The Placebo Effect: A treatment of the mind?

When a patient known as Mr. Wright was diagnosed with terminal lymphoma (cancer of the lymphatic system), the doctors battling to prolong his life were ultimately left with no option but to try a new ‘controversial’ anti-cancer drug – Krebiozen. Although doctors and scientists remained unconvinced about the drugs effectiveness, Mr Wright was confident that it would lead to an improvement of his condition. Despite being bed-bound and in extremely poor health, just three days after his first treatment he had enough energy to get out of bed. After ten days his tumours had shrunk significantly in size, and he was well enough to go home.

So what was this mysterious drug, and what caused the remission of his symptoms?

Krebiozen was marketed and endorsed in the 1950s by several physicians who claimed the drug possessed anti-cancer properties. One study claimed that of 22 patients with diagnosed terminal cancer, 14 remained alive after treatment. However, other scientists failed to reproduce these results and ultimately decided that the drug was of no benefit to cancer sufferers. The National Institute of Cancer verified this decision after finding that the drug consisted of nothing more than simple amino acids and mineral oil, with no active ingredients.

This drug was actually a placebo! Placebo treatments are usually given to patients in the form of sugar pills, but can also include injections and sham surgery. The key to the placebo’s success is ensuring the patient believes the treatment will improve their condition. Belief in the treatment can lead to a perceived or actual improvement of the condition.

The so-called ‘placebo effect’ appears, at first glance, to make no sense whatsoever. How could a simple sugar pill alleviate serious medical symptoms? The answer may be as simple as a positive mental attitude.  A patient’s mental well-being and perception of of their illness may be an important factor in influencing their medical prognosis. This is a remarkable concept, but how is it biologically possible? One suggestion is that the notion of medical intervention creates a mental cue which acts to kick-start an immune response within our bodies leading to self-healing. A similar response to seemingly unrelated external cues has in fact also been observed in Siberian Hamsters. When exposed to light levels which mimic winter days, hamsters show a depression of their immune response. If, however, they are exposed to lights mimicking summer days, the immune response increases and healing begins.

I was first inspired to write this article by a programme I watched a few weeks ago on Channel 4 titled Derren Brown: Fear and Faith. This show demonstrated the power of the placebo effect through a fake clinical trial. Subjects on this trial were given a placebo drug (Rumyodin) and were told that it could inhibit feelings of fear. Over the course of few weeks, we saw each of the subjects overcome their respective fears ranging from heights and confrontation to singing in public. The drug was also effective as a cure for smoking and allergies. The strength of the placebo was enhanced by the very convincing story behind the drug’s development, including a fictitious pharmaceutical company and the use of doctors to administer the drug. The placebo’s extremely powerful effects were probably due to this attention to detail, meaning subjects were convinced that the treatment would work.

So if placebos can offer such amazing results without the need for any active ingredient and all the side effects these may bring, why are they not used more regularly?

The ability of a placebo to alleviate symptoms is variable both in how often they succeed and the strength of the resulting symptom alleviation. Placebos appear to be more effective when symptoms are subjective such as pain or nausea and less effective for non-subjective symptoms such as abnormal blood pressure or heart rate.

A recent study in the US has suggested that genes may also play an important role in deciding whether or not an individual responds to a placebo. Preliminary results indicate that if a particular gene is present, individuals with irritable bowel syndrome are more likely to respond to placebo acupuncture. Whether this effect may be replicated for other conditions is unclear. However, these results do offer an explanation as to why some people are more susceptible to the placebo effect than others.

A study from 1985 hypothesised that the placebo effect relies heavily upon a belief that the medicine will make you feel better. Indeed, one study showed that the attitude of the prescribing doctor towards both the drug and the patient significantly altered the patients prognosis. In this study patient’s responses to a placebo rose from 44% to 62% when the doctor prescribing the treatment made a conscious effort to be positive.

This means that scientists are faced with a paradox when it comes to the use of placebos. Although there are clear ethical issues arising from their use, such as the controversy of introducing dishonesty into the patient-doctor relationship, ethical issues also arise from NOT using placebos. Is it unethical not to use something that could help improve a patient’s health? Despite this, the UK Parliamentary Committee for Science and Technology think that the placebo effect is unreliable and should not be used as a sole treatment on the NHS. In contrast, a study of GPs in Denmark has shown that 48% had previously prescribed placebo as treatments at least 10 times over the last year. Moreover, a study in 2004 uncovered that approximately 60% of physicians in Israel has used placebos in their practice.

What is important to remember, is that placebos are not a ‘one-size-fits-all’ cure that works for everyone. The effect that placebos have can be highly variable and often unreliable. Whilst some people respond positively to treatment with placebos, others experience no change to their condition. This positive effect appears to depend not only on the type of ailment the patient is suffering with, but also their mental attitude towards the treatment. However, what is clear is that a lot more research needs to be carried out to investigate exactly how and why placebos work, and why their success is so variable.

Post by: Sam Lawrence

The science of brain freeze

Everyone loves summer with its long days, blazing sun and ice-cold drinks – all too often accompanied with the head-splitting pains associated with so-called ‘brain freeze’. The culprits range from ice-creams and milkshakes to chilled drinks, all having the same effect of leaving you feeling like you’ve been poked in the brain by a large sharp object. Suffering from brain freeze is not uncommon so you’re not alone. In fact approximately 40-80% of the population experience brain-freeze at some point in their life.

The scientific name for this is Sphenopalatine ganglioneuralgia which literally means nerve pain of the sphenopalatine ganglion, the nerve found at the roof of your mouth.

Brain freeze is characterised by sharp stabbing pains in the head, particularly across the forehead and temples, associated with the quick consumption of cold food or drinks. Although the sensation can be extremely painful, the pain normally fades quickly. So what causes this mysterious and painful phenomenon?

Although it is certainly not caused by our brains actually freezing, some scientists have suggested that the pain may indeed be linked to a decrease in brain temperature. One particular study from Japan found that during bouts of brain freeze, brought about by consuming a large volume of ice, the temperature of patients heads (taken from the ear) actually dropped in accordance with the cold stimuli, suggesting that brain temperature also decreased.

So what aspect of brain ‘cooling’ causes the pain associated with brain freeze? A pioneering study carried out by Jorge Serrador at Harvard Medical School may have found the answer. The study monitored blood flow to the brain in 13 volunteers as they sipped ice cold water (directed, with a straw, at the roof of their mouths). When brain freeze was induced volunteers were asked to raise their hands as a signal, then raising them again once the pain subsided.

It was found that one of the brains major suppliers of oxygenated blood, the anterior cerebral artery, dilated (increased in size) whilst drinking the iced water. This lead to an increase in blood flow to the brain and was regularly followed by pain. Interestingly, as the cerebral artery shrunk back to its original size, restoring regular blood flow, the symptoms associated with brain freeze subsided. Serrador concluded that the increase in blood flow and therefore size of the cerebral artery was responsible for the pain associated with brain freeze. Specifically, he speculated that the pain may be brought about by an increase in cranial pressure caused by the increased blood flow.

The brain is one of our most delicate and sensitive organs; extremely sensitive to changes in temperature. It is possible that brain-freeze may be a defence mechanism, protecting our brains from large fluctuations in temperature. If the ganglion, in the roof of the mouth, detects extreme cold it causes an increase in blood flow to the brain, which is important to keep it warm. As more blood flows into the brain, the pressure inside the skull increases causing pain. The blood vessel then constricts again to reduce the pressure.

It’s also interesting to note that migraine sufferers are actually more likely to experience brain-freeze than those who don’t suffer from migraines. Indicating that the two may share a common mechanism.

So, that’s a quick run-through of the science behind what is actually happening to your body during brain freeze. So next time you’re in the pub and someone tells you they have brain freeze, you can astound them with your knowledge of the science behind it!

Post by: Sam Lawrence

Parasitic worms: Friend or foe?

Intestinal parasites infect more than a billion people world-wide, of which approximately 10% become ill. Although the thought of parasitic worms may be enough to turn people’s stomachs and put them off their food, for some sufferers of severe auto-immune diseases these worms may actually be able to provide relief or even remission of symptoms. We understand the negative effects worms can have such as nausea, vomiting and weight loss. However, research is now highlighting circumstances where their presence may indeed be beneficial in relieving symptoms of a number of diseases.

Helminthic therapy is a type of treatment where patients suffering from immune diseases are deliberately infected with parasitic intestinal worms in the hope that this will relieve their symptoms. Although this therapy is relatively new, there are a handful of promising studies indicating that worms may indeed represent a viable treatment for these diseases.

One of these studies was carried out by P’ng Loke, a parasitic immunologist. Loke’s work centred on the study of a man he met in 2007 who he later found had deliberately infected himself with parasitic worms. At first glance the man appeared to be perfectly healthy with nothing more than a genuine interest in parasites. However, it was soon revealed that, in an attempt to cure his inflammatory bowel disease (ulcerative colitis), he had infected himself with human roundworm which burrowed into the lining of his colon. Ulcerative colitis is an auto-immune disease characterized by open sores in the colon lining leading to intense abdominal pain and vomiting. Although the precise cause of this disorder is not well understood, severe cases have been linked to disruptions in mucus production within the colon. After coming across the controversial work of the parasitologist Joel Weinbeck, the man ingested a large quantity of the worm and was soon symptom free.

Endoscopic image of a bowel section known as the sigmoid colon afflicted with ulcerative colitis. The internal surface of the colon is blotchy and broken in places.

Colonoscopies of his intestines following infection revealed that wherever the worms formed colonies, there was a concurrent decrease in the number of ulcers. This decrease in ulceration is believed to be a beneficial side effect of the body’s immune response against these worms. Upon infection the body’s immune system increases production of both inter-leukin IL-22 (a protein important for healing the colon lining) and a number of mucus-producing cells found throughout the colon. This increase in intestinal mucus forms a protective barrier across the surface of the gut, protecting it from bacteria and thereby reducing inflammation.

Along with a possible role in the treatment of colitis in humans, studies in animals have found that infection with worms can either alleviate symptoms or entirely protect against diseases such as asthma, rheumatoid arthritis and some food allergies. A role in Crohn’s disease (a long term condition causing inflammation of the lining of the digestive system) has also been suggested. Results from a clinical trial show that ingestion of swine whipworm causes remission of symptoms in 72% of cases, and improvement but not remission of symptoms in a further 7%.

What is interesting is that the prevalence of auto-immune diseases in the developed world is high, but the incidence of parasitic worms is relatively low. In contrast, in the lesser-developed world where the incidence of worms is high, the occurrence of auto-immune diseases is sparse. Could it be that in our quest for sanitation and clean water, we may have damaged one of our friends, one of our bodies natural source of defence against itself; the intestinal parasite?

Although some cases show evidence that parasite infection may play a role in protecting against certain disorders, it is still impossible to predict how any one individual will respond to such an infection. Indeed, it may be the case that in some patients the worms may cause more harm than good. Therefore continued research into safe and effective forms of helminthic therapy is required before we can truly distinguish these parasites as friend or foe!

Post by: Sam Lawrence

The race between science and new doping techniques

With the Olympics being held in London later this year, and the controversial abolishment of lifetime banning for athletes caught using illegal performance enhancing drugs, there has never been a better time to try and cheat your way to the top. The desire to be the best in your field is what drives professional athletes to be at the top of their game. When this desire gets too much, it can push athletes to use illegal drugs and other performance-enhancing methods.

With rapid progress in the field of sports science, the ways by which athletes enhance their performance are evolving rapidly. New methods are emerging that threaten to undermine the efforts of those who try to win honestly.

Recent research has shown that drinking large amounts of green or white tea is enough to mask the illegal use of testosterone in deceptive athletes. The use of testosterone by athletes is currently illegal since it is known to increases muscle mass. Unfortunately it is extremely hard to detect athletes who are using testosterone since the hormone occurs naturally in both men and women. However, some tests are capable of detecting increased levels of testosterone. These rely on looking at the ratio between testosterone and another hormone found in urine, epitestosterone.  A study at Kingston University London has found that tea contains unusually high levels of anti-oxidants called catechins. These inhibit an enzyme required for testosterone to be excreted in urine, meaning that athletes drinking large volumes of tea will secrete less testosterone, so can evade detection by current doping tests. Therefore green tea can effectively help ‘fool’ scientists into thinking that an athlete is clean. Who knew the quintessentially British ‘cup of tea’ could benefit dishonest athletes, pulling the wool over the world’s eyes!

Another potential ‘game-changer’ facing the World Anti-Doping Agency (WADA) is the concept of using doping genes to improve an athlete’s performance. Research at the International Centre of Genetic Engineering and Bio-technology in Italy has found that injecting certain growth genes into mice causes  them to develop significantly more muscle mass than non-treated animals. A virus, acting as a carrier, is used to implant the gene for Insulin-Like Growth Factor 1 (IGF-1) into muscle cells in the mice. Mice injected with the gene are able to swim for three times as long as normal animals. Along with increased endurance, the IGF-1 gene also triggers production of 10 times more protein than is seen in normal muscles and an increase in genes controlling energy production, muscle contraction and respiration – all vital for a ‘super-human’ sportsman (or woman)!

When testing for indications of this in blood and urine samples from treated mice, there was no trace of any of the implanted gene, protein or virus. This may make it possible for doping cheats to get around the laws! Biopsies of athletes’ muscles would show up differences between the structure of the muscles of a trained athlete and a cheat, however, there are ethical concerns over subjecting athletes to such tests.

At a recent conference held in London, aptly called Tackling Doping in Sport, it emerged that new blood and urine tests were currently under development that could potentially expose ‘DNA doping’. If all else fails, authorities could expose cheats using this method of performance enhancement by creating a biological passport for each professional athlete. This file would regularly record the profiles of an athlete and would indicate when a dramatic change in their fitness is observed.

The idea of a biological passport is considered by some to be controversial. This could mean that honest athletes, who train and compete well within the laws of their sport, may end up being severely penalised because of corrupt athletes who want to cheat their way to the top. It is easy to argue that athletes join the profession knowing they are required to provide fluid samples if requested. However, muscle biopsies and biological passports may be considered a step too far!

Although regulating bodies have identified gene doping as an imminent threat to the sporting community, no athlete has yet been caught using this method.   Due to the growing potential of gene doping, WADA is taking a proactive stance to ensure that athletes attempting to use this method will be identified, and that structures will be in place to test for such cases.

The world of sport is being flooded with novel ways in which athletes can illegally improve their performance. This field is evolving from one where hormones in the body are elevated to improve performance, to a field where athletes could potentially use viruses to interfere with their DNA. The exact nature of how athletes will try to dodge drug tests in the future is not clear, although we can be certain that some will try their hardest! It will be interesting to observe the evolution of ways to test for illegal drugs in sport, to reflect novel performance enhancement ideas. Whatever happened to putting in the hard work yourself, and reaping the benefits?

Post by: Samantha Lawrence

Does embryo gender selection have a place in society?

Imagine a world where we are able to manufacture our own ‘designer baby’, where we could choose its eye colour, hair colour or even its build with just a single visit to the hospital. Where would it end? Would we ever be able to achieve perceived perfection in our children?

This may seem like some futuristic sci-fi fantasy, but in-fact it may not be as far off as you think. With rapidly advancing technology it is now possible to select the gender of your baby, like walking into a shop and choosing a book, so who knows what decisions you will be able to make about your child’s appearance and character in the near future. With a growing number of couples opting for so-called gender selection procedures abroad, is it possible that scientists have gone too far? At any rate, this  issue causes a lot of concern and raises the question as to whether gender selection has a place in our society.

So what is gender selection and how does it work?: This is a laboratory procedure which allows parents to choose the sex of their unborn child. Such gender selection can be achieved through a number of pre-implantation methods. The most common of which is known as In Vitro (outside the body) Fertilisation or IVF. In IVF, egg cells are removed from the mother and fertilised in a laboratory using sperm from the intended father. The fertilised eggs are then allowed to develop to a point where they can be separated on the basis of sex, embryos of the desired sex can then be re-implanted into the mother. A post-implantation blood test can also be used to confirm the sex of the baby. However this is often, unlawfully, followed by abortion if the sex is unwanted.

So where does society stand on this issue?: Currently, the UK law on gender selection (The Human Fertilisation and Embryology Act (1990, amended 2008)) prohibits selection of embryos on the basis of sex, except in cases of sex-linked genetic disorders. However, in contrast to Britain, countries such as the US and Russia openly practice gender selection for non-medical reasons; this is often rationalised as ‘family balancing’. The pro’s and cons of legalising this procedure are hotly debated, with extreme views held world-wide, this strong polarity in opinion makes the legalisation process extremely controversial.

Perhaps it would be apt at this point to consider the advantages and disadvantages of this type of selection:

One of the most prominent arguments for the legalisation of gender selection hinges on cases where there is a risk of diseases that may be passed onto the foetus. Many agree that when there is a risk of sex-linked diseases such as thalassemia (a blood disorder producing anaemia) and haemophilia (a disorder where blood clotting is impaired) being passed onto a child, it is morally justified to allow gender selection. This argument asserts that gender selection has a place in avoiding genetic conditions and preserving the health of future generations, a point of view that I empathise with. I believe that there is a need for gender selection to select away from life-long illnesses which would impact, not only on the individual, but also on the people that surround them. With rapidly advancing technology and sustained funding for research into such procedures, do we have a moral obligation to use this technology for the ‘greater good’?
It is also argued that, as individuals, we should be allowed the freedom to express our reproductive rights. Since each of us is free to take whatever path we choose when it comes to our own bodies, similar to the right to abort an unwanted child, we should also have the right to decide something as influential as the gender of our baby. However, I think we need to address the issue of whether it is moral to make such important decisions regarding someone’s life on their behalf, and without their consent.

Currently, doctors report an increase in the number of parents opting for abortion after discovering the sex of their baby. This drive to produce a baby of a certain sex can lead to a cycle which may continue until the desired sex is achieved. Some believe that legalising gender selection may help to put an end to the abortion of unwanted babies based purely on their sex. This is particularly relevant in countries such as China where there is huge pressure on parents to produce males to carry on the family name and to look after them when they retire. Here, gender selection is reinforced by the ‘One child’ policy that currently stands, meaning parents who have more than one child can be heavily fined. If gender selection was legalised in countries such as this, then there would be a massive reduction in the number of illegal abortions.

In contrast to this, supporting gender selection could have disastrous consequences demographically. A survey of 1500 couples in Hungary found that, of those who would consider using gender selection if it were made legal, 87% would want their first child to be male. In this case we would be left with a heavily male-dominated population. Such a population imbalance would undoubtedly lead to problems both with reproduction and the general structure of that society.

Many believe that one of the joys of parenthood is the unknown, the beauty of nature, the sheer surprise when you go for your first ultrasound. This opinion upholds that ‘tampering’ with an unborn child is something that should remain outside our control, and should be left to the hands of nature. If it is possible to choose the sex of our baby before it is even born, at what point would we stop trying to control every detail of our offspring, and actually get on with loving what we have been given?

Although it is apparent that making gender selection common practice in the UK should not be taken lightly, it is obvious that there is no clear-cut right or wrong. There are reasons for and against the UK following the US’ lead, and accepting gender selection into our future. In my view there are clearly positive connotations in legalising this procedure when selecting against genetic conditions that would otherwise have a negative impact on quality of life. I believe in cases such as these, society does not have the right to force anyone into having a child with a serious, perhaps even fatal, illness when the technology exists to prevent it. On the other hand, wide-spread legalisation is something I do not whole-heartedly agree with. I believe full legalisation of gender selection may be a step too far since such legislation may quickly lead to a heavily gender biased society whilst also opening the possibility of other types of genetic selection. However, the argument against gender selection centres heavily on leaving things as nature intended, but if this was the case then there would be no need for doctors and medicines, as we would be left to run our natural course without intervention. In conclusion, considerations need to be made based on whether it is morally acceptable to interfere with the course of nature, for medical or non-medical grounds.

With growing scope for genetic intervention the resulting moral maze will undoubtedly remain a topic of debate and conjecture across all walks of society (the above video shows one example of this discussion coming under scrutiny in the music industry).

Post by: Sam Lawrence