In prehistoric times it was believed that illness was the result of punishment from the gods or the consequence of magic. During the Middle Ages, people attributed disease to toxic vapors or decaying earth.

However in 1867 a scientist named Robert Koch discovered that anthrax is able to cause disease and was able to successfully transfer the germ from cows to mice. Since that time, bacteria have been implicated in an ever greater range of diseases.

Over the past few decades, scientists such as Lida Mattman, Alan Cantwell and Trevor Marshall have provided great evidence for the hypothesis that chronic diseases ranging from arthritis to Alzheimers are the result of bacterial infection. Nevertheless, a great majority of the medical community still feel that these diseases are caused by toxins in the environment or are autoimmune in nature.

Koch’s Postulates

After working with anthrax, Koch developed a series of ground rules to determine whether a given organism can cause a given disease. These rules, known as “Koch’s Postulates” state that a scientist must find the same microbe in every person with a given disease. Furthermore, the specific microbe must be able to be grown on pure culture medium in the lab and when reintroduced into a healthy animal or person must produce the disease again.

Many researchers still believe that Koch’s rules are universal and correct despite the fact that a massive body of research has shown that the principles are outdated and can no longer be applied to a modern understanding of disease.

For example, in the early 19th century researchers realized that viruses invalidate Koch’s Postulate because they require another living cell in order to replicate. According to TD Brock at the American Society of Microbiology, attempts to rigidly apply Koch’s postulates to the diagnosis of viral diseases may have significantly impeded the early development of the field of virology.

But the fact that scientists are still trying to apply Koch’s Postulates to bacteria is causing an even greater array of problems. For one, bacteria in the L-form cannot be easily grown in the lab and can only be studied in conditions that mimic those of the human body. As Gerald Domingue, Professor Emeritus at Tulane University states, “When it comes to L-form bacteria, Koch’s Postulates cannot be fulfilled because it is impossible to duplicate all the variables involved in disease expression.”

It is already widely accepted that some species of bacteria cause disease despite the fact that they do not fulfill Koch’s Postulates since Mycobacterium leprae and Treponema pallidum, (which are implicated in leprosy, and syphilis repectively) cannot be grown in pure culture medium.

Horizontal Gene Transfer

Another problem with the postulates is that they do not take into account a phenomenon called horizontal gene transfer. Horizontal gene transfer is a process in which organisms swap genetic material. The phenomenon is itself a challenge to Koch’s Postulates, which state that only one organism can be isolated, cultured, and held responsible for causing a single disease.

Over the past few decades, humans have entered into an age in which new technology has made it possible to sequence an organism’s genetic code. Scientists now know that bacteria can insert genetic material into the genomes of other pathogens or into the genome of their host. They often do this while in the form of plasmids, circular molecules of DNA that can replicate independently of a pathogen’s other genetic material.

For example, researchers at the Cancer Research Institute in Slovakia analyzed the bacterial DNA isolated from the intestinal tract of 11 American and 30 Slovak patients with HIV/AIDS. They found that the intestinal bacteria genes were more than 90% homologous to the corresponding sequence in HIV – suggesting that the bacteria and the HIV virus had traded a significant amount of genetic material.^[1]

James Lake, a researcher at the Molecular Biology Institute at the University of California, puts it, “Increasingly, studies of genes and genomes are indicating that considerable horizontal gene transfer has occurred between bacteria.” In fact, due to increasing evidence suggesting the importance of the phenomenon in organisms that cause disease, molecular biologists such as Peter Gogarten at the University of Connecticut have described horizontal gene transfer as “a new paradigm for biology.”

Gorgarten insists that horizontal gene transfer is “more frequent than most biologists could even imagine a decade ago” and that this reality turns the idea that we can classify organisms in a simple “tree of life” on its head.

Instead Gogarten suggests that biologists use the metaphor of a mosaic to describe the different histories combined in individual genomes and use the metaphor of a net to visualize the rich exchange of DNA among microbes.

Trading plasmids

This transfer of DNA among pathogens means that once harmless microbes can acquire properties that allow them to cause problems for the host. “The mobile nature of..gene islands, transported between bacteria via plasmids or phages, creates the potential for acquired virulence in previously innocuous microbes,” states researcher Dave Relman of Stanford University. “This concept should inspire some reflection the next time one receives a culture report reading “normal flora.”^[2]

Take, for example, the bacterial species Bacillus anthracis, a species of bacteria that has two plasmids. One plasmid codes for genes that allow the pathogens to create toxins, the other codes for proteins that help it evade the immune system by living inside the white blood cells that kill and digest bacteria.

Bacillus anthracis can be found in soil, so people can pick it up relatively easily. Once inside the body it comes in contact with other species of bacteria. Let’s say it encounters Bacillus cereus, a species of bacteria that causes foodborne illness. The two bacteria may trade genetic material. If Bacillus cereus picks up the plasmids for creating toxins and evading the immune system from Bacillus anthracis, it will be much more successful at staying alive, persisting inside the cells, and ultimately causing problems for the host.

Some bacteria have more than 20 plasmids. Also it should be noted that other types of pathogens such as viruses can and do engage in horizontal gene transfer. This activity must be accounted for. Consider this situation envisioned by biomedical researcher Trevor Marshall.

“If you take the 21 plasmids of Borrelia, they can transfer DNA in 21! (21 factorial) combinations with other species, which is a VERY large number. Then you have to add in the DNA in the plasmids of the other key species – Staph, Rickettsia, Strep, Treponema, E.coli, Bacillus, and then add all of their chromosomes, add in the remaining non-plasmid bacterial species (like Mycobacteria), add the viruses, stir the soup together, accumulating new components for a few decades, and the number of combinations of pathogenic DNA in our cells becomes virtually infinite.”

DNA “Soup”

The image of people acquiring their own unique “soup” or mix of pathogens is a good way to visualize chronic disease. Marshall’s molecular models indicate that chronic disease results when individuals begin to accumulate different species of L-form, biofilm or other choronic bacteria. Biofilm bacteria create proteins such as capnine which are able to bind and inactivate the Vitamin D Receptor (VDR), the fundamental receptor of the immune system. Thus, as an individual accumulates more and more disease-causing bacteria, their immune systems start to shut down.

When this occurs, people have a very hard time keeping other pathogens under control. They often find that childhood viral infections reactivate, or that they acquire Candida (pathogenic yeast) and mycoplasma as well. Thus, according to Marshall, every person who falls ill with chronic disease has a different mix of pathogens to kill depending on what microbes they have encountered during various stages of life.

It does seem that only one species of bacteria is involved in each disease, then patients with the same illness would manifest with much more similar symptoms. On the contrary, patients with the same chronic disease often report very different aches and pains.

This isn’t to say that people with the same diseases might not all have some species of bacteria in common, or that specific bacteria don’t generate specific symptoms. It simply means that a combination of pathogens all likely contribute to different aspects of an illness. Consequently, the idea that only one of the pathogens can be isolated, cultured in the lab, and blamed for the entire disease seems increasingly implausible.

Furthermore, as a result of horizontal DNA transfer, the mix of pathogens in the body is constantly evolving. Because plasmids can be swapped, new species or strains of bacteria with new characteristics can emerge at any time.

Horizontal DNA transfer can also make it easier for some of the most harmful and difficult to kill pathogens to survive. As mentioned before, bacteria often trade genes that help them effectively evade the immune system. As Marshall says, “The longer they have persisted in the host, the more the opportunity for horizontal DNA transfer”, meaning that the bacteria which are hardest to kill have more chances to pass on the genes that helped them evade the immune system.

Antibiotic resistant bacteria

Hua Wang, a researcher at Ohio State University has shown that pathogenic bacteria have the ability to engage in horizontal DNA transfer with various commensal bacteria and even beneficial bacteria, including those from the food chain.

Wang writes, “We have demonstrated not only that organisms carrying such intrinsic mechanisms have the potential to become an important reservoir for antibiotic resistance genes but, more importantly, that these intermediate organisms can disseminate antibiotic resistance genes in subsequent events much more effectively than the parental donor strain.

Once we no longer limit ourselves to foodborne pathogens and look at commensal bacteria, we will find that the magnitude of antibiotic-resistant bacterial contamination in the food chain is tremendous.”

Clearly, identifying the pathogens behind chronic disease is more complex than conventional wisdom would have it. It is a shame then that many researchers are still adhering to the idea that only one organism can cause a specific disease. As Marshall says, “Koch’s Postulates make little sense in the era of the Genome.”

SOURCES

Evans, A. S. (1976). Causation and disease: the Henle-Koch postulates revisited. The Yale journal of biology and medicine, 49(2), 175-95.

Gogarten, P. (2000). Horizontal Gene Transfer – A New Paradigm for Biology, Esalen Center for Theory & Research.

Grimes, D. (2006). Koch’s Postulates–Then and Now. Microbe Magazine.

Jain, R., Rivera, M. C., & Lake, J. A. (1999). Horizontal gene transfer among genomes: The complexity hypothesis. PNAS, 96(7), 3801-3806.

Marshall, T. (2006). Molecular genomics offers new insight into the exact mechanism of action of common drugs – ARBs, Statins, and Corticosteroids. FDA CDER Visiting Professor presentation.

Marshall, T. (2007). Bacterial Capnine Blocks Transcription of Human Antimicrobial Peptides. Nature Precedings.

Woese, C. R. (2004). A New Biology for a New Century. Microbiol. Mol. Biol. Rev., 68(2), 173-186.

REFERENCES

1. Zajac, V., Stevurkova, V., Matelova, L., & Ujhazy, E. (2007). Detection of HIV-1 sequences in intestinal bacteria of HIV/AIDS patients. Neuro Endocrinol Lett, 28(5). [↩]
2. Fredricks, D. N., & Relman, D. A. (1998). Infectious agents and the etiology of chronic idiopathic diseases. Current clinical topics in infectious diseases, 18, 180-200. [↩]