No, the Z-Pack won’t treat the flu.
So far, in our discussions on antibiotics, we’ve discussed what antibiotic resistance is and isn’t (Discussing the Disappearing Miracle) and how ordinary people accidentally contribute to this growing problem (Quitting When You Aren’t Really Ahead). While there is growing awareness that antibiotics in our protein supply (see SuperChickens?) can contribute as well, an area that becomes increasingly frustrating is over-prescription of antibiotics. This happens in two ways: patients, unaware of the difference between the causes of infections, may ask for antibiotics for illnesses even if they would be ineffective. Doctors, unwilling to see their patients suffer, offer something, anything, in an attempt to help. Unfortunately, neither scenario is truly harmless.
In order to understand why prescribing antibiotics all the time isn’t harmless, we must first understand a little bit about pathology, or how disease impacts the body, a little bit about epidemiology, how disease spreads in a population, and a little bit about microbiology and immunology, how the body defends itself from disease (and the causes of disease). I will point out that it is possible to get doctoral degrees in each of these fields and to go into far more depth than I intend to explore here. My plan is to just skim the surface and help you piece everything together to make a complete picture.
Raz and Aisha are a young couple working hard to make a home. When their new baby joins the family, they become familiar with all the sleeplessness that accompanies a new baby, the late night feedings, the endless diaper changes, and the wonder of rediscovering the world through the eyes of new life. It isn’t long before their new baby becomes an older sibling as the parents welcome their second child and everything is repeated. Raz and Aisha learn what every new parent learns at this point: Someone is always sick.
This is normal in homes with small children, even healthy children. In the first five years of a child’s life, the immune system is learning and growing as much as the child is. During prenatal development (while the fetus was in the womb, connected to mother via the umbilical cord), the child had the benefit of mother’s antibodies, circulating immunoglobulin G (IgG). As soon as that cord is cut, however, so is the supply. Now it is baby’s turn to make antibodies.
If mother can breastfeed (and not all mothers are able to, for a variety of reasons, but if they can, it is best), then baby gets another boost of antibodies from a secreted antibody known as IgA. This is excellent, because by about 4-6 months, mother’s supply of IgG is gone, but if baby is getting a constant supply if IgA, it can provide a boost of protection. Even at 12 months, baby’s first circulating antibodies are likely only around 80% of what they will ever reach at their best - little baby Sarah just doesn’t have the protection that her body needs to fight off everything that Raz and Aisha can. A year later, when baby Abram is born, Sarah will have grown, her body will have learned more, but there is still so much to learn - but Abram is starting from zero, just like Sarah did.
So we have a young family, mother and father and two precious small children with growing immune systems. They get vaccines for themselves and their children. Dad’s vaccines ensure that his strong immune system is ready to defend his body and keep disease from gaining a foothold - he provides a fence around his family. Mom’s vaccine is another link in that fence - when parents go to work, they encounter microbes, bring them home, but inside of Mom & Dad’s body, the microbes encounter strong immune systems capable of eliminating the microbe before it can cause disease, and thus removing the threat to the children. But if Mom can breastfeed, Mom adds another layer of defense: the antibodies she makes are passed on to her children in her breast milk, and the children get that defense as well (see why this is so important to breastfeed if you can?) The children are getting a carefully timed sequence of vaccines as well. Each is a very specific dose, in a very specific sequence, aimed to teach their growing bodies how to protect them against illness.
It’s also worth noting that vaccines are non-infectious, dead, weakened, or parts of viruses and bacteria. Vaccines can not cause the illness they protect against. Let me say that again. A vaccine cannot cause the illness it protects against. What vaccines accomplish is to allow the body to encounter pathogenic particles (bits of disease causing agents) in a controlled manner that stacks the deck in favor of the immune system. Instead of encountering wild viruses or bacteria that can and do cause disease in the human body with little to no preparation, vaccines train the body via the immune system so that when the body does encounter the wild pathogens (disease-causing agent), the body knows how to defend itself.
OK, so Raz and Aisha have been doing everything they can, and they take Abram and Sarah out to play. Maybe they go to their local house of worship. Maybe both parents work, and the children are in daycare. However it happens, Abram and Sarah encounter the great big world, where there are other people. It isn’t too long before one of the children wakes up Mom with a snuffly nose, a cough, and a fever (of course they wake up Mom. Even if they woke Dad, even if Dad is a pediatrician, they still asked for Mom and wouldn’t calm until they got Mom. That’s just how we are. We want our Mommies. It’s ok. Or maybe you prefer they want Dad. The point is that parent is disturbed by sick child).
Sick child cannot join other children. One of the parents must miss work, even if they decide that this isn’t worth a doctor visit yet. However Raz and Aisha decide, the decision is made, and the parents adapt to the needs of their child. Of course, the next day, the other child is ill, as well. Another day missed from work. Perhaps the parents opt to trade who misses. Maybe they’ve made other arrangements. But clearly whatever the children encountered in the wider world has defeated their own growing immune systems. Remember - these are small children, whose immune system hasn’t learned all the things that Mom and Dad have. It’s getting better all the time (as The Beatles said), but there just hasn’t been enough time yet.
But there’s another race going on: as the children’s bodies race to grow and learn from the world around them, inside their bodies are all the Sue Streptococcus and Reeking Jim and other bacteria. And the kids have a cold, a virus we can’t vaccinate against because there are just too many varieties making too many changes. The most common cold virus, rhinovirus, is effectively a protein instruction manual inside a protein coat looking for a factory, and everyone is a factory. Worse, while there’s really one kind of Sal, even if he does mutate and change, there’s 99 kinds of rhinoviruses, and they don’t get along. Even if we figure out how to deal with one of the 99 rhinos, there’s 98 more waiting, and that’s just the most common kind. You probably have more than one virus at a time, too, so you’re not just dealing with Sal and his copies going crazy, or a single rhinovirus setting up shop in the factory that is your nose, but as many as 200 different viruses possibly causing your cold.
So Abram and Sarah have a cold, which means they have multiple viruses that found their noses and mouths and decided to set up shop and start making copies. In response, their immune system has tried a few different things to protect them. To help kill the viruses, the immune system increases the temperature. Our body has a very specific temperature we like, but pathogens are even more picky. Often, a change in temperature can help kill the virus or bacteria causing illness. So up goes the body temperature, and up goes the misery. There’s viruses in the nose, so the immune system tries getting them out. Immune cells called neutrophils rush to the site, causing swelling and redness, which brings more heat and pain with it. This helps trigger mucus production and gives the kids runny noses. As the mucus runs down the back of the throat, it triggers a cough, too. In fact, if virus is in the airways, the immune response may continue there, causing sore throat and more cough. In fact, all the misery you feel from the cold is actually the result of your body fighting the cold. But if your body didn’t fight the cold, the virus would gradually take over enough of your cells to kill you. I think we can agree that given the choice between the misery of the cold and death by cold, death by cold virus is worse.
From start to finish, it takes 7-10 days for the human body to fight off a viral infection. Some take longer - if there are more viruses, it may take longer, for instance, or if you don’t give your body the tools it needs, like rest and fluids, it may take longer. But there is really nothing that can be done to shorten the length of time you have a cold. Because viruses have to get into your cells to work, anything that would shorten the length of time you are sick must first attack your own body, and finding a way to kill a virus without killing the cell it infected is incredibly difficult. This, by the way, is why the side effects for anti-viral medications like tamiflu sound incredibly like more of the flu but worse. It actually is. This is also why some anti-virals have such a narrow window of effectiveness - once the virus is inside the cell, medication aimed at keeping the virus out of the cell is far less effective.
Let’s get back to poor Abram and Sarah. Neither of them have the flu, right? They’ve got colds. And because colds are contagious, of course Raz and Aisha get colds and no matter how careful they are, Raz and Aisha share their colds, and everyone’s temper gets short because they’re discovering that when small children are present, someone is always sick. That’s how epidemiology works in families. Once the kids get older, that will happen less, but while they grow up, it will feel like someone is always sick, especially the more children there are and the more social the family is. This is actually good - their bodies are learning and growing and they will, in general, be stronger, healthier adults.
As the family recovers, just as the last of them starts to feel better, things get worse. One of Raz’s coworkers decided to share his flu, and Raz shares with the family without realizing. The family goes to the doctor who mistakes flu for an ongoing sinus infection and prescribes Z-Packs for the lot of them.
Here’s the thing. Streptococcal infections aren’t something to be ignored. If you have strep throat, take your antibiotics as prescribed, take every pill on time, finish the entire prescription, even when you feel better, and take them all. It’s very easy for your body to get confused and look at Sue and look at parts of you, like your heart, or your kidneys, and get mixed up. It’s called molecular mimicry, and when it happens, your immune system goes from being your best buddy to being a serious problem. It causes autoimmune problems like Scarlet Fever, where your body attacks itself instead of the bacteria. Before we had antibiotics, Streptococcal infections could be deadly even if you survived them. So we’re very eager to treat them, and it’s not a bad thing.
But antibiotics can’t treat a viral infection. Remember the talk about resistance versus susceptibility? If a bacteria never had a weakness to a drug, it could never become resistant to it because it was never susceptible to it. Viruses are not susceptible to antibiotics. They will never be susceptible to them. Viruses are instruction manuals inside of a coat (sometimes wrapped in armor). They lack the mechanisms that antibiotics target. This, too, is a good thing; if viruses could live outside of a cell, if they could copy themselves without needing us, they would wipe us out in no time. We want viruses to lack those mechanisms, to effectively be in suspended animation when they’re not inside cells.
So what happens when our little family makes the mistake of taking the Z-Pack for the flu? No harm, no foul, right? The have a viral infection that will wipe itself out in 7-10 days, so they’ll feel better if they take the pills or not (and we’ll pretend that they’re really good about taking them like they should). No big deal?
Except there are friendly Sues that live with the Reeking Jims and another organism, a fungus we’ll call Difficult Claus. Good ol’ C. difficile. Just like the viruses aren’t susceptible to the azithromycin in the Z-Pack, neither are Jim or Claus. But unlike the viruses, Jim and Claus live in our bodies, serving an important function, growing with us. And they can live inside or outside. They don’t go into suspended animation like the viruses do.
Normally, our Sues and Jims and Claus live with other organisms and with us in our intestines where they teach our immune system the difference between us and other, living off the food we eat and don’t need (all the food you eat has stuff you can’t use - that’s what they use). It’s a commensal relationship, not just between us and organisms, or microbiome, but within the microbiome itself. The Sues and Jims and Clauses all make sure everyone takes up just the right amount of space, that no one hogs all the best intestine. But when you take antibiotics, the Sues and the Jims start to lose, and Claus might grow out of control. In our happy little family, only Sue dies off. Jim and Claus stay behind, and now the children have unhappy tummies.
Oh, and Sue keeps making copies of herself, remember? Just like Sal did. And the Sues that survive are the SuperSues. So when the children get Strep throat, and they need that Z-Pack to kill the bad Sues, the ones that are making them sick, guess what’s going to happen? If you guessed resistance, you guessed right. And what happens when we can’t fight strep infections? Molecular mimicry can happen. The risk of very bad things start to increase.
So no. No Mom, No Dad, no, you may not have antibiotics for your cold, flu, or seasonal allergies. No, Doctor Meanswell, you may not prescribe antibiotics to help your patient feel better, even if you know it’s probably not bacterial. What you may do instead is insist on the test that will confirm that the infection is the bacteria or virus that will be treated by the drug you want, and then prescribe the most effective drug for that infection. Your future you will thank you.
This Thursday brings you a variety of information about blood types: First, there's an article from Wellcome Trust's Mosaic Science on why we actually have blood types. This is followed by a graphic from Wikimedia that illustrates the carbohydrate attachments that are actually responsible for the different ABO blood types. Finally, a graphic on the levels that the Japanese have taken all of this blood type to (if you don't already know, the fact that the Japanese are involved should give you a hint...)
Why do we have blood types?
When my parents informed me that my blood type was A+, I felt a strange sense of pride. If A+ was the top grade in school, then surely A+ was also the most excellent of blood types – a biological mark of distinction.
It didn’t take long for me to recognise just how silly that feeling was and tamp it down. But I didn’t learn much more about what it really meant to have type A+ blood. By the time I was an adult, all I really knew was that if I should end up in a hospital in need of blood, the doctors there would need to make sure they transfused me with a suitable type.
And yet there remained some nagging questions. Why do 40 per cent of Caucasians have type A blood, while only 27 per cent of Asians do? Where do different blood types come from, and what do they do?;To get some answers, I went to the experts – to haematologists, geneticists, evolutionary biologists, virologists and nutrition scientists.
In 1900 the Austrian physician Karl Landsteiner first discovered blood types, winning the Nobel Prize in Physiology or Medicine for his research in 1930. Since then scientists have developed ever more powerful tools for probing the biology of blood types. They’ve found some intriguing clues about them – tracing their deep ancestry, for example, and detecting influences of blood types on our health. And yet I found that in many ways blood types remain strangely mysterious. Scientists have yet to come up with a good explanation for their very existence.
“Isn’t it amazing?” says Ajit Varki, a biologist at the University of California, San Diego. “Almost a hundred years after the Nobel Prize was awarded for this discovery, we still don’t know exactly what they’re for.”;
My knowledge that I’m type A comes to me thanks to one of the greatest discoveries in the history of medicine. Because doctors are aware of blood types, they can save lives by transfusing blood into patients. But for most of history, the notion of putting blood from one person into another was a feverish dream.
Renaissance doctors mused about what would happen if they put blood into the veins of their patients. Some thought that it could be a treatment for all manner of ailments, even insanity. Finally, in the 1600s, a few doctors tested out the idea, with disastrous results. A French doctor injected calf’s blood into a madman, who promptly started to sweat and vomit and produce urine the colour of chimney soot. After another transfusion the man died.
Such calamities gave transfusions a bad reputation for 150 years. Even in the 19th century only a few doctors dared try out the procedure. One of them was a British physician named James Blundell. Like other physicians of his day, he watched many of his female patients die from bleeding during childbirth. After the death of one patient in 1817, he found he couldn’t resign himself to the way things were.
“I could not forbear considering, that the patient might very probably have been saved by transfusion,” he later wrote.
Blundell became convinced that the earlier disasters with blood transfusions had come about thanks to one fundamental error: transfusing “the blood of the brute”, as he put it. Doctors shouldn’t transfer blood between species, he concluded, because “the different kinds of blood differ very importantly from each other”.
Human patients should only get human blood, Blundell decided. But no one had ever tried to perform such a transfusion. Blundell set about doing so by designing a system of funnels and syringes and tubes that could channel blood from a donor to an ailing patient. After testing the apparatus out on dogs, Blundell was summoned to the bed of a man who was bleeding to death. “Transfusion alone could give him a chance of life,” he wrote.
Several donors provided Blundell with 14 ounces of blood, which he injected into the man’s arm. After the procedure the patient told Blundell that he felt better – “less fainty” – but two days later he died.
Still, the experience convinced Blundell that blood transfusion would be a huge benefit to mankind, and he continued to pour blood into desperate patients in the following years. All told, he performed ten blood transfusions. Only four patients survived.
While some other doctors experimented with blood transfusion as well, their success rates were also dismal. Various approaches were tried, including attempts in the 1870s to use milk in transfusions (which were, unsurprisingly, fruitless and dangerous).
Blundell was correct in believing that humans should only get human blood. But he didn’t know another crucial fact about blood: that humans should only get blood from certain other humans. It’s likely that Blundell’s ignorance of this simple fact led to the death of some of his patients. What makes those deaths all the more tragic is that the discovery of blood types, a few decades later, was the result of a fairly simple procedure.
The first clues as to why the transfusions of the early 19th century had failed were clumps of blood. When scientists in the late 1800s mixed blood from different people in test tubes, they noticed that sometimes the red blood cells stuck together. But because the blood generally came from sick patients, scientists dismissed the clumping as some sort of pathology not worth investigating. Nobody bothered to see if the blood of healthy people clumped, until Karl Landsteiner wondered what would happen. Immediately, he could see that mixtures of healthy blood sometimes clumped too.
Landsteiner set out to map the clumping pattern, collecting blood from members of his lab, including himself. He separated each sample into red blood cells and plasma, and then he combined plasma from one person with cells from another.
Landsteiner found that the clumping occurred only if he mixed certain people’s blood together. By working through all the combinations, he sorted his subjects into three groups. He gave them the entirely arbitrary names of A, B and C. (Later on C was renamed O, and a few years later other researchers discovered the AB group. By the middle of the 20th century the American researcher Philip Levine had discovered another way to categorise blood, based on whether it had the Rh blood factor. A plus or minus sign at the end of Landsteiner’s letters indicates whether a person has the factor or not.)
When Landsteiner mixed the blood from different people together, he discovered it followed certain rules. If he mixed the plasma from group A with red blood cells from someone else in group A, the plasma and cells remained a liquid. The same rule applied to the plasma and red blood cells from group B. But if Landsteiner mixed plasma from group A with red blood cells from B, the cells clumped (and vice versa).
The blood from people in group O was different. When Landsteiner mixed either A or B red blood cells with O plasma, the cells clumped. But he could add A or B plasma to O red blood cells without any clumping.
It’s this clumping that makes blood transfusions so potentially dangerous. If a doctor accidentally injected type B blood into my arm, my body would become loaded with tiny clots. They would disrupt my circulation and cause me to start bleeding massively, struggle for breath and potentially die. But if I received either type A or type O blood, I would be fine.
Landsteiner didn’t know what precisely distinguished one blood type from another. Later generations of scientists discovered that the red blood cells in each type are decorated with different molecules on their surface. In my type A blood, for example, the cells build these molecules in two stages, like two floors of a house. The first floor is called an H antigen. On top of the first floor the cells build a second, called the A antigen.
People with type B blood, on the other hand, build the second floor of the house in a different shape. And people with type O build a single-storey ranch house: they only build the H antigen and go no further.
Each person’s immune system becomes familiar with his or her own blood type. If people receive a transfusion of the wrong type of blood, however, their immune system responds with a furious attack, as if the blood were an invader. The exception to this rule is type O blood. It only has H antigens, which are present in the other blood types too. To a person with type A or type B, it seems familiar. That familiarity makes people with type O blood universal donors, and their blood especially valuable to blood centres.
Landsteiner reported his experiment in a short, terse paper in 1900. “It might be mentioned that the reported observations may assist in the explanation of various consequences of therapeutic blood transfusions,” he concluded with exquisite understatement. Landsteiner’s discovery opened the way to safe, large-scale blood transfusions, and even today blood banks use his basic method of clumping blood cells as a quick, reliable test for blood types.
But as Landsteiner answered an old question, he raised new ones. What, if anything, were blood types for? Why should red blood cells bother with building their molecular houses? And why do people have different houses?
Solid scientific answers to these questions have been hard to come by. And in the meantime, some unscientific explanations have gained huge popularity. “It’s just been ridiculous,” sighs Connie Westhoff, the Director of Immunohematology, Genomics, and Rare Blood at the New York Blood Center.;
In 1996 a naturopath named Peter D’Adamo published a book called Eat Right 4 Your Type. D’Adamo argued that we must eat according to our blood type, in order to harmonise with our evolutionary heritage.
Blood types, he claimed, “appear to have arrived at critical junctures of human development.” According to D’Adamo, type O blood arose in our hunter-gatherer ancestors in Africa, type A at the dawn of agriculture, and type B developed between 10,000 and 15,000 years ago in the Himalayan highlands. Type AB, he argued, is a modern blending of A and B.
From these suppositions D’Adamo then claimed that our blood type determines what food we should eat. With my agriculture-based type A blood, for example, I should be a vegetarian. People with the ancient hunter type O should have a meat-rich diet and avoid grains and dairy. According to the book, foods that aren’t suited to our blood type contain antigens that can cause all sorts of illness. D’Adamo recommended his diet as a way to reduce infections, lose weight, fight cancer and diabetes, and slow the ageing process.
D’Adamo’s book has sold 7 million copies and has been translated into 60 languages. It’s been followed by a string of other blood type diet books; D’Adamo also sells a line of blood-type-tailored diet supplements on his website. As a result, doctors often get asked by their patients if blood type diets actually work.
The best way to answer that question is to run an experiment. In Eat Right 4 Your Type D’Adamo wrote that he was in the eighth year of a decade-long trial of blood type diets on women with cancer. Eighteen years later, however, the data from this trial have not yet been published.
Recently, researchers at the Red Cross in Belgium decided to see if there was any other evidence in the diet’s favour. They hunted through the scientific literature for experiments that measured the benefits of diets based on blood types. Although they examined over 1,000 studies, their efforts were futile. “There is no direct evidence supporting the health effects of the ABO blood type diet,” says Emmy De Buck of the Belgian Red Cross-Flanders.
After De Buck and her colleagues published their review in the American Journal of Clinical Nutrition, D’Adamo responded on his blog. In spite of the lack of published evidence supporting his Blood Type Diet, he claimed that the science behind it is right. “There is good science behind the blood type diets, just like there was good science behind Einstein’s mathmatical [sic] calculations that led to the Theory of Relativity,” he wrote.
Comparisons to Einstein notwithstanding, the scientists who actually do research on blood types categorically reject such a claim. “The promotion of these diets is wrong,” a group of researchers flatly declared in Transfusion Medicine Reviews.
Nevertheless, some people who follow the Blood Type Diet see positive results. According to Ahmed El-Sohemy, a nutritional scientist at the University of Toronto, that’s no reason to think that blood types have anything to do with the diet’s success.
El-Sohemy is an expert in the emerging field of nutrigenomics. He and his colleagues have brought together 1,500 volunteers to study, tracking the foods they eat and their health. They are analysing the DNA of their subjects to see how their genes may influence how food affects them. Two people may respond very differently to the same diet based on their genes.
“Almost every time I give talks about this, someone at the end asks me, ‘Oh, is this like the Blood Type Diet?’” says El-Sohemy. As a scientist, he found Eat Right 4 Your Type lacking. “None of the stuff in the book is backed by science,” he says. But El-Sohemy realised that since he knew the blood types of his 1,500 volunteers, he could see if the Blood Type Diet actually did people any good.
El-Sohemy and his colleagues divided up their subjects by their diets. Some ate the meat-based diets D’Adamo recommended for type O, some ate a mostly vegetarian diet as recommended for type A, and so on. The scientists gave each person in the study a score for how well they adhered to each blood type diet.
The researchers did find, in fact, that some of the diets could do people some good. People who stuck to the type A diet, for example, had lower body mass index scores, smaller waists and lower blood pressure. People on the type O diet had lower triglycerides. The type B diet – rich in dairy products – provided no benefits.
“The catch,” says El-Sohemy, “is that it has nothing to do with people’s blood type.” In other words, if you have type O blood, you can still benefit from a so-called type A diet just as much as someone with type A blood – probably because the benefits of a mostly vegetarian diet can be enjoyed by anyone. Anyone on a type O diet cuts out lots of carbohydrates, with the attending benefits of this being available to virtually everyone. Likewise, a diet rich in dairy products isn’t healthy for anyone – no matter their blood type.
One of the appeals of the Blood Type Diet is its story of the origins of how we got our different blood types. But that story bears little resemblance to the evidence that scientists have gathered about their evolution.
After Landsteiner’s discovery of human blood types in 1900, other scientists wondered if the blood of other animals came in different types too. It turned out that some primate species had blood that mixed nicely with certain human blood types. But for a long time it was hard to know what to make of the findings. The fact that a monkey’s blood doesn’t clump with my type A blood doesn’t necessarily mean that the monkey inherited the same type A gene that I carry from a common ancestor we share. Type A blood might have evolved more than once.
The uncertainty slowly began to dissolve, starting in the 1990s with scientists deciphering the molecular biology of blood types. They found that a single gene, called ABO, is responsible for building the second floor of the blood type house. The A version of the gene differs by a few key mutations from B. People with type O blood have mutations in the ABO gene that prevent them from making the enzyme that builds either the A or B antigen.
Scientists could then begin comparing the ABO gene from humans to other species. Laure Ségurel and her colleagues at the National Center for Scientific Research in Paris have led the most ambitious survey of ABO genes in primates to date. And they’ve found that our blood types are profoundly old. Gibbons and humans both have variants for both A and B blood types, and those variants come from a common ancestor that lived 20 million years ago.
Our blood types might be even older, but it’s hard to know how old. Scientists have yet to analyse the genes of all primates, so they can’t see how widespread our own versions are among other species. But the evidence that scientists have gathered so far already reveals a turbulent history to blood types. In some lineages mutations have shut down one blood type or another. Chimpanzees, our closest living relatives, have only type A and type O blood. Gorillas, on the other hand, have only B. In some cases mutations have altered the ABO gene, turning type A blood into type B. And even in humans, scientists are finding, mutations have repeatedly arisen that prevent the ABO protein from building a second storey on the blood type house. These mutations have turned blood types from A or B to O. “There are hundreds of ways of being type O,” says Westhoff.
Being type A is not a legacy of my proto-farmer ancestors, in other words. It’s a legacy of my monkey-like ancestors. Surely, if my blood type has endured for millions of years, it must be providing me with some obvious biological benefit. Otherwise, why do my blood cells bother building such complicated molecular structures?
Yet scientists have struggled to identify what benefit the ABO gene provides. “There is no good and definite explanation for ABO,” says Antoine Blancher of the University of Toulouse, “although many answers have been given.”
The most striking demonstration of our ignorance about the benefit of blood types came to light in Bombay in 1952. Doctors discovered that a handful of patients had no ABO blood type at all – not A, not B, not AB, not O. If A and B are two-storey buildings, and O is a one-storey ranch house, then these Bombay patients had only an empty lot.
Since its discovery this condition – called the Bombay phenotype – has turned up in other people, although it remains exceedingly rare. And as far as scientists can tell, there’s no harm that comes from it. The only known medical risk it presents comes when it’s time for a blood transfusion. Those with the Bombay phenotype can only accept blood from other people with the same condition. Even blood type O, supposedly the universal blood type, can kill them.
The Bombay phenotype proves that there’s no immediate life-or-death advantage to having ABO blood types. Some scientists think that the explanation for blood types may lie in their variation. That’s because different blood types may protect us from different diseases.
Doctors first began to notice a link between blood types and different diseases in the middle of the 20th century, and the list has continued to grow. “There are still many associations being found between blood groups and infections, cancers and a range of diseases,” Pamela Greenwell of the University of Westminster tells me.
From Greenwell I learn to my displeasure that blood type A puts me at a higher risk of several types of cancer, such as some forms of pancreatic cancer and leukaemia. I’m also more prone to smallpox infections, heart disease and severe malaria. On the other hand, people with other blood types have to face increased risks of other disorders. People with type O, for example, are more likely to get ulcers and ruptured Achilles tendons.
These links between blood types and diseases have a mysterious arbitrariness about them, and scientists have only begun to work out the reasons behind some of them. For example, Kevin Kain of the University of Toronto and his colleagues have been investigating why people with type O are better protected against severe malaria than people with other blood types. His studies indicate that immune cells have an easier job of recognising infected blood cells if they’re type O rather than other blood types.
More puzzling are the links between blood types and diseases that have nothing to do with the blood. Take norovirus. This nasty pathogen is the bane of cruise ships, as it can rage through hundreds of passengers, causing violent vomiting and diarrhoea. It does so by invading cells lining the intestines, leaving blood cells untouched. Nevertheless, people’s blood type influences the risk that they will be infected by a particular strain of norovirus.
The solution to this particular mystery can be found in the fact that blood cells are not the only cells to produce blood type antigens. They are also produced by cells in blood vessel walls, the airway, skin and hair. Many people even secrete blood type antigens in their saliva. Noroviruses make us sick by grabbing onto the blood type antigens produced by cells in the gut.
Yet a norovirus can only grab firmly onto a cell if its proteins fit snugly onto the cell’s blood type antigen. So it’s possible that each strain of norovirus has proteins that are adapted to attach tightly to certain blood type antigens, but not others. That would explain why our blood type can influence which norovirus strains can make us sick.
It may also be a clue as to why a variety of blood types have endured for millions of years. Our primate ancestors were locked in a never-ending cage match with countless pathogens, including viruses, bacteria and other enemies. Some of those pathogens may have adapted to exploit different kinds of blood type antigens. The pathogens that were best suited to the most common blood type would have fared best, because they had the most hosts to infect. But, gradually, they may have destroyed that advantage by killing off their hosts. Meanwhile, primates with rarer blood types would have thrived, thanks to their protection against some of their enemies.
As I contemplate this possibility, my type A blood remains as puzzling to me as when I was a boy. But it’s a deeper state of puzzlement that brings me some pleasure. I realise that the reason for my blood type may, ultimately, have nothing to do with blood at all.
All red blood cells have a specific chain of carbohydrates, and then the presence or absence of specific carbohydrates at the distal terminal of the chain determines the blood type. There are 4 phenotypes in blood types, but that is determined by 6 genotypes. In other words, your mother gave you one set of genes, your father gave you another, and these combine to form your genotype which is expressed as a specific physical expression known as a phenotype. (If you've read the article, most of this should be review).
So, you can be AA, AO, BB, BO, AB, or OO: these are the 6 genotypes. AA and AO would both be expressed as type A blood, just as BB and BO would both be expressed as type B blood, which is how 6 genotypes distill into 4 phenotypes. But how does this tie back to the carbohydrates? Well, all cells have tags on them that identify them as you. These tags are proteins embedded in the lipid membranes of your cell with carbohydrates attached at the end. In the case of blood types, as I mentioned, all four blood types start with the same chain, varying only at the distal terminal. Add a galactose sugar on to your chain, and you have a B-type tag. Take that same galactose, swap out an amino for one of the carbons and attach an acetyl group and you get N-acetylgalactosamine - and now that's an A-type tag. Omit either sugar - galactose or the souped up version - and you have the O-type tag. Now, on your cells, you're going to have tags show up in pairs: you can have A-type tags, B-type tags, or O-type tags. If you have all O-type tags, you have type O blood. If you have any A-type tags but NO B-type tags, you've got type A, whether that's all type A (AA) or only half type A (AO). If you've got B but not A, you've got B blood (BB, or BO). It's when you get cells that have both the type A tag (N-acetylgalactosamine) AND the type B tag (galactose) that you get type AB blood. That's what this image is showing. I wanted to be sure to illustrate the biochemistry of this clearly.
And on to the Japanese hijinks...
This comic comes to you courtesy of Beatrice The Biologist:
This morning, my husband showed me a TED Ed talk about why tattoos are permanent. I could (and may well) do an entire post on why TED talks, be they TED, TEDx, or TED Ed, are not just fascinating, but incredibly useful, but for the moment, let's just enjoy this video: http://ed.ted.com/lessons/what-makes-tattoos-permanent-claudia-aguirre
(Please forgive my tardiness today!)
In another link from LinkedIn, we have a story about a study started 12 years ago, in Africa. In the US, iron supplementation is a common part of pregnant women's life; the benefits to the developing child can't be overestimated. In Africa, many children suffer from iron-deficient anemia. It seemed a natural solution to supplement the diet with iron supplements and other vitamins. However, during the study, more children on the supplement died than those not on the supplement, bringing the study to an abrupt and early end. I'll let you read the story for yourself; the reasons for the confusing results still aren't entirely understood, but are being sought out in order to hopefully correct both the nutrient deficient and the fatal result of correcting it in areas where malaria is endemic. I highlight it, however, not only because it's another LinkedIn story, but because it serves as an excellent reminder of the law of unintended consequences: solving one problem may cause another, or several others. While this is a large-scale example of unintended consequences, even in your lab work, you may encounter the same problems. Look for more detail on this idea in future posts.
Today's a twofer! Today's LinkedIn video reminded me of the paper I presented for my pathology class (which was more like a journal club). Both deal with the study of fruit flies (Drosophilia sp.) in space. The video focuses on the role of the flies in studies on the ISS in space, while the paper focuses on a specific study done in 2006 and the probable importance of that study. Specifically, the paper focused on the way that changes to gravity during the development of Drosophilia sp. resulted in altered immune pathways, leading to specific weaknesses in those flies raised in a microgravity environment. This finding in a model species (one that can be used to illustrate how humans work, but on a simpler scale), may help explain why many astronauts are more prone to illness upon return from space and may also help provide clues for how to counter the impact of gravity on immunity in the future.
I mentioned in an earlier post that I'd been stockpiling articles and posts for daily uploads. This is the first of those, but before I get into that, I want to share where many of these are coming from, because that is, by itself, an incredibly useful professional tool. Recently (between starting the blog and restarting the blog), I joined/became more active on LinkedIn. I found groups there, including groups by interest. Among them are microbiology & immunology groups, and many of the links I will be sharing were discovered when they showed up in my inbox via a LinkedIn group!
This may well be old news to many of you, but I didn't want anyone to overlook useful tools. Finally, remember: employers look at all online and social media when hiring, so be mindful of what you post (or what your friends may be able to post).
Now, with no further ado: A video on how the flu invades the human body. Because light microscopy can't capture viruses, this is an animation, but it is very well done and has explanation with it.
My husband shared this TEDMed talk with me tonight, and I wanted to share it with you, along with Dr. Attia's blog. It takes courage for doctors to deviate from traditional wisdom or the accepted dogma and consider new approaches to existing problems. However, I've found that, in my own personal experience, the evidence he seems to be describing is accurate: I've found that eating more whole grains and fewer refined carbohydrates is far better for me and my diet than any low-fat approach ever attempted (low-fat seems to always actually result in higher cholesterol for me, meaning that my body compensates for the lower dietary intake by raising the production, indicating an internal imbalance that diet alone can't correct). I'll be following Dr. Attia, and I hope to have more information for you in the months and years to come.
The NIH recently announced a pilot program to help speed up drug development. Most drug development focuses on finding new molecules or compounds to treat existing disorders. The new program is looking for researchers to find uses for existing compounds, hopefully reducing both the cost and time involved in developing new drugs.
Yesterday, I drove to my local donor center, went through the short screening that determines if I’m healthy enough to donate, and then gave blood. My blood type, O-, is known as the “universal donor”, meaning it can be safely donated to anyone in an emergency, without having to check the recipient’s blood type first. (I, on the other hand, can only safely receive O- blood, so while my blood can be safely donated to everyone, my body is very picky about what it will accept.)
Because I’m a universal donor, when the waiting period between donations is up (it takes 56 days for red blood cells to replenish themselves), I often get a phone call or email encouraging me to come in. I rarely need it - I make sure, when I leave, that I note when I’ll be eligible again, set a reminder in my calendar, and then work it into my schedule. But I still get the reminders - less than half of the population can safely donate, and not enough of us do.
That lack of volunteer donors creates a problem: the demand for blood often exceeds the supply. Science has been seeking an answer to this problem for decades, including producing synthetic blood products. However, nothing has replaced human blood... until now.
Actually, that’s not even really fair to say. Scientists in Scotland have gotten permission to pursue human trials of a synthetic blood product, but this product still has a human source. Grown from human stem cells, it takes a source of immature, not-yet-differentiated blood cells, clones them, and then mass produces blood from this stem cell line. Nor are these the controversial embryonic stem cells - these come from adult donors.
So this synthetic blood has an entirely human source, but is then mass produced outside of a human body. Before it can be widely accepted in hospitals around the world, it must go through rigorous testing, and this is the step being carried out now in Scotland. The first human trials have been approved. This means that healthy men and women will be given the new blood product and monitored. As long as there are no adverse reactions, testing will continue.
I’m certain there will always be a need for donors like me. But the fact that we may have a viable alternative means that maybe, someday, people need never die from a lack of safe blood again.
This time from The Scientist. Seriously, this is only good news. Thanks to Paula A. for the link to this article! (I may interview her for a future article - she is part of my inspiration to become an immunologist, because she's the first one I've ever known!).
In a demonstration of just how deeply entrenched science and medicine are in our everyday lives, an article in the Wall Street Journal today announced an important decision from the US Supreme Court: Human Genes cannot be patented. This has been hotly contested: those arguing for patent have argued that the research and development done with the genes is costly, and without the protection of patents, it is likely to go unfunded. Those arguing against patent have pointed out the flaw of patenting a gene carried by millions of people (or even just a few), and worse, the trouble that is caused when a carrier of a gene seeks treatment for their condition, only to find out their own genetic code is locked under patent protection.
I, personally, am an advocate of openness and freedom. I believe that keeping medical research like this locked under patent is absurd, and often hinders advancements in treatment. I will note, however, that I am not currently employed by any researchers, and thus I am not bound by any such privacy agreements myself. I can understand if a scientist's work and livelihood is dependent on funding and thus on signing privacy agreements. I may find them absurd, but at the end of the day, pragmatism still has its place.
Still, I think this was a victory for the open exchange of ideas. What do you think? Will this be a boon to medicine? Should it have ever been in question?
Gladstone scientists map process by which brain cells form long-term memories. Great discoveries are not made all at once, but rather in little steps, one at a time. One such little step seems to have uncovered the pathway by which learning goes from temporary into long-term storage, thus establishing new pathways in the brain long into adulthood.