Doobie-ous conclusions

I contribute quite a lot to the Herald & Guardian Comments sections.  And I’ve noticed something.  Whenever there is a story on cancer, eventually someone will post a message along the lines of “Cannabis Cures Cancer!!  Fact!!!!”  The Guardian in particular is rife with this sort of thing.  Every comments section for every cancer story has at least one of these.

Where has this idea come from?  Why have so many people latched onto this notion that Cannabis is A Secret Cure For Cancer?  And is it true?  Can it be true?

Well…….no, it can’t.  Sorry folks, but this is nonsense.  I think that a lot of people just love to think that there is a secret magic cure out there somewhere.  And if that secret magic cure is a recreational drug, then even better.  This is certainly the case for the “wine prevents cancer” stories that I mentioned in Just One Cornetto, and it is especially true in the case of an illegal drug like cannabis.  But I’m afraid that the facts just don’t stack up.

There has been plenty of research carried out into the potential clinical uses of cannabis.  Most of the research carried out so far has been in cancer cells cultured (ie. grown) in plastic dishes.  The researchers dosed the cancer cells with cannabinoid extracts to see what effect they had.  And hey presto!  Some of the cancer cells stopped growing!  Now this in itself is not that impressive.  It is relatively easy to kill cancer cells grown in culture dishes.  Loads of things do this.  Hydrochloric acid….Alcohol….even pure water can kill cancer cells in dishes.  This doesn’t mean that any of these things will have the slightest effect in human cancer patients.  Well…the water would be good for hydration, I suppose….. and the alcohol would get them tipsy.  But hydrochloric acid…?  Let’s just say, I wouldn’t recommend it!

Some researchers have also reported that cannabinoid extracts exhibited promising results in other preclinical models (ie. some animal models as well as cells in culture).  Now this is a bit better.  It’s still not conclusive proof that there is anything to this, but it certainly warrants further investigation.

Now spot that in the last few paragraphs, I didn’t say that cannabis has shown promise in preclinical models.  I said cannabinoid extracts.  And that’s the point.  Before commencing these studies, the researchers took the cannabis leaves and mushed them up in chemical solvents to break them down.  Then, they poured the resulting gloop into a special types of filter called a HPLC that separates out the constituent parts.  They could then collect a large number of fractions, each containing a large hotch-potch of different molecules.  It is the various fractions extracted from cannabis that have been under investigation. Not cannabis itself.

Even if there is a protein or enzyme in cannabis that has some efficacy, it is only one among hundreds, if not thousands.  What concentration is the active agent likely to be at in the plant itself?  It’s highly unlikely that there will be enough in the natural product to show efficacy.  Also, what are the thousands of OTHER components doing?  Are they beneficial?  Poisonous?  In fact, some research has shown that there are cannabinoid extracts that actually make the cancer cells grow faster.  So, whether cannabis has pro-cancer effects or anti-cancer ones will depend on the overall amounts of the good and bad components found in the leaves themselves.  The good stuff might be there at a higher level than the bad stuff, but it could just as easily be the other way round.

Still, it is certainly possible that an active anti-cancer compound could be purified from cannabis.  Does this mean that it would inevitably become a new treatment?  No.  I’m afraid not.  The sad fact is that there are numerous instances of new drugs that look very promising in these preclinical models, but fail when they enter clinical trials.  Therefore, you cannot just extrapolate preclinical effects to human cancer patients. If you could, then there would be absolutely no point in carrying out clinical trials.

Take a look at the figure below.  This is an estimate of the attrition rate for new compounds during drug development (ie. the rate at which compounds fail).  Now, the take home message is that for every 5-10,000 compounds that show early promise, only one will make it through the clinical trials process to become a new drug.  Just let me repeat that.  The most optimistic chance is 1 in 5,000.

Drug Discovery Attrition rates

Let me put it this way: What this statistic means is that all that the current research can tell us is that cannabinoid extracts have only a 0.02% chance of being effective in human cancer patients.  But let’s try to be positive here!  In fact, let’s be overly optimistic!  Let’s say that the cannabinoid extracts make it through the initial screening.  Let’s say that a compound is isolated, which can be chemically modified to improve its performance, and turn it into a potential new drug, and enough of it can be produced to undergoes full preclinical assessment.  This would mean that it would still only have a 1 in 250 chance, or 0.4% chance of being an effective anti-cancer treatment.

So, sorry folks, but the idea that cannabis is a secret Cure For Cancer, but that this knowledge is being repressed by The Man is just nonsense.

But, I’m a magnanimous guy. It’s Friday night as I write this, and I’ve had a few beers. So, if any of you still want to believe that cannabis is an effective cancer treatment, based on the premise that it contains tiny, no miniscule traces of a compound that has, at best, a 99.6% chance of being Completely Bloody Useless, then go ahead, knock yourself out.  Puff away, to your heart’s content. The result will be, quite literally, Your Funeral.

Further info on this can be found on the CRUK homepage.

AG McCluskey (2015). Doobie-ous conclusions Zongo’s Cancer Diaries


Just One Cornetto

It’s a helluva week for cancer stories!  This one’s from the Guardian:

Statins could halve risk of dying from cancer, says major study.  “Dr Ange Wang of the Stanford University School of Medicine, who led the women’s study, said the findings suggest that statins could play an important part in cancer treatment. “We’re definitely very excited by these results,” she said.”

The media just loves this kind of cancer story.

How many “Major Breakthrough!!” stories have you come across?  Or “Major Failings Found!!”?  This story falls into the same trap.  The important word in both the headline and the quote from Dr. Wang is “could”.  Statins could halve the risk…Statins could play an important part…

The thing is, the reported study was not a proper randomised trial.  Instead, the researchers looked at the outcomes for patients with a variety of different diseases, and then looked to see if there was a difference in the death rates of patients who taken statins compared to those who hadn’t.  What they found, was a correlation between taking statins and increased survival rates.  So, not definite proof, but a correlation.

This type of story appears all the time.  Some newspapers are worse than others.  The Daily Mail, in particular seems determined to separate the entire world into things which cause cancer, and things which cure cancer.  Or both:

Daily Mail:  Drinking wine causes cancer

Daily Mail:  Drinking wine prevents cancer

Now, these stories in the Mail cannot both be correct.  Or can they?  Well, in one sense they can.  Taking the Mail stories above, there will be some individuals, with certain types of cancer, where there is a positive correlation between wine consumption and risk of cancer (ie, the more they drink, the more the risk) and others where there is a negative correlation (ie, the less they drink, the less the risk).  But, alternatively, there will be other individuals, with different types of cancer, where there is an inverse correlation between wine consumption and risk of cancer (ie, the more they drink, the less the risk).  So, it is possible for wine to correlate with both an increase and a decrease in the risk of cancer, depending on the patients and depending on the cancer.

But, the thing is, just like in the Guardian’s statins story, all we are talking about here is a correlation.  And an important thing to remember in science is that correlation does not imply causation.  I’m just going to repeat that for you.

Correlation Does Not Imply Causation.

Just because two events happen at the same time, it doesn’t mean that they are connected.  At all.  So, in the examples above, while some studies have found a statistical association between wine consumption and cancer (good or bad), this doesn’t mean that the wine is causing these effects.  Likewise, just because some studies have found a correlation between taking statins and increased survival, this doesn’t prove that there is a causal link.  It may be a contributing factor, but it’s just as likely to be a coincidence.

Let me clarify by way of an example.  In the UK, the amount of ice cream that gets eaten increases dramatically during June-August.  And, also, the amount of professional football games that get played drop significantly during June-August.  Now, how do we explain this remarkable correlation?  What is the link between ice cream and football?  Well, if Correlation = Causation, then there would be an easy, simple explanation:  consumption of ice cream prevents football!  There must be some ingredient in ice cream…some strange, powerful factor…which takes away a footballer’s abilities.  That must be the answer!  When it’s hot and sunny, a footballer is more likely to eat ice cream, therefore his playing ability goes down.  That must be it!  Otherwise, how can you explain the amazing correlation between increased ice cream consumption and fewer professional football games?  Eh?  EH??

But of course, in reality, there is no link.  Correlation is NOT Causation.  It is a coincidence that the football season shuts down during the summer months**, when ice cream consumption is highest.  So, as tempting as it might be to attribute Rangers’ Play-off performances last week to Just One Cornetto too many, I’m afraid that just won’t fly.  Sorry Mr. McCall.

And when it comes to drinking wine, it might increase your risk of cancer … it might decrease your risk.  Or it might be just a big coincidence.  And taking statins might increase the survival rates in some cancer patients.  Or it might not.  The only way to tell for sure is a proper, randomised, double-blinded trial.

(** As an aside, I heard somewhere that the reason that the football season shuts down in the summer is that, at least in England, football was originally linked with cricket.  Cricket games can last, not just for hours at a time, but for days (and days and looong, interminable days).  So, sports clubs played cricket during the summer months, when you get the most daylight.  As the year progressed, and days became shorter, it became harder to play cricket, so the sports clubs would switch to football, which was easier to play in autumn & winter as the games were shorter.  Then, the following year, they would switch back to cricket again in late spring.  So, cricket was played during summer, and football was played from autumn through to the following spring.  And this has remained the tradition, even though the cricket-football link has not existed for decades.  This idea certainly seems logical in England, where cricket is bafflingly popular.  I’m not sure how it would work in Scotland though, where cricket is pretty much ignored.)

AG McCluskey (2015). Just One Cornetto Zongo’s Cancer Diaries

Shades of Grey……..

(Don’t worry, this isn’t about S&M…although please feel free to read on in your Gimp mask, if that’s your thing.)

An interesting weekend for cancer stories.

First, on Saturday we had a rather downbeat assessment of the effectiveness of chemotherapy drugs.   “Many modern cancer drugs are of very little benefit to patients, according to a group of leading European experts…,”

Then, this morning, we had the triumphant announcement of a major breakthrough in immunotherapy.  “Prof Roy Herbst, chief of medical oncology at Yale Cancer Centre in the US, said the treatment, which uses the body’s immune system to attack cancerous cells, as potentially replacing chemotherapy as the standard cancer treatment within five years.”:

Now, the first thing to say is that neither of these stories is 100% correct.  The efficacy of chemotherapy treatments is not as bad as the first makes out, and the promise of immunotherapy is not as spectacular as the second story implies.   You get this sort of story all the time.  The media, especially the newspapers, just love a nice, simple cancer story.  But the truth is a bit more complicated.  If you dig into the stories a bit more, you start to realise that things are not as black & white as they first appear.

First off, let’s look at  the assessment of chemotherapy.  The researchers took individual drugs or combined treatments and looked at the average effectiveness in different diseases.  They gave the overall efficacy a score of 1-5.  In their view, any drug or treatment which scored 3 or less was not an effective treatment.  Only those which scored 4 or 5 made the grade.  Now, what you have to realise first of all is that the researchers were not attempting to assess every drug in every disease.  They were trying to develop a tool to help in the critical assessment of clinical trial data.  So, for the media to report this as an investigation into the effectiveness of chemotherapy drugs in general, is misleading.  Also, the results of this study showed that the same drug, used to treat the same disease, can have different effects, depending on the circumstances.  If you’ve read my previous post, No cure for cancer….?, you’ll remember that I explained that, eg. Lung Cancer was not one single disease, but could be split into a variety of different diseases, each with their own sensitivities to treatment.  This same distinction is seen in the chemotherapy study.  So, for example, a Prostate Cancer treatment called Enzalutamide either has a score of 4 (ie. good), or a score of 3 (ie. not good), depending on the specific Prostate Cancer setting.  So the results are not black & white, but shades of grey.

Now, lets look at the triumphant immunotherapy story.  The treatment investigated used a combination of agents to kick-start an anti-cancer immune response by overcoming the MHC self-recognition system I talked about in No cure for cancer….?  This treatment showed efficacy in 58% of patients.  Now that is fantastic.  Seriously.  It’s a really encouraging result and shows that this treatment could be beneficial for a helluva lot of people.  But (you could tell it was coming, right?)  read that stat again.  Effective in 58%.  Therefore, this means it was not effective in 42% of patients.  So, again we see different effects in different patient cohorts.  Also, even in the 58% where the combined immunotherapy worked, the researchers added this caveat, “combining these treatments also increases the likelihood of potentially quite severe side effects.”  So, not quite the triumphant breakthrough proclaimed by Bill Turnbull on the breakfast news this morning.   Again, not black & white, but shades of grey.

So, whenever you see a cancer story in the paper, don’t take it at face value.  The world is more complex than is often reported.

AG McCluskey (2015). Shades of Grey…….. Zongo’s Cancer Diaries