This week, a couple of new studies (which can be found here and here) showed that we can track changes in a tumour through blood samples alone. To understand the importance of this it is worth knowing that chemotherapy is going through a radical change at the moment.
The last few years have seen the introduction of a new generation of cancer drugs. These are targeted therapies, ones that are targeted not only towards a specific cancer but also towards specific sub-types of that cancer, based on the mutations that they have in their DNA. Not only are these chemotherapies more effective, but they should also cause fewer side effects than ones used in the past. Several of these targeted therapies have proven to give remarkable responses, with tumours melting away better than we could have dreamed.However, as patients have taken these drugs, an unfortunate pattern has emerged: the patients show amazing responses for a few months, but pretty quickly resistance emerges and the tumours regrow, now insensitive to the therapy.In fact, the very specificity of these drugs is actually their Achilles heel. Because they are designed to target a specific mutation in a specific gene, if certain other mutations occur in the same gene, they can result in resistance to the therapy (for an example of this, see below).It is in this background that the studies mentioned above could prove very important. These studies showed that simply by looking at the blood of patients, the scientists could track what mutations were happening in the tumour. This is because cancers shed lots of DNA into the blood stream, and the researchers could detect and analyse this. They showed that they could track the tumour as it developed, looking at what new mutations were arising. In effect, they could predict resistance to a drug before it became apparent in the patient. Not only that, but they could see how the resistance was happening and suggest alternative therapies that may be effective.This is all very good news. Previously, the only way of doing this was to take a biopsy of the tumour itself, a very invasive procedure that carries its own risks, and one that cannot be carried out regularly. With this new method, we will hopefully be able to monitor the tumour much more closely (patients shouldn’t object to giving blood every couple of weeks), and be proactive in treatment, rather than reactive.This method is still too expensive to be made commonly available, but the cost is rapidly decreasing, and it should be accessible in the near future. Additionally, with the move in cancer treatment towards targeted therapy, this will hopefully majorly increase the effectiveness of our new generation of therapies. Example of resistance to a targeted therapyA drug designed for some lung cancers was targeted towards a specific mutation in a pro-growth protein called EGFR. In these cancers, EGFR was stuck in the “on” position as a result of the mutation, which meant it was driving uncontrolled growth. The drug was specifically developed to turn this protein off again, which resulted in it hitting the cancer, and largely leaving other cells unaffected. This therapy worked beautifully in patients for 10 – 14 months, but resistance appeared after that and we were back to square one in our options for treatment. When they looked at the new, resistant tumour, scientists found that the resistant cells had picked up additional mutations in EGFR, activating it in a different way. As a result, the cells were resistant to our targeted therapy.
The reproducibility problem
The scientific process is an amazing thing. Between the Palaeolithic era (the era between 2 million and 20,000 years ago) and the year 1900, the average life expectancy at birth hardly increased at all, remaining around 30 years. Since then, as a result of the application of the scientific process to health care, it has more than doubled, with the worldwide average now being 71 years. Consider that. In just 100 years we have given ourselves more life that we managed in the previous 2 million years! Through science (the process of making observations, developing a hypothesis, testing that hypothesis and then refining and building on it) we have transformed our lives.Science is based on the fact that observations are consistent. If, for example, a surgeon washes his hands before operating, his patients will consistently get fewer infections. Without this consistency, this ability to repeat an experiment and get similar results, the whole scientific endeavour stops. This is why a recent publication in the journal PLOS Biology is so worrying.The article suggests that 50% of life sciences research cannot be reproduced and is therefore useless. Furthermore, the authors estimate that $28 billion is wasted in the US every year on studies that are never repeated. It must be pointed out that the way the authors defined “reproducible” was extremely broad, and as a result, there is a large margin of error in their estimate. However, the study does shine an uncomfortable light on the current state of science. It has been acknowledged that there is a “reproducibility problem” in the life sciences at the moment. A previous study by scientists at Bayer Healthcare stated that their own staff could only reproduce 24 of 67 studies published in peer-reviewed journals.
These reports suggests that most of the irreproducibility is as a result of poor study design, biological reagents that are not publically available, badly described protocols, and poor interpretation of results. Poor study design is mostly due to (inexcusable) bad lab practice, whereas the problems with reagents and protocols largely result from an extremely restrictive word count applied to the material and methods section of most journals. This word count means that the way experiments are carried out isn’t adequately described, and as a consequence others can’t repeat it. Finally poor interpretation of results is down to a lack of understanding of statistics and a selection bias that exists in science. This selection bias means that positive results are far more likely to be published than negative ones. In the extremely competitive scientific environment, this unfortunately forces authors toward sensationalising their findings in order to get them published, often to the detriment of the study itself.Theoretically, the process of peer review (wherein papers are critically analysed by their peers before publication) should ensure good quality science. This process however does not tackle the problem of the editorial policy, which does not reward studies whose results are unspectacular but reliable. Such studies are essential for scientific progress. For example, a paper was published in the journal Nature in 2013 demonstrating a method of generating stem cells. However, the same journal refused to publish a study the following year that showed that this method was entirely false.At present, a scientist is measured by the standard of his/her publications. To be awarded a grant you have to show that you can publish in a high impact journal. As a result, there is little incentive in science to reproduce other’s work, even if it is just part of a study. Furthermore, if a study does fail to reproduce another, it is usually filed away in a drawer and is not published. Unfortunately, the quality and reproducibility of someone’s work is not included when they are being judged as a scientist.A lot of money is spent every year in life sciences research. In the US, the budget is around £35 billion ($56 billion). Numbers are harder to come by in the UK, but the total spend on science and engineering is roughly £5.8 billion. While in the grand scheme of spending, this is a small amount (pensions alone cost the UK £1.5 trillion per year) it is still vital that the money is spent efficiently. The public, either through charity or governmental means, largely funds the life sciences. If there is a public perception that the results cannot be trusted, science risks losing the confidence of the public, and potentially the funding that is so essential for this work. The advances in public health that we have made in the last centaury prove how important this research is and how important it is that we remedy this reproducibility problem.
The cost of a cancer breakthrough
A new combination of drugs marketed by Bristol-Meyer Squibb has been hailed as a breakthrough in cancer treatment. Almost every media outlet carried a story about the results of a trial that were announced at a conference in Chicago yesterday, with the usual hype. The results are quite remarkable. 58% of metastatic melanoma patients treated with this new drug combination saw their tumours shrink, with the tumours stable or shrinking for a median of 11.5 months. This is amazing when you consider that metastatic melanoma was thought to be largely incurable as recently as 5 years ago. The drugs are each a form of immunotherapy. This refers to a therapy that works by making the patient’s own immune system attack the tumour. In this case, the combination targets two separate mechanisms tumours use to avoid the immune system. Firstly, one drug (Ipilimumab) targets CTLA-4, which is made by the tumour to suppress the immune system. The second drug (nivolumab) targets a protein called PD-1, which prevents the immune system from killing the tumour cells, even if it does recognise them as bad.This is quite a significant breakthrough in the treatment of melanoma but it does come at a cost however. The treatment has significant side effects, with over 80% of patients experiencing these. Furthermore, 55% experienced severe side effects, and 36% of patients had to stop treatment as a result.There is also the issue of cost, a problem I have discussed in a previous blog. Ipilimumab has already been approved by NICE at a cost of at least £42,200 per QALY. Nivolumab hasn’t yet been appraised by NICE, so it’s cost per QALY isn’t available, but in the US it is slightly more expensive than Ipilmumab, costing roughly $150,000 dollars per patient per year. As a combination, it is estimated that it will cost patients in the US $295,000 per year. This may well prove a stumbling block for an already creaking NHS. However, as both Merck and Roche have their own versions of these drugs, the hope is that the competition will force the manufacturers to drop their prices. Whether they will or not remains to be seen.Unfortunately, this breakthrough isn’t the cure that some articles say it is. Between cost and side-effects, there will be problems prescribing it to many patients. It is a welcome advance however, and does herald the development of immunotherapy as another arm in our treatment of cancer.Edit (03/06/05): The $295,000 figure comes from adding the list price of the two drugs. Some outlets are reporting that a discount may be applied to that, making the drug considerably cheaper, potentially bringing it closer to $200,000 per patient per year. While this is a significant discount, $200,000 per patient per year is still a staggering cost. To put it in perspective, if every patient with late stage melanoma was given this drug, Bristol-Meyer Squibb would make over $2,000,000,000 per year from it. When you consider that this is from only the late stage patients, with only one type of cancer, you can see why some people have a problem with the pricing of this and other drugs.
Why are some drugs not provided on the NHS?
The decision not to provide a drug on the NHS can have a devastating impact on patients and their families, and often causes a negative public reaction. However, therapies are getting increasingly expensive (particularly cancer therapies) and NHS has a very limited budget. As a result, in spite of the impact on patients and public opinion, 36% of cancer drugs evaluated since the start of 2014 (see pie chart) have been rejected, usually on the basis of cost.Whether a drug is made available or not on the NHS is decided by the National Institute for Health and Care Excellence (NICE). This is an independent body that looks at the efficacy and cost-effectiveness of any new therapies, and makes recommendations based on their findings. In Scotland, there is a separate organisation (the Scottish Medicines Consortium) that makes the decision.The main metric that NICE uses to make these decisions is the Quality Adjusted Life Year (QALY). This takes into account the quantity AND quality of extra life given to the patient by a particular chemotherapy. So if a drug gives a patient an extra year of perfect health, it is given a QALY of 1.0. If the extra year is not in full health, it is given a value below 1 to account for this. For example, if a new treatment allows a patient to live for 2 additional years compared to the old treatment, but only with a quality of life weight of 0.6 (perhaps the patient is in severe pain as a result), then the treatment gives 2 * 0.6 = 1.2 QALYs to the patient.NICE has set guidelines on how much it can pay per QALY gained. That price is around £30,000, but can rise to £50,000 in some rare circumstances. Now compare that figure with the table below showing NICE recommendations on cancer drugs since the start of last year, and you can begin to see why it has had problems with some cancer therapies, with many drugs estimated to cost over the £30,000 threshold.
| Drug | Recommendation | Cost per QALY* | |
| Pixantrone | Optimised¶ | £22,000 | Link |
| Aflibercept1 | Not Recommended | £44,000 | Link |
| Pemetrexed | Not Recommended | £74,500 | Link |
| Afatinib | Recommended | £11,000 | Link |
| Bortezomib2 | Recommended | £17,800 – £39,600 | Link |
| Enzalutamide | Recommended | £22,600 | Link |
| Ipilimumab | Recommended | £28,600 | Link |
| Dabrafenib | Recommended | £11,000 | Link |
| Imatinib | Recommended | £16,700 - £30,000 | Link |
| Sipuleucel-T | Not Recommended | £48,700 - £512,000 | Link |
| Axitinib | Recommended | £33,500 | Link |
| Pomalidomide3 | Not Recommended | £50,000 - £70,000 | Link |
*depending on treatment ¶Recommended for a smaller group than applied for 1Aflibercept in combination with irinotecan and fluorouracil-based therapy 2Bortezomib in combination with dexamethasone, or with dexamethasone and thalidomide 3Pomalidomide in combination with dexamethasoneThis problem has been partially addressed by the creation in 2010 of the Cancer Drugs Fund, which provides funding for treatments that NICE haven’t judged on yet, or has deemed too expensive. This fund is due to finish in March 2016, but for the time being it provides an additional £340 million per year to pay for cancer drugs. The UK government have yet to comment on the long-term prospects of this fund.It must also be pointed out that this is not a problem with cancer drugs specifically. Many other diseases are facing the same problems. The cystic fibrosis drug Ivacaftor, for example, has had the same issues after it was priced as one of the world’s most expensive medicines (between £335,000 and £1,274,000 per QALY). Despite the cost, this drug is being used for a small number of patients in the UK. There was an extremely good article about the ethical concerns the over pricing of this drug in the British Medical Journal last year that I would encourage everyone to read it (available here for those with access, and by e-mailing us via the contact page on this site for those without).This all brings up another issue: are pharmaceutical companies over-charging for their treatments? According to a 2014 report, the cost of developing a new drug is now $2.6 billion (£1.7 billion), and takes over 10 years. The pharmaceutical companies argue that they have to make their drugs expensive in order to recoup their costs, and this is a valid point. This statement is slightly dented however, by the fact that the industry spends more on marketing than on research, a point well made by John Oliver in his show Last Week Tonight (below). Add to this the fact that the pharmaceutical industry makes a higher profit margin than any other industry, and the pricing of these drugs begins to look unreasonable. This issue is beyond the scope of this blog but you can find more information in this excellent BBC article.It is said that we are beginning the era of “personalised medicine”. Each person will receive a specific treatment for their cancer depending on the genetics of their disease. While this will mean more effective treatment of the disease, it also means that fewer patients will be getting any one drug. Cancer drugs will be used on smaller and smaller subgroups of people, which is likely to increase their price, as the cost of drug development is unlikely to drop. This raises difficult questions for an already struggling NHS. In a time of increasing drug prices and increasing cancer incidence, the challenge of funding these therapies will be a pressing issue for years to come.
[embed]https://www.youtube.com/watch?v=YQZ2UeOTO3I[/embed]
Can we predict cancer a decade in advance?
The Daily Mail, The Telegraph and The Independent are among the many media outlets that reported this week that we could predict cancer a full decade before it appears. Some outlets even went as far as to claim that we could predict it with 100% accuracy 13 years in advance. Unfortunately however, this is media hype of a study that makes claims its data cannot support, helped by a poor press release. There is some interesting science behind this headline, but the simple fact is that we cannot detect cancer that far in advance. If a news story appears too good to be true, then it probably is.The cancer test that these articles are referring to is telomere measurement. Telomeres are protective caps on our DNA. They are found at the end of every chromosome and protect the DNA from degradation. They are often compared to the plastic tips at the end of shoelaces, which protect them from unravelling. They are needed because cells in your body divide at an incredible rate, and every time a cell divides new errors can be introduced to the DNA.To try to get around this problem, every very time a cell divides the telomeres get a little shorter, and when the telomeres get too short, the cell stops dividing. This ensures that no more damage is accumulated, and makes sure that older, damaged cells stop dividing. As a result, telomeres play an important role in ageing (older cells have shorter telomeres than young cells), but also in cancer. Cancer cells, which divide indefinitely, are able to overcome this natural stopping mechanism by building their telomeres back up. Because of this, telomeres have been studied in cancer for decades.This week, a study was published in EBioMedicine which tried to relate changes in telomere size with the odds of developing cancer. To do this, the authors tracked the changes in telomeres in our blood cells over the course of 14 years. They then looked at these changes in patients who developed cancer during the course of the study, as opposed to those who were cancer free. What they report is that patients who are going to develop cancer lose their telomeres at a quicker rate until 3 – 4 years pre-diagnosis, when the trend reverses and the telomeres loss slows down. They suggest that this could be used to predict cancer years before standard diagnosis is possible.The paper has several problems, particularly with the interpretation of the findings. I have included a more technical explanation of some of these problems in “Further Explanations” below, but the authors themselves acknowledge some of these in their discussion.
“Thus, caution should be exercised in interpreting our results as different cancer subtypes have different biological mechanisms, and our low sample size increases the possibility of our findings being due to random chance and/or our measures of association being artificially high.”Hou et al. EBioMedicine 2015
They correctly point out that various cancers act very differently, and crucially that their conclusions may be down to pure chance. This type of correlational study (where measurements are taken and then compared with other things to see if they correlate) is useful as initial data to inform what needs to be studied further, but it is very prone to false positives. It is inevitable that pure chance will cause some correlations in the data. For example, in this study they also reported that less educated people have longer telomeres than their more educated counterparts. Whether this, or the correlation they found with cancer, is true or not can’t be determined without further study.The scientific method is based on the reproducibility of experiments, with the more implausible the finding, the greater the need for repetition. In this case we have an implausible finding using questionable interpretations of the data. While it can’t be ruled out that there is some truth in this finding, it would need to be extensively studied further before any concrete conclusions can be drawn about telomere length in the blood and cancer. But for the time being, we can say that we won't be predicting cancer with this method any time soon.Further Explanation
The biggest problems I have with this paper are in Figure 2 (above). Firstly, the authors base their conclusion on the fact that there is a statistically significant difference between the groups 3 – 5 years pre-diagnosis (demonstrated in the Figure with “*”). This seems like “cherry picking”, whereby people pick their data to suit their hypothesis. As you can see, any difference between the groups disappears in the 1 – 2 years before diagnosis, a fact that is ignored by the authors. Should their hypothesis be correct (and the cancer is causing decreased telomere degradation), the difference in telomere length should persist.Secondly, the comparison they make in this figure is between the years before people got diagnosed with cancer, versus years before the end of the experiment. As the people who get cancer are inevitably younger than the people who get to the end of the experiment without it, the cancer-free people in this analysis are likely to be significantly older than those diagnosed with the disease. The authors have already shown that telomere length declines with age, so this could be playing a major role in the observed results.
Can dogs smell cancer?
This week the Guardian reported on the ability of dogs to detect prostate cancer.
Dogs trained to detect prostate cancer with more than 90% accuracy The Guardian - 11/04/2015
Italian scientists published a study this week that showed that two dogs they tested were able to detect prostate cancer with remarkable accuracy. One of the dogs correctly detected all cases of prostate cancer and the other detected 98.6% of cancers. On the other hand, the dogs falsely detected cancer in 1.3% and 2.4% of the negative samples too. Both dogs are German Shepherds that had previously been trained for bomb detection, and while their success as bomb sniffers was not addressed, the paper shows that as prostate cancer sniffers they are pretty amazing.How does this compare?In real terms, what do these numbers mean?Consider the UK male population of roughly 30 million, with 0.15% of them being diagnosed with prostate cancer every year. That is 45,000 men.If we test all 30 million men every year, the more accurate dog will detect almost all of the 45,000 cancers each year. However, as it also detects 1.3% false positives, it will also falsely identify the disease in 390,000 perfectly healthy men (1.3% of 30,000,000).This number of false positives may not sound very impressive, but let’s put it in perspective: the standard lab-test for prostate cancer (PSA test) would detect around 27,000 of the 45,000 cancers, but crucially would detect a whopping 3,900,000 false positives! (The exact numbers for this depends on various variables, but I have used the estimates from here, using 3.0 ng/ml testing). So not only does it falsely detect many more prostate cancers than there really are, but importantly almost half of men that do have the disease walk away undiagnosed.This is still a hypothetical situation as PSA is not used routinely to screen for prostate cancer in the general population, but it does emphasise just how effective these dogs are at detecting this disease. I have included a little explanation of cancer screening below for anyone who is interested.Practicalities of using dogs in the clinicThis isn’t the first time dogs have been suggested as good cancer detectors. There have previously been reports of them detecting lung cancer, breast cancer and bladder cancer (albeit with far less impressive results than this). However, at the moment it is just not viable to introduce dogs to the clinic. A test used for cancer detection has to be reliable, and other studies haven’t proven as successful as this one. Add to that the practicalities of using live animals in the clinic (training, housing, feeding and handlers), and you can begin to see why this is not currently planned.However, if scientists can figure out what it is the dogs are actually detecting (at the moment they have no idea), it may be possible to design a much better lab-test for it which will be far easier to get into the clinic. These “electronic noses” are already in clinical trials for lung cancer, and are showing promising results. Whether these will prove to be cheaper and more effective than dogs remains to be seen, but for the time being it is a very active and interesting area of research. And, let’s be honest, most people are likely to prefer having their urine sniffed by a dog than have a rectal examination, the current standard test for prostate problems… Screening for cancerScreening for a disease means testing an entire group of people for the disease, regardless of whether they show symptoms or not. The NHS in the UK provides a screening service for breast, cervical and bowel cancer. These are tests that people undergo as part of a normal health check-up, once they reach a certain age. These screens aim to flag up any potential problems, so the patients can go for further tests.While we have tests for many other cancers, these are the only three that it is deemed cost effective to screen for. Take the PSA test for prostate cancer, mentioned above. The cost to the NHS to further test the high number of false positives would be immense. On top of that there is the worry and stress experienced by people who test positive wrongly. There has been debate in the medical field as to whether breast cancer screen is worth doing, for the same reason.Obviously it would be very desirable to screen the population for every cancer. The earlier a tumour is caught, the better. However, the tests we have for the large majority of cancers are either not reliable enough, or are too expensive, for screening purposes.
Vaccinating ourselves against cancer
Several news outlets carried a story this week regarding very promising results of cancer vaccines trials. This was a very small trial (on just three patients) who had an aggressive and late-stage skin cancer known as melanoma. In all three patients the cancers stopped growing, and they were alive and well at the time of publication. In spite of the low number of patients, this study provides a tantalising glimpse of a brand new form of cancer therapy.
So how would these vaccines work? The aim is to teach the patient’s own immune system that cancer cells are bad. That way, our own bodies could potentially mount a natural and effective response, free of the side-effects of conventional chemotherapy. Myriam has previously posted a great blog on how the immune system works (which can be found here), so I’ll stick to the basics.Our immune system recognises invaders or abnormal growths by reading what molecules are sticking out from the surface of cells. These molecules are known as antigens. If the immune system recognizes a cell's antigens as being foreign or abnormal, it will mount an immune-response to clear it from our system. The key is to correctly differentiate foreign antigens from normal, and this is the responsibility of a group of “teacher” immune cells which differentiate friend from foe and teach the other immune cells to do the same. These teacher cells include cells known as “dendritic cells”, which were used in this study.However, cancer cells are problematic for these “teacher” cells. Because cancers arise from a cell that was once healthy, they are sometimes not recognised as being abnormal, and as a result the immune system isn’t alerted to the problem.What these scientists did was to analyse the cells in a biopsy of the patient’s tumour to understand what molecules (antigens) are sticking out from the surface of only the cancer cells. The next step was to train the teaching cells (dendritic cells) to see these specific antigens as foreign. These newly-educated dendritic cells were then put back into the patient’s blood, where they could teach other immune cells to attack the tumour. Encouragingly, after the dendritic cells were infused back into the patients, they mounted a massive immune response to the tumour. It remains to be seen whether this presents a long term solution to these people’s cancers, but it is an exciting “proof of principle” study.This is a very promising new therapy for cancer. It has the potential to be very specific to the tumour and hence have very few side effects. Large scale use of such technology is still quite a few years away, but his is a very exciting step along that path.
The dangers of anecdotal evidence
Occasionally (too often) a newspaper publishes a story that is just downright irresponsible. This story from the Daily Express fits into this category.
'I beat cancer by eating pineapples' Brave woman, 31, shuns chemotherapy to self-medicateDaily Express – 30/03/15
Any reader of this blog will understand that this is rubbish, but it’s worth looking at why anecdotal stories like this are useless as evidence for therapy.Anecdotal evidence is essentially a story told by an individual or individuals. We are a story-telling species, and people generally find anecdotes highly compelling. That isn’t surprising really. In the past it was advantageous for us to err on the side of caution; it is usually harmless to mistakenly see two things as connected (my friend ate those berries and got sick), while not seeing things as connected could do you real damage (my friend ate those berries and got sick, but I’m sure I’ll be fine). As I discussed in a previous blog, we are very good at seeing patterns, whether they are real or imaginary. While that was a very useful strategy in the past, in the world of scientific medicine our trust of anecdotes is a damaging thing.An example of this is the old story of “smoking can’t be dangerous; my granddad smoked 20 a day and lived to 92”. This is known as reporting bias. If the granddad had died earlier (or the woman in the article above had not recovered) the story would not have been repeated. We only hear about it the times when something appears to have worked, and not the times when the same thing didn't work.This is also similar to another form of bias that we are all prone to, confirmation bias. This is the well-known phenomenon that we are more likely to remember something if it confirms an opinions we already have. So people who believe that chemotherapy is doing more damage than good are more likely to remember and repeat a story like this than another with a worse outcome.Another major fault with anecdotal reports is that they are seen in isolation and not in a wider context. If someone is feeling ill they may try multiple things to see if they feel better. Most of the time they will get better all by themselves, but will give the credit to the last thing they tried. This is how most cold and flu "medicines" work, relying on the fact that people make this mistake. Just because one event happens before another (I took this product and then felt better), doesn’t mean that the first caused the second.Modern medicine uses clinical trials as evidence for whether a therapy works or not. In many ways they are the exact opposite of anecdotes: they are blinded, so control for doctor and patient bias and the placebo effect; they expect random results like spontaneous regression and can see them in the wider context; and they typically have large numbers of people included (thousands) as opposed to tiny numbers of people in anecdotes.
So back to this article. The author credits “cancer-zapping bromelain” for the regression of the cancer. In fact, there is very little suggestion that bromelain has anticancer activity. There are some studies on cells growing in a dish, but these are not reliable. It has been suggested to be effective in lessening the side-effects of chemotherapy, but there is no evidence for this (there was a registered clinical trial, but this has been completed and not reported results, suggesting a negative outcome).The reality of this story is that people sometimes get better spontaneously. Even the deadliest cancers have spontaneous, unexplained regressions. A story like this can do no good, and has no place in the public sphere. Congrats Daily Express, you are just as bad as the Daily Mail.
Does the "Mozart Effect" exist in adults?
It used to be thought that listening to Mozart when pregnant or when a child was under three made for smarter babies. This has been thoroughly disproven 
and explained by the fact that children from houses where classical music is played tend to be better educated. However, people keep jumping on the bandwagon every time a study about classical music is published. This article was published in the Daily Mail on the 15th of March:
Classical music can help slow down the onset of dementia say researchers after discovering Mozart excerpts enhanced gene activity in patients-Daily Mail (15/03/15)
According to the article, classical music can help slow the onset of dementia. The study they are talking about was published in PeerJ, an open access journal. However, to be clear, there is nothing at all in the actual study to suggest that listening to classical music delays the onset of dementia (more on that below).Sadly, the blame only partially lies with the tabloids. It was the press release that accompanied this paper that made a lot of the exaggerated claims that were repeated in the Daily mail article, including the dementia one. While the tabloids did exaggerate the claims, the press release opened the door by suggesting a link to neurodegenerative diseases.This problem of a bad press release isn’t an isolated one apparently. A study from the University of Cardiff recently suggested that most poor science reporting is as a result of a bad press release. Journalists do, however, further exaggerate claims from these press releases. While it remains the case that News Outlets have a responsibility to check the claims of their sources, this obviously highlights a major issue in the communication of science to the general public. I may expand on this in a future blog, but for the time being it is safe to say that the “Mozart Effect” is still firmly in the domain of rubbish science.What’s wrong with the study?In this study, the authors try to address what effect listening to music has on the global activity of the genes. It is a very good example of what we call in science “a fishing trip”, which is a broad experimental approach that will give you a big amount of data to see what you can get from it. It is actually not in the scope of the study to research a link between classical music and dementia, and the paper does not conduct any experiments to explore that.The authors look at gene expression in the blood (assuming that this is the same as the gene expression in the brain, which is not the case). They divide their sample in “highly musically educated people” versus “less musically educated people” and compare their blood after listening to 20 minutes of classical music versus 20 minutes of conversation. In the less musically educated group they discard the changes they see because they are not “functionally relevant” (great, discarding data because you can’t make sense of it). In the more musically educated group they do find “functional relevance” based on small changes in a small subset of genes; changes that they do not confirm by any other technique.So where does dementia fit in to this? One of the 97 genes they found to be changed has previously been associated with neurodegenerative diseases. This is essentially nothing.So to conclude, the authors (a) study the wrong samples (b) to come up with conclusions their data didn't back up and (c) didn't confirm their findings in any other way, which is something you learn to do on your first day in the lab. Good science guys.
Are antioxidants actually good for you?
Another week, another “superfood”.A new variety of plum is being heralded as the next wonder-food. According to a British supermarket's “food technologist” (whatever that is), the plum has ten times as much anthocyanin, which is a powerful antioxidant, as normal plums. This is obviously just marketing, but the idea that antioxidants are always good for you is one that deserves a closer look.Antioxidants are enzymes that clear our cells of harmful molecules, so on the surface, it seems reasonable that they would be good for us (there is a deeper discussion of how antioxidants work in the “Further Explanation” below). They have been shown to play a protective role in neurodegenerative diseases like Parkinson’s and Alzheimer’s, and they may lower the rate of heart disease among type 2 diabetics. Another study showed that the Vitamin E, a well-known antioxidant, could halve your chances of contracting ALS.However, as more studies have been carried out, we have seen a darker side to antioxidants. For example, a 2011 study showed that men taking Vitamin E had a 17% increased risk of developing prostate cancer (although this finding has been recently questioned). A meta-analysis carried out in 2007 suggested that far from being good for you, antioxidants increased mortality, rather than decreasing it. Furthermore, interventions that are known to increase lifespan (like calorie restriction) may no longer work if the animal is on antioxidants. The authors of that study conclude, “treatment with different antioxidants and vitamins prevents extension of life span”. Finally, a review of the human literature concluded that taking antioxidant supplements does not reduce mortality.Ultimately, the literature is very mixed when it comes to antioxidants, but one this is certain: they are not the panacea that the health food industry would have you believe. When it comes to health claims about food and drink, it’s best to stay sceptical. The old advice of “moderation in all things” is still the best we have. AntioxidantsWhen your cells produce energy, one of the by-products are reactive oxygen species (ROS). These are chemically reactive molecules that can cause damage or death of the cell. However, they also play a role in normal cellular health, so controlling their levels is of utmost importance. Antioxidants are molecules that soak up the ROS, controlling their levels, and there are multitudes of naturally occurring antioxidants that help maintain the proper balance. There are times, however, when high levels of ROS are needed. For example, one of the bodies defences against cancer is to increase the level of ROS, causing the cancer cells to die. So in theory, antioxidants could be bad for you if you have a tumour.
Best (worst) tabloid story of the week - 12/05/15
MailOnline: Incredible moment baby shocks his parents by saying 'hello' at just SEVEN WEEKS oldAccording to the MailOnline, a baby was filmed saying hello to his parents (video below). While undeniably cute, this isn’t a genius child, mastering language at 7 weeks. It is, however, an example of pareidolia. Pareidolia is the effect of seeing patterns in random things, and is a fascinating quirk of the brain. Well known examples are seeing a face on the moon or hearing words in a song played backwards.http://www.youtube.com/watch?v=ITyxSN1MggsPareidolia is thought to be an evolutionary adaptation to help us spot enemies or predators in low visibility conditions. The advantages to our ancestors of being able to quickly identify potential danger (whether real or not) are obvious. In a world where this is no longer important though, pareidolia has resulted in us thinking we see a face on Mars, or hearing a baby say hello amid its random gurgling.It’s obvious to anyone watching the video that this is just a baby, making baby sounds. With lots of news outlets reporting this (including the Daily Mail, The Mirror, CBS and ABC), apparently that’s enough to make it into the tabloids. Although, considering that the video has so many views, it isn't very surprising! <Edit: Even The Guardian has this story now! It appears that cute babies are enough to make good papers too.>
Smoking is even more dangerous than we realised
The UK government has finally decided to push ahead with legislation on plain packaging for cigarettes before the general election in May. This comes after years of inexcusable delay and extensive lobbying by the tobacco industry. In a brazen attempt to bully the government, the tobacco companies have even threatened to sue for damages if such legislation is introduced. Plain packaging is already required in Australia (and is now being introduced in Ireland) and has been shown to be an effective anti-smoking measure (evidence of which can be found here, here, here and here).We are all fully aware that smoking is one of the most dangerous activities that you can do, but recent work has emphasised just how dangerous. Two studies (one in the New England Journal of Medicine, the other in BMC Medicine) have shown that smoking is associated with more diseases than previously thought, and plays a role in far more deaths. The first study was carried out in Australia, and followed over 200,000 people for 4 years to assess the effect of smoking on their lifespan. This was a well carried out, prospective study (see below for explanation). They found that death rates in smokers were 3-times higher than in non-smokers, and that smokers die an average of 10 years before their non-smoking counterparts. Furthermore, up to 67% of deaths in smokers can be attributed to their habit. To put it simply, for every three people you see smoking outside a pub, two of them will eventually die from a smoking related illness if they don’t quit. It’s a shocking toll.The second study was a meta-analysis (see below for explanation) of 5 previous US studies, including nearly a million people. They showed that at least 30 diseases are associated with smoking, including cancers of almost every site (pancreas, bladder, breast, kidney...). It’s a terrifying list, which I have included below, but there is some good news. The BMC Medicine study confirmed that if somebody stops smoking, not only will the damage stop accumulating, but the body can begin to heal itself. The earlier the smoker quits the better, and those who quit early have the same lifespan as non-smokers.These studies emphasise the need for continued efforts to reduce the levels of smoking. Measures such as the plain packaging of cigarettes, and the banning of smoking in cars are positive steps. The UK government's vote on the issue before will take place before May, so hopefully there will be progress soon. Fingers crossed.https://twitter.com/CRUK_Policy/status/573898151842701312Diseases associated with smokingLaryngeal cancer - 103.8 times more likely to die from than non-smokersLung cancer - 22.9Lip and oral cavity cancer - 5.6 Oesophageal cancer - 5.1Urinary bladder cancer - 3.9Pancreatic cancer - 1.9Liver cancer - 1.8Stomach cancer - 1.7Colorectal cancer - 1.6Breast cancer - 1.3Kidney and renal pelvis cancer - 1.2Acute myeloid leukaemia - 1.1Rare cancers - 1.1Cancers of unknown site - 2.7Chronic obstructive pulmonary disease (COPD) - 25.0Aortic aneurysm - 10.1Ischemic disorders of the intestine - 6.1Other arterial disease - 5.6Ischemic heart disease - 3.0Liver cirrhosis - 2.6Infection - 2.5Hypertensive renal disease - 2.4Unknown causes - 2.2Stroke - 2.1Atherosclerosis - 2.1Other digestive diseases - 2.1Additional rare causes - 2.0Other heart disease - 1.9Pneumonia, influenza, and TB - 1.9Hypertensive heart disease - 1.9Other respiratory diseases - 1.9Renal failure - 1.9 Diabetes - 1.5Further ExplanationProspective study: This is the gold standard of medical studies. In a prospective study, people are recruited to look specifically at a certain thing (in this case, the effect of smoking on lifespan). The study is planned ahead of time, and controls are put into place to ensure the highest quality data. This differs from a retrospective study, where data that has already been gathered is analysed to draw conclusions about a certain outcome. This type of study can be prone to significant bias, because unlike a prospective study, you cannot control the population you are studying. It is also more difficult to separate correlation from causation using a retrospective study. It is far easier and cheaper than a prospective study however, and very often the only option.Meta-analysis: This type of study involves the combining of several studies in the hope of revealing patterns in the results of those studies. A meta-analysis allows the study of far larger numbers of people, but can be severely affected if one or more of the individual studies is poorly carried out.
Best (funniest) tabloid "health" story this week - 05/03/15
Our selected piece of the week is this ground-breaking report from the Daily Mail (we're not going to link to the story from here. There's no point in giving the Daily Mail any additional hits. Google will direct you to the story if you really want to see it):
Daily Mail Online Health Section: How your star sign could dictate your dieting success
This hard-hitting piece reveals that Leos should avoid sauces. Poor Leos. Luckily, light marinades are ok. We are also informed that Geminis should avoid fast-food, which I take to mean that it is ok for everyone else. Except for Cancerians, who have to avoid unhealthy food they ate in childhood. If they didn't eat fast food in their youth however, it seems to be ok.Of course, this is astrology, and hence nonsense. The idea that the apparent positions of stars and planets at the moment of you birth can have a lasting effect on your personality is nothing short of ridiculous. As such, this blog should be some light-hearted hilarity, but unfortunately there is a depressingly relevant news story associated with it.British MP David Tredinnick, suggested this week that astrology be used by the NHS to treat patients. What's worse is that Tredinnick sits on both the Health Select Committee and the Science and Technology Select Committee. He supports homeopathy and radionics (the use of blood or hair to heal people remotely), and in 2009 told Parliament that blood does not clot under a full moon. And, I'll repeat, he sits on both the Health Select Committee and the Science and Technology Select Committee. You have to despair if this is the level of science literacy required for positions like these.Instead of despairing though, I'm going to as much ice-cream as possible. After all, as an Aries that's perfectly ok for me to do!
