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The Window on Disease

By Dr. Jim Ferguson

The chief professor of medicine during my internal medicine residency held that all disease was the result of some infectious process.  Jesus used hyperbole (exaggerated speech) to get people’s attention, and I suspect my professor was doing the same.  Because Dr. Stollerman was an expert in infectious diseases and did the original investigations of streptococcal infections, such as strep throat and nephritis (kidney inflammation), he was vigilant that germs were the root cause of disease.

We take for granted a functioning immune system until it is damaged by chemotherapy, radiation or with autoimmune diseases like Lupus.  Lupus occurs when the immune system dysfunctions and begins to recognize a patient’s own blood vessels as alien.  The resulting attack produces inflammation in the vessels, a process doctors call vasculitis.  A similar immune mechanism occurs in rheumatoid arthritis when the immune system pathologically identifies a person’s joints as foreign and attacks them.  The resulting   pain, swelling, and redness is the result of joint inflammation.

Our immune system consists of white blood cells made in the bone marrow, the lymph glands, and blood stream antibodies produced by certain white blood cells.  Cancer specialists (oncologists) often give chemotherapy that hopefully does more damage to out of control and rapidly growing cancer cells than healthy tissue and the immune system.  You may find it surprising, but antibiotics merely support the patient until their marrow recovers from harsh chemotherapy.  Inevitably, without bone marrow and immune system recovery, death ultimately ensues from microbial invasion.

Most of us have read about the atom bombs that were dropped on Hiroshima and Nagasaki to end World War II.  As horrible as it seems today, all-out war was then waged not only on military targets, but on civilian populations who supported war industries.  However, that was long ago and we’ve forgotten that many died after the blast from radiation damage to the survivor’s bone marrow.  The closest modern equivalent is the Chernobyl meltdown in the Ukraine and the Fukushima disaster in Japan.  We probably will never learn the number of later deaths from radiation exposure in the Ukraine.  Many emergency workers died from acute exposure as they fought the meltdown generated fires.  We do know that the supervisor at the Fukushima plant stayed at his post and ultimately died from acute radiation exposure.

Many of us remember the story of Alexander Fleming who fortuitously discovered penicillin in 1929, ushering in the antibiotic age.  Fewer of us know about Ignaz Simmelweis.  This Hungarian physician challenged established thought in 1847 with his proof that the life threatening infections associated with labor and delivery called child-bed fever (puerperal sepsis) could be drastically reduced by doctors washing their hands with a chlorinated lime solution.  He was ridiculed and ultimately was committed to an asylum where he died after being beaten by guards shortly after his incarceration.  He was ultimately vindicated when Louis Pasteur established the “germ theory.”  We now take for granted hygienic measures and use hand sanitizers and sterilize the skin before surgery.

I still read multiple medical journals, and recently the New England Journal of Medicine (NEJM) closed the loop for me on the common disease age-related macular degeneration (AMD).  My grandmother lost her vision to the “dry” subset of this disease associated with proteinaceous deposits in and atrophy (withering) of the retina.  The “wet” type also has the additional feature of abnormal blood vessels (neovascular) in the retina.  These new vascular structures bleed more easily accelerating damage to the delicate retina.  Scientific advances have led to therapies that retard growth of these unstable vessels and limit bleeding.  Interestingly, when doctors look through the pupil (window) they can directly observe the vascular system and the course of disease.

Researchers have recently discovered a genetic aberration that can lead to dysregulation of the immune system and produce an inflammatory complex in AMD called an inflammasome.  This in turn activates components of the inflammatory cascade similar to that seen in gout and another joint problem called pseudogout.  I have written previously about inflammatory mechanisms in diseases like Alzheimer’s Disease and arteriosclerosis (hardening of the arteries).  I find it fascinating that AMD, another disease associated with aging, is also associated with dysregulation of the immune system and inflammation.

The immune system regulates itself through proteins produced by white cells called cytokines.  These signaling chemicals enable cells to “talk” to each other and modulate the immune response to foreign invasion or injury.  Apparently, congenital genetic defects and those acquired through radiation, chemo or even aging can lead to immune system dysregulation and disease.  Perhaps my old professor was, in part, correct.  If the skin is damaged allowing bacteria to invade, or if the immune system breaks down, disease results.  We now see farther into the mechanisms of disease.  At one time we asked the question, “what went wrong?”  Now, we ask “why did it go wrong?”

Science explores the universe with what is called reductionism.  This is a process where a complex whole is broken down into its component parts in an attempt to understand the whole by comprehending the integral parts.

Yes, we do see farther than we once did, and I suspect this will continue as we strive to learn about our world and explore our purpose.  I’ve been in medicine forty years and it is intriguing to find that complex and seemingly diverse conditions like heart disease, dementia, gout, and AMD may all have a similar etiology.  Maybe my old professor was right and these common diseases are all triggered by some obscure viral or other infectious stress on the immune system of a genetically predisposed patient.

The Apostle Paul once observed that we “see dimly as in a mirror.”  Someday we will see more completely.  Until that time I’ll keep my eyes open.  After all, they are the windows of disease and the soul.

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