In the 1960s my dad had ulcers causing painless profuse rectal bleeding and prostration. He hemorrhaged a number of times. Doctors admitted him to the hospital where he got 6 or 8 units of blood. His doctors thought bleeding ulcers were caused by aspirins which he used hardly at all. NSAIDs like ibuprofen, the first one available, were not yet in use. He bled so profusely transfusions saved him but as the saying goes, if we only knew then what we know now. I was a kid at the time.

Was he predisposed to ulcers? No other family member had ulcers or bleeding. Doctors suggested that spicy foods as stress were involved. Who doesn’t have stress? He drank little alcohol. We now know that none of these supposed causes applied to him.

In the 1980s the bacterium Helicobacter pylori was found in stomach ulcers and associated with gastritis, an ulcer precursor. Prior to that there had been occasional reports of curly bacteria within the stomach in ulcers and the stomach wall, but these were dismissed as inconsistent with the acidic environment unfriendly to bacterial growth. Nowadays everyone accepts that life lives practically everywhere. Bacteria in particular extremophiles, are comfy in volcanic vents. In fact, such extreme environments are where life seems to have originated. H. Pylori are at home within the stomach. They figured out ways to burrow into the stomach lining with their 6 flagella and convert urea into carbon dioxide + ammonia which makes the stomach less acidic. Medical scientists weren’t aware of this in the ’70s but we now know almost two thirds of humans harbor this bacterium and a minority of these develop ulcers. These bacteria are most common single cause of gastric and duodenal ulceration. Other factors working synergistically with H. pylori such as NSAID or alcohol use, predispose to ulcers.

Although this cause was not yet a glimmer in the eyes of his physicians, it is far more likely that my dad had a Helicobacter pylori infection. In my father’s time, not too long ago, the medical treatment of ulcers, was in a primitive state. Powerful proton pump inhibiters (PPIs) like Prilosec hadn’t been invented yet and endoscopy wasn’t as widely used. He required an open surgery, pyloroplasty + vagotomy. Very probably he also got Hepatitis C from his transfusions as doctors were at that time also unaware of that disease. Recipients of transfusions had a risk of up to 33% of acquiring what was later called, non-A, non-B viral hepatitis later defined as Hepatitis C. In the early 1990s Hep C was defined and could be tested for and transmission through transfusion prevented. Over 150 million persons harbor Hepatitis C today. Most Americans with the infection were born in 1960s and 1970s very likely because they were infected through the bloodstream by transfusion or IV drug use. The prevalence of Hepatitis C has plummeted among younger Americans.

The moral of this story is on many levels. Not long ago, within my own lifetime, doctors had no idea about the true causes of a number of disease processes in this one patient. They could treat the condition by giving blood and stop bloodloss surgically, but hadn’t knowledge of the infectious processes or how to prevent a second serious infection that they had not even imagined at the time.

Both H. Pylori and Hep C are chronic infections that have long lived with humankind. Studies have shown these organisms have infected large swaths of human populations, and co-migrated with humans over 10s of thousands of years. They are more fellow travelers with men than are dogs, with us since hunter-gatherer days or cows or sheep which we have lived with since agriculture. In fact they are closer to us than any domestic mammal. One way to follow the migrations of human populations out of Africa and subsequent spread all around the world, is to look at our own genetic variation. If you want a better idea of your remote ancestry, look no further than genetic changes that accumulate over time and follow migration patterns. I did so some years ago looking at the y chromosome which can be followed in men, and mitochondrial DNA which is inherited only through one’s mother. These can be had for a few hundred dollars. In my case, there were no surprises. My father was my father, as I know better now as I look more like him as I age, but I understand is often not so in some 10% of people, depending.

H. pylori and Hep C genomes are so common and so tightly associated with humans, that it is possible to follow their genetic variations in exactly the same way as our own, mirroring human migration and communities. The same is true for a host of infectious organism associated through tens of thousands of years, especially Herpes viruses including Epstein-Barr virus. Technically, these infectious agents are not permanently admitted to our genome so are not part of us, yet since they segregate with humans so closely, theirs and our unique genetic heritage are ours as well so that they are, in a sense part of us, part of what I would call a genetic aura of humankind.

Our own mitochondria that are part of us, inherited from our mothers, are likely remnants of a very ancient infectious agent, a primitive bacterial type organism such as a mycoplasma, that infected the earliest ancient cells with true nuclei. Mitochondria and other organelles which we now consider part of us, actually constitute a phylogenetically old infection or at least a merging of different organisms, way back in evolution. Animals and plants composed of eukaryotic cells, which means the vast amount of macroscopic familiar lifeforms, have all transmitted these organisms which have left in their wake, membrane bound organelles in true cells. Mitochondria whose job is to make energy from sugars and fat, and chloroplasts which do the opposite, harness sunlight to produce chemical energy, are parts of ancient symbiotes now co-opted into our cells.

In previous offerings on this site I talked about a basic principle of infection, how increasing familiarity between host and invader correlates with decreased virulence. By this measure, humankind’s exposure to Ebola must be very short since mortality is quite high. Even within a particular Ebola epidemic and many of these are known within recent decades, the disease tends to get milder with lowered mortality as it persists in the population. Both pathogen and host adapt to each other. More resistant hosts tending to survive. Less aggressive pathogens reproduce more copies of themselves inside a long-lived host.

Accounts of infection given here have started with acute infections as with Ebola and pathogens of recent acquaintance. These cause acute brief serious disease on average as pathogen and host have not had time to adapt to one another. The host has few defenses and the pathogen has not yet learned how to survive for long periods within the host, ordinarily by inducing less serious disease or no symptoms at all. This gives it all the more opportunity to reproduce and spread. Many cause acute illness such as the common cold, and pneumonias which attack swiftly either to be cured but kill especially if you are weak. In the era of antibiotics and antivirals these acute illness is most person’s model of infectious disease yet not what occurs in the vast majority of infections.

The other side of the spectrum is when the pathogen persists for decades. One model is Hepatitis C. It affects now about one percent of Americans and up to 2.5% of humans worldwide. The infection persists in the liver and remains asymptomatic for years. Hep C may either be picked up on routine blood work or cause some mild symptoms such as malaise.

Most people don’t realize how commonly infection is the causes cancer. Hepatitis C is a common cause of liver cancer throughout the world. Chronic infections are now known to be behind many cancers, Epstein-Barr for various lymphomas and nasopharyngeal carcinoma, H. pylori in stomach cancer among them. (Epstein-Barr causes mononucleosis which is when you look at it, an acute mild lymphoma that is brought under control by the immune system. It is probable that Epstein-Barr is the cause of at least some cases of multiple sclerosis serving as a chronic source of immune reaction in the nervous system.) They may either alter genes which control the rate of reproduction of cells, oncogenes and tumor suppressing genes, after all viruses work by inserting their own genes into cells’ reproductive machinery, or as a chronic irritant causing increased cellular proliferation (as with the liver fluke flatworm Clonorchis). Chronic infections also damage organs over many years, Hepatitis implicated in cirrhosis, TB in lung damage etc.

If you see creatures that live with us, live in us, on us, as parasites that should be obliterated, killed, that humans need to be sterilized from, think again. Chances are that any organism which which we have a long association performs some service for us and we for them. The relation as a parasite eventually blossoms into one as symbiotic or commensal. I mentioned how infection gravitates into less virulence over the length of association, but more than that, it may be beneficial to both sides, like the example of mitochondrion. The vast majority of bacteria inhabiting the human gut are doubtless beneficial in many ways that researchers have yet to spell out. Some of our hapless hospitalized patients, subjected to one course of industrial strength antibiotic after another, have needed to restore their normal bacterial flora. Recently fecal transplants, however unpalatable that might sound, have come into vogue for our sickest patients with recurrent infections. Cleansing of the colon and other body parts of good bacteria has made way for even meaner more virulent organisms such as Clostridium difficile that causes severe colitis recurrent infection and often fatal disease all due to profligate overuse of antibiotics. We witness unusual organisms such as Candida proliferating in pharynx and vagina. Antibiotic use may seem at first to be life-saving but comes at great cost. Wise clinicians have learned that the best treatment isn’t always the obliteration of naturally occurring organisms and how much all of us depend on our personal microbiome of biological fellow travelers.

Now we have been confronted with the real possibility that stamping out all bacteria is not all good. The microbiologist Martin Blaser in his book Missing Microbes may be on to something. Infection with H. Pylori, the cause of most stomach ulcers, is prevalent around the world. H. pylori is lifelong inhabitant of the stomach very likely transmitted through the process of vaginal delivery birth, from mother to child. The combined overuse of cesarean sections a product of unscrupulous legal suits, and early use of antibiotics, have decreased the prevalence of H. pylori in wealthy countries. Where the infection is found to be symptomatic as in stomach ulcers, the bug is stamped out vigorously. But H. pylori has positive as well as some occasional negative consequences. The absence of H. pylori is blamed for increased prevalence of acid reflux into the esophagus which is related to Barrett’s esophagus, precursor to esophageal cancer. The occurrence of Barrett’s esophagus and a specific type of esophageal cancer has skyrocketed in more advantaged populations lacking the H. pylori infection. So sterilizing humans of common invaders is not always good. Undoubtedly the alteration of gut and other body flora will have immense fallout. This has yet to be proved but according to Dr. Blaser the epidemic of obesity and diabetes in the developed world may also be consequent to antibiotic overuse and may even be associated with being cleansed of this same organism.

As a clinician I had access to antibiotics throughout my life, so much so that when I look back at movies of WWI or the Civil War era, I always think of the characters as equivalent miserable poor folk. I wonder, how did these people exist in those days under the constant threat and worry of dying of some infectious disease, be that TB, or appendicitis, childbed fever, urinary infections, smallpox or a host of things which we now easily cure and prevent, and are not scourges for us anymore. The other side of this is the transformation of the hospital ward I’ve seen in very recent years, in which we’ve acquired a new fear and respect for infections we may fail to cure. Something we did not do even a few years ago, the over-dependence on constant hand washing and sterilizing gels, donning of gowns, masks and gloves, which were not necessary only a short time ago. And in our struggle with bacteria they are beating us, mindlessly mutating and adapting faster the speed of human invention of new antibiotics. It all leaves you with the feeling, I hope it isn’t well founded, that humankind’s industrial strength killing or organisms will be overtaken with the genius of bacterial adaptation.

(Up until very recently I thought of infections as pathological acute processes needing to be stamped out. I saw so many as a clinician over the years that we always killed with antibiotics. Infections became manifest when they sickened patients and killed them. Otherwise I was unaware of them. But in recent years I’ve come to understand there are two kinds of infections, acute and chronic. Chronic invasions by bacteria, viruses and other organisms can eventually present as acute illnesses surfacing as sickness, reaching a threshold of disease causation or by some weakening or aging in the host. Most invasive species live with us less as parasites than as symbiotes or commensals. We and they derive mutual benefits. Both acute and chronic invasions can cause severe disease and even death. I’ve come to understand that acute infections are actually a small minority of our relations with the microbial world. Most acute bacterial infections are brief exacerbations of chronic colonization kept under wraps by immunity. A good example is Hemophilus influenza of the middle ear of children. The strategy of using antibiotics should be thought of merely as a beating back of a chronic infection that has spread further than as a chronic colonizer. Often clinicians should be satisfied with controlling inflammation and it may not be beneficial to sterilize patient from organism.)