The Third History of Man

By John Bershof, MD

In the spirit of medieval writer Chaucer, all human activity lies within the artist’s scope, the History of Man Series uses medicine as a jumping off point to explore precisely that, all history, all science, all human activity since the beginning of time. The jumping off style of writing takes the reader, the listener into worlds unknown, always returning to base, only to jump off again. History of Man are stories and tales of nearly everything.

The Third History of Man leaves bacteria in the rear-view mirror and jumps to viruses and viral infections, the cold, the flu and COVID-19, not just another flu. We’ll cover epidemics, pandemics, and vaccines, the pox infections, and the Spock principle that the needs of the many outweigh the needs of the few … or the one. From COVID and the rise of Zoom, we’ll venture into the rise of Homo sapiens and the fall of Neanderthals, the high sea adventures of Darwin aboard and the high sea adventures of dementia. Our travels will take us along the Silk Road and Spice Trade, another visit with the Age of Discovery when masted ships and European explorers went looking for that elusive sea route to the Far East, and looking for gold, annihilating huge swaths of indigenous Americans at every port of disembarkation, not by the pointy end of a sword, but by tiny infectious microbes. We’ll examine colonialism at its finest, the sordid European history of imperialism and the land grab into Africa and the New World Americas.

• Language: English
• Publisher: Lulu.com
• Release date: May 18, 2024
• ISBN: 9781304347145

Book preview

INTRODUCTION

This Introduction will be short and sweet. This book is the third in a series loosely termed History of Man Series. Initially I was to start the series with a single book that used infection as the underlying frame by which I'd jump into stories, history, science and the like. I am a storyteller, and subsequently that first book using infection expanded into six books. Otherwise, had I kept it as a single book it wouldn't have been of much use, so thick and heavy its only practicality would have been to stand on it to reach the top shelf of a kitchen cupboard for those who are vertically challenged. One book became six books.

I hope you read the books in order as some stories continue from one book to the next, and with that said, the Introductions in the first two books should suffice. The First History of Man uses infection in general as the underlying frame, The Second History of Man concentrates on bacterial infections as jumping off points, this The Third History of Man as well as The Fourth History of Man focuses on viruses and The Fifth History of Man is mostly parasite infections while The Sixth History of Man delves into the all too entertaining sexually transmitted diseases. The stories, that is, are entertaining, not having a sexually transmitted infection.

As is usual, the jumping off into history, science, and the like is really what these books are about, about human history, world history, that sort of rot. And true to form, in each book there are over-arching personal medical vignettes that roughly correspond to the some of the jumping off subjects.

So, with that said, let's get cracking ... shall we?

1

MELLOW YELLOW

Denver, Colorado. It was Monday, May 28, 2001, in the early afternoon. The weather had been unseasonably cool. The sky was cloudy, gray for guessing. The medical ambulance arrived at the nursing home. Not one of those call 911, sirens-blaring ambulances rushing to an emergency patient. Rather a medical transport ambulance, the kind that deals in the non-urgent transfer of patients too ill, too incapacitated, to be transported to the hospital in the family station wagon, with a snot-nosed kid and the family dog along for the ride in the back seat.

Although in the terminal stages of dementia, totally locked out from the world, Edward’s eyes betrayed a fear as he was carefully lifted from his nursing-home bed and cautiously placed on the gurney by a couple of youthful EMTs, a good sixty years younger than him. The contrast could not have been more apparent. Edward knew something was different despite being shut off from the world. Perhaps the unrecognizable faces surrounding him, or the way he was lifted, forced a terror that coursed across his normally vacant face, the blank stare of a clueless, terminally demented person.

Back in the day, fifty-five years earlier—the year 1946—Edward had the good fortune and good sense to marry the beautiful nineteen-year-old Arlene, fourteen years his junior. Talk about robbing the cradle. Yet Arlene, always attentive, always by his side, both now in the twilight of their years, could offer little comfort to allay Edward’s fright as he lay there on the uncomfortable-by-design gurney. It was just a year or two back that her face was the last face he recognized, and now even that was lost.

Edward was born in Denver, Colorado, in 1912, the youngest of three children belonging to Sam and Jenny, Jewish immigrants from the Pale of Settlement who had made their way to America in the late 1890s. Why Jews fled Czarist Russia or were chased out, and why that area of Russia was called the Pale, are subjects we will cover in more detail further along the pages of this narrative. But suffice to say, like many immigrants to America during the nineteenth and early twentieth centuries—Irish, Italians, Germans—the Jews were fleeing religious persecution, as well as searching for work and a better way of life. Even the Pilgrims, the first British colonists in the so-called New World, landing at Plymouth Rock around 1620, did not cross the pond out of any sense of adventure. Not in the way that Christopher Columbus and his fellow explorers had ventured across the Atlantic over 100 years earlier during the Age of Discovery.

The Pilgrims fled England in the 1600s for similar reasons the Jews fled Russia in the late 1800s, early 1900s, religious persecution wrought upon them by the Church of England—a church they felt had become too corrupt, too rooted in ceremony and relics not found in the Bible. Which is rather interesting, and a bit ironic, since it was that very Anglican Church, the Church of England, a Protestant offshoot, that had come into its existence during the Protestant Reformation when it swept across Europe during the sixteenth and seventeenth centuries for similar lamentations: the Catholic Church in Rome had, in their eyes, become too corrupt, with too many relics and too many intermediaries between God and man, and woman too.

Just as the Protestant Reformation had found the Catholic Church’s interpretation of the basic tenets of Christian belief off the mark, so too did the Pilgrims find the Church of England off the mark—sort of like a reformation within a reformation. The same was true of the Puritans—often confused with the Pilgrims—who, when they landed in the New World in 1630, forming the Massachusetts Bay Colony, likewise had determined that the Anglican Church had gone astray from the basic teachings of Christ and the Bible. What, you might ask, was the difference between the Pilgrims of 1620 and the Puritans of 1630, as they disembarked into the New World, each a religious sect disillusioned with the Church of England? The former were separatists: the Pilgrims desired to start their own religion, their own church, separate from the Church of England. The Puritans, on the other hand, wanted religious freedom but to remain a branch within the Anglican world—sort of like the three denominations within Judaism: Reform, Conservative, and Orthodox.

Of course, Martin Luther in Germany and John Calvin in France, whether with or without doubt, offered loftier reasons for splitting from the Catholic Church during their version of the Protestant Reformation than those more questionable motives that drove Thomas Cranmer, the Archbishop of Canterbury, to establish the Protestant Church of England. Cranmer, you see, had a slightly less noble, less spiritual goal in mind than religious freedom when he created from thin air the Church of England: his boss, King Henry VIII, was unable to secure a divorce from his first wife under the rules of the Roman Catholic Church, and it was Cranmer’s job to fix that situation. Wife one, Catherine of Aragon, could not deliver on a male heir, so King Henry wished to marry Anne Boleyn, who would indeed become his second of six wives. The Church in Rome was not about to grant an annulment—because they don’t do annulments, not even for a king, and especially not an icky English king.

Apparently poor Anne was not able to deliver on a male heir either, experiencing a few stillbirths. But unlike Catherine of Aragon, who the king divorced and who was given a dowager position, Anne lost her head over the situation. Kings do that. Imagine, if you will: you create the Anglican Church so you can divorce your first wife to marry your second wife, and then you lop off your second wife’s head over trumped-up charges of infidelity, so you can marry your third wife, Jane Seymour, who was, we are told, Henry’s favorite wife, even though three more were to come. It is Twilight Zone material. Where is Rod Serling when you need him? Jane, luckily, did deliver on the male heir thing, producing the sickly Prince Edward. Jane died from childbirth complications soon after birthing the young royal—who, at age nine, would become King Edward VI of England after Henry passed on … only to die a few years later, at age fifteen.

Edward’s cause of death is unknown. Speculation raged that he was poisoned by English Catholics dead set on having his older half-sister, Mary—the only issue from Catherine of Aragon—ascend to the throne. Mary, reputed to be a good Catholic girl, would then happily dispense with the Protestant religion along English shores, returning England to Catholicism and within the fold of Rome. Keep in mind that Princess Mary’s mother, Catherine, also a stout Catholic, was the daughter of the very Catholic King Ferdinand II and Queen Isabella I of Spain. So, like mother like daughter like granddaughter: Mary was very Catholic, too. And, just as those apparently devious English Catholics desired, when King Edward died, his older half-sister Princess Mary became Queen Mary of England, all but shuttering Protestantism within her domain. She also became known as Bloody Mary. But more on that later.

Returning to Edward, even while Catholic forces in England may indeed have wanted him dead, forensics suggest that the sickly King Edward was not assassinated but rather met his maker from more natural causes than poison: he is believed to have suffered a pulmonary ailment, likely dying from pneumonia or quite possibly tuberculosis. Historians believe he had childhood smallpox and might have soon after contracted tuberculosis, which eventually consumed him. Tuberculosis or simply TB is, after all, also called consumption, because it slowly, oh so slowly, consumes its victim. We’re talking years and years here. Others suggest Edward might have been born with cystic fibrosis, an inherited pulmonary disease that would have set him up for death in his teens.

Cystic fibrosis is primarily a lung ailment, resulting in a buildup of tenacious mucus in the respiratory passages, and similar deposits can develop in the pancreas and kidneys. Although known to have existed since around at least 3000 B.C., when the genetic aberration quite possibly first reared its ugly head, it was not described as a disease until the nineteenth century, by one Carl von Rokitansky, and later fully defined by Dorothy Hansine Andersen in 1938. That King Edward was sickly since soon after birth makes the scales slightly tilt toward the presence of such an inherited ailment as cystic fibrosis.

Returning to the Edward of our story—not Prince Edward, not King Edward, but the elderly man with Alzheimer’s laying on that gurney—at the time of his birth in 1912, his father, Sam, was working as a skilled cigar roller for the Cuban Cigar Company in Denver. Despite the name, the company had nothing to do with Cuba or with Cuban cohibas, which is the Taíno word for tobacco, the Taínos being the original inhabitants of Cuba before Columbus and friends arrived in the 1490s. By the early 1900s, genuine Cuban cigars were world famous, but as for the Cuban Cigar Company of Denver, it was merely a cleverly named, locally owned company riding the coattails of a well-known reputation, by design of a man who had a knack for marketing. He also had a knack for disliking trade unions—a point that figures heavily as Edward’s story unfolds.

Edward’s mother, Jenny, was a stay-at-home mom to the three children, the oldest being Morris, born in 1901, followed by Esther in 1904, both of whom were born in Philadelphia before the family journeyed west to Denver in search of what was, for them, that elusive American Dream. Jenny tended to her children when she was not tending to herself, a woman sadly saddled with several issues of her own. Understanding the exact nature of her ailments all these years later requires bits and pieces to be patched together: a mixed bag of female gynecologic problems, intestinal infirmness, and emotional lability (lability, from the Latin for slip, when attached to emotion signifies a fluctuating mood disorder). Adding to Jenny’s emotional troubles was the unfortunate reality that her husband had baggage of his own—and I don’t mean suitcases he had brought over from the Old World, from the Pale. Sam had, by all accounts, a first-rate mind, but he was unable to parlay that into any sort of meaningful career—a lifetime of business failures and financial woes saddled him, Jenny, and their three children: Morris, Esther, and Edward.

It is not surprising that Jenny’s three children were clueless, or mostly clueless, about the constellation of health issues that troubled their mother. One need look no further than the cultural norm that remains fairly common even today: keeping children in the dark when a parent takes ill with a serious disease let alone a terminal ailment. Almost as if it’s taboo to discuss such matters in front of the children. Instead, we often move to shield children, us well-intentioned parents dancing around the issue with hyperboles, never quite spelling it out with much detail. It’s a behavior that’s rooted, perhaps, in the mistaken belief that children cannot handle the stark reality of life … or death. I think Neil Simon, in his fabulous 1982 Broadway play and subsequent 1986 film Brighton Beach Memoirs, said it best through the main character Eugene, played perfectly by Jonathan Silverman, when Eugene encounters the funeral of a local shoemaker passing along the street of his neighborhood in Brooklyn. He asks an elderly Jewish bystander:

Eugene: Who died?

Elderly Lady: Mr. Nunzio.

Eugene: The shoemaker? Wow, what happened?

Elderly Lady: He had [whispers] cancer.

Eugene then launches into a dialogue as he walks along the street talking to us, the audience, about how people deal with diseases:

Eugene: Why do old people always whisper … what someone dies from? Like my Uncle Dave, Aunt Blanche’s husband. He died from a [whispers] coronary. People from the old country … think it’s bad luck to say a disease out loud. Like if God hears you, he’ll give it to you. My grandfather died from [whispers] diphtheria. Anyway, after Uncle Dave died, he left Aunt Blanche with no money … not even insurance. She couldn’t support herself because she has [whispers] asthma. Mother took her in with her two daughters. My father had to take another job … to support us all. Besides cutting raincoats, he sells party favors to nightclubs. I think it’s getting to him because I heard Mom say … Pop was developing [whispers] high blood pressure.

Such was the situation with one of my childhood friends. His mother lay terminally ill in bed for months, and her three children—along with all of us neighborhood brats—were never exactly told what was sapping the very life out of her. It was cancer, we would find out many years later. At five years of age, a kid won’t dig too deep, won’t ask too many questions except Are we there, yet? With little in the way of explanation, one day an ambulance picked up my friend’s mother and whisked her away. She never came home. And that was that.

Cancer, especially, has historically carried a stigma among some narrow-minded groups—though fortunately not so much today. It used to be as if dying of cancer was a stain upon the family. I once cared for a young woman who had [whispers] breast cancer. She had undergone a double mastectomy—removal of breast tissue and nipples—and I performed her breast reconstruction. She was in her thirties, a rather disturbingly young age to receive a breast cancer diagnosis. Her parents were from Eastern European, here meaning old-country, Russian Orthodox, set-in old ways, not terribly burdened by anything as factual as science. This caused a few problems, notably her mother pointing the finger of condemnation! While the stigma around cancer has mostly gone away, there are, unfortunately, still many Americans like that today untethered to anything so provable as science. Especially if you dare to venture across the expanse of Facebook, you will readily find your science deniers, taking their cues from those who go around misinforming others for personal gain. As I write these words, a former Facebook employee, a whistleblower, has gone so far as to testify that Facebook products stoke division and weaken democracy. Some supposed religious leaders and even presidents engage in such disinformation, cooking up batches of alternative facts—a polite way of saying liars. And such people truly believe the right to free speech, even if that speech is lies, protects them.

Freedom of speech, despite what some think, does not mean a person can say whatever they want. At least in the United States, not all speech is protected speech—a point lost on too many. Unprotected speech, or lesser protected speech, or, to put it simply, speech—speech in this regard, with regards to the US Constitution, includes spoken, written, imagery, pictures, film, symbolism, pretty much all forms of expression—that is not free, includes child pornography, obscenity, the twin pillars of libel and slander, false advertising, speech that incites imminent lawlessness, true threats of harm, intellectual and copyright infringement, and, most important for our purposes, false statements of fact.

As for my young breast reconstruction patient, when she was diagnosed with [whispers] breast cancer, her Eastern Orthodox mother told her she was being punished for the sins of her ways. And then her mother did a most unfortunate thing: she disowned her daughter for having breast cancer. Who does that to their child? Disowning a child if they’re a murderer or rapist, sure, I get that. But because your child has [whispers] cancer? Sadly, some years later, the [whispers] breast cancer recurred, and recurred with a vengeance. [Whispers] Cancer does that. Despite reaching out to her parents as her few remaining days dropped away like sand in an hourglass, they never made peace. Her mother couldn’t rise above her false beliefs. The young woman did not die alone, fortunately—her friends, her chosen family, were around her when she drew her last breath.

Now let’s visit a happier scene: the Roaring Twenties in America. Flappers, flouted prohibition laws, a booming economy—nearly everyone in America was supposedly happy. And yet there was Jenny, in the depths of depression, an illness treated like a stain similar to cancer. And so, there was Jenny, driven into seclusion, rarely venturing from the family home, hiding under the bedcovers. Even today, 100 years later, despite public education and more openness, mental illness is still all too often hidden from view, ignored, spoken about in hushed tones—in, you guessed it, whispers. For Jenny, the 1920s was a decade marked by ever deepening depression, an abyss of despair, driven further into isolation, one poisoned thought after the other polluting her days.

Her two oldest children, Morris and Esther, had already come of age and exited the family home, escaping Jenny’s cloud of anguish and Sam’s perpetual financial strain. Morris went to work for the Cuban Cigar Company, alongside his father, where he staked out a life of his own. As for Esther, she married as soon as the law would permit—maybe even a little before. As for Edward, he was just entering his teenage years; he wasn’t going anywhere. He was stuck in a home with little money and two depressed parents.

It would be safe to say that depression was a huge part of Edward’s familial DNA—a bloodline coursed through with labile emotions, certainly extending back to the old country. That is some pretty ominous genetic penetration that hovered over young Edward like a rain-filled cloud, with both parents perennial melancholics. Depression is not much different than heart disease or diabetes running amok through the family tree: you can’t easily escape inheritance patterns. In other words, as the saying goes, you can’t pick your parents. You can modify predetermined inherited illnesses with lifestyle choices—modify them for the better or the worse—but totally liberating oneself of their DNA destiny is often easier said than done.

Depression is not an all-or-none affliction—it has varying degrees. Like a functional alcoholic, which is a person who drinks every day but keeps it under control to navigate the daily tasks of life, Edward was at times a functional depressive: a person who vacillated between moments of happiness and levity punctuated with occasions of sadness, flying just enough under the radar to get through the day, to get through life. Of course, Arlene certainly kept Edward’s ship afloat, buoying his spirits—wives can do that—carrying the load so he wouldn’t sink into the abyss. A partner who can help shield from life’s vicissitudes is an invaluable partner.

Before we drive down that lonely road of depression, a path that crisscrosses the lives of many, a little clarification of what exactly the Roaring Twenties was, cannot be passed up. In the aftermath of World War I and the 1918 Spanish flu that came on the heels of war—that flu killing some 50 million people worldwide in two and a half years; by comparison, the current COVID-19 epidemic stands at 6.3 million dead in a little over two years—America entered a period that witnessed near unprecedented economic growth. During the 1920s, the nation’s wealth doubled, consumerism was at an all-time high, and despite the 18th Amendment on the prohibition of alcohol in July 1920, cups runneth over. Bootleggers and your gangsta types, especially the Chicago and New York outfits, made sure America did not go thirsty. The Roaring Twenties was also marked by the 19th Amendment of August 1920, granting women’s suffrage. And it was not just the right to vote that buoyed them: the national mood freed women from domestic bondage, thrusting them into a world of freedoms such as working outside the home, formal college education, drinking and smoking in public—freedoms their mothers could hardly have imagined. (Should I be whispering here?)

Perhaps nothing better typifies the Roaring Twenties than the birth of jazz, a genre of music mostly originating within the African American communities in New York’s Harlem neighborhood and New Orleans. Combining blues with ragtime, jazz spread like wildfire to the masses. With the brass and percussion instruments of Joe King Oliver, Duke Ellington, Lionel Hampton, and Louis Armstrong playing in the background, smoke-filled speakeasies with flappers dancing the Charleston were all the rage. At the same time, the blues, a genre originating in America’s Deep South in the 1860s, became more mainstream during the Roaring Twenties, with one of the genre’s first recording—Crazy Blues by Mamie Smith—released in 1920.

Speaking of the blues, depression, mood disorder, or the blues is part of many, if not most, people’s biorhythm: a normal swing of emotions—the baseline evenness punctuated with moments of elation, opposite moments of sadness, sometimes for no particular reason. None at all. We’re all probably prone to mood swings that look an awful lot like the dance of the flapper, going between subtle highs and subtle lows. One day you wake up happy, the next day sad. It’s the rare person who is always happy, or, for that matter, even even-keeled … unless they’re smoking something or there’s something in the water.

That is to say: it’s normal for our brains to fluctuate between slightly elevated and unelevated moods, to swing back and forth in a rhythmic fashion so faint it’s scarcely noticed by the casual observer, or even by the not-so-casual observer. For others, these normal fluctuations are not so subtle, yet still fall within the range of medical normalcy. It’s like waking up on the wrong side of the bed or, for that matter, the right side of the bed. Some days a person wakes up feeling blue; other days, they wake up feeling sunshine yellow. Certainly, a good night’s sleep figures heavily into our moods, but that’s not the entire game. Mood swings became more than a normalcy, become more of a medical disorder, when they interfere with daily life. Like the functional alcoholic tipping over into a nonfunctional alcoholic, losing jobs, losing friends, losing the wife.

Yellow, I have come to understand, is the color of happiness, as blue is the color of, well, blueness. Yet it is interesting that feeling blue is the only time a color is regularly assigned a mood. You don’t hear someone say, I am positively feeling yellow today, or I feel a touch red today, or You seem rather purple these days. Yet it is not unusual at all—and a tad annoying—when someone comments that you’re looking a little blue today. Well, unless your blueness is due to hypoxia. Then you should thank them for pointing out you need a swift visit to the ER.

According to color psychology, all the colors on the color wheel have meaning. For instance, light red is passion, pink is love, and dark red can be vigor or anger. Red-orange (besides a beautiful sunset) is sexual desire, yet dark orange is deceit. I wonder if there’s a connection there? We’ve mentioned light yellow is sunshine—happiness and freshness and joy—but dull yellow is caution, sickness, and decay. Dark green is greed, yellow-green, like a nice puke green, is sickness, and olive green of course is peace, as in extending an olive branch. As for the blues (other than the jazzy blues), light blue is tranquility, dark blue is knowledge and power, and plain old blue is where we started: sadness.

Mellow Yellow is a 1966 song by the Scottish singer-songwriter Donovan, which I guess uses the color yellow to describe a mellow yellow mood. The initial story—an urban legend—was that Donovan’s mellow yellow phrase was a coded message that smoking dried banana peels has hallucinogenic properties. Which it isn’t, and it wasn’t then, either. According to Donovan himself—who is still performing today despite being in his seventies—the phrase mellow yellow refers to a cool, easygoing, laid-back person. There’s an actual hidden meaning in Mellow Yellow, though: the song mentions an electrical banana, which is, I’ve come to understand, meaning a vibrator used by women. I guess we are left to assume that a vibrator has the power of mellowing, but I’m still slightly flummoxed as to why it was incorporated into Donovan’s hit song. Maybe a subtle marketing tactic?

Spinning that color wheel back to blue, now—for whatever reason, it has come to pass that we most associate blue with depression. Besides swinging into a bluish depression for no apparent reason—those mood swings or biorhythms previously mentioned—the most common reason people get depressed is what’s called situational depression. It’s really simple math: something depressing happens, and you get depressed. Whether the death of a loved one, getting swindled, flunking your organic chemistry exam, getting fired, getting divorced, getting married, experiencing chronic illness, and so on and so on, life throws us blue curves all the time. Unexpected situations can depress the hell out of any one of us, which is why it’s termed situational depression. The situation begs the depression, but once the situation is resolved, or once enough time has passed for unresolvable situations to dim, I believe psychologists call that coping, the depression slowly fades away. Not to place too fine a point on it, but we all suffer situational depression at various times in our lives. If a person goes through life faced with depressing events and does not get depressed, that would be a problem. That would, in fact, be strange.

As for coping, well, when a depressing thing happens, you can always rely upon Elisabeth Kubler Ross and David Kessler five stages of grief as outlined in their landmark book On Death and Dying 1969. Passing through, or even being able to pass through the five stages characterizes a person who has some measure of coping skills. How long each stage lasts, how they might overlap, is pretty much individual dependent, and the coping just doesn’t apply to death and dying. In order, they are Denial where the person doesn’t believe it happened. But once they believe it Anger sets in, anger that it happened, even anger at the person who it happened to and likely anger at oneself for being angry. Bargaining is the next stage of coping, making deals with oneself to lessen the pain, making deals with God to reset the events, like a computer, back to an earlier operating system. The main feature that sets in is Depression, realizing it happened and that there will be no bargaining. This is the grief phase and can go on for quite some time. Finally, hopefully, Acceptance or the fifth final stage of coping sets in, the pain eases, and that needs little explanation.

Other than regular rhythmic moods—the waxing and waning moods we all experience, however faint or grand—and the situational depression just discussed, there are, of course, other causes for tumbling into sadness, into the blues. And wouldn’t you know it: it can be the pills we pop for other ailments. That is to say, some prescribed medicines cause depression as a side effect—and just the thought of that is depressing. The list of such pills is disturbingly long and includes some very common drugs, like beta-blockers for high blood pressure, birth control (it’s the progesterone), cholesterol-lowering drugs like the statins (atorvastatin known as Lipitor, pravastatin called Pravachol, simvastatin or Zocor—really any statin), and the very common over-the-counter proton pump inhibitors for acid reflux, Prilosec being perhaps the best known. If you need the medicine and the bluishness is not too blue, you grin and bear it. But if the drug is the cause of too much blue and you need more yellow in your life, you and your doctor will need to find a more suitable pill for whatever ails you.

To make matters worse, folks with anxiety are often prescribed one of the benzodiazepine derivatives, like Valium or Xanax, which are designed to lessen anxiety but very well might, in some people, have the unwanted side effect of replacing that anxiety with depression. Treating anxiety with a pill that might make you sad seems like it might make a person more anxious. You’re right back where you started, except now you’re both anxious and sad. That’s two for the price of one, and I don’t necessarily mean the 1981 ABBA song by the same name with these lyrics:

If you dream of the girl for you

Then call us and get two for the price of one

We're the answer if you feel blue

So call us and get two for the price of one

The larger mood swings experienced by many people might be partially genetic, as mood swings seem to run in certain families. And as for situational depression, well, that can strike anyone at any time, unless they’re a cybernetic organism, a cyborg, who can’t feel emotion, heck cyborgs don’t feel anything. And as we reviewed, some drugs can have as an untoward fallout a depressed mood—that’s an uncommon side effect, and perhaps can also be described as situational depression: the drug is the situation causing the blahs.

This brings us to the categories of major and persistent depression, which are different from your garden-variety depression, different from mood swings, and different from situational depression. Major depression and persistent chronic depression, the latter also termed dysthymia, are two different forms of depression but, for our purposes, we can consider them together. Both take on certain clinical features that are more evident, more palpable, more visceral, and more resistant to conventional treatment. And they tend not to get better with time, only worse. If you have a touch of situational depression or are experiencing a temporary down note as part of a rhythmic mood condition, you might wear a frown, eat comfort food to satisfy the hole in your heart, or alternatively not eat to satisfy that hole in your heart. You might shuffle glumly through your daily duties. But, for the most part, you carry on and those blues go away, at least for a period of well-needed time.

But major depression and dysthymia are entirely different constructs, characterized by not just profound melancholia that never wanes but also a bunch of other constitutional symptoms. Constitutional symptoms are general symptoms that affect the entire body that may or may not be directly the result of primary issue, that is they are non-specific. An example would be strep throat with fever causing general constitutional symptoms such as malaise, loss of appetite, weakness, and so on which can also be the same constitutional symptoms of systemic lupus. Such constitutional symptoms witnessed with big brother major depression but also evident with little brother dysthymia include malaise, insomnia, anxiety, depression, impaired thinking, and unexplained physical problems such as back pain, headaches. Among the characteristics of both are an impaired ability to interact with people, shrugging off school and work, retreating into isolation, and staying in bed with the sheets pulled over your head (like Edward’s mother Jenny), accompanied by those physiological changes to be discussed momentarily. It is believed that the underlying problem in these forms of depression is altered functioning of brain neurotransmitters, and the top candidates here are dopamine and serotonin.

The emotional and general constitutional physiological changes seen in these forms of depression besides sadness include hopelessness, helplessness, sleep disturbance, fatigue, disinterest in nearly everything and everyone, listlessness, flat affect or your basic robotic response, decreased energy, poor concentration, slow thought processes, digestive problems, poor appetite, weight loss, nearly spontaneous crying, diminished libido, social isolation, insomnia, anxiety, and, if the depths are really deep, suicidal ideation. It is a bucketload of constitutional symptoms that plague the individual afflicted with major depression, with what feels like no end in sight.

Perhaps the only difference between major depression and dysthymia is that the first is so pronounced upon presentation, its symptomology so dishearteningly palpable, so visceral, that the diagnosis can be assigned after only two weeks of being so depressed, whereas the diagnosis of its milder little brother, persistent depression, or dysthymia, isn’t made until two years of the disorder been observed. Why two years? Probably to make sure it isn’t just a protracted course of situational depression. Take the death of my own mother, for instance: it’s been over eight years, and I’m still depressed-to-hell over it—but it is situational depression, not dysthymia. Why? Because my sadness has been slowly fading over time, that five stages of grief coping mentioned previously.

In people with underlying brain chemistry predisposed to either major or persistent depression, other factors that trigger or worsen these conditions include alcohol and drug use, as well as some prescribed medications previously mentioned, chronic illness, and a history of traumatic life events, that is, various forms of post-traumatic stress disorder, or PTSD. The other reason we can lump together major depression and persistent depression, for our illustrative purposes here, is that their treatment is similar: psychotherapy and prescribed drugs.

Self-care measures although well-intentioned, just don’t cut it with managing major depression. The most commonly prescribed medications are the selective serotonin reuptake inhibitors, better known as SSRIs, such as Prozac and Zoloft. How exactly do these drugs make us feel less blue? Good question, and the key to the answer was already mentioned: those previously mentioned brain neurotransmitters, dopamine, and serotonin, are at the heart of the matter—or, more precisely, at the brain of the matter.

In that part of the brain involved with mood, commonly the frontal lobe—that bit of brain right there, behind your forehead—the most prevalent neurotransmitter that appears to control our moods, our ups and downs, doing its work along the synaptic pathways, is serotonin. To feel blue, to perceive sadness, serotonin must first be inside those nerve endings and programmed for the sole purpose of conducting sorrow. When a blue wave comes over a person, serotonin is released like a torpedo from those specific nerve endings into the nerve junction space, and, in so doing, triggers the next nerve in the blue wave to conduct blue feelings. Sort of like the wave at an NFL football game. Blue moods are conducted through this knock-on release of serotonin.

This next bit is important and is essential to understanding how basically all antidepression drugs work. Once the serotonin has done its part to propagate the blue wave from one brain synapse to the next, it must be reabsorbed into the nerve endings from whence it came to be ready and able to conduct the next blue wave. The serotonin must undergo re-uptake by the nerve ending from when it was released, and I’m sure you are seeing where I am heading. If that serotonin molecule is not reabsorbed into the nerve ending, or more precisely, if a bunch of serotonin molecules remain in the synaptic junction—if reuptake is inhibited—the propagation of blue wave after blue wave cannot take place.

The reasoning goes that if you can keep serotonin within the nerve junction space, not allowing it to be reabsorbed into the synaptic ending, then you can halt blue mood conduction by halting serotonin conduction. And that is precisely why drugs like Prozac, Zoloft, Celexa, Lexapro, and Paxil are known as