Lake Bled, Slovenia
It’s established code of belief that the immune system develops a memory of a microbial pathogen, with a correspondingly enhanced readiness to combat that microbe, only upon exposure to it or to its components through a vaccine. But a discovery by Stanford University School of Medicine researchers casts doubt on that system of belief.
In a path-breaking study published online Feb. 7 in Immunity, the scientists found that over the course of our lives, CD4 cells—key players circulating in blood and lymph whose ability to kick-start the immune response to viral, bacterial, protozoan and fungal pathogens can spell the difference between life and death—somehow acquire memory of microbes that have never entered our bodies. Several implications flow from this discovery.
In the study, newborns’ blood showed no signs of this enhanced memory, which could explain why young children are so much more vulnerable to infectious diseases than adults. Moreover, the findings suggest a possible reason why vaccination against a single pathogen, measles, appears to have reduced overall mortality among African children more than can be attributed to the drop in measles deaths alone. Scientists may have to rethink the relevance of experiments conducted in squeaky-clean facilities on mice that have never been exposed to a single germ in their lives. It may even provide an evolutionary clue about why kids eat dirt.
The pre-existing immune memory of dangerous pathogens our immune systems have never seen before might stem from our constant exposure to ubiquitous, mostly harmless micro-organisms in soil and food and on our skin, our doorknobs, our telephones and our iPod earplugs. CD4 cells are members of the immune club known as T cells. CD4 cells hang out in our circulatory system, on the lookout for microorganisms that have found their way into the blood or lymph tissue.
In order to be able to recognize and then coordinate a response to a particular pathogen without inciting a Midas-touch overreaction to anything a CD4 cell bumps into (including our own tissues), our bodies have to host immensely diverse inventories of CD4 cells, each with its own narrow capacity to recognize one single pathogenic body part or, to be more scientific, epitope—and, it’s been believed, only that contact with that epitope can cause a CD4 to whirr into action, replicating rapidly and performing the immunological equivalent of posting bulletins, passing out bullets and bellowing attack orders through a bullhorn to other immune cells. This hyperactivity is vital to the immune response. It is CD4 cells that are targeted and ultimately destroyed by HIV; the virus responsible for Human immunodeficiency virus-acquired immunodeficiency syndrome.
In the early 1980s, Davis, now the Burt and Marion Avery Family Professor of Immunology at Stanford, unraveled the mystery of how organisms such as us, equipped with only 20,000 or so genes, can possibly generate the billions of differing epitope-targeting capabilities represented in aggregate by T cells. He found highly re-shufflable hot spots in a rapidly dividing T cell’s DNA trigger massive mix-and-match madness among these genetic components during cell division, so each resulting T cell sports its own unique variant of a crucial surface receptor and, therefore, is geared to recognizing a different epitope. That variation accounts for our ability to mount an immune response to all kinds of microbial invaders, whether familiar or previously unseen. But it doesn’t account for the phenomenon of immune memory.
CD4 cells, like other T cells, can be divided into two groups: so-called "naïve" CD4s randomly targeting epitopes belonging to pathogens they haven’t encountered yet; and CD4s that, having had an earlier run-in with one or another bug, have never forgotten it. These latter CD4 cells are exceptionally long-lived and ultra-responsive to any new encounter with the same pathogen. When a naïve CD4 cell comes across its target pathogen, it takes days or even weeks before the immune system is fully mobilized against that pathogen. But an activated-memory CD4 cell can cause the immune system to mount a full-blown response within hours. That’s why this newfound abundance in healthy adults, and total absence in newborns, of memory CD4 cells targeting microbes those individuals have never encountered before is so important.
For the past 20 years, Dr Petri has led a team conducting medical interventions in an urban slum in Dacca, the capital of Bangladesh. There, the average infant experiences a half-dozen diarrhea-inducing infections and as many upper-respiratory-tract infections within the first year of life, many of them within the first few months. The consequence is rampant malnutrition, with corresponding cognitive deficits and high mortality—this, despite the fact that Petri’s group provides free health-care and education services and visits homes twice a week.
A sophisticated technique invented by Davis in 1996 and since refined in Dr Petri’s and others’ laboratories permitted the Stanford team to identify a single CD4 cell targeting a particular epitope out of millions. Using this technique, Dr Petri’s team exposed immune-cell-rich blood drawn from 26 healthy adults, as well as from two newborns’ umbilical cords, to various epitopes from different viral strains. They were able to fish out, from among hundreds of millions of CD4 cells per sample, those responsive to each viral epitope. Nearly all of the 26 adult blood samples contained cells responsive to HIV; to HSV, the virus that causes herpes; and to cytomegalovirus, a common infectious agent that often produces no symptoms but can be dangerous to immune-compromised people.
This wasn’t surprising, given humans’ exhaustive inventories of divergent CD4-cell affinities. What was surprising was on average, about half of the virus-responsive CD4 cells in each adult sample bore unmistakable signs of being in the "memory" state: a characteristic cell-surface marker, gene activation patterns typical of memory T cells, and rapid secretion of signature biochemical signals, called cytokines, that communicate with other immune cells—even though highly sensitive clinical tests showed that these individuals had never been exposed to any of these viruses in real life. The newborns’ blood contained similar frequencies of CD4 cells responsive to the same three viruses. However, all these cells were in the "naïve" rather than memory state. This explains, at least in part, why infants are so incredibly susceptible to disease.
About one-fifth of the adult samples boasted cross-reactive memory CD4 cells responsive to other harmless environmental microbes. For example, CD4 cells selected specifically for their reactivity to HIV turned out to be able to recognize a large number of common environmental microbes, including three gut-colonizing bacteria, a soil-dwelling bacterial species and a species of ocean algae. Considering that the investigators tested only a negligible fraction of all the microbes a person might encounter, it’s a sure bet that this measure of CD4-cell cross-reactivity was an underestimate.
The scientists recruited two adults who hadn’t been vaccinated for flu in five years or longer, and then vaccinated them. In these volunteers, memory CD4s proliferated and otherwise became activated in response to exposure to certain components of the influenza virus, but also to epitopes of several different bacterial and protozoan microbes. This cross-reactivity could explain why exposure to common bugs in the dirt and in our homes renders us less susceptible to dangerous infectious agents; which raises another point.
We grow and use experimental lab mice in totally artificial, ultra-clean environments that are nothing like the environment that we live in. The CD4 cells from adult mice in the lab environment are almost entirely in the naïve state. They are more representative of newborns than of adults. The new study is paradigm-shifting. It was one of those rare, seminal findings that changes the way we think about the immune response. This study offers hope that some of the immunity conferred by a vaccine extends beyond the specific microbe it targets. This adds support to the impetus to vaccinate infants in the developing world. As many as 30 different pathogens can cause diarrhea, so vaccinating small children against all of them—even if those vaccines existed—would require so many separate injections as to be logistically hopeless. Understanding the mechanism by which cross-reactivity occurs might further allow immunologists to develop wide-spectrum vaccines that cover a number of infectious organisms.
Journal Reference: Immunity, provided by Stanford University Medical Center
After long dismissing the search for a human pheromone (pheromones are airborne chemicals which are emitted to attract the opposite sex) as folly, scientists have begun to take a second look at how human body odor influences sexual attraction. The magic scent is not some romantic elixir but the aromatic effluence of our immune system. The only trouble is we don’t give it half a chance. How do we humans announce, and excite, sexual availability? Many animals do it with their own biochemical bouquets known as pheromones. Why do bulls and horses turn up their nostrils when excited by love? Darwin pondered deep in one of his unpublished notebooks. He came to believe that natural selection designed animals to produce two, and only two, types of odors—defensive ones, like the skunk’s, and scents for territorial marking and mate attracting, like that exuded by the male musk deer and bottled by perfumers everywhere. The evaluative sniffing that mammals engage in during courtship were clues that scent is the chemical equivalent of the peacock’s plumage or the nightingale’s song; finery with which to attract mates.
In the following century, rich array of animal pheromones were documented for seals, boars, rodents, and all manner of other critters. Some of Darwin’s contemporaries embraced human uniqueness in this regard as evidence of our inevitable ascendance, as if Nature’s Plan somehow called for the evolution of a nearly naked two-legged primate with a poor sense of smell to conquer the Earth. The French physician Paul Broca—noting that primates’ social olfactory abilities are diminished compared to those of other mammals asserted that monkeys, apes, and humans represent ascending steps from four-legged sniffing beasts to sight-oriented bipeds. Monkeys, he argued, have smaller "smell brains" than other mammals, and apes’ brains are even smaller than that. Among humans, only the tribal "primitives," Broca wrote, could still attach erotic import to the bodily smells of man.
More enlightened researchers dismissed such views as racist tripe. But they still noted that humans engage in very little scent-driven socializing; compared to, say, the urine-washing displays of monkeys; during which urine is rubbed on the feet to attract mates. To make matters worse, humans seemed to lack the hardware for communicating by scent. Pheromone reception in other species is the business of two little pits (one in each nostril) known collectively as the vomeronasal organ. Few scientists claimed to have been able to locate a human vomeronasal organ. Those who did complained that the vomeronasal organ is so small that they could detect it only rarely. But most scientists, without bothering to look, simply dismissed the idea of a vomeronasal organ in humans. It’s been scientific dogma for most of this century that humans do not rely on scent to any appreciable degree, and that any vomeronasal organs found are vestigial throwbacks. Then, in the 1930s, physiologists declared that humans lack the brain part to process vomeronasal organ signals; firmly closing the book on any role for body odor in human sexual attraction. Even if we had a vomeronasal organ, the thinking was, our brains wouldn’t be able to interpret its signals.
Recent discoveries suggest, however, that the reports of our olfactory devolution have been greatly exaggerated. Some suspected as much the whole time. Smell researchers Barbara Sommerville and David Gee of the University of Leeds in England observed that smelling one another’s hands or faces is a nearly universal human greeting. The Eskimo kiss is not just a rubbing of noses but a mutual sniffing. "Only in the Western world," the researchers point out, "has it become modified to a kiss." Hands and faces may be significant choices for these formalities; they are the two most accessible concentrations of scent glands on the human body besides the ears.
Inquisitively, remembering a smell is usually difficult, yet when exposed to certain scents, many people of whom Proust is the paragon may suddenly recall a distant childhood memory in emotionally rich detail. Some aromas even affect us physiologically. Researchers exploring human olfaction have found that a faint trace of lemon significantly increases people’s perception of their own health. Lavender incense contributes to a pleasant mood, but it lowers volunteers’ mathematical abilities. A whiff of lavender and eucalyptus increases people’s respiratory rate and alertness. The scent of phenethyl alcohol (a constituent of rose oil) reduces blood pressure.
Such findings have led to the rapid development of an aromatherapy industry. Aromatherapists point to scientific findings that smell can dramatically affect our moods as evidence that therapy with aromatic oils can help buyers manage their emotional lives. Mood is demonstrably affected by scent. But scientists have found that, despite some extravagant industry promises, the attraction value in perfumes resides strictly in their pleasantness, not their sexiness. So far, at least, store-bought scent is more decoration than mood manager or love potion. A subtle "look this way" nudge to the nose, inspiring a stranger’s curiosity, or at most a smile, is all perfume advertisers can in good conscience claim for their products; not overwhelming and immediate infatuation.
Grandiose claims for the allure of a bottled smell are not new. In their haste to mass-market sexual attraction during the last century, perfumers nearly drove the gentle musk deer extinct. In Victorian England, a nice-smelling young lady with financial savvy could do a brisk business selling handkerchiefs scented with her body odor. So it should come as no surprise that when physiologists discovered a functioning vomeronasal organ inside the human nose, it was a venture capitalist intent on cashing in on manufactured human pheromone who funded the team’s research. That was in the mid 1980s. Using high-tech microscope probes that were unavailable to vomeronasal organ hunters earlier in the century, a team led by Luis Monti-Bloch of the University of Utah found a tiny pair of pits, one in each nostril, snuggled up against the septum an inch inside the nose. The pits are lined with receptor cells that fire like mad when presented with certain substances. Yet subjects report that they don’t smell a thing during such experiments. What they often do report is a warm, vague feeling of well-being. The olfactory bulb that neurophysiologists couldn’t find in the 1930s isn’t absent in human brains at all, researchers recently discovered. It’s just so enveloped by the massive frontal cortex that it’s very difficult to find. This finding, coupled with the discovery of a functional human vomeronasal organ, has ushered in a new chapter of the story of a human pheromone.
For an animal whose nose supposedly plays no role in sexual attraction or social life, human emotions are strongly moved by smells. We appear to be profoundly over-equipped with smell-producing hardware for what little sniffing we have been thought to be up to. Human sweat, urine, breath, saliva, breast milk, skin oils, and sexual secretions all contain scent-communicating chemical compounds. Zoologist Michael Stoddart, author of The Scented Ape (Cambridge University Press, 1991), points out that humans possess denser skin concentrations of scent glands than almost any other mammal. This makes little sense until one abandons the myth that humans pay little attention to the fragrant or the rancid in their day-to-day lives.
Part of the confusion may be due to the fact that not all smells register in our conscious minds. When those telltale scents were introduced to the vomeronasal organ of human subjects, they didn’t report smelling anything, but nevertheless demonstrated subtle changes in mood.
Humans possess three major types of skin glands: sebaceous glands, eccrine or sweat glands, and apocrine glands (A type of gland that found in the skin, breast, eyelid, and ear. Apocrine glands in the breast secrete fat droplets into breast milk and those in the ear help form earwax. Apocrine glands in the skin and eyelid are sweat glands. Most apocrine glands in the skin are in the armpits, the groin, and the area around the nipples of the breast. Apocrine glands in the skin are scent glands, and their secretions usually have an odor. Another type of gland called eccrine gland or simple sweat gland produces most sweat). Sebaceous glands are most common on the face and forehead but occur around all of the body’s openings, including eyelids, ears, nostrils, lips, and nipples. This placement is particularly handy, as the secretions of these glands kill potentially dangerous microorganisms. They also contain fats that keep skin supple and waterproof and, on the downside, cause acne vulgaris. Little is known, however, about how sebaceous glands contribute to human body odor.
The sweat glands exude water and salt and are non-odorous in healthy people. That leaves the third potential source of a human pheromone—the apocrine gland. Apocrine glands hold special promise as the source of smells that might affect interpersonal interactions. They do not serve any temperature-managing functions in people, as they do in other animals. They occur in dense concentrations on hands, cheeks, scalp, breast areolas, and wherever we possess body hair—and are only functional after puberty, when we begin searching for mates.
Men’s apocrine glands are larger than women’s, and they secrete most actively during times of nervousness or excitement. Waiting colonies of bacteria turn apocrine secretions into the noxious fumes that keep deodorant makers in business. Hair provides surface area from which apocrine smells can diffuse—part of the reason why hairier men smell particularly pungent. Is it any coincidence that hair at the arm pit and the genitals sprouts at puberty, when apocrine glands start producing food for our skin bacteria?
Apocrine glands exude odorous steroids known to elicit sexual behavior in mammals. Androsterone—a steroid related to the one that nearly doomed the hapless musk deer—is one such substance. Men secrete more androsterone than women do, and most men become unable to detect the stuff right around the time they start producing it themselves—at puberty. In 1986, the National Geographic Society organized the World Smell Survey to investigate whether people from all cultures experience odor in the same fashion. They distributed over a million scratch-and-sniff cards and questionnaires about subjects’ detection and perceptions of intensity of smells, from banana to the sulfur compounds added to natural gas as a warning agent. Included in the survey was the scent of human androsterone. The steroid itself is not pleasant to smell. Worldwide, those who could smell it rated it second to last in pleasantness—just ahead of the sulfur compounds put in natural gas; a foul-smelling pheromone? It’s hardly what scientists expected to find.
Despite the poor showing of androsterone in smell ratings, Karl Grammer of Austria’s Institute for Human Biology thought it might be the sought-after human pheromone and studied women’s reactions to it. He expected to find that women have a strong, favorable reaction to the smell of androsterone around ovulation, when their sense of smell becomes more acute and when they are most likely to conceive. Changes in female bodies’ estrogen levels around ovulation were suspected may change how women react to androsterone’s smell. Grammer found that women’s reactions to androsterone indeed change around ovulation, but not in the manner he expected. Instead of attraction, Grammer’s ovulating volunteers shrugged their shoulders and reported ambivalence. Androsterone, it seems, offers little hope to men looking for a $19.95 solution to their dating slumps.
The empirical proof of odor’s effect on human sexual attraction came out of left field. Medical geneticists studying inheritance rules for the immune system; not smell physiologists, made a series of crucial discoveries that nobody believed were relevant to human mate preferences—at first. Research on tissue rejection in organ transplant surgery patients led to the discovery that the body recognizes an alien presence; whether a virus or a surgically implanted kidney because the body’s own cells are coated with proteins that our immune system recognizes as "self." But the immune system gets a lot more subtle about recognizing "nonself" intruders. It can recognize specific types of disease organisms, attach protein identifiers to them, and muster antibodies designed specifically for destroying that particular disease and it can "remember" that particular invader years later, sending out specific antibodies to it.
A segment of our DNA called the major histocompatibility complex codes for some of these disease-detecting structures, which function as the immune system’s eyes. When a disease is recognized, the immune system’s teeth—the killer T cells—are alerted, and they swarm the intruders, smothering them with destructive enzymes. Unlike many genes, which have one or two alternative versions like the genes that code for attached or unattached ear lobes, major histocompatibility complex genes have dozens of alternatives and unlike earlobe genes, in which the version inherited from one parent dominates so that the version inherited from the other parent is not expressed, major histocompatibility complex genes are "co-dominant." This means that if a lab mouse inherits a version of a major histocompatibility complex gene for resistance to Disease A from its mother and a version lending resistance to Disease B from its father, that mouse will be able to resist both diseases.
When a female mouse is offered two suitors in mate choice trials, she inevitably chooses to mate with the one whose major histocompatibility complex genes least overlap with her own. It turns out that female mice evaluate males’ major histocompatibility complex profile by sniffing their urine. The immune system creates scented proteins that are unique to every version of each major histocompatibility complex gene. These immune byproducts are excreted from the body with other used-up chemicals, allowing a discerning female to sniff out exactly how closely related to her that other mouse is.
By choosing major histocompatibility complex dissimilar mates, a female mouse makes sure that she doesn’t inbreed. She also secures a survival advantage for her offspring by assuring that they will have a wider range of disease resistance than they would had she mated with her brother. It’s not that she seeks out diverse major histocompatibility complex genes for her young on purpose, of course. Ancestral females who preferred the smell of closely related males were simply outrun through evolutionary time by females who preferred the scent of unrelated sires.
Since humans show little interest in one another’s urine, few researchers thought that the story of major histocompatibility complex in rodent attraction could shed light on human interactions. But then someone made an eyebrow-raising discovery: Human volunteers can discriminate between mice that differ genetically only in their major histocompatibility complex. If human noses could detect small differences in the immune systems of mice by giving the critters a sniff, excited researchers realized, we may well be able to detect the aromatic byproducts of the immune system in human body odor as well.
A team led by Claus Wedekind at the University of Bern in Switzerland decided to see whether major histocompatibility complex differences in men’s apocrine gland secretions affected women’s ratings on male smells. The team recruited just fewer than 100 college students. Males and females were sought from different schools, to reduce the chances that they knew each other. The men were given untreated cotton T-shirts to wear as they slept alone for two consecutive nights. They were told not to eat spicy foods; not to use deodorants, cologne, or perfumed soaps; and to avoid smoking, drinking, and sex during the two-day experiment. During the day, their sweaty shirts were kept in sealed plastic containers and then came the big smell test. For two weeks prior, women had used a nasal spray to protect the delicate mucous membranes lining the nose. Around the time they were ovulating when their sense of smell is enhanced, the women were put alone in a room and presented with boxes containing the male volunteers’ shirts. First they sniffed a new, unworn shirt to control for the scent of the shirts themselves. Then the women were asked to rate each man’s shirt for "sexiness," "pleasantness," and "intensity of smell."
It was found; by Wedekind and his team that how women rate a man’s body odor pleasantness and sexiness depends upon how much of their major histocompatibility complex profile is shared. Overall, women prefer those scents exuded by men whose major histocompatibility complex profiles varied the most from their own. Hence, any given man’s odor could be pleasingly alluring to one woman, yet an offensive turnoff to another. Raters said that the smells they preferred reminded them of current or ex-lovers about twice as often as did the smells of men who have major histocompatibility complex profiles similar to their own, suggesting that smell had played a role in past decisions about who to date. Major histocompatibility complex similar men’s smells were more often described as being like a brother’s or father’s body odor… as would be expected if the components of smell being rated are major histocompatibility complex determined.
Somewhat more surprising is that women’s evaluations of body odor intensities did not differ between major histocompatibility complex similar and major histocompatibility complex dissimilar men. Body scent for major histocompatibility complex dissimilar men was rated as less sexy and less pleasant the stronger it was, but intensity did not affect the women’s already low ratings for major histocompatibility complex similar men’s smells. That strong odor turned raters off even with major histocompatibility complex dissimilar men may be due to the fact odor is a useful indicator of disease. From diabetes to viral infection to schizophrenia, unusually sweet or strong body odors are a warning cues that ancestral female in search of good genes for their offspring may have been designed to heed. In the case of schizophrenia, the issue is confounded—while some schizophrenics do actually have an unusually sweet smell, many suffer from delusions of foul smells emanating from their bodies.
Nobody yet knows what roles major histocompatibility complex may play in male evaluations of female attractiveness. Females’ superior sense of smell, however, may well be due to their need to more carefully evaluate a potential mates merits—a poor mate choice for male ancestors may have meant as little as a few minutes wasted, whereas a human female’s mistake could result in a nine-month-long "morning after" and a child unlikely to survive.
Perfumers who really want to provide that sexy allure to their male customers will apparently need to get a genetic fingerprint of the special someone before they can tailor a scent that she will find attractive. But before men contemplate fooling women in this way, they should consider the possible consequences. The Swiss researchers found that women taking oral contraceptives; which block conception by tricking the body into thinking it is pregnant reported reversed preferences, liking more the smells that reminded them of home and kin. Since the Pill reverses natural preferences, a woman may feel attracted to men she wouldn’t normally notice if she were not on birth control—men who have similar major histocompatibility complex profiles.
The effects of such evolutionary novel mate choices can go well beyond the bewilderment of a wife who stops taking her contraceptive pills and notices her husband’s "newly" foul body odor. Couples experiencing difficulty conceiving a child—even after several attempts at tubal embryo transfer—share significantly more of their major histocompatibility complex than do couples who conceive more easily. These couples’ grief is not caused by either partner’s infertility, but to an unfortunate combination of otherwise viable genes.
Doctors have known since the mid-1980s that couples suffering repeated spontaneous abortions tend to share more of their major histocompatibility complex than couples for whom pregnancies are carried to term and even when major histocompatibility complex similar couples do successfully bring a pregnancy to term, their babies are often underweight. The Swiss team believes that major histocompatibility complex related pregnancy problems in humans are too widespread to be due to inbreeding alone. They argue that in-couple infertility problems are due to strategic, unconscious "decisions" made by women bodies to curtail investment in offspring with inferior immune systems; offspring unlikely to have survived to adulthood in the environments of our evolutionary past.
When Broca and other social Darwinists pointed out that "uncivilized races" were more sensitive to body odor, they may have been correct—insofar as Europeans tend to go to greater lengths to perfume and wash away their natural scents. But this is hardly evidence of European superiority over "less evolved" peoples, as Broca insisted. Paying careful attention to the health of others and their suitability as sires to one’s offspring in the disease-rich tropics, whose cultures Broca derided, actually makes exceedingly good sense.
Perfume; daily soapy showers; convenient contraceptive pills—all have their charms. But they also may be short-circuiting our own built-in means of mate choice, adaptations shaped to our unique needs by millions of years of ancestral adversities. The existence of couples who long for children they cannot have indicates that the Western dismissal of body scent is scarcely benign. Those who find offensive the notion that animal senses play a role in their attraction to a partner need not worry. As the role of smell in human affairs yields to understanding, we see not that we are less human but that our tastes and emotions are far more complex and sophisticated than anyone ever imagined.
How to smell a mate? How does body odor affect a woman’s sexiness?
Scientists don’t know for sure, but they do know that a man’s allure depends in part on how many immune system genes he shares with a potential mate. Since it’s known that women can detect genetic compatibility by smell—it’s not that men can’t but that so far no one knows—the onus is on females to sniff out a suitable squire. Choosing a genetically compatible partner can be difficult in today’s perfume rich postindustrial jungle, and getting your immune system genes profiled can be expensive. Before you run to a doctor for blood work to see whether your mate is a suitable match—and sire for your future children—try listening to your nose. Unfortunately, the sniff test will only work if you’re not taking birth control pills.
Declare a deception-free day for the nostrils. Have your beau shower with fragrance-free soap and wear clean cotton clothing for a day, away from smokers and the perfumed masses. Be sure you don’t have a cold, and that you yourself haven’t been around smokers for a few days. After he spends a day and a night in his cotton clothes, before he tosses them in the direction of the hamper, wrestle them from him and have a "smelldown." Make it a romantic experience. If your man’s shirt doesn’t offend, you should be safe. Find the scent alluring or sexy? Even better! That attraction is nature’s way of telling you he’s a safe contributor to your offspring’s genetic ensemble. If your man’s odor reminds you of your father or of a brother, you may want to consider getting in touch with your doctor and ask about genetic tests before trying to conceive a child. Tell the doctor you’re concerned that you may share a close major histocompatibility complex or human leukocyte antigen, is a technical tag for human major histocompatibility complex. Meanwhile, a deceptively pleasing gift of cologne might be in order. Genetic incompatibility is not the only reason you may find his odor offensive. Does his body scent seem unusually intense? He might have a medical condition that explains the smell. Ask him to bring it up at his next medical checkup. A very sweet scent is sometimes evidence of diabetes or schizophrenia—both of which appear to be heritable. It is wise to discuss these issues with each other, and with a doctor, before having kids. Before you decide that your relationship stinks, check your mate’s diet; a taste for spicy foods or overindulgence in garlic can cause strong body odors. If your mate still offends, don’t head for the hills just yet. Some clothing detergents can prove to be a bad mix with a fellow’s scent. Ask that the next time he visits the laundry, he change brands—and give the stinker a second chance!
Most of us know that the trick to staying healthy is a balancing act between diet, exercise and healthy relationships. Yet more often than not, one thing or another gets neglected as we rush through our daily activities. With bills to pay, children to raise and schedules to keep, sometimes we forget about the basics of self-care. While it may be easiest to put our own needs last, especially in a pinch, it is important to remember that your meeting your own needs is the core to a balanced mind and healthy immune system.
Making the basics work for you is the best way to affirm self-love and keep your life moving in the direction of your dreams.
Most of the time, we grab whatever is convenient without ever realizing that what we eat and drink directly affects our energy levels. The funny thing about food is that it is more than just fuel. Food literally runs the show, and yet most of us pay little attention to the choices that we make in the kitchen or at a restaurant. Usually, our attention goes toward the cost of food. In other words, how can we get more for less? Instead, maybe we should ask ourselves, “What can I give to receive the best?” This means putting our attention on giving, rather than receiving. It means making the best more important than just good enough. In the heat of a second, a candy bar is just good enough. But a candy bar doesn’t give you what you need to thrive. And it may even push your body into deeper exhaustion or depression. So, really, we need to make best a priority. Steer clear of anything that is packaged. Focus on whole foods and super-foods. These foods are even more nutritious when fermented.
Physical, mental and spiritual wellbeing comes next. When we are unhealthy or in pain, how can we enjoy life, our family or our friends? Many of us ignore the body. Whether it is from necessity or exhaustion, we can spend most of the day sitting: sitting at work, in our car, at the dinner table or on the couch. Our bodies are designed for activity and to move in incredible ways and it is good for us, too! Twenty minutes of walking, yoga or deep breathing in the morning will not only help balance your circadian rhythm and hormones, it will also prime your digestive tract for your first meal.
Maintain healthy relationships. When we get wrapped up in negative self-talk, we defeat our purpose, which is to express our divinity and shine our light. On a biochemical level, negative self-talk shuts down the immune system and cause our energy to plummet. Instead giving into to worry, stress or frustration, slip into the eternal now. Open your consciousness to knowing that all is provided for and that all is well. When you trust, chances are you will make better choices.
Whatever problems a relationship or interaction may hold, forgive and apologize for your own part. That is where true power lies—in taking responsibility for our perspective and what we are creating. Focus on good aspects of the relationship or interaction and practice a state of infinite love and gratitude.
A genetic vulnerability to depression may protect you from infectious disease. Clinical depression is a problem that we know affects tens of millions of people in the United States alone every year. We know there is a genetic vulnerability to getting depressed, along with environmental contributors such as childhood trauma and recent stress. But why are humans vulnerable to depression? It doesn’t seem to be a very adaptive trait, after all. Hard to imagine a depressed hunter-gatherer making it for very long, raising children, collecting food.
A Deal with the Devil
However, there may well be a genetic advantage that comes with the vulnerability to depression. It became important more so when humans began to live with animals in large groups, leading to the spread of infectious disease. But infectious disease has caused strong selection pressure on the human population in the recent millennia, so these genetic vulnerabilities could easily become widespread.
Here is the theory. Depression as we know is associated with certain types of inflammation in the brain. There are certain red immune system flags we see with the syndrome of depression quite frequently, most specifically increases in the cytokines TNF-alpha, IL-6, and C-reactive protein. These chemicals found in the blood and spinal fluid tell us a brigade of our immune system is on high alert. Problem is, when there are no invaders or they are too clever and elude our defenses, our brains get the full onslaught and neurons die and then you can’t concentrate, and you avoid social activities, and you may find yourself crying a lot, and your primary care doctor might recommend that you see a therapist or someone.
And we certainly know that genes in combination with stress will predispose us to depression. But some folks are bulletproof. They won’t get depressed in the direst of circumstances. Other people seem to be far more vulnerable. All it takes is a bit of a mismatch between temperament of parent and child and we have major psychopathology. A predisposition to depression is hereditary; therefore it must be encoded in our genes. But what genes? The PATHOS-D authors would suggest that the genes that predispose us to depression also protect us from infection.
Infection? All of us humans in the brave new modern world have endured 10,000 years of agriculture, which brought with it dense population and massive infectious disease. Tuberculosis, for example, is said to have killed most humans who have ever lived. The same genes that might give us a genetic advantage against infectious pathogens may lead to vulnerability to depression.
Inflammation, like an army, is a double-edged sword. People with trigger-happy immune systems are more likely to survive many infections; though a tricky beast like the 1919 flu killed the young adults with the most robust immune systems via massive pulmonary immune reactions and septic shock. Since infections in the developing world tend to preferentially kill young children, there is strong selection pressure for genes that will save you when you are young, even if those genes have a cost later in life. The selection pressure would have to be strong, as a clinical depression has obvious survival downsides, for both the person affected and his or her offspring. Depression tends to be chronically recurring and also will strike folks in 20s and 30s, unlike, say, Alzheimer’s or most cardiovascular disease, thus selection pressure against depression alleles would likely be significant…unless those same alleles protected against something even more deadly that often strikes even younger, like infectious disease.
The evidence is, just as in schizophrenia, geneticists have tried to brute force hack the human genome in order to find a “depression gene.” Just like in schizophrenia, they haven’t had a lot of success. The answer again, similar to schizophrenia and probably a lot of other diseases that don’t fall into a simple single-gene model will likely lie in looking at a group of genes for particular functions say, immune function, or brain communication and finding many different problems in those pathways in those who are genetically predisposed to depression. In all the genome searching, a couple of genes have come up consistently involved with depression in certain predisposed families. Both of them happen to be involved with cytokine signaling/immune function. That would be a heck of a coincidence.
One allele, -308A, is found to be associated with increased risk of depression along with decreased risk of tuberculosis infection, parvovirus B19, hepatitis B, and a lower risk of death when hospitalized while critically ill.
What about other genes those have been found to be associated with depression risk but weren’t found on large population genome-wide association studies? MTHFR 677T is a version of methylenetetrahydrofolate reductase with reduced activity. That means the folate we eat in our diets will have a harder time being transformed into the folate that is active in the brain (methyl folate). Since folate is necessary to make things such as neurotransmitters and DNA, a brain without folate is in a sad state.
Low MTHFR is associated with increases in homocysteine and overall inflammatory tone. Since low folate is also associated with devastating birth defects, one would think there would be pretty strong selection pressure against this gene, but it is actually fairly common in the population. Why? Well, the inefficient version of MTHFR is found to be protective against cytomegalovirus infection, sexually transmitted disease, and hepatitis B. In places where there is sufficient folate in the food, MTHFR inefficiencies may not be devastating and could mean protection against infections that cause other devastating birth defects and disease. In sub-Saharan Africa there is low folate availability, and the MTHFR 677T allele is nearly absent there.
ApoE is another molecule brain scientists find very interesting, primarily because different ApoE alleles confer different risks to certain diseases such as Alzheimer’s Dementia. ApoE is a signaling molecule located on the surface of lipoproteins; you might know of them as “good cholesterol” or “HDL” and “bad cholesterol” or “LDL,” which carry around fats and cholesterol and vitamins. ApoE4 is the original, ancestral allele, and those who carry it have a higher risk for both Alzheimer’s disease and depression. E4 is associated with increased inflammation in general. E2 is a protective version and means decreased risk of major depressive disorder and Alzheimer’s compared to E4. The E4 allele may be protective against childhood diarrheal illnesses, while those with E2 seem to be more vulnerable to tuberculosis and malaria.
The most studied alleles associated with depression are so-called short and long form of the 5HTTLPR. This gene is a promoter region that tells the cell to make a serotonin transporter. Those with the short allele (particularly with two short alleles) seem to have a much higher risk of developing major depression when exposed to early childhood trauma, whereas the long form of the gene is protective. However, the short gene isn’t all bad. Those who have it seem to have a lower risk of dying from sudden infant death syndrome, and the gene is associated with higher circulating cytokines in response to stress, which could protect you if the stress is from being wounded or an infection. In populations where the short gene is more common, there also tends to be more exposure to epidemic infections, suggesting selection pressure for the short gene.
Finally, there is some thought put into the clinical syndrome of depression and how it might protect you and your offspring if you do have an acute infection. It is well known that inflammatory mediators (such as IL-6 or interferon) induce depression symptoms on their own. If you have come down with an infectious disease, being depressed would keep you isolated and conserve energy, reduce appetite (maybe to induce ketosis to improve viral and bacterial immunity?)
The strength of an evolutionary/ancestral paradigm for studying disease helps to provide a sensible framework, like the PATHOS-D theory. Clinically, it helps us to focus on the immune system and inflammation, and how that may have been altered by modern diet, stress, lack of parasites and pseudocommensals, changed sleep, infectious burden, and physical activity. Forget the random crapshoot of mere brute force epidemiology. There are too many confounders, and it will lead us in the wrong direction as often as not.
Here I am using the clinical definition of depression. Not just a sad mood for reason, such as grief. Usually, we are talking about a sad mood with inability to enjoy things we used to enjoy, poor concentration, poor or unrestorative sleep, appetite change (classically poor appetite), guilt, self-doubt, and even suicidal thoughts.