Tuesday, October 29, 2013

Grumbleweed Does Reality TV - Gets Screwed

Here's a rather funny story (but, on your honor, dear reader, you must keep this to yourself)........

Earlier in the year, this guy I know flew down to New Orleans to audition for a certain TV talent show. He wore a Scottish kilt to stand out from the crowd. This was probably a good move as it caught a lot of attention - and some flack. Some rednecks were laughing quite openly - "Look, there's a dude in a dress"!

A kilt similar to the one worn by this guy I know

It was a long slog, as all of the city's star-struck hopefuls - about 6,000 people - had to line-up for 5 hours to register with the show's support crew, and then turn up two days later to line-up again for the privilege of standing on a small, silver duct-tape cross on the floor to sing 90 seconds of acapella to a couple of stern-faced producers. No celebrity judges at this stage. No backing tapes. No instruments. Just sing (and dance if you have that in you). And this guy I know doesn't dance, but he had to sing with a serious case of dry-mouth!

There were about 20 curtained-off areas on a stadium floor, each one about 10 feet by 10 feet. Like a black cloth barn with black cloth cattle stalls. This is where all of the hopefuls got to 'do their thing'. It was weird and distracting, as this guy I know could hear everyone else 'do their thing', including some kids whose parents should probably know better, and some ambitious and delusional airheads who would undoubtedly make it through for comedic value.

The "open cull" booths. I borrowed this image from the Google machine

Anyone who was close to what the producers might be looking for was given a "Golden Ticket" (actually a piece of yellow photocopier paper) and went through to another large room to fill out a questionnaire. Anyone who was unsuccessful at this stage was given instructions to leave immediately and had to do the "walk of shame" out of the arena. Do not pass GO, do not collect $200. Several youngsters left in tears, devastated, being almost carried out by their parents or other supporters.

The coveted "Golden Ticket"

This guy I know - as I said, with nerves causing all the spittle to evaporate from his mouth - sang to two lovely lady producers, and did a verse of Michael Bolton's "How Am I Supposed To Live Without You", but then launched into a raucous chorus of  "Oh Darling" by the Beatles, allowing him to finish on a crazy high note - "I'll never DOOO YOOOOUU NO HAAAAAAAAAAARM"!

This apparently had the desired effect and took the ladies by some surprise, so a "Golden Ticket" was promptly handed over, allowing this guy I know to advance to the next stage. Exciting! He attempted to give the ladies a hug, but they backed away as this was apparently not allowed. So they all did "virtual hugs", which, had they been caught on camera, would have looked amazingly "campy". The thought of that still makes him shudder a little.

The support crew in the second room - full of excited and wide-eyed "OMG, I got through" folks - explained to everyone that they should wear the same outfit upon return "for continuity". Oh goody, thought this guy I know - another day of  "Look, there's a dude in a dress"! 

The next stage was on the following day. Not knowing beforehand that this would be a possibility, this guy I know had to rearrange flights, car hire and hotel. Gaaahh! THAT was a fun afternoon!

On the following day, the 6,000 people had been whittled down to (a guess) 1,500. Still a pretty big crowd. The curtained-off, cloth barn areas on the stadium floor were now fewer and a little larger, but it was the same process all over again. Line up, wait your turn, stand on the duct tape, answer a few personal questions - try to be "interesting" and sing your song. On this occasion, this guy I know faced two different lady producers (nope, still no celebrity judges). They seemed to like his stories about touching Ziggy Stardust's hand when he was 14 and about how amazing it had been to become a daddy again at aged 52! He sang his "How Am I Supposed to Live Without You : Oh Darling" bit again and got a red card (more colored photocopier paper), meaning that he was through to the THIRD stage. He deftly avoided the virtual hugs and made his way through the curtains.

The third stage audition was that same afternoon. PHEW! Thank goodness there weren't MORE changes to flights etc.! What had been some 1,500 hopefuls remaining after the first stage became something like 800 hopefuls (another guess) after the second stage. Now they were getting serious!

More long lines and more waiting around and then - finally - individual auditionees were ushered into a small room (about 20 feet square) to face four guys. GUYS! Singing a "lurve song" to four guys was going to be interesting, but whatever!

So this time, it was a cameraman, a sound engineer and two executive producers (you shouldn't have to ask, but NO - still no celebrity judges). More questions, more "Hey, look at me, I'm cool and interesting"-type answers - but now all to camera. "What's with the kilt?" they asked. "What first got you into performing?", "What do you do for a living?", "Tell us a little about your musical history", "Are you British?", "Any kids?", etc., etc. This guy I know took each question and fitted it to a fairly well practiced anecdote, and he thought it went well. At least the producers laughed when he expected them to!

Mixing things up a bit, he sang the verse of a Gavin DeGraw song - "I'm Not Over You", but instead of going into the chorus, he hit the chorus of "You Oughta Know" by Alanis Morisette. He knows with that Alanis song that if he hits the first note at the top of his full voice range, the song doesn't go any higher, so it all comes out nice and powerful! One of the producers started head-banging! It felt good! More questions and a request for another song. From a prepared list, they asked for "Bed Of Roses" by Bon Jovi. That felt pretty good too, but after such long days and very little refreshment (the venue had confiscated food and drink from everybody's bags and back-packs and expected everyone to pay concessions prices for shitty food and beverages), his voice was a little crackly on the top notes of the chorus. He had quipped when he had first walked in and the executive producers had asked "How are you?" that he was exhausted and in desperate need of a good cup of coffee, so he thought that maybe he got away with those odd crackly notes! Such things never did Rod Stewart any harm!

Everyone was told at the beginning of the day that they would not be given a "Yes" or "No" at the end of the day. The producers take all of their notes, all of the tapes and all of the video footage back to LA and decide who - out of those last 800-odd people - gets to travel back to New Orleans later in the year to face the celebrity judges (YES, that's when they finally show up!) This is the bit everyone thinks is the almost spontaneous "walk off the street and audition for The Voice, or America's Got Talent, or The X-factor or any of those shows". In fact, in each city, these shows have already culled the wanabees, probably down to less than 100 people from the initial several thousand - those few people that get the final call-back, and no doubt half of whom are the cute and funny delusional airheads that help to bring the ratings up. Everyone for this show was told that if they hadn't heard anything by early June, then they could assume that they didn't make it. There is no call if you don't get through.

So this guy I know went home and played a hideously painful waiting game. Was he interesting enough? Did the camera hate him? Was his voice good enough to put him in with a chance? Does the one lady producer to whom he sang on the first day and who threw him a lovely smile when she saw him on the second day have any influence? Is he really what a reality show is looking for? Is he insane? Is that a squirrel? .....so many questions!

All hopefuls had signed a document promising not to tell the world about the process or how they did (under threat of disqualification), but I think telling you in a private blog post - this long afterwards - is ok. Especially as this is all third-hand. I mean, it was this guy I know, not me at all.

In a last comment that he suddenly felt compelled to throw out there at the executive producers, this guy I know said something along the lines of "Off the record, and regardless of the outcome of today's audition, I'd just like to say thanks to you guys for doing what you do. You give old buggers like me some hope again - allow us to live the dream one more time". It was meant quite sincerely and he was tired and emotional. He could hear the wobble in his voice. Oh he knows these shows are all big marketing ploys and that they chew-up and spit-out more souls than is probably decent or humane; but they also help a few people live the dream again. He met many such people over that very long weekend, all with great stories - all with histories like his own. Nobody forces any of them to indulge in that potential humiliation. It is done willingly because they all think, "Just maybe, just this once it will all work out - this is the time the dream will come true".

And don't some of those well-established rock stars just LOVE to criticize reality TV shows. "Why don't these pathetic wannabees do what I did and go pay their dues - go play smoky bars and clubs and send demos into record companies and get a few rejections. Rather than taking the easy way out and getting famous by going on a faky, commercialized, sell-out TV show, maybe they should try some hard work and get some real talent"? The most disappointing comment like this I have seen was made by none other than Dave Grohl (Nirvana and Foo Fighters) - someone I otherwise admire and respect. Well, chances are that Dave would be wearing a paper hat and asking "D'ya want fries with that?" if he hadn't been given a break - a chance or two - some opportunities - by someone he's apparently forgotten along the way. Maybe if he hadn't met - oh I don't know - Kurt fricken' Cobain, for example? Susan Boyle didn't even win Britain's Got Talent but the exposure led to her selling millions of records and turned her into an international star. Why is that any less credible than the way Dave Grohl sells fricken' records? The point is that artists bring entertainment to the public - who gives a crap what bus they took to get there? Grohl should count his many blessings and let others gather theirs however they can. Muppet!

Anyway, it had been just over three weeks since the audition and this guy I know was climbing the walls. He wasn't sleeping well and couldn't focus. It was weird times, dudes! It was like he was back in his twenties, waiting on some record company executive who had FINALLY deigned to come to one of a thousand or so gigs in a smoky club or bar to make a decision that might make or break him! Or like that time when a record producer in Germany had wasted an entire year with promises of a major production deal and then just walked away. Or like the time a major record label in the USA had promised to sign him and then changed their minds after a few months for bullshit political reasons. Or the time he played to a packed theatre in Litchfield, UK and a major record company executive sat in the bar sulking because the band hadn't offered him any cocaine. You know, like the stuff Dave Grohl reckons all of these auditionees should have done.

But just in case, this guy I know had been in the studio and recorded the backing tracks for the hybrid songs he sang, you know, just in case he got the call-back and needed to do that on stage in front of the actual judges (one of them sounded something like this, https://soundcloud.com/adrian-grimes/you-oughta-knover-you - but, obviously, that's only my version and not the one by this guy I know).


So, one lunchtime in May, this guy I know was with his young daughter and walked into an office on the local University campus to collect some free tickets for the Children's Museum in the town where he lives. Lots of ladies were standing around, eating cake and drinking Coke or 7-Up or something. A birthday party, he assumed. They all looked at his cute little girl and started with the customary "Aaaaah - isn't she adorable"- type stuff (well, she IS)! 

Then this guy I know heard his phone start to ring and he couldn't get to it and, while fumbling around in his pocket, managed to drop it, cutting-off whomever was trying to call.

Ten minutes later, as he walked out of the building, he redialed the number and a lady answered "Freemantle Media, can I help you?"

The lady on the other end of the phone - Miss Freemantle - couldn't divert the call as this guy I know had obviously cut the caller off and it didn't go to answerphone, so he didn't know who from the company - F-R-E-E-M-A-N-T-L-E (do I really have to spell it out?!) had actually called.

Dude - he just put the effing phone down on the effing X-Factor.


And they never called back. 

Yes, he almost got to perform on Prime-Time National TV in front of millions of people, but ........he dropped his phone.

How's that for a story about "the one that got away"?

Tuesday, October 15, 2013

Vaccines (again)

(updated 17th October)

Note to readers - advertising disclaimer: As always, I have provided links to help explain, validate and support any assertions made in my post and I strongly recommend following those links. However, there doesn't seem to be anything I can do about it, but the intertube goblins have decided to randomly place advertisement links throughout my posts. These tend to be underlined and non-italicized and a different color to my links, which are underlined and not italicized. Avoid these advertisements if you can!

I've covered the anti-vaccine stuff before - here.

I thought I'd leave it at that, but then I saw this posted to Facebook yesterday:

Cards on the table. I have only had the flu vaccine once - last year - because I am not entirely convinced that I am in a "high risk category" and I am relatively unimpressed by the vaccine's efficacy in any given year (more details on that below). But I will now have the shot regularly because I have a young child who is in a higher risk bracket and I don't want to feel responsible if she gets the flu. My concerns are now of lesser importance than her well-being. But, as the header on this blog suggests, I feel an obligation to add to the sum of accurate information in the world and I would like people to be able to make important decisions based on that.

If you wish to waste your time with (or have a laugh about) the details of this list of 11 reasons to which this image linked on Facebook - it is here. Of course, it is a list full of half-truths, misrepresentations, scientific ignorance and plain lies. But let's break it down and start with what this particular vaccine - the influenza vaccine - DOES achieve.

Some background - why do we even need a vaccine?

Each year, an average of 5 to 20% of the U.S. population has symptomatic influenza - that can be up to around 60 million people. 226,000 are hospitalized and 24,000 DIE due to influenza-associated illness. 90% of deaths are in folks age 65 and older, but deaths also rarely occur in otherwise healthy children and young adults.

I think it would be safe to assume that only a crazy person would believe the influenza vaccine hospitalizes around a quarter of a million people or kills more than 24,000 people a year, so we can at least start from the obvious observation that the vaccine is absolutely NOT "more dangerous than the flu itself". But is the vaccine effective?

Well, the most up-to-date scientific data (2013) suggests that the flu vaccine is moderately effective in those who receive it and that it prevents about half of influenza-associated symptomatic illness, outpatient visits, hospitalizations and deaths. This is, of course, a quite deliberately vague number (about half), because it is dependent upon the particular year, particular age groups, the particular health status of individuals, and how well the vaccine of that particular year matches the particular strains of the influenza virus circulating. Some years are good, some are not so good.

But think about that term "moderately effective" for a moment. …  The flu vaccine "prevents about half....." - meaning that thousands more people might have died in an average year if it wasn't for that terrible, awful vaccine. Yes, if it wasn’t for those evil scientists and the horrors of modern medicine and its dastardly flu vaccine program (that SAVED the lives of thousands and prevented another few million people from getting the flu), the world would be a better place!!!

Or not.

So, with that in mind, let’s look at these "11 reasons" why you apparently SHOULDN’T vaccinate.

I have provided the first line of each of the items in the list of "11 reasons" in quotation marks and in bold. Underneath each quote, I give a refutation based on Science. You know, that stuff that allows you to read a blog on the internet; that stuff that eradicated small pox and has helped improve human health and increase longevity. That stuff that put a man on the moon. Yes, that science thing. You'll see that there are plentiful links to other sources to support my wild and crazy sciency 'claims' (something that the list of "11 reasons" didn't provide - I wonder why not?)

So - let's go!

1. “Have you ever noticed how vaccinated children get sick almost immediately following a vaccination?

D'ya know, I HAD noticed that. Good heavens – you mean to tell me that the vaccine elicits an immune response???? And there was me thinking it was all magic! All smoke and mirrors! I thought it was the best New Orleans Voodoo!

And then this is possibly my favorite 'lack of scientific understanding' statement from the entire list:

the fact that it causes individuals to get ill following a shot indicates immuno-suppression”..

Bull. And sh*t. This is utter hogwash. Getting ill does not indicate immunosuppression. Immunosuppression is a very specific form of “getting ill”. Some types of “getting ill” involve the opposite of immunosuppression (inflammation, for example, or auto-immune diseases like lupus erythematosus or multiple sclerosis). Immunosuppression CAN be an issue for patients undergoing long-term treatments that involve multiple vaccines. This is why there is a lot of concern over the potential for therapeutic cancer vaccines to be poorly tolerated. But people vaccinated with the flu vaccine are not immunosuppressed - they are mounting an immune response. Their immune system is being stimulated. Think Sesame Street - "One of these things is not like the other"!

Strike one. Poor understanding of science.

2. "It is now a known fact that flu vaccines contain mercury”.

Oh Really?? Well it is also now a known fact that this statement is bunk. Or at least very misleading. It is as accurate as claiming that "cars run on electricity". Why, yes - some cars DO run on electricity - and SOME flu vaccines contain mercury. However, while multiple dose vaccine bottles contain thimerosal (a preservative that produces ethyl mercury when it breaks down), there is no mercury - ZERO - in individual-dose bottles of the flu vaccine. NONE. And every single year, manufacturers produce far more of this thimerosal-free (mercury-free) vaccine than people use. If you want you or your child or your frail great great step-uncle to get the vaccine with ZERO mercury, just ask your provider for a single-dose bottle and then you avoid this boogy-man ethyl-mercury compound that has, in any case, NEVER been shown to be harmful as a vaccine preservative (Andrew Wakefield and his thimerosal/autism "hey let's make some money out of scaring people" circus was a FRAUD)!!

And by the way, if you want to jump in now and complain about how we've all been told how mercury in fish is bad for us, so OBVIOUSLY mercury in vaccines MUST be bad for us....well can I suggest that you look up the difference between mercury (the element), ethyl mercury (C2H5Hg+) and methyl mercury ([CH3Hg]+). Then Google this man: Philippus Aureolus Theophrastus Bombastus von Hohenheim, who once most famously said "Alle Dinge sind Gift und nichts ist ohne Gift; allein die Dosis macht, dass ein Ding kein Gift ist." And he was correct!

Strike two. Lying by omission.

(Update: It is a generality, but the "mercury in vaccines" scare tends to be perpetuated by people of a "Whole Foods persuasion" - healthy folk who don't like the idea of putting anything "unnatural" into their bodies. I'd just like to point out that the sea salt they use instead of processed table salt is precipitated by evaporating sea water and thus contains a lot of other trace elements - some of which may be good for us. But it also contains mercury - along with arsenic, cadmium, fluorine, lead, dioxins, PCBs and anything else that has been dumped into the ocean since the dawn of the industrial revolution. The trace amounts - a few parts per million - probably won't do you any harm, even if you consume it every day, but it is worth pointing out the inconsistency when it comes to freaking out about trace amounts of mercury in SOME vaccines that you might get once a year).

3. "The flu shot can cause Alzheimer’s disease”. 

This is as ludicrous as claiming that bad spirits cause headaches. Or that NASA faked the moon landings. It is absolute nonsense. In fact, a 2001 study of more than 4,000 adults in Canada showed that past exposure to several vaccines, including diphtheria, tetanus, polio, and influenza, was linked to a DECREASING chance of developing Alzheimer's. The false statement in this list of "11 reasons" can be traced back to one man - Dr. Hugh Fudenberg – a "researcher" whose license was suspended in 1995 for dishonorable, unethical and unprofessional conduct. It is not based on any scientific work whatsoever. In short, he made it up. Just pulled it out of his old, retired ass. And, by the way, he now makes a living selling alternative therapies for autism. No obvious conflict of interest there, is there? His "patented" therapy (with his partner ANDREW WAKEFIELD!!) is apparently based on rolling-out cells from his own bone marrow on the kitchen table. I kid you not. Yuk!

Strike three. Pure horse puckey - but let's continue.

4. “The very people pushing flu vaccinations are making billions of dollars each year”.

Oh my gosh! I'd never thought of that.

Then again, so are the people pushing gasoline to fuel our cars. Welcome to Capitalism. You expected them to do it for, what, peanut butter cookies?!!!

Strike four. Meaningless.

5. “Lack of real evidence that young children even benefit from flu shots”.

There is also a lack of "real evidence" that the statement above is true...

This is “cherry picking” of the worst kind.

Let's see - if I perform a quick PubMed search using the search terms "influenza vaccine efficacy", I can see 2088 scientific studies. The list of "11 reasons" above mentions just 51. So the problem here is that important details about the “studies” being cited are missing. When and where were these particular studies conducted? Was this a single retrospective study looking at 51 previously published studies (what we call a "meta-analysis")? How many of the 2088 studies I found show the opposite effect? Were the studies performed in “good” years or “bad” years? In a study conducted in 2003-2004, for example, 99% of circulating influenza strains were due to the influenza A virus, and only 11% of influenza A specimens were similar to a strain included in that year's vaccine. This would have been a “bad” year and would have skewed the data in the “ineffective” direction. Studies published in a “good year”, where there is a good match between circulating strains and the vaccine, would skew the data in the “effective” direction.

Another question - which type of vaccine was being investigated in these selected “51 studies”? This is important because live-attenuated vaccine has been shown to be more effective for young children than inactivated vaccine. If these “studies” were performed before this fact was known (pre-2007), or if these folks deliberately picked 51 studies that looked at inactivated virus vaccines, they would undoubtedly have skewed the data in an "ineffective" direction. You see, scientists need details in order to form an informed and educated opinion. In this list, there is no real evidence of any detail.

If you really want to get into the complexities of epidemiology, here's a starter. Warning - it isn't as simple as we'd like..

Strike 5. More lying by omission.

6. "Makes you more susceptible to pneumonia and other contagious diseases".

This is an interesting hypothesis and it seems quite plausible - if you believe the other stuff about immuno-suppression and if you ignore the fact that flu itself also makes you up to 100-times more susceptible to pneumonia and other contagious diseases. But anyway, until you show me a series of science-based clinical trials that demonstrate its veracity, then this claim is mere conjecture - it is guess work. Someone pulled it out of their ass (and see 5 above).

Strike 5. Not supported by scientific data.

7. "Vascular disorders -  Medical research shows flu shots are associated with an increased risk of vascular inflammation”.

Apart from the fact that "vascular inflammation" and "vascular disorders" are not the same thing (Sesame Street again), this statement might be almost true - with the caveat that the inflammation is temporary and not serious (see 1 above). This is called “eliciting an immune response” and is part of the reason why vaccines work. In some people, these symptoms can be quite severe, but in the vast majority they are not.

Note that inflammation is an immune response. If you were immunosuppressed, you might not get inflammation. In fact, doctors sometimes prescribe immune suppressing drugs (e.g., methotrexate) to people who have inappropriate inflammatory conditions such as rheumatoid arthritis. This is more evidence that the whole "immunosuppressed" thing above (in item number 1) was clap-trap. Inflammation shows that your immune system is working. Importantly, if you have a pre-existing "vascular disorder" or if you have heart disease, you really should consider getting a flu vaccine as it might minimize the risk of complications.

Strike 7. Poor understanding of immunology and scientific terminology.

8. “Children under 1 years of age are highly vulnerable to a neurotoxic breach of the delicate nerve center surrounding the brain and central nervous system”.

What a wonderfully evocative statement. And this sentence - in isolation - may actually be true. But - yay! we have our inevitable classic "straw man" argument. This is like saying you shouldn't get the flu vaccine because you might get brain damage if you drop a hammer on your head. Babies are vulnerable to all kinds of things - which is why scientists and healthcare providers would NOT inject a neurotoxin into a baby (see 2 above). Lead is a neurotoxin. Whisky is a neurotoxin. Botulinum toxin is a neurotoxin. Attenuated viruses are NOT neurotoxins. And single-dose vaccines DO NOT CONTAIN MERCURY (just thought I’d stress that fact again)!

Strike 8. Informal fallacy.

9. "Increased risk of narcolepsy".

Hooray! This is the item on the list that is closest to being scientifically accurate. However, it doesn't quite get there because the devil - as always - is in the detail. There was indeed a particular flu vaccine linked to narcolepsy. It was in Europe in 2009 and that vaccine (Pandemrix from GlaxoSmithKline) has not been used since. It was also NEVER licensed for use in the USA because it contained a particular adjuvant (a substance that stimulates a local inflammatory response), and the CDC and FDA don’t want that particular adjuvant here. So, for USA citizens (and anyone else who lives in 2013 and isn't lost in a pre-2009 time warp) – this point is irrelevant. No vaccine used ANYWHERE since carries any such risk. So this "reason" is like saying you shouldn't go to the doctor for a headache because he might drill a hole in your head to let the bad spirits out. We don't do that anymore.

Strike 9. Completely irrelevant to any vaccine developed before or after 2009.

10. "Weakens immunological responses".

We went through that in 1 and 6 above. Hog and wash. Vaccines work by eliciting – not weakening - immunological responses. To claim otherwise is silliness.

Strike 10. More scientific ignorance

11. "Serious neurological disorders"

It is true that almost 4 decades ago (in 1976) an increased prevalence of Guillain-Barré Syndrome was noted in populations receiving a particular flu vaccine. The rate was 1 in 105,000 above “background rates”. This "background rate" at the time in the USA was between 80 to 160 cases each week – regardless of vaccination. Scientists have multiple theories on why this slight increased risk may have occurred, but an exact reason for the association remains unknown, meaning that the vaccine may – but also may not – have been directly responsible. Correlation is NOT the same as causation. Of note – and demonstrating how complicated such numbers are - a more recent study of 90 million people in China who were vaccinated during the 2009–2010 flu season found that only 11 people - yes just 11 out of 90 million people, or 0.00000012% of the vaccinated population - were subsequently diagnosed with Guillain-Barré Syndrome, which was at a LOWER level than in the population that was NOT vaccinated. So IT WAS PROTECTIVE (well, not really - as I said above, correlation is NOT the same as causation). There is also the 2001 Canadian study (mentioned in 3, above) that showed lower levels of Alzheimer's in vaccinated populations. As these studies involved more recent vaccines, perhaps there is actually a DECREASED risk of serious neurological disorders, and we should all run out and get an EXTRA flu shot just to keep the old Alzheimer's away??!!

One more detail to take into account is that people who get the flu are 40- to 70-times more likely to develop Guillain-Barré Syndrome than the uninfected population. Maybe you should take that detail into account when deciding whether you want to minimize your risk of "serious neurological disorders".

Strike 11. Lying by omission and poor grasp of statistical methods.

So, there you have it. That was the 11 reasons why the flu vaccine is supposedly "more dangerous than the flu itself". And if you still believe any of those reasons, well I have a natural cure for cancer I'd like to sell you (it is good for tennis elbow, acne and athletes' foot, too). Seriously, whether or not you get the flu vaccine is entirely your choice, but make that choice based on whether or not you want a slightly increased chance of getting the flu and/or passing it on to a loved one by NOT being vaccinated. If you decide not to based on ANYTHING on this ludicrous list of anti-science poop flying around the intertubes, then you deserve the flu and absolutely no sympathy when you get it!

And if you choose not to get the shot and you end up having to cope with a miserable, sick child, well just put it down to bad luck. I mean, it's not like you could have done anything to prevent it, is it?

Monday, August 26, 2013

Evolution For Dummies - Part 4

Welcome back to Evolution for Dummies, a multi-part series on the sometimes thorny topic of The Theory of Evolution.

What I’ve told you about so far (in Part 1, Part 2 and Part 3), is that you can use family trees to follow lines of inheritance - or lines of gene transfer - from offspring, back through time to the common ancestors that gave rise to groups of relatives, or groups of animals. I've told you that populations are immensely important and that they arise quite rapidly - even in species such as the human, in which the individuals don’t produce large numbers of offspring very quickly (humans have what we refer to as a long generation interval). And that it is in populations that genetic changes occur, and those genetic changes provide for diversity in characteristics such as morphology – shape, size, muscularity, skin color, eye colour, male-pattern baldness, etc., etc. I’ve also given you a primer on how to interpret phylogenetic trees to identify the interrelationships between animals and to trace the common ancestors of entire groups of animals.

So moving on. In this Part, we'll try to answer the big question. Why is this important? Why do we care?

So what??!! 

To get at this question, I'm going to introduce you to animal models. 

First, though, I should explain that there is a subtle difference between what my youngest daughter might think is meant by animal models - shown below - and what biologists mean by animal models.

Model animals. Not very useful in biology.

In the context of biology, when we talk about animal models, what we generally mean is, rather than performing our experiments on actual human beings, we use some other appropriate animal - such as laboratory mice, for example. These are used as surrogates on which we can perform our experiments to study biological processes, and then from those experiments we can make inferences about how those biological processes may occur in humans. I already mentioned the laboratory mouse, but there are many model species you might hear about in the news, including, but not limited to, pigs, rats, frogs, zebrafish, worms, and even fruit flies. 

Now, there are some very valid ethical considerations when using animal models for biological experiments. The welfare of animals used in research is extremely important and, in addition to ethical reasons, there are good scientific, legal and economic reasons for making sure that animals are looked after properly and used minimally. I won't go into the reasons here, but I will say that scientists, in general, are very aware of these considerations and, in fact, must jump through all kinds of hoops to justify the use of animal models in every single experiment they propose. Every scientist in The USA (or, indeed, in most of the world) is aware of the principle of "The 3 R's" - and it is worth laying those out as they are the foundation of good scientific endeavor:

1. Replace the use of animals with alternative techniques, or avoid the use of animals altogether.
2. Reduce the number of animals used to a minimum, to obtain information from fewer animals or more information from the same number of animals.
3. Refine the way experiments are carried out, to make sure animals suffer as little as possible. This includes better housing and improvements to procedures which minimize pain and suffering and/or improve animal welfare.

So, with that out of the way, in the context of this series of posts, what I want to stress is that the study of evolution validates our ability to study model animals to understand many aspects of human biology. Things such as how we are made, how the processes that determine how we are made can go wrong to cause birth defects and disease, and how we respond to our environment and to various stressors such as drugs and poisons. And this word "validates" is important. 

This is because, actually, for centuries, man has been carving up animals and noticing the similarities and differences between them and/or the differences and similarities between those animals and us humans. An ancient greek hunter, for example, might have noticed how a deer heart looked similar to the heart of a duck. This sort of observation would have been the beginning of what we now know as comparative anatomy - "this looks the same, this looks different".

The hearts of a deer (left) and a duck. Even an ancient Greek hunter would have recognized the similarities
In fact, without delving too deeply into the history of the study of evolution, even ancient Greek philosophers were trying to work out the interrelationships between animals, and it was Aristotle – back some two and a half thousand years ago -  who came up with the idea of "The Great Chain Of Being", which, although imperfect by modern standards, set the stage for many other thinkers who followed. He also identified the heart as the most important organ of the body, the first to form according to his observations of chickens in their eggs. He described the heart as being the seat of intelligence, motion, and sensation. Perhaps a little overstated, but there is no arguing the importance of the heart! 

Another Greek, a man called Claudius Galen, lived back in the second century AD and was (among other things) a physician to gladiators! He advanced the field of comparative anatomy by performing dissections on animals such as monkeys and pigs. This looks the same, this looks different. Interestingly, even though Galen's work was ultimately shown to be - shall we say - naive, it was so convincing that it remained effectively unchallenged until well into the Renaissance, over 1,000 years later!

Galen's famous (and not quite accurate) sketch of the heart

Leonardo da Vinci (1542 - 1519 ) was famed for his drawings of comparative anatomy. This looks the same, this looks different:

Leonardo da Vinci's legs (actually, they are the legs of a dog and a man)

But now we have entered an era of fascinating discoveries about the molecules of life. We can look at - and study - DNA, proteins, and the interactions occurring within and between individual cells, and now we understand the interrelationships between animals based on these minutiae, rather than on just "this looks the same, this looks different". So we now know that the reason an ancient Greek hunter might have noticed how a deer heart looked similar to the heart of a duck was because, actually, they are constructed throughout embryonic development in very much the same way, using very much the same genetic programs. We see high levels of conservation (meaning the percentage of genes that are identical, or the degree of 'identicality' between genes of different animals) in those genes that are utilized in the embryonic development of a human and of many other species.

To illustrate this point, I have another question for you. Would you think that this creature - the lowly fruit fly, the annoying little pest that buzzes around your overripe bananas in the summer - would be useful as an animal model to inform us about the embryonic development of a human heart, for example?
The fruit fly (Drosophila melanogaster)

Well, in fact, many of the genes that are known to be important for the proper development of a human heart were first identified in a fruit fly! A gene called Tinman, for example, was discovered in the fruit fly and if this is rendered non-functional in the fly then it doesn't develop a heart and dies. Hence the name Tinman, who was the character in the Wizard of Oz who didn’t have a heart. If the equivalent gene is rendered non-functional in humans, the result is also serious cardiac defects.

To give another illustration of genetic conservation, below is a photograph of a chicken heart taken at a stage of embryonic development just before hatching. What is important is that it is colored by two highly specific reagents - for the purposes of this post, let's just call them "dyes" - to color one type of muscle red and another type of muscle green. Actually, these dyes are highly specific biological molecules called antibodies that recognize a minute portion of a protein expressed inside the individual cells that form chicken muscle. The muscle "dyed" red is the beating heart muscle - called myocardium - and the muscle "dyed" yellowy-green is the vascular smooth muscle in the arteries.

Earlier in development, the chicken heart looks like this, 

but we can still see that the muscle is dyed by these highly specific chicken muscle markers demonstrating that the proteins are already being expressed in the heart.

Now when I use these exquisitely specific chicken muscle dye molecules, these antibodies, on the heart of a shark, we see that they bind to exactly the same compartments of the heart. They dye the shark myocardium red and the shark vascular smooth muscle yellowy green.
Shark heart

What this means is that minute portion of a protein that exists within the cells of the chicken heart also exists within the cells of the shark heart. And perhaps you will already know (but I'll explain anyway), proteins are the product of genes, so this is a very effective demonstration of genetic conservation. It shows that in spite of the millions of years that separate sharks and birds - you would actually have to travel back in time about 400 million years to find the common ancestor of sharks and chickens - these two species, that now lie as contemporaries at the tips of the tree of life, use very much the same gene program to construct a heart. And it also suggests that the common ancestor of sharks and birds had a heart constructed by very much the same genes and passed those genes on down those lines of gene transfer - those lines of inheritance - to both populations derived from its offspring. Populations that gradually gave rise to sharks and birds.

And, in fact, these same highly specific chicken muscle labels work in the zebra fish - this is a zebrafish heart. 

Zebrafish heart

And, these same highly specific chicken muscle markers work in a mammalian model, the mouse.

Mouse heart

And, while I don't actually have an image to show you, I can tell you that experiments with biopsies have shown that these same highly specific chicken muscle dyes work in the human heart, too - again suggesting that the common ancestor of sharks, fish, birds, mice and even humans possessed a heart constructed of very much the same genes and proteins, driven by very much the same genetic program.

To labor the point about why this might be an important observation, I'm going to show you a very particular region of the heart. The region of the heart where these two colors meet - the region where the beating myocardium (dyed red) connects to the smooth muscle of the arteries (dyed green) - is known as the cardiac outflow tract. It is a kind of obvious term, as this is where the blood flows out of the heart - hence "outflow tract". This is where the blood leaves the heart and flows out into the vascular system. And - importantly - in humans it is the region of the heart that is most commonly affected by congenital heart defects.

I can show you this region in a little more detail by taking an idealized drawing of a heart - and cutting it open

Idealized cartoon of the heart

I know this picture is in 2 dimensions, but just imagine it is in 3D and I am going to take a machete and slice the heart right down the middle - down the plane of the screen - and then remove the front half. Like this:

The heart - cut in half

Then, by making another cut just a few fractions of a millimeter behind this first cut and removing the back of the heart, we get what is called a section. It is an extremely thin slice of the heart, often only a few thousandths of a millimeter thick.

"section" of the heart

The outflow tract of the heart is shown below, highlighted by the superimposed circle, first in a full section, and then in a zoomed-in, detailed image just below it.

The circle highlights the outflow tract of the heart

I can now dye that section of the heart with those highly specific chicken muscle dyes again. What you can see is an overlap between the beating myocardium and the smooth muscle of the arteries - where these two types of muscle form a junction:

The outflow tract of the heart - now in pretty colors
In 3D, this would be like the connection of two pipes, or the connection between a hose pipe and a spigot, where one fits snugly just inside the other. The red myocardium effectively forms a collar around the green "pipe" of the artery.

Well, this dude I know - while doing his post-doctoral research - was able to show in 48 different species, including representative species of sharks, fishes, lungfishes, amphibians, reptiles, birds and mammals, that this portion of the heart has extremely high levels of genetic conservation in the way it is constructed through embryonic development. This means that we can effectively study the development of the heart and the way the outflow tract is constructed in any one of possibly thousands of species. And by identifying any subtle differences in the way these various species connect the heart to the arteries, we may be better equipped to recognize and address the possible ways by which the human gene pool may occasionally get things wrong and produce a defective heart.

Evolution has allowed this, because the interrelationships between animals means that we don't have to redesign the wheel every time we investigate a new animal species. We humans have known about these similarities for many centuries, but only in the last few decades have we been able to work out why these similarities exist. Evolution has validated much of that previous work and now validates the much more effective application of the "Three R's". We can certainly Replace the use of fluffy animals with alternative, less sentient animals, such as zebrafish, for example. We can thus Reduce the number of fluffy animals used to a minimum and Refine the way experiments are carried out, by utilizing frogs, or snakes, for example.

I'd like to finish this post by introducing you to a truly amazing person whose work inspired me to go on and learn more about evolution and embryonic development.

Helen Brooke Taussig

This is Helen Brooke Taussig, who pretty much on her own began the scientific discipline now known as pediatric cardiology. At Johns Hopkins hospital in Baltimore, she pioneered surgical interventions that have saved the lives of countless children born with a condition known as blue baby syndrome and she was very influential in the drive to have the drug thalidomide taken off the shelves. Sadly, she died in a car accident in 1986, just short of her 88th birthday, but she was still performing research even in retirement - trying to better understand the impact of genes and genetic defects on the way a baby’s heart grows during embryonic life. She had a profound understanding about how evolution has fashioned the human heart and how the study of the heart in other species can help us better understand the way a human heart is formed and how that can go wrong to cause conditions such as blue baby syndrome. After her death, two highly regarded cardiologists, Edward Clark and John Opitz, wrote that she understood how:

everything that develops has evolved; that nothing can occur in development, whether normal or abnormal, that has not been made possible by evolution; and that all analysis of birth defects is the study of evolution in the clinic or at the bedside”.

And I should stress here that the word “develops” here refers to embryonic development – the way an embryo grows from a single cell through to an independent, fully formed animal.

So - in summary - what I hope I have impressed upon you in this series is that common ancestry or common descent is a central theme of evolution and is applied by tracing back lines of inheritance or gene transfer through often millions of generations to infer the interrelationships between animals. You can't draw a straight line between any two populations of animals or any two modern species - you have to trace the lines back through the parents, the grandparents, the great grandparents, and so on, until you find the common ancestor.

I've told you that although there are some cases of rapid evolution, as we humans have managed with domesticated dogs, more usually natural selection works over eons - millions of years - and occurs as a result of genetic diversity within populations.

You should now be more familiar with family trees and how phylogenetic trees are constructed by assessing characteristics such as morphology and the similarities and differences in genetic information.

And, using embryonic development of the heart as an example, I have shown you how animal models are being used in biology and how evolution validates that endeavor.

Thanks very much for reading. Please feel free to comment or to share with others.