F@%&ing enzymes, how do they work?!

The new age crowd is always an excellent source of fodder for science-y bloggers who enjoy taking a critical look at their claims.  Everything from good vibrations (in a literal sense) to conspiracies about flouride in tap water seem to fall under the "new age" umbrella.  Today's post is brought to you by the folks over at Natural News regarding a "news" story by Charmaine D. Mercado called The Healing Power of Enzymes for Treating Disease.  It announces the importance of enzymes for all sorts of things, ranging from preventing heart disease and cancer to relieving allergies. Let's take a closer look, shall we?

My favourite part of almost all woo-based reporting is the constant referral to "many studies" without actually taking the time to cite them. Seriously, if you read an article that goes on and on about how there are lots of studies supporting their claim without specifying which ones, that's a good indication that the source isn't trustworthy. In this case, a "growing number of studies" are alleged to be demonstrating that enzymes (no, they're not going to tell you which ones) are great for treating diseases and improving health.

This is probably a good time to step back and have a quick refresher on what enzymes actually are. Enzymes, broadly speaking, are catalysts used by living organisms to increase the speed of the chemical reactions they're involved in. A lot of enzymes are made of protein(s) but some can be made of RNA (riboszymes) as well. Usually (but not always), enzymes are named after what they do and they end in "ase". For example, transferases transfer functional groups from one molecule to another.

So how do enzymes perform biological magic according to Mercado? It would seem that the first step is learning your enzymes. No, put that biochemistry textbook down! We can't trust textbook publishers! They're in bed with Big Pharma and whoever is responsible for putting rainbows in your sprinkler! The only one you can trust for the Truth™ is some stranger on an obscure new age natural cures site.

Remember when I said that enzymes speed up reactions? Not according to Mercado! Forget biochemistry class, enzymes also slow down or even stop reactions. In that case, I'm pretty sure they'll wash your car and balance your cheque book too (if you ask nicely). Consulting a biochemist (or anyone who is familiar with basic biochemistry for that matter) regarding enzymes will probably begin with a discussion on the 6 main classes of enzymes.

Of course, this article doesn't refer to anything based in reality so it only discusses three "types" of enzymes: digestive, metabolic and food. Yeah, I'm not entirely sure what makes all of those different either. It seems digestive enzymes are to be broken into four of their own classes: amylase, protease, lipase and cellulase. While these are all real enzyme groups, I'm not sure why they're grouped together like this. Proteases are not exclusively involved in breaking down protein for human digestion. I once learned about proteases first hand when I bought a fresh pineapple that I cut myself. Pineapples have a protease called bromelain which is present throughout the fruit with the highest concentration in the stem followed by the tissue near the rind. After eating quite a bit of the pineapple, I began to notice my mouth was feeling really raw and sore. This was a result of the bromelain breaking the peptide bonds that hold the proteins in my mouth together. Incidently, bromelain from pineapple juice is sometimes used as a meat tenderizer.

There's a less painful way of investigating enzyme activity at home. Human salivary amylases break down long chains of sugar (such as starch) into individual sugar molecules. If you take an unsalted cracker and leave in your mouth for a few minutes you should notice the taste change from somewhat salty to distinctively sweet.

That's more than enough real science for now, back to the article! Metabolic enzymes are the subject of the next paragraph. It appears metabolic enzymes are produced by the body, unlike digestive enzymes. The salivary amylase experiment I mentioned earlier will only work if the magic enzyme fairy secretly adds enzymes to your spit when you're not looking. I'm still not totally sure what "metabolic enzymes" are supposed to be but they seem to be involved in all sorts of delightfully ambiguous processes like "transportation of blood" and "detoxification of the cells". In case you haven't heard, haemoglobin is also a Big Pharma conspiracy I guess.

Finally, we are told about "food enzymes". This is where it all starts to make sense. This article is essentially pushing raw food diets. The idea is that cooking food denatures enzymes that help aid digestion. By denaturing said enzymes, the body has to make more of its own which is supposed to be exhausting... or something. There is a giant leap from enzymes found in food to immune suppression because of energy wasted making replacement enzymes. 

Of course, none of this is even remotely true. Different enzymes have different optimal environments. The enzymes of an arctic fish will work best at low temperatures and will lose function at temperatures that we would still consider quite cool. Conversely, thermophilic bacteria have enzymes that work just fine at 72°C.  Temperature isn't the only way to denature (break-apart) an enzyme either. Another important factor is pH.  If the pH of the surrounding environment is not optimal, the enzyme can become denatured. The pH of stomach acid can be anywhere between 1.5 and 3.5. Last time I checked, the pH of broccoli cells was well above that range so its enzymes will either stop functioning or completely denature in a human stomach.

That's not the only problem with this picture though. If our foods contain the enzymes needed to digest them, why aren't they digesting themselves as we speak? Seriously. Why aren't apples sugary soups by the time they get to the super market or my house? I don't think most of these raw food vegans who make claims similar to those in this article have thought this through.  Either way, without this mysterious dietary enzyme deficiency, the rest of claims collapse.

There are so many other things wrong with this story I won't be able to through everything, but there's one last issue I think should be addressed. At one point, Mercado suggests that proteases could even be used as an effective cancer therapy since cancer cells are made of protein and proteases break proteins apart. Maybe the enzyme fairy is supposed to stop the proteases from destroying non-cancer cells too. The stupidity is quite mind boggling. I suspect our friend Charmaine has never eaten a poorly cut pineapple.  I shouldn't be too hard on Charmaine. After all, the things she's advocating don't seem to be her original ideas. Like so many other crazy ideas pushed by fringe groups, there seems to be a single source for the claims. Thanks to Cappi for bringing it to my attention!

Ants, atavisms and bad science journalism

Some of you may have heard about a study investigating an inducible atavism in ants which was published earlier this month in Science. An atavism can be thought of as the reappearence of an ancestral trait in derived species (ie: a species that has evolved more recently). There are actually quite a few examples of this kind of thing happening. Some cetaceans have been documented with marginal rear limb development.  In fact, we have known about chickens that develop teeth for over 50 years. In the case of the chickens, the mutations in nature are lethal which prevents the birds from even hatching but they survive long enough to grow teeth. Some human examples of atavsisms include development of a dorsal cutaneous appendage (tail) and supernumerary nipples. Atavisms shouldn't be confused with vestigeal organs, though. Atavisms tend to re-emerge suddenly due to some sort of mutation that changes the way genes are expressed. Vestigeal organs are ancestral traits that are still present in the population but in a greatly reduced form.

Atavisms are particularly cool because they provide some excellent proof of evolution. A lot of people tend to think that the fossil record is the cornerstone of evolution. That may have been true in the past, but now the vast majority of our understanding of evolution is being generated by molecular genetics. It is possible to examine the ancient past by investigating genes that once played a role in the development of ancient traits. For a more indepth look at how atavisms relate to evolution (and how they cause issues for creationism), this is a good post to read.

In the case of the study on ants, the discovery of an inducible atavism in the genus Pheidole has changed the way we look at how that genus evolved. The atavism, in this case, is the development of the supersoldier ant subcaste. Previously, it was thought that supersoldiers evolved independently a number of times. The most striking difference between regular worker ants and supersoldier ants is size. The head is particularly large when the two are compared. 

The study revealed that some species without supersoldiers in the genus Pheidole could have them induced by introducing a chemical called methoprene (an insect hormone analog). This is some pretty compelling evidence that the supersoldier subcaste is actually an ancestral trait which has been lost multiple times. This is very different from the previous hypothesis that supersoldier subcastes are derived/new traits that have evolved multiple times more recently.

As I alluded to earlier, the ability to chemically induce atavisms isn't exactly new. Axolotls are a paedomorphic (they retain juvenile traits into adulthood) species of salamander that are closely related to Tiger Salamanders. If you expose them to iodine, they will undergo metamorphosis and develop traits that more closely resemble the adults of related salamanders and their ancestors.

So, how do you think the general media reacted when this study was published?  MSNBC decided to introduce the story like this:

Apparently, everything I told you about the study earlier was entirely wrong since, according to MSNBC, the real purpose was just to see what supersoldier ants do. Also, it seems supersoldiers  in Pheidole don't exist at all anymore. Who knew?

The Daily Mail decided to introduce the story with this headline:

Yeah... I'm not even going to comment on this one.

I really shouldn't be surprised at this point. This isn't the first time that atavisms have been butchered in the media, particularly by the Daily Mail. Check out what they had to say when scientists were able to induce teeth in otherwise normal chickens:

...sigh.

Teaching Science: Ur still doin' it wrong

Ok, I know this post is really long so the tl;dr version is: don't go to premed2 for information on genetics.

Alright, it's time for premed2's second video: More on Genes!

This video was by far the worst of the two because it had way more glaring errors. The last video pretty much only had one gigantic error in it that could be attributed to the Scientific American article itself being misleading. I can't really imagine what our self-proclaimed "premedical sciences" tutor was thinking when he produced the second video.

Now where to begin....  I know! How about with this image!

The most obvious error in the entire video was the reversal of "transcription" and "translation". I probably would have let it slide as just a typo if he hadn't:
                                  a) had it right in the first video
                                  b) read the two terms in the wrong order multiple times
                                  c) taken the time to underline the words
I mean, really? He couldn't even be bothered to put an annotation over top or re-recorded it? It's not like he spent a load of time creating the video in the first place. Transcription and translation may be obvious to people with a background in this sort of thing but this is youtube. The reason this sort of thing irritates me so much is because people are learning things that are incorrect and it's much harder to re-learn things properly the second time around.

Now, premed2 goes on to talk about how the Humane Genome Project (HGP) was supposed to result in a golden age of medicine. According to him, one of the secondary reasons the golden age of medicine has not become a reality is, in part, because of epigenetics. Now, let's keep in mind that the term "epigenetics" itself was first coined in 1942 by C. H. Waddington. It's not like the scientists participating in the HGP were taken completely by surprise when it came to epigenetics and human gene expression.

Moving right along, premed2 dazzles us with the revelation that the scientists working on the HGP learned that RNA could "act as a protein"... only they didn't. RNAs that have enzymtic properties (a ribozyme) were first theorized by Crick, Orgel and Woese in 1967. Thomas Cech was the first to actually identify ribozymes in nature during the early 1980s and eventually won a Nobel prize (along Sidney Altman) for his work 1989. Keeping in mind that the HGP was initiated in 1990 and completed in 2003, it's hard to imagine it resulted in a discovery that was made more than two decades earlier.

Premed2's next interesting "fact" involves the hypothetical number of genes that code for functional RNA. Chris and I spent quite a bit of time trying to figure out what his source for this estimate was but we were unsuccessful. Premed2, if you're reading this, mind helping us out here? We really have no idea what you're talking about.

We did find some cool papers that discussed the potential number of genes that could code for functional RNA. The best of those papers gave a few estimates combined with a lot of disclaimers about how they are highly speculative (not unlike the original estimates made for protein coding genes). This means that the estimates could be off by orders of magnitude, but here's what we know from this paper published in 2007(unfortunately not open access):

•  De novo gene-prediction programs have identified ~30,000 regions that could code for structured RNA. Again, it is important to note that the false positive rate for the programs is expected to be quite high.         
• ~4000 noncodingRNA (ncRNA: RNA that does not code for a protein product) genes have been detected using conservative automated methods
• Only about 1500 ncRNA have been manually identified.     

Again, as the paper points out, most of these numbers are highly speculative. It's incoherent to declare ribozymes as rare or common at this point. The one thing I can tell you for sure is that we have been aware of their existence for quite some time. Epigenetics and ncRNA genes were not discovered during the HGP nor were they unexpected.

Now this next claim deserves a timestamp because it's really strange. At 5:30, we are told that another reason the golden age of medicine has been delayed is because an assumption made by the "vast majority of scientists" was demonstrated to be incorrect. What is this assumption? The Common Disease-Common Variant (CDCV) hypothesis, of course!

The hypothesis basically went like this: common genetic diseases in a given population are likely to be caused by common variants (alleles/copies of a gene). In human beings, autosomal chromosome genes have two copies, one from your father and one from you mother. It gets a bit complicated with sex chromosomes but that will have to be saved for another post. The "versions" of a gene you inherit are called alleles (also sometimes referred to as variants). Typically, a healthy individual will have two alleles per gene (one on each chromosome). Within a population there can be any number of alleles present for a given gene. In population genetics, we typically describe an allele as common if it is present in a frequency ≥ 1%. In other words, 1% or more of the total copies of a given gene are of a specific allele.

I'm not really sure why premed2 thinks that the CDCV hypothesis was widely held before the HGP. It was never widely held. In fact, it seems it was first proposed in 1996 (6 years after the HGP began). It was never accepted as more than hypothetical and has been discredited for some time now. For a cool paper that discusses why the CDCV hypothesis was a bit unusual this would be worth checking out.

I'm sure there's more I could pick apart but this has gone on long enough. Premed2, if you can't be bothered to get things right, don't bother at all.

Teaching Science: Ur doin' it wrong

So a few weeks back, a couple of people I know sent me the same video called "More on Genes" by premed2 to review. After watching it I was pretty surprised by how sloppy the work was (varying anywhere from being misleading to flat out wrong). Urged on by a morbid curiousity, I decided to look at the prequel of said video with my friend Chris over at In Vivo. Both videos were apparently inspired by an article in Scientific American that was published last month. We both agreed that it was pretty bad so we left some critical comments. This is where the situation got interesting....

Now, premed2 claims to be a tutor in "premedical sciences". I honestly thought that meant he just tutored intro biology. In reality it seems he is actually a fairly decent ogranic chemistry tutor who is fumbling with genetics. I was under the impression that someone who helps students learn scientific concepts would, at the very least, be a little embarrassed by the errors and perhaps would take steps to rectify the mistakes. Boy, was I wrong. Apparently, having some sort of respect for accuracy while teaching a subject is purely optional and only employed by neurotic people. The sad part is that he has some how managed to convince a decent chunk of his audience that they're learning something. The main purpose of this post is to correct his errors so that if anyone sincerely wants to understand these topics they will have a starting point.

I have a feeling that addressing both videos in one post is going to bring the total length perilously close to tl;dr so I'll deal with his second video More on Genes later.

Video 1: Epigenetics: Addiction/Bullying/Depression

Now, there are some minor issues with this video. One of the little nitpicks I have is premed2 never actually specifies that he's talking about humans when he mentions that chromosomes are linear and that there are 23 pairs. That's not that big of a deal.

What really got me with this video was the incorrect definition of "epigenetics". Every time I have encountered the term in an academic setting there was always an emphasis on the heritable component. The term itself still seems to be debated when it comes to the precise definition but all of them include some form of heritability. An article in Science called "What is Epigenetics?" states pretty clearly that an epigenetic system:

...should be heritable, self-perpetuating, and reversible.

Another article that discussed the conclusions of  a meeting held with the express purpose of defining epigenetics had this to say:

An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence.

Now why does any of this matter? The generally accepted definitions are pretty specific which means that what our friend premed2 here is teaching is not eipgenetics, he's teaching gene regulation. Some histone modifications** can definitely be epigenetic if they are heritable. In this case, heritability can either mean one of two things. It could mean from cell to cell (think about when a skin cell divides - it becomes another skin cell - one of the reasons for this is epigenetics). Alternatively, it can mean from parent to offspring. The histone modifications discussed in premed2's video seem to be simple gene regulation. He points out that mice that are bullied undergo "epigenetic" changes as if it's something shocking and unpredicted. I find this confusing because any time you introduce an organism to a stressful environment one would expect to see regulatory changes (including histone modifications) to its genes.

Looking back at the Scientific American article premed2 used as a "primary" source when learning about epigenetics, I can see why he was confused. It seems that Dr. Nestler (the author of the article) is using a relatively obscure definition. Dr. Nestler isn't some backwater scientist on the fringe of academia. He's a medical researcher with a pretty impressive library of publications. I could go on a rant about medical research and how it relates to science in general but suffice to say I have a feeling that Dr. Nestler's unusually broad usage of epigenetics might have something to do with the current popularity of epigenetics as a field and securing funding.

Either way, this still doesn't excuse premed2's attempts to teach a subject which he only understands from a single Scientific American article.

I'd also like to take a second to suggest people be wary of Scientific American. While it was once a fairly respectable publication, in recent years it has taken a pretty serious dive. For example, notorious HIV/AIDS denialist Peter Duesberg was given a glossy 8 page full colour spread devoted to his latest nonsense rallying against cancer being primarily caused by mutation.  Just sayin'.

**I've already had some people ask me what histones are so I'll describe them briefly here. Histones are proteins which DNA is wrapped around. This helps maintain chromosomal structure etc. The modifications of histone proteins include methylation (which causes DNA to be wrapped more tightly) and acetylation (causes DNA to be more loosely wrapped). Methylation of histone proteins essentially causes the DNA to become so tightly wrapped that the transcription machinery cannot access it so any genes in that area will not be expressed. Acetylation has the opposite affect. 

The reason this works is because DNA has a net negative charge while histone proteins have a net positive charge. By adding chemical groups with different charges to the histones (or to the DNA)  the charge is changed and as a result there are changes to how tighly or loosely the DNA is bound to the histones. These modifications can (but not always) be inherited from cell to cell. During gametogenesis (production of sperm and eggs), a lot of histone modifications become reset so regulatory changes are not always inherited by the offspring.

Yes, I started a blog.

Some of you may be familiar with my youtube channel sofiarune. For those of you who aren't familiar with me, I'm a student of evolutionary biology with experience in botany and entomology and ambitions to pursue a career in academia.

The reason I'm switching from producing youtube content to blogging is primarily due to time constraints. The number of videos I really want to make far exceed the amount of time I can designate to creating them. Some of my subscribers have expressed a desire have the information I would have been addressing in video format, so this is for you guys!

Some of the video series I started (that are now on private) will probably be showing up here in the future. Particularly my HIV/AIDS denialism series will likely be finished and posted in the near future. Also, a revised version of the circumcision series will be available at some point.

For my first real post, I intend to fufill my promise to premed2 by outlining why intellectually lazy people should not teach.  :D

Edit - Oh yeah and special thanks to my friend over at In Vivo for designing the banner and putting up with my neuroticism regarding the background.