Cell Notes: Cellular Bridges – Connecting Koch’s Postulates to Cell Therapy

In her monthly column "Cell Notes," AABB's Christina Celluzzi, PhD, MS, CABP(H), shares insights, findings and commentary on emerging topics in biotherapies. Subscribe to CellSource, AABB's biotherapies newsletter, to receive "Cell Notes" and the latest news directly in your inbox.  

March 24 marked the observance of World Tuberculosis Day — an annual event commemorating the day when Robert Koch, a German physician and microbiologist, discovered the bacterium responsible for tuberculosis. His work not only earned him the 1905 Nobel Prize in for Medicine in but also revolutionized our understanding of infectious agents and their impact on global health.

A solid understanding of microbiology is crucial for ensuring the safety and quality of biologics.

Koch’s legacy extends far beyond his laboratory work. His principles originally formulated in the 1880’s, known as Koch’s Postulates, laid the groundwork for establishing causality between a microbe and disease. By delving into the concepts, we can gain valuable perspective and appreciation. 

Let's explore Koch’s Postulates and how they resonate in the realm of cell therapy:

Koch’s First Postulate: Microorganisms Must Be Abundant in Diseased Organisms

Microorganisms must be abundant in all organisms suffering from disease but absent in healthy ones. In the context of cell therapies, we seek specific cellular targets for effective treatments. Consider cancer stem cells, a subset found in solid tumors. These elusive cells, unlike their healthy counterparts, could be viewed as “pathogens” within the tumor microenvironment. Identifying and isolating them pose challenges, but they can serve as potential targets for cell-based therapies. Another way of contrasting this postulate with cell therapies is to explore the ‘players.’ While Koch looks for microbes, cell therapists look for the cellular players involved in tissue repair, immune modulation, and regeneration.

Koch’s Second Postulate: Isolation and Pure Culture

The microorganism responsible for a disease must be isolated from a diseased organism and grown in ‘pure’ culture, which is crucial for establishing a causal link between the microbe and the disease. Koch emphasized the need to isolate the causative microorganism. In cell therapy, this translates to identifying and characterizing the specific cell populations responsible for therapeutic effects. Just as Koch sought to isolate bacteria, cell therapists aim to pinpoint the key cellular components driving desired outcomes.

Koch's Third Postulate: Reintroduction and Disease Replication

Koch's third postulate asserts that a cultured microorganism should cause disease when introduced into a healthy organism. However, it wisely uses the term "should," recognizing that not all exposed individuals will necessarily experience illness. This concept resonates with cell-based therapies, where patient responses can vary significantly. Some patients experience positive outcomes, while others show no therapeutic effect. Factors like immune responses, genetic makeup, and overall health play a crucial role in determining how cells interact with the host. Monitoring patients to assess disease progression aligns with the spirit of this postulate, emphasizing individual variability. Another parallel of this postulate to cell therapy is that of the reintroduction of modified or enhanced cells armed with regenerative potential to patients. Hematopoietic stem cell transplantation exemplifies this principle in restoring blood cell production for patients with leukemia, patients with the goal to replicate health, not disease.

Koch's Fourth Postulate: Re-Isolation and Identical Behavior

The fourth postulate demands that the microorganism be re-isolated from the inoculated host and identified as identical to the original causative agent. In the realm of cell therapy, we encounter similar principles. Cell therapy seeks to identify and characterize specific cell populations responsible for therapeutic effects. After administering cell-based treatments, scientists closely monitor the fate of these cells using techniques like genetic markers or imaging. Just as Koch emphasized the need for re-isolation, cell therapy protocols strive for consistency by preparing well-characterized cell populations. Verifying that the introduced cells align with the desired therapeutic outcome becomes paramount. 

I have presented connections of cell therapies to the principles; however, it is important to realize there are some exceptions and modern realities to Koch’s Postulates in the microbial world with respect to virus, immune functioning, and genetic immunity. Not all exposed individuals acquire infection. Proper immune function, previous exposure, vaccination and genetic immunity play roles. Koch’s universalist requirement in postulate one was abandoned as there can be asymptomatic carriers (e.g., viral diseases such as polio). Postulate two does not apply to pathogens incapable of growing in pure culture (e.g., viruses, obligate intracellular parasites rely on host cells for growth). Some pathogens cause multiple diseases (e.g., varicella-zoster virus causes chickenpox and shingles).

In essence, however, while Koch's postulates are rooted in the microbial world, their emphasis on causality, identification, isolation, and consistency resonates in the evolving field of cell therapy. Just as Koch's work revolutionized bacteriology, ongoing research and innovation in cell therapies hold promise for advancing modern medicine and improving patient lives.