclic acid in the form of willow (Salix alba) leaf tea circa 400 BCE, to naturally relieve the pain of childbirth. Not unlike the great physicians and surgeons of today, Hippocrates’s contribution to medical practice was characterized by strict attention to ethical rules of conduct, an open-minded, un-biased approach, close observation of clinical symptoms (empiric strategy) and a strong inclination towards academic debate and discussion regarding the genesis of human ailments and disease. Some 2300 years after the introduction of his pillars of medical education and practice were erected, every medical student in the United States and most countries across the globe commits to the Hippocratic oath, “ὅρκος horkos” upon graduation, which contains the Pythagorean duties of justice, secrecy, respect for teachers and solidarity with peers. The role for biologics in orthopedic surgery and other branches of medicine continues to be defined, mandating strict adherence to these principles to limit additional false starts and maintain focused scientific methods to ensure best practices. US FDA commissioner Scott Gottleib has indicated a focus on ensuring safety and efficacy to limit the way in which biologics are being marketed and delivered to American consumers. The immunologic knowledge base that will be established by virtue of the emergence of molecular medicine and biologics represents disruptive technology for orthopedic surgeons and physicians in every field of medicine going forward. As doctors, we love to learn. The immune system is what we are and additional mastery will unlock the mysteries of many human diseases including congenital disease and cancer. The next two decades offer the potential for fantastic innovation juxtaposed against the triumph of technology over reason.

Cito tuto jucunde

No less important in the history of orthopedic molecular medicine is Asclepiades of Bithynia, the physician molecularist (124-40 BCE) who was the first physician who created a crude health and disease theory with a basis in molecular medicine. Most of his theories were incorrect and treatments were generally limited to diet management, healing touch, bathing, music therapy and exercise, but many of these treatment modalities, while still not justified by modern medical science consistently account for a large component of healthcare expenditures in the United States and elsewhere. According to the NIH National Center for Complementary and Integrative health, 38% of US adults representing 83 million patients, spent $33.9 billion out of pocket on complementary and alternative medicine (CAM), compared to $3.3 trillion for overall national health expenditures in 2016.

Asclepiades believed that the human body was composed of molecules and voids. His theoretical, atomic approach was based on the leading science of the times and often opposed the humoral doctrine of Hippocrates that shunned surgical intervention. He believed disease followed a disruption of the natural harmony by causing alteration in the form or position of a patient’s “molecules”. He was the first to classify diseases as acute or chronic and the first known physician to discuss concepts related to what we refer to as molecular medicine today. Asclepiades of Bithynia used recognition of behavioral signs and use of empirical records. In spite of his focused scientific-based approach, his great clinical success in treating patients has often been at least partially ascribed to his heartheld belief that patients should be treated Cito tuto jucunde (Quickly Safely and Pleasantly), not often customary during that time period.


CONTINUE READING Autologous Biologics and Molecular Medicine

S. Austin Yeargan III, MD Orthopedic Surgeon Molecular Immunobiologist

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