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Bloodletting Is Still Happening, Despite Centuries of Harm

An illustration of a bloodletting, circa 1675.
An illustration of a bloodletting, circa 1675.

In the shadow of India’s largest mosque, the gutters run red with blood.

It’s a bizarre scene, if you’ve never seen a modern-day bloodletting. First, men wrap patients’ arms and legs with straps as tourniquets, to control the blood flow. Then they use razor blades to make tiny pricks in the hands and feet, and blood trickles into a concrete trough stained red with the day’s work.

The bleeding people look pretty happy, though. After all, they’ve paid for the service. They come to be cured of everything from arthritis to cancer.

(Video: Meet the bloodletters of Delhi and their patients.) 

But why? How has the bloodletting business, which many doctors today would rank along with reading bumps on the head as olde timey quackery, managed not to dry up?

The appeal seems to be in its simple logic.

Muhammad Gayas runs his bloodletting business in the garden of the Jama Masjid mosque in Old Delhi. He says pain and illness happen “when the blood goes bad,” which is pretty much the same basic premise that bloodletters have sold the public since Hippocrates advocated balancing the four humors—blood, black bile, yellow bile, and phlegm—more than 2,000 years ago. 

Bloodletting has been practiced around the world even longer than that, tracing at least 3,000 years ago to the Egyptians. It remained an obsession among many Western doctors through the 19th century, and was still a recommended treatment for pneumonia in a 1942 medical textbook—lest you think it went out after the Middle Ages along with the laying on of leeches. (Oh, and leeches still get some play, too, mainly for drawing down pockets of blood after plastic surgery or vascular microsurgery.)

So Does Bloodletting Ever Work?

It may be helpful for people with a few particular blood abnormalities. Doctors still use bloodletting, for instance, in cases of polycythemia—an abnormally high red blood cell count—and in a hereditary disease called hemochromatosis, which leaves too much iron in the blood.

I also came across a preliminary study suggesting vascular benefits in some diabetics with high iron levels, but this is far from a general treatment for the disease. Another small study in BMC Medicine got a lot of press in 2012 for showing that 33 people who gave up to a pint of blood had improved cholesterol ratios and blood pressure six weeks later compared with people who didn’t give blood, which the doctors also attributed to a reduction of iron levels. (Note that the amount of blood removed in the study was fairly low—a pint is about as much as you’d give when donating blood, which for the record is  a great thing for healthy people to do and is not the same thing as bloodletting.) 

When George Washington developed a swollen sore throat in 1799, doctors drained nearly half his blood and created blisters in his throat. Within a day, he died.
When George Washington developed a swollen sore throat in 1799, doctors drained nearly half his blood and created blisters in his throat. Within a day, he died.
Life of George Washington, Junius Brutus Stearns, 1851

But the design of that study doesn’t rule out a placebo effect—which has certainly contributed to bloodletting’s popularity in the past. What’s more, other studies suggest that too little iron is bad for cardiovascular health, so again, the potential benefit of removing blood is unclear.

Meanwhile, depleting the body’s blood supply can be risky. Not only is there the risk of losing too much blood, causing a dangerous drop in blood pressure and even cardiac arrest, but people who are already sick take their chances with infection or anemia. Not to mention that in most cases, bloodletting doesn’t cure what ails you.  

So no, we don’t need to revive the tradition of the neighborhood bloodletter. In a sense, though, their legacy is still around: Red-and-white barber poles represent blood, bandages, and the stick that patients would grip during barbers’ days as bloodletters.

How Bloodletting Bled Out

It took the great bloodletting wars of the 1800s to begin turning the tide against the practice. The prominent doctor Benjamin Rush (a signer of the Declaration of Independence) set off a fury when he began bleeding people dry during the 1793 yellow fever epidemic in Philadelphia. By all accounts, Rush was a bloodletting fanatic and in general a real piece of work: “unshakable in his convictions, as well as self-righteous, caustic, satirical, humorless, and polemical,” writes doctor Robert North in a biography.

Rush recommended that up to 80 percent of his patients’ blood be removed, and during the yellow fever outbreak, North recounts that “so much blood was spilled in the front yard that the site became malodorous and buzzed with flies.”

Bloodletting’s detractors grew in numbers after that, and eventually Pierre Louis, the founder of medical statistics, began convincing doctors to rely on statistical evidence over anecdotal “recoveries” of patients who had been bled. A particularly impressive analysis showed that bloodletting did not help pneumonia victims in Europe, and after bitter disputes among doctors in the 1850s, the practice began dying out.

In fact, one history of bloodletting refers to the stamping out of the practice—over the objections of the medical establishment, no less—as a triumph of reason and “one of the greatest stories of medical progress.”

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Scientists engineer suicide bomber bacteria to kill other bacteria

In a lab in Singapore, scientists are designing and breeding suicide bombers. If their efforts pan out, they will be applauded rather than jailed, for their targets are neither humans nor buildings. They’re bacteria.

Nazanin Saeidi and Choon Kit Wong have found a new way of killing Pseudomonas aeruginosa, an opportunistic species that thrives wherever humans are weak. It commonly infects hospital patients whose immune systems have taken a hit. It targets any tissue it can get a foothold on – lungs, bladders, guts – and it often causes fatal infections. To seek and destroy this threat, Saiedi and Wong have used the common lab bacterium Escherichia coli as a sacrificial pawn.


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Evidence that placebos could work even if you tell people they’re taking placebos


In many medical studies, even people who take “fake” treatments, such as sugar pills with no active ingredients, can still feel better. These are the puzzling “placebo effects”. They are common, diverse and powerful and they raise an interesting ethical question – can doctors justifiably prescribe placebos to their patients? The standard answer is no. Doing so patronises the patient, undermines their trust, and violates the principles of informed consent. It compromises the relationship between doctor and patient. At worst, it could do harm.

But many of these arguments are based on the idea that placebo effects depend on belief; people must expect that treatments will work in order to experience any benefits. For a doctor to prescribe a placebo, they’d need to deceive. But according to Ted Kaptchuk from Harvard Medical School, deception may not be necessary. In a clinical trial, he found that patients with irritable bowel syndrome (IBS) felt that their symptoms improved when they took placebo pills, even if they were told that the pills were inactive.

Fabrizio Benedetti, a placebo researcher at Turin Medical School who wasn’t involved in the study, says, “Although several studies suggested that placebos can be equally effective without deception, this is the first rigorous study that provides scientific evidence for this.”

Referring to an earlier study published in the British Medical Journal, he says, “We did the study because we knew that physicians were giving placebo to patients secretly without informed consent. Our study was designed to test whether placebo effects could be harnessed without this secret deception.”


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Gene therapy saves patient from lifetime of blood transfusions

Gene_therapyThe patient known as P2 is just 18 years old, but he has been receiving monthly blood transfusions since the age of 3. P2 has a genetic disorder called beta-thalassaemia. Thanks to a double whammy of faulty genes, he can’t produce working versions of haemoglobin, the protein that allows red blood cells to carry oxygen around the body. Regular transfusions were the only things that kept him alive but for the last 21 months, he hasn’t needed them.

An international team of scientists have managed to partially correct his genetic faults, granting him his independence. It’s a major victory for gene therapy, the act of editing faulty genes within living cells in order to treat diseases.


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Sniff-detector allows paralysed people to write messages, surf the net and drive a wheelchair

In Israel’s Loewenstein Rehabilitation Hospital, the patient known as LI1 is a prisoner of her own body. She is a 51-year-old woman who was paralysed by a stroke several months ago. Suffering from “locked-in syndrome”, she is completely aware but unable to move or speak. She cannot even control the blinks of her eyes. And yet LI1 has recently been able answer questions from her doctors and communicate with her family through written messages. All she has to do is sniff.

LI1 uses a ‘sniff controller’, an incredible new technology that allows paralysed patients to control machines with their noses. It’s the brainchild of Anton Plotkin and Lee Sela at the Weizmann Institute of Science. Whenever a patient sniffs, the device measures the change in pressure inside their noses. It converts these into electrical signals that are passed to a computer via a simple USB connection. With just a sniff, people can move a cursor on a screen, allowing locked-in patients to write messages. Quadriplegics can even use the device to surf the web, or drive a wheelchair.

This technology was developed almost by accident in the lab of Noam Sobel, who studies the way of brains process our sense of smell. The group use a device called an olfactometer, which produces waves of smell to see how sensitive a person’s senses are. For one of their experiments, the team rigged the olfactometer so that volunteers triggered the odour pulse themselves when they sniffed. “We noticed that sniffs are a very good and fast trigger,” says Sobel. “It then simply dawned on us that instead of triggering odor, we could trigger anything: letters in a text writer or turns of a wheelchair.  The rest just flowed (or rather, rushed) from there.” It’s a fantastic example of the useful and unpredictable roads that basic scientific research can lead to.


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Fighting bacteria with bacteria – common nose germ provides new weapon against superbugs


Our bodies are under siege, constantly fighting back assaults from disease-causing bacteria. But we are also home to many harmless bacterial species that are share our bodies to no ill effects. Now, it seems that these ‘commensals’ could be our hidden allies against their harmful cousins. In one such ally, a group of scientists has just discovered a potential new weapon against Staphylococcus aureus.


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First ever molecule that protects against ricin

Ricin_castor_beansIn 1978, Bulgarian dissident Georgi Markov was walking across Waterloo Bridge in London when he felt a sharp stinging pain in his leg. A passer-by had jabbed him with the tip of an umbrella and, having apologised, the two parted ways. Three days later, Markov was dead. The umbrella had fired a small poisoned pellet into his leg, turning Markov into the most famous victim of one of the world’s deadliest poisons – ricin.

Ricin is a great example to cite to people who think that “natural” equates to “healthy”. It’s a protein that comes from the castor bean, which is easy to grow, used in a wide variety of products, and delivers large amounts of its lethal chemical payload. One milligram can be lethal, and there is no known antidote. All of these qualities make it a potential bioterror weapon, and they have galvanised the quest for an antidote. That quest has just taken a big step forward, for Bahne Stechmann at the Curie Institute has discovered the first small molecule that protects mice against ricin.

Stechmann’s drug, known as Retro-2, not only saves mice from death by ricin, it also defends them against a related class of poisons called Shiga-like toxins. These are produced by disease-causing strains of the gut bacterium Escherichia coli and while less toxic than ricin, they can also be fatal. So Stechmann’s new discovery is a two-for-one defensive deal.

Both ricin and Shiga-like toxins have similar structures. One half of each protein – the A subunit – does the killing. It irreversibly breaks ribosomes, the factories that cells use to produce new proteins. A single ricin protein can knock out 1,500 of these factories every minute and without the ability to create new proteins, our cells perish. But a weapon is useless if it can’t be fired in the right place.

Getting the A subunit into range of the ribosomes is the job of the other half of the protein – the B subunit. It’s a backstage pass that sticks to docking molecules on the surface of our cells and allows the entire protein to be smuggled inside. Once there, it gets shuttled from one structure to another until it reaches the endoplasmic reticulum, where ribosomes live. If you block this chain of transport, you neutralise ricin and Shiga-like toxins; after all, the proteins cannot destroy what they cannot reach. And that’s exactly what Stechmann’s team has managed to do.


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Treating tinnitus with an individually tailored piece of music

Many of us have just spent the Christmas season with a persistent and irritating ringing noise in our ears. But now that the relatives have gone home for the year, it’s worth remembering that a large proportion of the population suffers from a more persistent ringing sensation – tinnitus. It happens in the absence of noise, it’s one of the most common symptoms of hearing disorders, and it’s loud enough to affect the quality of life of around 1-3% of the population. 

There have been many suggested treatments but none of them have become firmly established and most simply try to help people manage or cope with their symptom. Now, Hidehiko Okamoto from Westfalian Wilhelms University has developed a simple, cheap and enjoyable way of reducing the severity of the ringing sound. The treatment has showed some promise in early trials and even better, it is personally tailored to individual patients. 

The method is simple. Find out the main frequency of the ringing sound that the patient hears – this becomes the target. Ask the patient to select their favourite piece of music and digitally cut out the frequencies one octave on either side of this target. Get the patient to listen to this “notched” piece of music every day. Lather, rinse and repeat for a year.

Okamoto tried this technique in a small double-blind trial of 23 people, eight of whom were randomly selected to receive the right treatment. Another eight listened to a piece of music that had a random set of frequencies cut out of it, while seven were just monitored. The treatment seemed to work. After a year, the treatment group felt that their ringing sensation was around 30% quieter, while the other two groups showed no improvements.


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Retrocyclins: a defence against HIV, reawakened after 7 million years

Blogging on Peer-Reviewed ResearchHIV is an elusive adversary. The virus is so good at fooling the immune system that the quest for an HIV vaccine, or even a countermeasure to resist infections, has spanned two fruitless decades. But maybe a defence has been lurking in our genomes all this time.

Nitya Venkataraman from the University of Central Florida has managed to reawaken a guardian gene that has been lying dormant in our genomes for 7 million years. These genes, known as retrocyclins, protect monkeys from HIV-like viruses. The hope is that by rousing them from their slumber, they could do the same for us. The technique is several safety tests and clinical trials away from actual use, but it’s promising nonetheless.

Retrocyclins are the only circular proteins in our bodies, and are formed from a ring of 18 amino acids. They belong to a group of proteins called defensins that, as their name suggests, defend the body against bacteria, viruses, fungi and other foreign invaders. There are three types: alpha-, beta- and theta-defensins. The last group is the one that retrocyclins belong to. They were the last to be discovered, and have only been found in the white blood cells of macaques, baboons and orang-utans.

In previous experiments, Venkataraman’s group, led by Alexander Cole, showed that retrocyclins were remarkably good at protecting cells from HIV infections. They are molecular bouncers that stop the virus from infiltrating a host cell. The trouble is that in humans, the genes that produce retrocyclins don’t work. Over the course of human evolution, these genes developed a mutation that forces the protein-producing machinery of our cells to stop early. The result is an abridged and useless retrocyclin.

But aside from this lone crippling mutation, the genes are intact and 90% identical to the monkey versions. Now, Venkataraman has awakened them. She found two ways to fix the fault in human white blood cells, one involving gene transfer and the other using a simple antibiotic. Either way, she restored the cells’ ability to manufacture the protective proteins. And the resurrected retrocyclins did their job well – they stopped HIV from infecting a variety of human immune cells.


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Drugs and stimulating environments reverse memory loss in brain-damaged mice


You swallow the pill. As it works its way through your digestive system, it slowly releases its chemical payload, which travels through your bloodstream to your brain. A biochemical chain reaction begins. Old disused nerve cells spring into action and form new connections with each other. And amazingly, lost memories start to flood back.

Dementia results in massive neuron loss, but that doesn't mean memories are destroyed.The idea of a pill for memory loss sounds like pure science-fiction. But scientists from the Massachussetts Institute for Technology have taken a first important step to making it a reality, at least for mice.

Andre Fischer and colleagues managed to restore lost memories of brain-damaged mice by using a group of drugs called HDAC inhibitors, or by simply putting them in interesting surroundings.

They used a special breed of mouse, engineered to duplicate the symptoms of brain diseases that afflict humans, such as Alzheimer’s. The mice go about their lives normally, but if they are given the drug doxycycline, their brains begin to atrophy. The drug switches on a gene called p25 implicated in various neurodegenerative diseases, which triggers a massive loss of nerve cells. The affected become unable to learn simple tasks and lose long-term memories of tasks they had been trained in some weeks earlier.

Fischer moved some of the brain-damaged mice from their usual Spartan cages, to more interesting accommodation. Their new cages were small adventure playgrounds, replete with climbing frames, tunnels and running wheels, together with plentiful food and water. In their new stimulating environments, the mice returned to their normal selves. Their ability to learn improved considerably, and amazingly, seemingly lost memories were resurrected.


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Sneaking medicines past the brain’s defences


Blogging on Peer-Reviewed ResearchUsing genetic engineering, a group of scientists have developed a way of sneaking a virus past the brain’s defences. Don’t panic – this isn’t some nightmare scenario. It could be the first step to curing a huge number of brain diseases.

The blood brain barrier controls the import of molecules into the brain with the tight security of airport immigration.The brain seems incredibly well protected amid its shell of bone and cushioning fluid. But even the strongest of forts needs supply lines, and brain is no exception.

A dense network of blood vessels carries vital oxygen to its cells. These vessels are a potential vulnerable spot, providing access for bacteria and other disease-causing organisms to migrate in from other body parts.

But even these weak spots are heavily guarded. The blood vessels in the brain are lined with a tightly packed layer of cells that restrict the flow of molecules from blood to brain. These cells form a protective shield called the blood-brain barrier, or BBB.

It is a superb defence but it can do its job too well. Not only does it block out dangerous microbes, but it can also exclude large proteins and drugs designed to treat brain diseases. Usually, these large molecules need to be distributed throughout the entire brain to be effective. With the BBB in the way, they don’t stand a chance. Now, Brian Spencer and Inder Verma from the Salk Institute of Biological Studies have come up with a way to disguise helpful molecules to sneak them past the brain’s defences


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Drugs that work against each other could fight resistant bacteria

Blogging on Peer-Reviewed ResearchWhen normal bacteria are exposed to a drug, those that become resistant gain a huge and obvious advantage. Bacteria are notoriously quick to seize upon such evolutionary advantages and resistant strains rapidly outgrow the normal ones. Drug-resistant bacteria pose an enormous potential threat to public health and their numbers are increasing. MRSA for example, has become a bit of a media darling in Britain’s scare-mongering tabloids. More worryingly, researchers have recently discovered a strain of tuberculosis resistant to all the drugs used to treat the disease.

New antibiotics are difficult to develop and bacteria are quick to evolve, so there is a very real danger of losing the medical arms race against these ‘super-bugs’. Even combinations of drugs won’t do the trick, as resistant strains would still flourish at the expense of non-resistant ones. Antibiotic combos could even speed up the rise of super-bugs by providing a larger incentive for evolving resistance.

Clearly, fighting the rapidly evolving nature of bacteria is a dead end. So Remy Chait, Allison Craney and Roy Kishoni from Harvard Medical School used a different strategy – they changed the battle-ground so that non-resistant bacteria have the advantage. And they have done so using the seemingly daft strategy of using combinations of drugs that work poorly together, and even those that block each other’s effects.


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Lymph node injections provide safer, faster and easier relief against hay fever

Blogging on Peer-Reviewed ResearchIf you’re anything like me, then you will find that the onset of spring is a time of great rejoicing and equally great woe. The longer days, rising temperatures and greening world also signal the arrival of pollen, microscopic granules of hell determined to make you breathe fresh air only in the short spaces between sneezes, and enjoy the increasingly beautiful world through watery eyes.

But help is at hand. Allergens in the air can cause misery for about a third of people in Western countries, but a new clinical trial suggests that injecting allergens directly into someone’s lymph nodes can offer them long-lasting protection from hay fever symptoms, with few side effects.

Currently, hay fever sufferers can get only get long-term relief through ‘allergen immunotherapy‘, where they are injected with increasingly large doses of the allergen they are sensitive to. The treatment works but it is inconvenient and gruelling. Possible side effects include anaphylaxis, where patients experience massively disproportionate reactions and require the attentions of emergency  personnel. It also requires up to 70 visits to the doctor over three to five years. Small wonder then, that patients tend to drop out of therapy, preferring instead to treat symptoms as they turn up, using sprays and pills.

Now, Gabriela Senti and colleagues from University Hospital Zurich have solved many of these problems by changing the site of injection from the skin to the lymph nodes – part of the immune system where immune cells gather and foreign particles are trapped.



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Magnifection – mass-producing drugs in record time


Blogging on Peer-Reviewed Research
Imagine reading the paper to find that a new wonder drug has been created that could save your life, if only you could afford it. Alternatively, put yourself in the shoes of the authorities that must decide not to offer powerful new drugs on the NHS because they simply aren’t cost-effective enough. These situations are all too common-place and are often due to the extremely high costs of drug development. But a couple of years ago, scientists at Icon Genetics and Bayer Bioscience made an exciting step toward lowering these costs for some of the most promising new treatments.

Pills.jpgThe treatments in question are called ‘monoclonal antibodies’ or ‘MAbs’, synthetic versions of the natural antibodies that our immune systems use to identify and neutralise infectious agents. MAbs are specially shaped to act like molecular gloves, sticking onto a target of choice and inactivating it by blocking interactions with other molecules.

The most famous member of this group, the breast cancer drug Herceptin, is one of a handful of currently available MAbs. But they are about to be joined by many more – over 150 MAbs are in development and the market for them is likely to exceed £10 billion.

But no matter how good these new biotechnological wunderkinds are, they will be worthless unless they reach the patients they are designed to benefit. And with the cost of treatment courses exceeding tens of thousands of pounds, that is looking unlikely. Every stage of the manufacturing process from raw materials to equipment is exorbitantly expensive and drives the inflated prices of the end product. As such, only better, cheaper and more effective production methods will enable scientists to fully realise the potential of these designer molecules. A new technique called ‘magnifection’ could be just such a method.


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Drug improves endurance without need for exercise

Blogging on Peer-Reviewed ResearchFor the first time, scientists have developed drugs that mimics the effects of endurance exercise. With the aid of two chemicals, Vihang Narkar, Ronald Evans and colleagues from the Salk Institute managed to turn regular lab rodents into furry Paula Radcliffes – mighty mice that were capable of running further and for longer than their peers. One of the drugs only worked in combination with exercise, but the other managed to boost stamina without it.

Using drugs to boost performance isn’t a new development. Steroids can help body-builders to build their bodies, while giving athletes an extra burst of speed. But this is the first time that scientists have managed to develop chemicals that improve stamina, as opposed to strength or speed. One of these drugs only worked when taken in conjunction with exercise, but the other boosted endurance in inactive, couch-potato mice too.

The changes lay in their muscles. The body’s skeletal muscles (the ones attached to bones) are made of two major types of fibre – the “fast-twitch” kind that burn sugar, and “slow-twitch” ones that prefer to burn fat. The bulkier fast-twitch varieties contract more quickly and powerfully, and provide short bursts of speed and strength; they are plentiful in the bodies of sprinters and body-builders. The slow-twitch versions are more resistant to fatigue and can carry on working for hours rather than minutes; they are the province of marathon runners and mountain climbers.

Endurance training triggers a suite of genetic changes that converts the fast-twitch fibres into the slow-twitch ones, imbuing the muscle with greater staying power. Narkar’s two chemicals emulate the effects of exercise by tapping into the same genetic pathways for reprogramming muscle.