Category: Uncategorized

What’s the difference between #scicomms and communicating science?

Last week an article written by Prof. Catherine Brooks was published by Scientific American. In it, Brooks asserted that people don’t trust scientists and questioned whether science communicators are the problem by “relying too much on gripping headlines or in trying to get science information to viral” which might be “somehow undermining the critical role of trust in scientifically based work”.

Now, I’m a bench scientist. But I’m also an amateur science communicator. I blog and tweet, I write occasional news articles, I’ve podcasted fortnightly for over three years, I’ve been actively involved in skepticism for over six years. I give talks – to lay audiences across the world, to academics and to industry collaborators. I do workshops with kids of all ages.

Some kids stood at a table I ran with the Merseyside Skeptics Society at Big Bang North West science fair in 2014
A set of workshop tasks I ran with the Merseyside Skeptics Society at Big Bang North West 2014.

I talk about science with every person I meet – from taxi drivers to GPs, from family to friends, I once did a science test in the changing rooms of a rugby club with a rugby kicker. My mother-in-law left school at 16 and hadn’t thought about science for decades but she still asks me how my cells are doing. We talk about the science behind her vision problem and how cancer works.

I work in academia – but I live in science communication.

I understand the frustration that some people are losing their trust in science. I find it hard to see so many people, especially people living with cancer, turn to conspiracy theories. But I also see, every day, a lot of people who trust science.

The logo for AsapSCIENCE a YouTube channel created by Canadian YouTubers Greg and Mitch
The logo for AsapSCIENCE a YouTube channel created by Canadian YouTubers Greg and Mitch

The problem is not with making science popular using YouTube or Instagram. The problem lies precisely with the solution Brooks suggests. In her article Brooks says “we need to keep science information findable in a busy digital culture by simply presenting the data while relying on emotional appeals to a lesser extent”. But findable isn’t the same as seen. And seen isn’t the same as engagement.

People know that they can find science information “out there”. Sticking with my Mother-in-law, her favourite response to any question is “Google it”. Anything is findable. But do people know that they can understand that science without speaking the academic language? Or do they know it can be fun, exciting or awe-inspiring? Instead of those drab school lessons they had decades ago which left them putting science in a box labelled “not for me”.

laptop and mobile phone on a garden table with Google search page open on the laptop

Science communication is far more than just communicating science. It’s about knowing your audience, knowing what engages them and the ideas they relate to. And sometimes that means finding a way to appeal to their emotions. That shouldn’t be at the expense of good science, but what’s the point in doing good science if you can’t convey the benefit of it? Sometimes, science communication is about persuading your audience to open up that box, and challenge the idea that science isn’t for them. It’s about making science accessible for everyone.

five people stood in front of a white screen. Their heads and feet are cropped out of the image.

Every fortnight for Skeptics with a K, I read through many, many articles that report science dreadfully – either they miss the point of the study, or they misrepresent it, or they leave out the science of a topic entirely. But for all its faults, there are many things we can learn from the media, too. Sure, clickbait and listicles drive us all spare…but the media uses them because they work. We can learn something about human nature from which types of article the media prefers. Sure an article headlined “top ten things….and you won’t believe number nine!” might be frustrating, but why can’t we write a list that our audiences will engage with? Like that wonderful article from Cancer Research UK: Don’t believe the hype – 10 persistent cancer myths debunked (which I still re-read every few months despite it being written nearly five years ago). And maybe we’re all frustrated by those YouTube videos your great aunt Irma posts on Facebook about “the one cancer cure your doctors won’t tell you about” but maybe we can use that video model to teach people critical thinking.

10 persistent cancer myths debunked cover photo from CRUK
Image taken from CRUK website

Remove the emotion from science and you leave scientists sat in their ivory tower as elite academics who don’t know how the real world works. But out here in the real world – a lot of science communicators are using the best techniques to engage with people from all walks of life and bring science in to the hands of the “people” – where it belongs.

What is CAR-T therapy and why did NICE recommend against it?

You might have seen in the news today that NICE has denied patients access to a ‘pioneering’, ‘breakthrough’, ‘revolutionary’ treatment.

But what actually is this treatment?

CAR-T

CAR-T therapy is a type of immunotherapy that takes advantage of the cell killing capabilities of cytotoxic T cells. This particular type of T cell is an important part of the human immune system which for many years, researchers have hoped might be useful in treating cancer.

Cytotoxic T cells surround a cancer cell
Cytotoxic T cells surround a cancer cell (taken from NIH)

The problem is, cancer cells are derived from your own cells so your immune system has no reason to target them for destruction. That’s where CAR-T therapy comes in. In CAR-T therapy, the T cells of the patient are taken from the blood and genetically modified so they express a chimeric antigen receptor (CAR). A CAR is basically a signalling molecule on the surface of the T cells that allow them to recognise cancer cells as worthy of destruction. These genetically modified T cells are then put back into the patient’s blood to target and kill cancer cells.

Because we know that different types of cancer typically have different types of signalling molecule on their surface, we can then use different types of CARs to help draw the cell killing T cells to the cancer cells. For example – nearly all types of B cell acute lymphoblastic leukaemia (ALL) have a protein called CD19 on the surface of cells so researchers have been working on CARs that specifically target cells which have CD19 on them.

B cell lymphoma cell is recognised by a T cell which has a CAR protein expressed on it
Modified from here.

Yescarta

The specific therapy that NICE has reported on this week is one called Yescarta from a company called Kite Pharma. Yescarta consists of taking T cells from the patient then using a system hijacked from retroviruses to genetically modify the cells. The genetically modified cells are then reintroduced to the patient in a single dose.

Clinical Trials of Yescarta have been initially promising. A phase II single-arm trial found that of 101 patients treated with Yescarta, 54% had a complete response and 52% survived over 18 months. All of these patients had refractory large B-cell lymphoma – that means they had a type of blood cancer that had already failed treatment and the patients had an average expected life expectancy of 3-4 months. While the trial showed that all patients had significant adverse events related to Yescarta, only 3% of patients died from the treatment itself.

Yescarta logo

Based largely on this trial the FDA approved Yescarta for certain types of lymphoma late last year and the European Commission granted Marketing Authorisation for the treatment this month.

Why not recommend it?

But NICE had some concerns. Firstly, they were concerned that the clinical trials for Yescarta, while promising, were insufficient to allow recommendation of the drug. While this particular type of lymphoma doesn’t have a standard therapy, yet, most patients are treated with scavenger chemotherapy and the Yescarta clinical trials haven’t proven that Yescarta is better than scavenger chemotherapy. The two therapies haven’t been compared side by side. This is quite a significant concern because, without side by side comparison, we can’t be sure that diverting patients from one treatment type to the other is actually beneficial for the health and life expectancy of those patients.

NICE aren’t saying no to Yescarta, they’re saying “not yet”.

The second concern NICE has is that the treatment is currently very expensive. The cost to the UK has not been made available, but in the US the treatment can cost $373,000 per patient. And this is something that NICE has to weigh up in its cost-benefit analysis. So far, Yescarta has been shown to prolong life by approximately 14 months in around 50% of patients. Is it justifiable to divert so many funds to a treatment that only works 50% of the time and we can only say extends life by a year (so far)?

A woman standing at a laboratory bench facing away from the camera and wearing a lab coat

The company that makes Kite Pharma was bought by Gilead Sciences last year, just two months before Yescarta was approved by the FDA. Last year Gilead Sciences had a revenue of $30.4 billion and a free cash flow of $15.9 billion. Gilead Sciences spent $12 billion in order to acquire Kite Pharma and its marketable therapy Yescarta. NICE perhaps has reason to be cautious.

Any other concerns?

If Yescarta were approved for the use in the UK, it would be the first of its type to be approved. There are potential concerns we need to consider when introducing both genetically modified cells into patients and playing around with the immune system in patients. In his article for McGill, Jonathan Jarry pointed out that “Autoimmunity is when our immune system improperly responds to something that belongs to us” and in the case of Yescarta we’re actively training the T cells to recognise cancer cells derived from our own cells. In fact CD19 isn’t just expressed on cancerous B cells, it’s found on all B cells – even the healthy ones. In the case of terminal cancer this might be a price worth paying but it has to be taken into consideration. Sudden activation of T cells in the body is such a strong response that patients can get very sick and even die from a condition called cytotoxic release syndrome.

We must also consider the reproducibility of the initially promising clinical trials. There is evidence that when repeated, less than 50% of clinical trial results are reproducible and many negative clinical trials go entirely unpublished which means a high likelihood of false positives, it seems prudent to take care when making decisions based on single clinical trials.

Conclusion

NICE - national institute for health and clinical excellence logo

While many patients were hoping for the approval of Yescarta by NICE, the limitations have proved too high at this stage. I don’t think this decision should be used to criticise NICE or the NHS, rather to encourage further research using reliable controls and a focus on bringing down the prices of promising new treatments. It also highlights an example where the novelty of new treatments can overtake scientific sense and lead to approving treatments which might currently be lacking sufficient clinical evidence supporting their use.

Meanwhile, the NHS will not withdraw funding for any patients already undergoing Yescarta therapy and will reconsider their decision given further research or reduced costs.

 

 

Cool science: Kick and Kill to cure HIV – an update.

A little while ago I wrote about an exciting new potential for HIV treatment. The cool idea was looking to solve a problem we haven’t yet figured out how to solve when it comes to treating HIV infection. You see, HIV is particularly tricky to treat because it forms what we call latent viral reservoirs. These are a group of cells that are infected with the virus but within which the virus isn’t ‘active’.

Antiretroviral drugs are really great, but they only target ‘active’ virus which means these reservoirs are essentially hidden away and protected. This is why people living with HIV need to stay on treatment for their entire lives.

So, researchers came up with a great idea – what if they could ‘kick’ the virus in the reservoirs into action and then ‘kill’ the now active virus using standard therapy. This scientific basis behind this ‘kick and kill’ approach made researchers think that this might hold the key to curing HIV and allowing people living with HIV to eventually come off their medication. Early studies were really promising and there was good evidence that this might be a useful approach to trial in patients.

So what happened next?

RIVER

The Research In Viral Eradication of HIV Reservoirs (or RIVER) study began in 2015 and concluded this year. This study was a randomised control trial (RCT) where 60 people recently diagnosed with HIV in trial centres across London and Brighton were split into two groups. One group received standard therapy – antiretroviral therapy (ART) only – this group acted as a ‘control’ group that could be used to compare the test group against. The test group were given a test therapy which consisted of four steps:

  • Patients were treated with standard ART until the ‘active’ virus was undetectable in the blood
  • Patients were then given a vaccine which would train or ‘prime’ the immune system to recognise the HIV virus
  • Patients were treated with Vorinostat which would ‘activate’ the inactive virus in the reservoir cells – this step is the ‘kick’ part of the process
  • The ‘primed’ immune system would then be able to ‘kill’ the newly activated virus

A four step diagram outlining the four steps included in the RIVER study - Step 1, ART is used to make sure HIV is undetectable. Step 2, two vaccines train the immune system to recognise cells which will be activated. Step 3, Vorinostat is used to wake the sleeping cells. Step 4, the immune system boosted by the vaccine attacks and kills the newly activated cells

What did RIVER find?

The results were surprising and unexpected. RIVER found that there was no significant difference in the size of the latent HIV reservoir between standard treatment (control) and ‘kick and kill’ treated (test) patients. It looked like ‘kick and kill’ was no better than standard therapy.

Even more surprisingly, each of the components –the standard antiretroviral medication, the vaccine which primed the immune cells and the Vorinostat which ‘kicked’ the inactive virus into action – all worked exactly as they should. But combining the multiple components wasn’t any better than ART alone.

Chief Investigator on this study, Prof. Sarah Fidler of Imperial College London said “In the RIVER study, we found that all the separate parts of the kick and kill approach worked as expected and were safe. The vaccine worked on the immune system, the kick drug behaved as we expected it to, and the ART worked in suppressing viral load in the body, but the study has shown that this particular set of treatments together didn’t add up to a potential cure for HIV, based on what we’ve seen so far.”

Does this mean we should drop the kick and kill approach?

Well, no, not really. Because this was just one iteration of the kick and kill approach using a combination of one type of medication and two types of vaccine. Researchers on the RIVER study aren’t really sure why it didn’t work as planned but until we understand the answer to that question it might still be a useful avenue for research.

a drawing of an HIV viral particle surrounded by blood cells and coloured with dark purple and brighter patches of fushia

The co-principal investigator and scientific lead from the University of Oxford, Prof. John Frater says “It is possible that the combinations of drugs we used weren’t quite right, but for this first study we didn’t want to compromise on safety by using stronger agents that might work better but could cause toxicity to the participants. It is possible that vorinostat was not quite potent enough to wake up as much HIV as was needed for the newly trained immune system to recognise. Equally, it is possible that a different sort of immune response to the one we induced is needed to target the HIV reservoir. All of these possibilities need to be teased out and considered to guide our next move in searching for an HIV cure.”

So what next? Collaborative research.

This RCT is an important step in investigating the possibility of curing HIV infection. Professor Abdel Babiker of the MRC Clinical Trials Unit at UCL, said “Although the results are disappointing, they are unambiguous because of the randomisation and completeness of follow up assessments. Because ART is so effective at reducing viral load, without the randomised control group of participants taking ART alone to compare against, we couldn’t have been so confident in knowing whether the kick and kill drugs had made any impact. It’s important that future HIV cure trials follow this approach and compare their outcomes to an ART-only group.”

A woman standing at a laboratory bench facing away from the camera and wearing a lab coat

Scientific experimentation using RCTs allows us to be confident in the findings – even if those findings are not as promising as we hoped they would be.

This particular trial was part of a UK collaboration group called CHERUB but there are collaborative groups like this all over the world. The value of collaboration allows experts from different backgrounds, with different expertise to come together and conduct research with wide ranges of participants. The importance of participant engagement in particular was praised by Prof. Fidler who said “They are not just volunteers, they are active advocates for support and they push us to go further all the time. They are helping to define where this research can go next and they are the real pioneers of new treatments.”

 

Find out more about this trial here and here.

 

 

Is Cannabis a Cure-all?

You might have seen in the media lately a lot of coverage about the use of cannabis to treat epilepsy and other conditions. It all started with the case of a young boy with severe epilepsy who was using cannabis oil to manage his seizures, with apparently great effect. Until, that is, his mother was unable to bring his treatment into the UK and his medication was seized at the airport.

These stories raise three questions:

  • What does UK law regulate in the case of medications based on cannabis
  • What is a cannabis oil?
  • Can cannabis treat any medical condition?

UK Law

In the UK, cannabis is a Class B drug – you aren’t allowed to possess or supply it and doing so can result in jail-time. This is a regulation under the Misuse of Drugs Act 1971, however cannabis is also regulated by The Misuse of Drugs Regulations 2001 which control the therapeutic use of drugs. Under this legislation, cannabis is regulated as a Schedule 1 drug which means it is not available for medical purposes and possession and supply are prohibited unless the Home Office approves.

cannabis plant seedlings

Cannabis: the sum of its parts

Cannabis refers to a group of plants which produce compounds called cannabinoids. Cannabis plants contain 113 different cannabinoids – so what exactly are we talking about when we talk about cannabis oil?

The two important cannabinoids to consider are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main part of cannabis that gives its psychoactive effects. It’s the compound that will make you feel ‘high’ if you smoke marijuana although this response is mediated by other cannabinoids too. It also stimulates release of the hunger hormone, ghrelin, which explains why people have an increased appetite when they take cannabis. It does this by binding to a specific receptor on the surface of cells in the brain.

CBD is non-psychotropic and it acts in a very different way to THC. But it might also enhance THC activity by increasing the number of receptors available for THC to bind to. It might also increase the levels of those natural endocannabinoids in the body.

In the UK, CBD is legal which means cannabis oils containing only CBD are legally available whereas THC is not legal.

four brown glass unlabelled bottles containing oil

Can cannabis treat disease?

In the UK, there are already two cannabinoid based treatments licensed for prescription. Nabilone is used to treat nausea and vomiting in people undergoing chemotherapy. There are other conditions it has been indicated for including IBS, fibromyalgia, chronic pain and parkinson’s disease however in the UK it is only permitted to help treat the side effects of chemotherapy.

The second cannabinoid based treatment available in the UK is Sativex which is used to treat the symptoms of multiple sclerosis including neuropathic pain and spasticity. Sativex is a cannabis extract which contains both THC and CBD.

Cannabis for epilepsy

When it comes to epilepsy – there is considerable evidence that THC can control convulsions through regulation of neuronal excitability and inflammation. But because it can make you high – it’s not an ideal avenue for therapeutic exploration.

Research into CBD for treating epilepsy is relatively new but initially promising at least for certain types of epilepsy and there is a drug awaiting FDA approval which can treat Lennox-Gastaut syndrome and Dravet syndrome, two severe forms of epilepsy. But this might not be sufficient in all cases – some patients may require different mixtures of THC and CBD to see an effect.

Cannabis for cancer

Cannabis can be useful in managing cancer-associated side effects in patients. It can act as both a pain reliever and a way to reduce nausea and enhance appetite. But there is early research that it might also kill cancer cells and stop them growing. In these cases researchers have looked at highly purified THC and CBD. Some trials have shown that combining chemotherapy with cannabis might have some promise. However, we have insufficient evidence to support its use as a cancer treatment either due to small study sizes or the research predominantly taking place in cells in the lab which is just not a good representation of what would happen in humans. We don’t know which types of cannabinoids are most useful, what doses are needed, what types of cancer respond, how to take them effectively and whether they should or shouldn’t be combined with other treatments.

Cannabis research

If cannabis is so promising, why don’t we do more research on it to bring it to clinical trial? Cannabis is a Schedule 1 regulated drug, it can only be used in research with Home Office approval. Schedule 1 drugs are so classified because they are not deemed to have medical usefulness. But researchers like Professor David Nutt are concerned that the medical usefulness of cannabis cannot be proven if research is prohibited.

Importantly, the recent media interest in cannabis use as a medical treatment has been useful in encouraging a UK government review on the therapeutic value of medications based on cannabis. This review will be undertaken by the Advisory Council for the Misuse of Drugs and may lead to a change in the legal status of cannabis and cannabinoids with regards to their use in medicine.

A woman standing at a laboratory bench facing away from the camera and wearing a lab coat

Alternative medicine

In the meantime, it is important to remember that while cannabis holds some promise as a potential therapy for many conditions, it is crucial to always follow professional medical advice when considering medical treatments. The research supporting cannabis use is limited and there are many questions about safety and efficacy that remain unanswered. For many conditions that cannabis might be useful for, we already have good medical treatments that can be used before considering an as-yet, unproven treatment. Cannabis oils are poorly regulated and might have wildly variable levels of cannabinoids and may even contain ingredients that are harmful. It is never advisable to buy medical treatments online or take medical advice from someone other than a qualified medical professional.

 

I talked more about this on my podcast, Skeptics with a K – on this episode. You can follow me on Twitter @AliceEmmaLouise for more.

Kitchen cupboard “cures” – number one: turmeric

Wouldn’t it be great if we could cure all our ills with ingredients we can find in our kitchen cupboard? Plenty of people claim that it can be done and with the popularity of ‘natural’ medicines it’s not just your Nana who recommends it because that’s what her Nana taught her.

Kitchen cupboard remedies have become so mainstream that they become potentially dangerous when recommended for life-threatening diseases such as cancer. In fact, just a few months ago the Express asked “Can turmeric really cure cancer? Woman says benefits of golden spice ‘cured’ her disease”.

the express
Headline from the Express: “Can turmeric really cure cancer? Woman say benefits of golden spice ‘cured’ her disease”

But sometimes we wonder, if so many people believe it, maybe there’s really something in it?

In this series I will cover kitchen cupboard “cures” to investigate the claims made, and what the science really says. The series begins with the tasty Indian spice turmeric.

Turmeric

Turmeric is often reported as some sort of wonder spice. People who promote its use claim turmeric is anti-inflammatory, reduces cholesterol, treats diabetes, prevents Alzheimer’s disease and both prevents and cures cancer.

glass jar of orange coloured ground turmeric on a tea towel with a wooden spoon on the worktop next to it and turmeric on the spoon and counter

But actually, while this seems like a bizarre old wives’ tale, there is evidence supporting some of the claims for turmeric. The active ingredient in turmeric is curcumin or diferuloyl methane. Experiments in the lab show that curcumin alters the expression of genes in cells and some of these genes are related to specific pathways. For example, curcumin alters the expression of proteins related to inflammation in rat liver cells in a petri-dish and also alters the production of cholesterol in cells. Curcumin supplementation might also help manage some of the side effects of diabetes but only in conjunction with standard therapy. There is even some early evidence from mice with Alzheimer’s disease that curcumin can slow cognitive decline.

However, the science is also quite complicated. When it comes to cancer there is some evidence that curcumin can slow the growth of cancer cells in the lab but plenty of things slow cancer growth in the lab and never go on to prove useful therapies. Having said that, some clinical trials have shown that curcumin might one day prove useful as an adjunct to some cancer treatments in some cancer patients with some types of cancer.

The Express article above did discuss a case of a woman with myeloma, a type of blood cancer. This article was based on a single case published in British Medical Journal Reports in which a patient who had been on conventional treatment for many years suffered a relapse and was advised that there was nothing else doctors could do to help treat her cancer. The patient decided to take 8g chemical curcumin in tablet form per day in the hope it would treat her cancer. Her cancer has subsequently stabilised. This is a potentially interesting case – however it is only one single case that has been observed. Subsequent studies have not been done to investigate why this patient stabilised and there is insufficient evidence that it was the turmeric that was responsible. In fact, there are rare cases in which cancers such as myeloma can go into spontaneous remission without treatment and doctors believe this might be due to the patient’s own immune system targeting the cancer cells.

Important caveats

It would seem that the early research is fairly promising, however there are some very important caveats to remember here. So far, these studies are largely done in cells in a petri-dish or animals like mice or rats. We are not yet able to translate the findings to humans and we’re a long way from finding useful therapies using this compound.

Importantly, the studies use chemical curcumin rather than dietary turmeric and usually have specific measured doses. If curcumin becomes a useful therapy, the dose will change between different diseases and different patients. There is no evidence supporting the use of turmeric in isolation to treat disease. In all studies it is used as a supplement to standard therapy.

Clear capsules with orange powder inside

Medical treatments should always be managed by a medical professional. Any ‘herbal’ remedy has the risk of interacting with conventional drugs. In the case of curcumin research has shown that the chemical can inhibit some cancer treatments so it is important we understand the role curcumin plays in reacting with other medications before using this to treat patients.

It is because of this risk of interaction with other medications that it is really important patients taking any herbal remedy supplements speak to their doctors about whether these supplements might harm themselves or the efficacy of their treatments. It is important to note that many supplements are not fully regulated and therefore may contain ingredients that cause harm. For example, some curcumin supplements have been shown to contain anti-inflammatory drugs which can cause liver damage if taken in excess.

Summary: while there is some early evidence the active ingredient of turmeric might one day prove a useful supplement to conventional therapy we’re a long way from this being clinically useful. We need much more research to confirm the efficacy of curcumin and to establish which compounds work best and at which doses.

Next week I’ll be writing about Rosemary. If you have any specific requests for a Kitchen Cupboard “Cure” for me to cover, please leave a comment or send me a tweet @AliceEmmaLouise.

For more information on turmeric and cancer you can see CRUK’s review.

Sources:

 

 

 

Skincare, anti-aging (and cancer)

The world of skincare is not a place for the faint-hearted. It is such a dizzying mix of advice and recommendations, advertising and ‘science’ that any wander through this world leaves you feeling like you are not doing enough for your health or appearance. The only way to make yourself feel better, it would seem, is to spend sometimes hundreds of pounds on products you will use religiously for a few weeks before you end up exhausted by all the time you’re spending slathering on potions, oils and creams.

Why do we do it?

There are a range of reasons we feel we have to invest time, money and energy into our skin. One of the main reasons seems to be to maintain a youthful appearance for longer. Anti-aging is a huge part of skincare marketing and people (women especially) are targeted from an early age to start protecting their skin from the effects of aging.

The science of aging

There are two types of aging – intrinsic and extrinsic.

Intrinsic aging is the type that is genetically accounted for. It happens naturally pretty much no matter what you do. This is the kind of aging that leads to changes in skin elasticity. This type of aging is also called chronological aging and is the one you cannot really do much to change.  The characteristics of intrinsic aging include smooth, unblemished skin with a loss of elasticity, fine wrinkles and paling of the skin. The skin gets thinner and the small blood vessels in the skin reduce in quantity.

In addition to the natural course of aging, we also have extrinsic aging. This is the one our behaviour has a say in. By far, the two biggest factors which cause extrinsic aging are smoking and exposure to UV light.

Smoking reduces the elasticity of skin and reduces collagen levels in the skin. This means the skin gets hardened, slack and rough. We have evidence from multiple studies over a number of years showing that smokers have increased wrinkling compared to non-smokers. The evidence is consistent and overwhelming – smoking tobacco increases skin aging.

Photoaging

Exposure to UV light from the sun is thought to account for up to 90% of visible skin aging. UV light causes an increased level of specific proteins in the skin called enzymes. The enzymes that are increased in skin exposed to sunlight are responsible for degrading important connective tissue. After repeated exposure the skin starts to sag and to form wrinkles. Sunlight exposure increases the production of reactive oxygen species (ROS) and free radicals in the skin. ROS and free radicals damage the DNA which increases your risk of skin cancer, but they also increase the levels of those degrading enzymes even more. In addition to all of that, UV radiation interferes with the immune system and may even prevent cell death in sun-exposed skin which can also contribute to an increased risk of skin cancer. The characteristics of photoaged skin include nodular, leathery, blotchy skin with coarse wrinkles and furrows. The skin has irregular pigmentation and obvious marking on the skin and the elasticity is severely damaged. Blood vessels become dilated and there is pronounced inflammation.

What works?

It should be clear, now, that the two most useful ways to prevent visible skin aging are to minimise intake of cigarette smoke and to minimise skin exposure to damaging UV rays.

Sunscreen

To protect your skin from UV damage, applying a daily sunscreen with a high factor SPF and high-quality UVA protection (4 stars or above). SPF protects your skin from burning and from the damage associated with that but it does not protect against UVA radiation. UVA damage is invisible, although it does cause darkening of pigmentation, and is very deeply penetrating. You need a sunscreen that protects against both UVA and UVB damage.

image of a person's knee with white sunscreen and a hearth drawn into the sunscreen

Topical Retinoids

While most skincare products have very little evidence supporting their use in preventing or reversing the signs of aging, there is one active ingredient that does seem to help.

Retinoids are a family of chemicals which include retinol (vitamin A) and similar compounds. The potential of retinoids in treating aging was discovered in the 1980s when scientists treating photoaged mice noticed repair of the skin and reduction in wrinkling. We now know that retinoids encourage cell growth and can reverse some of the effects seen in photoaged skin and you can buy skincare products which have retinoids in them. There are two downsides to using retinoids on your skin – firstly, retinoids can cause some sensitivity making the skin red and sore which means some people cannot use it at all and most people need to build up their usage from a low dose (0.1%) used infrequently (1-2 times per week). Retinoids can also make your skin more sensitive to UV damage. This means if you are using retinoid skin products you need to be extra careful about staying out of the sun.

Prevention is better than cure

Ultimately, the best thing you can do for your skin to prevent visible aging is to protect it from harmful damage caused by smoking or sun damage. Of course, if you enjoy the relaxation of using different products on your skin, then go right ahead. But the best way to protect your skin is to use a decent sunscreen and to refrain from smoking.

You will also be doing wonders for your risk of lung and skin cancer!

Sources:

Read more about skin cancer here:

http://www.cancerresearchuk.org/about-cancer/skin-cancer/about-skin-cancer 

 

 

 

Trends in Pseudoscience: Raw Water

Trend:

Water consciousness movement/raw water

What is it?

The water consciousness movement is a trend towards eschewing tap or bottled water for drinking and instead turning to unfiltered, unpasteurised, unsterilised spring water.

But why?

Proponents and, indeed, suppliers of this trend say that tap water in the US has been filtered – removing bacteria and minerals that they believe benefit the body. One supplier of ‘raw’ or ‘live’ water, Live Water, claims that “you can attempt to remineralize filtered water, but those minerals will never be bio-available like in fresh living spring water”. The bacteria content in ‘live’ water is lauded with Live Water announcing “there could be countless other beneficial microbes present, scientists just haven’t discovered yet”. They claim that beneficial bacteria, which they refer to as probiotics, are crucial for the proper digestion of food and the promotion of good health. Not only that but some raw water proponents are fearful of fluoride present in tap water. The founder of Live Water, Mukhande Singh, told The New York Times “Call me a conspiracy theorist, but it’s a mind-control drug that has no benefit to our dental health.”

And why not?

The filtering process applied to US tap water is and important step in making water that is safe to drink. It removes bacteria which can include organisms like E.coli but also parasites and viruses. A telling indication of the microorganisms present in ‘raw’ water comes from Mukhande Singh who told The New York Times of his company’s ‘live’ water: “If it sits around too long, it’ll turn green. People don’t even realize that because all their water’s dead, so they never see it turn green”. Water going green over time is a sure sign that something is growing in it. The water is alive, just not in the way that Mr Singh claims. Water borne diseases are not a problem for many Americans, these days, because we solved the problem with the availability of clean drinking water. The blight of the 1800s, cholera, a disease caused by water contaminated with a bacterium called Vibrio cholerae taught us a lot about the dangers of drinking unsanitary water. Sufferers of the ‘blue death’ often succumbed to a rapid death caused by severe dehydration, a consequence of incessant diarrhoea and vomiting.

Cholera_bacteria_SEM
Scanning electron micrograph of the rod shaped cholera bacteria (Vibrio cholerae). Source: http://remf.dartmouth.edu/imagesindex.html

US tap water is carefully regulated to ensure safe levels of microorganisms. US tap water is fluoridated which is scientifically proven to improve dental health. But there’s another benefit to drinking water that is regulated to prioritise health and safety. These regulations are subject to changes based on the evidence as our scientific understanding of certain contaminants develops. For instance, arsenic naturally occurs in water. Since the 1960s the regulations sustained arsenic below 50ug/L but by 2006 all drinking water in the US was required to have a level of 10ug/L or less. Studies show that this reduction in the regulated level in US drinking water has resulted in a reduction in the diagnosis of lung, bladder and skin cancer each year.

‘Raw’ water, is not regulated in the same way. The contamination of each ‘batch’ of water might not even be monitored. Not only might customers be drinking dangerous contaminants – they have no idea of which contaminants and at what level might be present in the ‘raw’ water they consume.

A list of alternative cancer therapies and a Good Thinking Society

Recently I worked on an interesting project with the Good Thinking Society.

The Good Thinking Society are a great charity who are small in size but are making great waves. The charity was founded by Simon Singh and their goal is “to encourage curiosity and promote rational thinking”.

One thing the Good Thinking Society does excellently is working in the medical field – they have been fundamental in changing the environment of NHS funding for treatments which lack scientific support for their use.

In 2010, The House of Commons Science and Technology Committee reported that homeopathy is no better than placebo. Despite this, this scientifically implausible treatment continued to be funded on the NHS to the tune of three to five million pounds per annum. This is a figure that the Good Thinking Society determined after working systematically through each CCG in the UK to identify which of them continued to fund homeopathy and how much they spent. Good Thinking Society supported many of those CCGs still funding homeopathy in reviewing their funding policies and succeeded in initiating the removal of this funding in many areas across the UK. They have also been instrumental in NHS England calling for homeopathy to be added to the NHS Blacklist of items which cannot be prescribed by GPs.

Good Thinking Society have some excellent resources on specific alternative therapies which you can find under their heading ‘Good Thinking About’. In particular they have an excellent primer on Gerson Therapy, a ‘treatment’ promoted as a cure for cancer which I have discussed here before.

Recently, I helped the Good Thinking Society compile a list of treatments which might be offered by alternative practitioners to vulnerable cancer patients. The list brings together a summary of the evidence for each treatment and outlines some of the potential risks and dangers of those treatments.

Here is a sample from this list:

Cancer list

Go take a look at their website and the list of alternative cancer treatments. And while you’re there – donate to their cause. They exist on donations and they need your support.

Autism Spectrum Disorder (ASD) and Aluminium

Recently, Professor Chris Exley from Keele University claimed that his research “provides the strongest indication yet that aluminium is a cause of ASD”. In an article originally published in the Hippocratic Post and reproduced by the Daily Mail, Exley claimed that brain tissue from five donors diagnosed with Autism Spectrum Disorder (ASD) contained “some of the highest values yet measured in human brain tissue” of aluminium. He postulated “perhaps we now have the link between vaccination and autism”.

This controversial claim comes almost two decades after Andrew Wakefield published the now discredited and retracted research into ASD and the measles, mumps and rubella (MMR) vaccine which was linked to a decline in vaccination rates and recent outbreaks of measles.

I spoke to Tom Chivers from Buzzfeed about my concerns with this paper. In his article you can read concerns from myself and eminent academics Professor Dorothy Bishop and Professor Jonathan Green, renowned experts in neurodevelopmental biology and child and adolescent psychiatry respectively.

Such a controversial claim which can affect the health of children worldwide really needs some solid supporting evidence. So, let’s take a look at the paper itself.

Aluminium in brain tissue in autism

The paper is due to be published in the Elsevier Journal of Trace Elements in Medicine and Biology in March 2018 and the accepted paper is available to read online. The authors introduce the study saying “we have measured aluminium in brain tissue in autism and identified the location of aluminium in these tissues”. The paper can be split into two sections.

Section one

The authors measured the levels of aluminium in brain tissue taken from five donors aged 15 to 50 who had all been diagnosed with ASD prior to their deaths. They took 0.3g tissue samples for four (occipital, frontal, temporal and parietal lobes) or five (they added hippocampal tissue where it was available) brain regions. They measured three replicates of each brain region using spectrometry.

The problems with the methods and data from this section are three-fold:

  1. The authors took samples from only five brains – all five donors had died with a diagnosis of ASD. There were no healthy control samples used anywhere in this study. This is a particular problem because without a healthy control, it is impossible to really say whether the aluminium levels measured in the brains of the donors is actually higher than that of a non-autistic brain. There is nothing to compare the measurements to.
  2. Importantly, the authors do not provide information on how the donors died. We have to take their word that the cause of death does not account for variation in brain levels of aluminium. An important part of the scientific publication framework is that this sort of information should be easily available to the reader. We need to be able to come to our own conclusions based on the data presented. That this information is missing is quite concerning.
  3. Finally, in some cases the three replicates from each brain region per donor did not corroborate each other. In one case there were three measurements of 0.01, 0.64, and 18.57μg/g. Similarly, another donor had measurements of 2.44, 1.66, and 22.11 and another, 1.71, 1.64, and 17.10μg/g. The authors averaged these data, however such an average does not represent any of the three measurements and is an inappropriate way to analyse these figures. In fact, such variation between measurements might even hint at an anomalous result, which requires further assessment to adequately rule out.

Section two

In the second section of this paper the authors took samples of brain tissue from the valuable Oxford Brain Bank. Again, they took tissue from a selection of donors who had been diagnosed with ASD before their death. Again, the authors failed to express how the donors died. The authors took samples from 10 donors aged 14 to 50 and stained them with a dye that specifically sticks to aluminium. The dye can then be visualised with a fluorescent microscope to see where in the brain tissue it can be seen.

Again, the issues with this section are three-fold

  1. This section also lacks the use of ‘healthy’ controls. The authors do show presence of aluminium in the tissue samples of their ASD donors but we have no indication of whether this is, in fact, more than we might see in a healthy brain.
  2. This section is also lacking a positive control – a sample that has a known amount of aluminium in it. This is important for interpreting the staining of the dye; if the dye is very sensitive then we might see loads of staining for just a small amount of aluminium. We need to compare it to a known sample.
  3. Later in their interpretation of these data the authors discuss the presence of aluminium in specific cell-types which they surmise might be lymphocytes. However, they do not use any detectable markers to propose this, they base it only on how the cells look. Cell appearance (also known as morphology) is a useful initial indicator of cell-type but it is important to confirm this using specific markers for those cells.
1-s2.0-S0946672X17308763-gr1
A figure taken from the paper which apparently shows the accumulation of aluminium in specific cell types

Overall the data from this paper is insufficient to draw the conclusions made in the Hippocratic Post and The Daily Mail and it is my concern that such reporting is irresponsible. While the two articles conclude that aluminium present in the brains of people with ASD might be caused by vaccination, there is no investigation whatever into the source of such aluminium in this study. There are no data presented in this paper sufficient to implicate vaccination in these findings. To draw the link between aluminium in the brain of people with ASD and vaccinations makes for a striking headline but the data do not support this claim and it could therefore be viewed as scare-mongering.

I am surprised that this paper was published in the Journal of Trace Elements in Medicine and Biology because the lack of control data makes the findings inconclusive. I am yet more surprised that this inconclusive data has been reported in such a paper as The Daily Mail, when such media attention can lead to parents making potentially dangerous decisions for the health of their children.

Please let me know below what you think about the reporting of this science?

How many mutations does it take to create a cancer?

Last week I wrote a post all about how we understand cancer to arise. I explained how mutations in certain genes for certain proteins can drive cancer and I explained some of the important families of proteins such as oncogenes and tumour suppressors.

But even that complicated post was an over-simplification. Sure, a single mutation in a single gene for a single protein might cause cancer, but actually we know that many cancers have several mutations. Sometimes, several hundred mutations.

Several hundred mutations

many mutations per cancer
Image adapted from this paper. A graph showing a number of non-synonymous mutations per tumour against tumour types ranging from colorectal cancer to glioblastoma. (See the text for some example figures).

The above is an image which shows just a few examples of some cancer types and the number of mutations you might expect to find in them. Recognise the word non-synonymous from last week? Non-synonymous mutations are those which cause a change in a protein. Whereas synonymous mutations are effectively “silent” (they don’t change a protein) so we tend to focus on non-synonymous ones when it comes to disease. You can read more about them here.

From the image you can see that some types of cancers can have several hundred mutations per tumour – colorectal cancer for example can have between 500 and 1200 mutations. Lung cancer can have between 100 and 200 (interestingly this is much lower for lung cancer in the “never-smoked” category which has a considerably smaller number of 25) and breast cancer between 25 and 100 mutations per tumour.

The problem

What this means is that when it comes to understanding what drives cancer we need to know how many of these mutations are actually relevant to the disease. Do they all contribute to “driving” cancer or are some of them “passenger” mutations? If only a few contribute, then how many?

Often, we treat cancer by designing drugs which target specific proteins. If we suspect a cancer is “driven” by an overactive protein then we can treat patients with an inhibitor of that protein – something that blocks the protein’s function. But for us to do this, we need to know which mutation, potentially hundreds, is actually relevant. It’s like trying to find a needle in a haystack.

The study

The paper published in October 2017 in Cell is an analysis of 7,664 tumours across 29 different tumour types. They looked at all of the mutations each of those tumours had and focussed on the non-synonymous ones, the ones that actually change the proteins inside the cell. But they knew that even with protein changes, not all of the mutations present actually cause cancer. They wanted to establish how many might be responsible for the disease.

“Normal” cells acquire mutations all of the time but this happens at random so sometimes it will affect proteins and sometimes it won’t –  we get a reliable mixture of non-synonymous and synonymous mutations that are all mostly harmless even if there is a change in a protein. This is useful information because we can establish an “expected” ratio between the two. In cancer cells, the mutations that change proteins and allow a cell to survive and grow more than it should (i.e. the mutations that drive cancer) are passed on to more cells as the cancer cells replicate. This means you get a skewed ratio in cancer cells – more non-synonymous mutations than synonymous ones. By figuring out how many more mutations there are than we expect from the “normal” cells we know that those are the ones allowing cells to replicate in an uncontrolled way – therefore those are the ones that are driving the cancer.

And that’s exactly what the authors of this study did.

What they found

What they found was that although some cancer cells have hundreds of mutations, only a few of those actually drive the cancer. The average number of cancer drivers per cancer type is just four and the numbers only range from one to ten. So, we can narrow our focus to between one and ten mutations per tumour. We just need to figure out which ones.

This is phenomenally useful information because we can then build further on this knowledge to understand which mutations are the common driver mutations and focus our drug development on those specific mutations. We have a significantly smaller haystack and we can start to really get very specific with our cancer therapies! The better our understanding of how cancer really works, the more complete our understanding of all of the complicated processes involved, the better able we are to design clever therapies that really benefit patients.