Coffee contains – gasp! – CHEMICALS!!!!!!

Ever wonder just what is in a cup of coffee? At first, you might not want to.

Photo source: Simone♠13

On the short list, in addition to caffeine, your average brew also contains:

• Dimethyl disulfide, which contributes to the odour of human waste
• 2-Ethylphenol, a cockroach pheromone
• Putrescine, a toxic breakdown product of rancid meat 

While I don’t believe the article writer set out to have this effect, a couple comments indicate he has in fact scared some readers. Of course, it all depends on how you want to take it. Some might be made uneasy at the mention of strange-sounding chemicals with scary qualifiers, and opt to eschew their coffee tomorrow morning. I, however am not about to abandon my sweet, caffeinated nectar of the gods morning cup just yet.

Coffee’s been around for a while now, and (debates about small effects on overall health aside) it’s safe to say that the compounds in coffee, especially at cup-a-day levels, are harmless. This presentation of facts is a good illustration that one shouldn’t be scared of something just because it has chemical names attached to it. The unknown is scary and chemicals particularly intimidating, but any everyday material could be made to sound scarier if placed in the right light.

That cup your coffee’s in? Aluminum and silicon oxides
The table it’s sitting on? Reducing sugar polymers and lignins
The spoon you mixed with? Smelted iron-carbon alloy

You don’t even want to know what sort of nasty phytochemicals are in that banana you were about to eat.

The point being, just because you can name something chemically (and even describe potentially unsavoury places it might be found in nature or industry), that doesn’t make it bad for you. When someone says that a product contains (cue spooky music) chemicals, that person is trying to scare you, usually to buy their product. Case in point:

Note that they never say those chemicals are not present in their product (they are), just that they are present in the competitors. Sneaky bastards.

Anyways, that said, I’m thirsty. I’m off to grab a nice cold glass of dihydrogen monoxide.

Source:
Wired Science: What’s Inside a Cup of Coffee?

DNA Nanotechnology

In recent years the term “DNA” has become a bit of a buzzword in pop culture, thanks in part to several well-written and researched science fiction shows, and also some that aren’t. The use of the term has come to the point that I often find myself wincing at its use whenever it pops up outside the realm of science, and even sometimes within it. Often when someone should say “gene” or “genome” they instead say “DNA”, which ends up confusing the terminology, and ends up mystifying what DNA actually is, making it seem as if scientists don’t know what the chemical actually does or looks like.

Scientists often say that DNA is a blueprint for life. Not quite. The genome is the blueprint for life (all of the information), a gene is a single sketch, and DNA is the substrate (blueprint paper) on which it is drawn.

If this is the case, new technologies involving DNA turn this on its head and instead of following the blueprint, instead use the properties of this “blueprint paper” to construct new constructions, particles and nano-machines.

Source: Science/AAAS, via Wired 

So where am I going with this? Well, my aversion to the term DNA except in actual scientific journals means that I greet articles that plug DNA technology revolutionizing a field with an extreme degree of skepticism. Turns out for once those preaching the merits of DNA are on to something.

The same properties that make DNA such a good encoding molecule for biological information also makes it a great candidate for creating machines on the nano-scale. What’s more, 40 years of research in molecular biology has given us many of the tools to manufacture and manipulate DNA in ways that just aren’t possible yet for other nano-materials.

By just changing sequences of stretches of DNA we can make them self-assemble into micro-machines that can be used as filters, scaffolds, cages, even happy faces:

Source: TED.com

It may be reaching at this point, but ever larger and more complex structures seem to be materializing in the future with this technology – and hints of the fabled DNA computer (though this goes into the realm of science fiction so far).

Source: TED.com

I expect big things from this field in the future. The simplicity by which DNA is manipulated (via the tools of molecular biology) makes this approach to nanomachines easily automatable, scalable, and replicatable than other comparable technologies. DNA nanotech shows promise. I look forward to what this will bring us in the future.

Wired: Self-Assembling DNA Makes Super 3-D Nano Machines
Read more: Tag-teaming with nature to build nanomachines
New York Times: Scientists Use Curvy DNA to Build Molecular Parts

Insect repellent DEET is a potential neurotoxin

Unfortunate but somehow unsurprising recent research finds that DEET, the compound widely used as an insect repellent, is potentially neurotoxic, based on its ability to inhibit the crucially important enzyme acetylcholinesterase. The enzyme, known to biochemists as a classic example of catalysis, is centrally involved in the nervous system and the target of several particularly nasty compounds, notably Sarin.

Scared? Well calm down. It will be ok. I promise.

I don’t subscribe to the “all chemicals are evil” attitude quite popular in some circles, notably organic food and anti-pharmaceutical crowds. That said, I’m not a fan of blind faith in chemicals either. There’s a cost-benefit balance with any compound. One shouldn’t dismiss the utility of a compound because it has some negative effects; there can be safe applications of a compound if used correctly. Conversely, one shouldn’t assume that there are no negative effects of chemical products and use them indiscriminately. Use should be in moderation, and only when genuinely needed. Acetaminophen (Tylenol™) illustrates this point well. The compound is quite benign and functions as an effective painkiller in normal doses, but high doses can cause severe liver toxicity.

DEET, long sprayed in high doses frequently, may need to have its use curbed, pending further research on the actual effect (if any) that it might have on mammals and humans specifically.

However, we need to make sure we don’t forget that there are important benefits as well.

DEET-containing insect repellents are not merely used to avoid a nuisance. In the case of diseases like malaria, Dengue Fever, and West Nile virus, the repellence of insects can markedly reduce the risk of disease. The continued use of DEET will depend on the renewed evaluation of the safety of the compound, balanced with its efficacy as a repellent.

Now, I’m going to go duck as the irrational public storm about the safety of insect repellents picks up speed. We all know it’s going to get ugly.

Where I first caught this: Report: Deet, popular and potent insect repellent, is neurotoxic
On ScienceDaily: Popular Insect Repellent Deet is Neurotoxic
And the article on BMC Biology: Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet

The Good Old Days of Drug Marketing

Just what the doctor ordered.

For an enlightening look into the past of pharmaceutical marketing, check out this article to see lots more vintage ads:

Weed, Booze, Cocaine, and Other Old School “Medicine” Ads

While some inevitably take this as a condemnation of the pharmaceutical industry, I see it as a testament to the naïveté of the past and indeed how far we have come in our understanding of medicine.

What gaffes might we see on such a compilation in another hundred years?

Source: http://www.pharmacytechs.net/blog/old-school-medicine-ads

The Evil Pixie of Reaction Mixtures

Anyone who has worked in organic chemistry or structural biology can appreciate this cartoon:

Cartoon by Nick D Kim, lab-initio.com

Blue Rats and Gatorade Shenanigans

A cool bit of research published Monday in PNAS showed that rats injected intravenously with a blue dye shortly after spinal cord injury appear to fully recover function after healing, while without it, they remain paralyzed. The photogenic side effect is, one might imagine, becoming a Smurf.

Cool, interesting research. Hopefully it pans out.

From Wired Science, Blue Food Dye Treats Spine Injury in Rats:

“We just had proof of principle,” Nedergaard [the researcher]said. “We didn’t have anything we could give to patients.” Then, while searching for chemicals with structures similar to the P2X7 receptor, the scientists came across FD&C blue dye No. 1, completely non-toxic and approved by the FDA in 1928.

Cool, but hold on. From the telegraph, under the vastly overstating headline Blue M&Ms 'mend spinal injuries':

The compound Brilliant Blue G blocks a chemical that kills healthy spinal cord cells around the damaged area - an event that often causes more irreversible damage than the original injury.

There’s one slight problem here. FD&C blue dye No. 1 and Brilliant Blue G are not the same chemical. They’re similar, to be sure, but a simple Wikipedia search shows that Blue No. 1 and BBG are not the same. Maybe I’m nitpicking. Maybe I’m not.

I know the desire to say that Gatorade and M&Ms cure disease is tempting. I know that saying that sort of thing is bound to draw in readers, and a slight omission seems prudent, but when CNN writes (title: Same blue dye in M&Ms linked to reducing spine injury):

The same blue food dye found in M&Ms and Gatorade could be used to reduce damage caused by spine injuries, offering a better chance of recovery, according to new research.

I call foul. Lazy, lazy journalism. F minus. See me after class.

But perhaps “Compound that manages to ruin every biochemist’s favourite shirt has potential therapeutic application” just doesn’t sound as nice to the public.

 

See the article at PNAS: Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury
And previous work establishing the use of Coomassie Brilliant Blue G on the relevant receptor: Brilliant Blue G Selectively Blocks ATP-Gated Rat P2X7 Receptors

Glyco-wha?

Once upon a time, I was taught about a magical process called glycolysis. I learned how this amazing process can, through a series of reactions, generate energy for life, and all of the fascinating steps along the way. I then wrote an exam on the subject, and promptly erased it from my memory.

A year later, once again I was taught about glycolysis, but this time alongside her slightly backward fraternal twin sister gluconeogenesis. Again, fascinating. Again, quickly forgotten. (image from Lehninger Principles of Biochemistry)

Still another year later came the fantastic experience that was BIOC 4230, Metabolic Processes. And guess who was there. That’s right, old friend glycolysis, with a few more tricks to show off. Learned. Exammed. Vigorously scrubbed from recollection.

One might have guessed she would come back into my life once again, and she has. I thought it was over. I thought I could move on.

But alas, the problem with a pathway being one of the first biochemical processes worked on is not just that it was the first one studied, but that in being so, it paved the way for many new studies to follow, and in many cases, techniques that are used in labs even today. This is similarly the case with the pioneering gene-regulation system lac operon, and bacterial/phage genetics prototype lambda phage system (I’m sure there are lots of other examples), both of which have become intimately integrated into routine techniques of molecular biology.

Glycolysis, the workhorse of biochemistry and dread of all intro biochem students, seems to have a pretty bad reputation. What I’ve come to appreciate is that not only does it provide an understanding of a central energy pathway in life; not only does it provide multiple examples for the study of biochemistry conveniently in one place, but remains useful to new applications to this day. It’s relative age, while making it seem like stuffy, boring science, means that most if not all kinks have been ironed out; essentially everything about the enzymes of glycolysis is known, at least from a technical standpoint.

This flies in the face of the oh-so-common undergraduate lament (that I, of course, never uttered) of:

“Why should I have to learn this if I am never going to use it? It is old science that no one needs to know anymore. I want a degree without having to learn anything!”

…or some less cynically distorted variation thereof. Well, case in point, readers. One student has found himself actually needing to know his basic biochemistry for his biochemistry work. This calls for a celebration!

But it will need to wait for a while. The fact that glycolysis and its enzymes are so well established means that if I’ve spent two weeks getting a reaction to work that continues to sit in a cuvette like so:

then I can’t blame glycolysis for stupid pyruvate kinase stupidly not carrying out the stupid reaction to give me a stupid signal and get some stupid data to get my stupid project off the ground. Stupid.

Why Biochemistry?

I'm back.

I want to go through why I chose to study biochemistry, and to pursue it into the future. But to do that we must go back, back, back, in to a simpler time. A time when things were simpler. The pace of life moved a bit slower. People dressed a little differently.

2004.

Figure 1: 2004 Fashion. From Apropos of Something

Back then, a 12th grade high schooler facing the daunting task of selecting the route of my post-secondary education, I had a good idea what school I would be going to for university, but little clue what for. My interest in science went back to grade 2, where I was put on the spot to say what my favorite subject and replied "science" (remembering a recent super-cool demonstration involving milk, soap, and food colouring). However, science alone is not as specific a subject as it may seem to a 7-year-old. When university loomed and choices presented themselves, I found that I must decide between biology, physics, or chemistry, or something that falls somewhere in between (think chemical physics, molecular biology, and quantum ecology).

Being...ahem....a rock nerd at the time,

Figure 2: Rocks are pretty. From tourist_on_earth

I thought that geology - no, geochemistry - might be an appropriate career choice. But so I didn't sound so crazy, I tacked on biochemistry as something similar I may also be interested in. At that time, in one of the most misled moments of my life, I thought the TCA cycle was interesting. Then:

Dad: "It's a lot easier to find a job in biochemistry"

And my decision was effectively made for me.

5 years later, I have an undergraduate degree in the subject, and pretty intricate familiarity with it. Did I make the right choice? Yes and no.

I made a right choice, though i'm sure others would have led me places just as interesting, and carried me on just as far. I couldn't have known at the time that years later I would remain interested in the subject, but I am. I had little idea what biochemistry, or any other sciences (including geochemistry) was actually like. I suspect many others finish high school in a similar situation. However, my choice was a good one. I don't doubt that I would find a niche in any of several other areas, but the one I have is just right for me.

Choices are inevitable, and sometimes lead where you can't know you're going. The trick is to adapt, to learn, and to be happy with wherever you end up.

Did I think that I would enjoy study in biochemistry? I had no idea.
Did I know anything about the subject? None at all.
Am I happy with where my education has taken me? Absolutely.
Might I have been happy in a different discipline? Probably.

Yet here I am. Ready to move on, open a new chapter of my life, and close some more doors as I go. As they shut, the path ahead becomes a little narrower, a little clearer. While those doors don't open again, the ones I walk through take me on. On to new places, new experiences, and new opportunities. I can't wait.

Figure 3: Being forced to make choices is a good thing. From Mikael Miettinen

All laboratory research ever has just been invalidated

Well, not quite.

Researchers have found that ordinary laboratory plastics contain contaminants that can greatly affect results of biochemical and other research.

Two things:

1. Of course they do! Plastics and the things we put in them are organic molecules, and biological systems use organic molecules extensively.
2. Why hadn't researchers, or more importantly, manufacturers, thought of this before? I know some definitely have, but

This makes me think of classic situations where one person gets results that no one else can replicate under supposedly the same conditions, or someone gets a result once and can never repeat it, or cells that were happily maintained spontaneously die with no discernible reason. I know that in my experience that if needed, different types of tubes, tips, can typically be used interchangeably, without needing to worry about controlling for this source of variation.

The good news is that researchers can hopefully take this effect into account and more effectively troubleshoot, finding the sources of error. Who knows, this could even reverse some file-drawering, and research "cold cases" could be reinvestigated if whatever shelved the research may have been plastic contaminants.

The bad news is this opens the possibility for some published research to actually be incorrect, as a common (and necessary) assumption in research is that your tools and implements are essentially contaminant-free.

Though this comes as a big "duh" moment, i.e. no one can be too surprised that this is the case, the publication of real data shows that plastic contaminants can be a real problem. In the past researchers by and large haven't been too concerned about this possibility. Maybe now they should be.


Science 322 (5903): 917

On Wired: http://blog.wired.com/wiredscience/2008/11/common-lab-gear.html

Memorization and the amino acids

A student of biochemistry, I've often heard the complaint "I have to learn all my amino acids again?"

The trick is not to forget them. And this extends beyond my little corner of the academic world to the periodic table, taxonomic groups, irregular verbs, and schools of philosophy. One must be able to speak the language of their subject so that others can understand them, and so that one can effectively communicate in their discipline. But good luck convincing those who don't want to bother learning.

As much as I dislike the procedure of memorization for school, as I believe that it does not really test your ability as a student, there are cases where it is just plain necessary. At those times if you are doing it right, you shouldn't be working on memorizing each thing, because they should come with an understanding of the process. Past scientists may not have been the smartest when it comes to nomenclature and systematics, lacking the hindsight that we now have, but usually there is still a reason for the names and that helps to know what we're talking about. For example, isoleucine is an isomer of leucine. Did not see that coming. Histidine is the protonable ring. Cysteine forms bridges, proline forms kinks, and glycine is flexible because it's smallest. Glutamine is the amide of glutamate, asparagine is the amide of aspartate. Sure, they're not easy to know but the things that make each one unique are what makes them memorable, and by learning this way, it is a lot easier than beating one's head off the wall trying to figure out how to draw arginine again from thin air memorizing how the N, C, and H's line up.

Like my professor said a few years back, "You need to decide which amino acid you are like. Are you large and negative, like glutamate, or are you small and polar like serine? Maybe you're extremely bulky like tryptophan."

Megatron-ase?

So somewhere in between enzymology studying and preparing for Germany and everything else, for some reason, I got this image of the enzyme of study in the class and how the function of it might look if you were to look at it in 3D-space. I came to realize that although manufacturers of textbooks like to define proteins as

a) circles
b) ovals
c) ellipsoids
or d) oblong

and better textbooks show them as ribbon diagrams (one of which you can see at the top of this page), all of these pictures paint a really static picture of enzymes and proteins, and we really don't do them justice.

I came up with a better analogy than circles for proteins.* Transformers. Thousands of moving parts, all coordinated to align together for perfect function. In the case of allosteric enzymes, you have a complete transformation form one form to another. One form can perform reactions, but nowhere near as well as the others. Just like Optimus Prime can fight the Decepticons as a truck, but he's much badder ass in battle mode, complete with sword and all. My adrenaline is rising just writing this. You laugh, but just you wait.

Do you see what I'm doing? Combining science (boring) with a summer blockbuster movie (exciting!). I should teach this stuff. Or maybe I could turn it into a business. You pay me, I give you a sweet-ass analogy. We need more of me running the show when it comes to this stuff.

Patting myself on the back is the funnest thing ever.

Seriously, though, the reductionism that biochemists use to study proteins in many ways loses sight of the dynamics of the system. It becomes all to easy to forget that you're talking about a system that is extremely complex in its entirety when you're looking at what Asp36 binds to and how His253 is protonated and .......zzzzzzz.....

It may be time for a better, more holistic (though I hate that word) approach to biochemistry. And why stop there? molecular biologists get really hung up on the concept of genes and particular, specific functions of them, evolutionary biologists spend ages reflecting on relative rates of evolution and other mundane details, ignoring the big picture. We need a little more Hollywood in science.

Let's get Michael Bay in on this, he could make it happen.

*rather, it came to me in a bout of inexplicable inspiration