Sunday, 29 May 2011

Fir-Tex: Bullshit in vest form.

Move over Q-ray, there's a new nonsense product in town.

Everyone is familiar with Q-Ray bracelets. Little more than two ball bearings attached with a piece of steel cable, Q-Ray bracelets are marketed as some sort of mystical device that will revitalize your "bio-energy" (whatever that means). Despite being a known fraud, the Q-Ray bracelet remains popular. In the face of mounting evidence that it's a load of baloney, we've seen the nonsense "bio-energy" fad expand in the last year. Products like the phony Power Balance bracelets have hit the market (and like the Q-Ray before it, have been debunked a thousand times over by the skeptic community). But if you've ever said to yourself "I really wish I had a similar product that covered my entire torso", then you've been out of luck.

Until now.

Introducing "Fir-Tex", the latest in wallet-draining pseudoscientific technology. Fir-Tex claims to be the first "energized textile", that can be fashioned into clothing. Products such as Wear Wings - brought to you by Red Bull - are being marketed as the world's first in "energy fashion". Having a slow day? Feeling drained at work? Don't worry, just send in a big cheque, pull a Fir-Tex vest on over your body and your motor will be revving like a chihuahua on speed.

But how does it work? Or better yet, does it work?

Bold Claims
Before we get into the "science" behind Fir-Tex, let's take a look at just what the product has been claimed to do. A banner at the bottom of the Fir-Tex splash page tells us that Fir-Tex clothing will "improve energy and wellbeing", allow you to "jump 10% higher", "improve performance", "boost power by 10%" and "optimize balance and microcirculation". These claims are pretty generic as far as "energized" products go. You'll see similar claims made for Power Balance and Q-Ray bracelets. Also note that claims like these are incredibly ambiguous. What exactly does "improved wellbeing" mean? How do you "optimize" microcirculation? How do you "boost" power, and for that matter, how do you measure power in order to determine that it's been boosted? These claims are little more than technobabble; they're utterly meaningless strings of sciency-sounding words. Just how ridiculous the Fir-Tex gobbledygook is can easily be illustrated. Of the following three items, one is related to Fir-Tex and the other two are taken from Star Trek. Can you tell which is which?
  • decyon field fluctuations
  • biogenic energy in the 40 to 50 micron range
  • aggregate field of plain polarization
Fir-Tex stops short of making  any sort of medical claims, however. They're probably aware of how Q-Ray's medical claims worked out (very poorly), and to avoid lawsuits, they've added a disclaimer to their site:
"So by entering this website you must first acknowledge that FIR-TEX has not been designed for and does not make any claims whatsoever to be any kind of medical cure. Because it isn’t! The aim of FIR-TEX is to bring technological fabrics on the market and their products will help some subjects to simply perform better or feel better while others won't experience any difference or could even feel discomfort."
So despite their claims of "increased performance", they acknowledge that "others won't experience any difference". How convenient. If Fir-Tex doesn't work for you, it doesn't mean the product is a fraud, it just means that you're different.

But enough about bogus product claims, let's get down to some science.

Im in ur body vibratin ur waterz
So how does Fir-Tex work? Luckily for us, the Fir-Tex site has a science section. According to their site, Fir-Tex works on the principle of Far Infrared Rays. These are energetic rays that lay just outside the visible spectrum. They have wavelengths greater than that of visible light, but shorter than that of microwaves. What do far infrared rays do? Well, I'll let the Fir-Tex folks explain it to you:
"The human body is a reservoir of all kinds of bio-toxins which cannot be expelled immediately and become stored in the body, thereby triggering illness. When toxic gases such as sulfur dioxide and carbon dioxide, or potentially fatal heavy metal toxins such as mercury, lead and chlorine, meet large water molecules, they are encapsulated by clusters of water and trapped in the body. Where these toxins are accumulated, blood circulation is blocked and cellular energy is impaired. However, when a 7 to 11 micron FIR wave is applied to these large water molecules, the water begins to vibrate. This vibration reduces the ion bonds of the atoms which are holding together the molecules of water. As the water evaporates, the encapsulated gas and toxins can be released and this is exactly what FIR technologies can do for the human body."

Wait....what? It took me a few times to read that paragraph to understand what they're trying to say. From what I understand, it's this: "bio-toxins" accumulate in your body by being "encapsulated" by water, and causing illness. FIR "vibrates" the water, "reducing" the ion bonds, causing the water in your body to evaporate and setting the toxins free so they can be expelled from the body.

This paragraph also represents a massive chemistry fail. When toxins enter your body, they do not become "encapsulated" by water molecules. This is another instance of technobabble - water cannot "encapsulate" anything, let alone toxins1. Perhaps they mean that toxins will bind with water molecules, but this won't happen either. Water molecules won't bind with gasses, nor will water bind with mercury.

The paragraph continues to tell us that applying far infrared rays to water, the molecules will vibrate, and this vibration "reduces the ion bonds". They're correct in stating that applying far infrared rays will cause the water molecules to vibrate; this is because applying ANY kind of energy will make water molecules vibrate. Think back to junior high chemistry class. When you apply energy to molecules, what happens? They speed up, move around faster, begin to vibrate more. If you put a glass of water in the microwave, what will happen? It boils. The microwave radiation increases the energy of the water molecules and they start moving faster and faster. Applying infrared radiation is no different - it increases the energy of the water molecules and they will move around faster. This is the whole idea behind the infrared heat lamps you see keeping the burgers warm at McDonald's. So while infrared rays will make water vibrate, they aren't special in their ability to do this.

Furthermore, even though infrared heat can get water vibrating faster, it won't "reduce the ion bonds of the atoms which are holding together the molecules of water" because water does not contain ionic bonds. All bonds are not the same. Some bonds have more energy than others. Some bonds are made by sharing electrons between atoms, while some are made by the transfer of an electron from one atom to another. The different types of chemical bonds are given different names to distinguish them from one another. Ionic bonds are once such type of bond. They're formed by the electrostatic attraction of two differently charged ions. Sodium ions and chloride ions will forms ionic bonds and produce salt, for example. Water does NOT form ionic bonds. Water forms hydrogen bonds. These are a very different type of bond.

But perhaps that's just semantics. The point Fir-Tex makes is that applying far infrared rays will make the water molecules in your body evapourate, and allow toxins to be removed. Now, if you don't immediately see how that incredibly terrible that is, then read it again. Let's ignore the fact that it would take an extraordinary amount of radiation to make the water molecules evapourate. Considering how important water is for the proper functioning of your body, does evapourating the water from your very tissues sound like a good idea? And, if the water is supposedly "encapsulating" toxins, wouldn't freeing them from the ensnaring water molecules be even worse? Then they would have free reign to move about your body. Take mercury as an example, since it is one of the toxins mentioned by Fir-Tex above. Mercury does its damage by accumulating in neurons and inhibiting the formation of myelin. At high concentrations, it can cause severe impairment of mental faculties and can potentially be fatal. If mercury were "encapsulated" by water molecules in the blood, it would actually prevent mercury from reaching your central nervous system and doing damage. Fir-Tex products would actually be doing more harm than good!

It's also interesting to note that Fir-Tex is not the only "far-infrared technology" on the market. However, Fir-Tex does claim to be "different" from all those other products. How is it different? Well, Fir-Tex doesn't seem to want us to know:
"During our meetings with our customers we explain the difference between our product/technology and any other product using FIR technologies. The technical information is not public for the moment for obvious reasons which one would of course understand."
No, actually, I don't understand.

So the principle by which far-infrared technology is supposed to rely on is nonsensical at best and utterly batshit-stupid at worst. Does Fir-Tex have any evidence that it works?

Science, schmience. We use Chinese medicine!
The Fir-Tex website's science section has a page called "Live Blood Analysis", which they present as scientific evidence that their product works. I'll get to that in the following section. What I want to go through first is this "scientific presentation" that can be found on their website.

The presentation begins with a summary of infrared rays. They claim that infrared rays are "most beneficial" for "the living beings". In what ways they are "most beneficial" is not explained. They do, however, give three properties of infrared rays. First, they "can generate heat by direct irradiation but localized objects can also reflect them". Well, so can microwaves, but sitting next to a microwave tower is a bad idea. In fact, that's WHY it's a bad idea. Secondly, they "deeply penetrate the living tissues". Well, so can X-rays, but again, basking in X-rays isn't a good idea either. And finally - and this one's a doozy - they "activate (water) molecules, increasing overall temperature of the system". Increasing the overall temperature of the system is the same thing as generating heat, mentioned in the first point. But what does it mean to "activate" water molecules. Are all the water molecules in your body normally "inactive"? How do they become "active" in the presence of infrared rays? This is yet more technobabble (sensing a theme here?). These three properties, Fir-Tex says, are why far infrared rays are called “bio-genetic rays” (another made-up word).

Continuing on, Fir-Tex evokes Wein's displacement law as some sort of justification for their claims. Wein's Law takes the form of λ=K/T, where T is temperature in degrees Kelvin, λ is wavelength in nm, and K is a constant, equal to about 2.896x10-3m.K. Using this equation, Fir-Tex calculated the "frequency of emitted radiation" at 35°C as 9.4μm. If you whip out your calculator, you'll see that their math checks out. Human bodies (at 37°C, not 35°C, but whatever) do emit infrared heat at about 10μm, and this is what IR cameras are calibrated to measure. Armed with this number, what does Fir-Tex do? They conclude that "this explains why human body [sic] easily absorbs far infrared rays between 4 and 16 microns". Holy non sequitor, Batman! Using Wein's law shows what wavelength the human body emits, but says nothing about what wavelength it absorbs. And even if it did show that the body absorbs light of a certain wavelength, how does that show it is the "most easily" absorbed wavelength? What would that even mean?

What does any of this have to do with Fir-Tex's brand of far infrared technology? Well, as the presentation points out, our bodies are composed of large amounts of water. Infrared radiation can make water warmer. Fir-Tex
"works like an active mirror; it captures/receives the thermal radiations from the body heat. Then it reacts and uses these thermal/Far Infrared rays (rays of life) to send energy back into the body with multiple beneficial consequences on cells and tissues."
In other words, Fir-Tex is the world's most expensive blanket! All it purports to do is trap the heat radiated by your body. The same effect can be achieved by a wool blanket. $30 at Bed Bath and Beyond and you can be soaking in all the Rays of Life (whatever that means) that you want.

But Fir-Tex is firm in their belief that infrared radiation is beneficial. Afterall, it's what Qigong masters use!
"Energy medicine is very old, at least as old as the first Qigong masters and other ancient practitioners of healing touch therapies. These healers all had in common the ability to emit energy through their hands, and so do many modern day healers, such as Dolores Krieger, Ph.D., R.N., who began teaching healing touch techniques in the U.S. in the 1970s. Contemporary researchers have now proved that these forms of energy medicine use wavelengths in the infrared range."
Qigong "healers'" hands emit radiation in the infrared range? Does this come as a surprise to them? That's the range at which everyone's body emits radiation. That's what the Wein's equation above showed!

But none of this actually shows that Fir-Tex works at all. Fir-Tex's supposed evidence can be found in the Live Blood Analysis section of their Science page.

Live Blood Analysis, or How Not to do a Scientific Study
Prior to this, I had not heard of Live Blood Analysis (LBA). I'm more than familiar with haemotological techniques, but Life Blood Analysis was not a technique that I knew. A few minutes on Google, and I discovered that LBA is a technique pioneered by a company called Sevenpointfive. Who's Sevenpointfive, you ask? They're a South African naturophathic company that pushes their brand of "natural supplements". They present the same, tired "modern medicine is wrong, buy our products instead" line as every other "natural supplement" company. Their schtick, though, seems to be their LBA technique. What they do is simple. They take a drop of your blood, and look at it under a microscope for "imbalances" and "deficiencies". Whether or not Sevenpointfive's "technicians" can accurately diagnose physiological conditions using LBA is rather dubious to me. As far as I can tell, LBA is not a proper technique used by the medical community.

It's this exact method that Fir-Tex used to test their product. They took blood samples of individuals, then gave them all Fir-Tex vests to wear for 10 minutes, and took another sample. Then they compared the two. That is as detailed as their test gets. There's a huge problem here: they didn't use a  negative control subject (or if they did, they never mentioned it or showed the results)! This is a gigantic experimental flaw, and any results from their tests are worthless because of it. They also make no mention of what kind of activities the subjects were doing when they were using the Fir-Tex vests? Were they sitting still for ten minutes? Were they exercising? Was this controlled at all? Their methodology is severely lacking. Such a study would never get published in any reputable medical journal, which is probably why it exists only on the Fir-Tex website.

What were the results of their "tests"? Well, I haven't the slightest clue. Take a look at what they present as evidence:

Maybe it's because I don't have sufficient training to understand what I'm looking at, but I don't see a significant difference in the two treatments. All I see are alot of erythrocytes with some platelets here and there, in both cases. Nevertheless, Fir-Tex claims results like these indicate that their product protects cells from damage from free radicals (free radicals, according to Fir-Tex, are "atoms that are missing ions", a laughably stupid statement), reduces cholesterol, and boosts the immune system. None of their LBA pictures indicate any of these things. It is interesting to note that Fit-Tex admits "that each individual reacts differently to the same treatment, the results are thus never the same", but they don't accept this as evidence that their product does nothing. Quite to the contrary, they take this as evidence that Fir-Tex does work, just in different ways in different people. These tests definitely do not bolster their earlier claims of increasing your jump height by 10%, or "optimizing your balance". And even if they DID show such results, we have no way of knowing any of this is attributable to the Fir-Tex vests because of their shoddy methodology!

No doctor worth their medical degree would produce a medical study as awful as this. So who is responsible? Fir-Tex informs us that the tests were performed by "Dr Annelise Bunce, certified Clinical Metal Toxicologist and certified Dark Field and Multi Phase Microscopy and expert in Live Blood Analysis". Here is her CV. Masters in homeopathy? Oooh. That explains it.

More money than sense
So just what will one of these babies set you back? Between €325 and €475 (that's $453CAN to $663CAN). Hell, while you're at it, €525 will get you a saddle for your horse. This is an unbelievably colossal waste of money. Fir-Tex does nothing more than make you warm. The "science" behind it is complete and utter nonsense, none of their claims can be validated and it simply does not work. Just like the Power Balance and the Q-Ray before it, Fir-Tex is a scam that will have its manufacturers laughing all the way to the bank.

1. It's been brought to my attention that this point is not entirely correct. Water molecules can, in fact, "encapsulate" some ions. This is called a "solvation shell". It occurs when a positively charged ion is attracted to the electrostatically negative oxygen of water molecules. Water molecules will effectively form a shell around the ion. I have my doubts about whether water can form a solvation shell around toxins, which are rather large compounds. Perhaps a more chemistry-minded reader could clarify this.

Thursday, 26 May 2011

Central Dogma not so challenged after all?

In last week's This Week In Science, I summed up a paper published in Scicence by Li et al.1 which was hyped up as being a challenge to the Central Dogma of molecular biology. The authors compared the RNA sequences from numerous individuals to the original DNA sequences they were derived from. What they found were a multitude of sites where the RNA sequences differed from that which would be expected given the original DNA sequence. Moreover, these variations were shared across individuals, indicating that they were not likely due to random mutation. Furthermore, the team found proteins that matched the varied RNA sequences and not the DNA sequences. These results suggested that there exists some yet unknown editing step during transcription that alters individual nucleotides in the resulting RNA transcripts.

However, declaring the Central Dogma to be toppled may have been a bit premature. According to Lior Pachter at the University of California, Berkley, the variations discovered by the researchers could be artifacts caused by their sequencing equipment. Many of the sites that were found to contain altered nucleotides lie in regions which are known to often cause RNA sequencing errors. In other words, the variations that the team observed, in many cases, might just be sequencing mistakes. 

Further skepticism has been shown by Joe Pickrell at the blog Genomes Unzipped (which I highly suggest reading, as he goes into quite a bit more detail than what I've presented below). He points out that the differences in RNA and DNA that the authors discovered might be false positives created by attributing a particular RNA sequence to the incorrect DNA sequence. For any given DNA sequence, there are bound to be other sequences very similar - even almost identical - to it2. If you are given an RNA sequence, then, how do you determine which of the very similar DNA sequences it is derived from? Unless one takes steps to remove the incorrect sequences, it is very likely that you will end up with a false-positive. It would appear that Li et al. did not take such steps.

Pickrell points out another problem with sequencing and mapping through RNA splice sites. Mammalian genes are frequently alternatively spliced, and a cDNA library like the ones Li et al. used will have multiple isoforms of a gene. When mapping such transcripts back to the genome, you have to keep in mind that the genomic sequence will still contain the introns that have been excised in the mature mRNA transcripts. If you compare the shorter, edited mRNA to the longer, unedited DNA, you're likely to find many differences between the two. Mapping a particular sequence read to the wrong isoform will generate false-positives. Pickrell shows that Li et al. did just this on at least one occasion.

So widespread RNA editing in humans might not be a reality. It's possible that it is, but problems with the procedure used by Li et al. raise many doubts. I'm looking forward to reading the follow-up research. Until then, as perhaps Mark Twain would say, reports of the death of the Central Dogma have been exaggerated.

1. M. Li et al. "Widespread RNA and DNA sequence differences in the human transcriptome". 2011. Science. doi:10.1126/science.1207018

2. It should be obvious that the larger the given sequence, the fewer (near)identical sites there will be.

Tuesday, 24 May 2011

This Week in Science! (May 22, 2011)

This week1 saw quite a few interesting papers in biology. Here's a few that caught my attention:

  • Mammalian brain evolution driven by smell - One of the biggest characteristics that distinguish mammals from other animals is that we have relatively large brains in relation to body size. Just why mammals evolved rather large brains has been a point of speculation, but a paper published in Science this week suggests that a reliance on our sense of smell resulted in our bulging brains. The research by T. Rowe et al. involved examining the fossils of two species of Jurassic cryodonts, the group of ancient reptiles which would diverge to become the mammalian lineage. They used a technique called X-ray computed tomography to reconstruct endocasts of the cryodont brains, and compared them to those of earlier, Triassic cryodonts. They first looked at the endocast from Morganucondon oehleri, and noted that the brain was 50% larger than in earlier cryodonts. But there were other important differences: the olfactory bulbs were larger, there was expansion in the cerebral hemisphere, and the cerebellum extended to cover the midbrain. They next looked at the endocast from Hadrocodium wui, the closest known fossil to living mammals. They observed another 50% increase in brain size, with even larger cerebral hemisphere and olfactory bulbs. These observations lead the team to speculate that increased dependence on olfaction drove the evolution of larger brain sizes in early mammals. Given that early mammals were likely nocturnal, and had to rummage around in the dark for food, this idea does make sense. The researchers are now looking for evidence that might indicate that early mammals were indeed nocturnal.   
(T. Rowe et al. "Fossil evidence on origin of the Mammalian brain" 2011. Science. 332(6032): 955-957)
  • Another strike against the Central Dogma - Every student in biology is brought up to know the "Central Dogma" - the idea that can be summed up as "DNA encodes RNA encodes protein". This is not a had and fast rule, though, and the discovery of things like ribozymes have shown the Central Dogma to be less dogmatic. A new paper published in Science this week furthers this point. A team of researchers lead by M. Li from the University of Pennsylvania in Philadelphia compared the DNA sequences from 27 different individuals to their corresponding RNA sequences. In a very large number of cases, they discovered that the RNA sequences that had been transcribed from the DNA sequences were different than would be expected; that is, the RNA sequences contained sites where the nucleotides had been changed. These changes in RNA sequences were shared across many of the individuals studied, indicating that the changes were not likely due to random mutation. Furthermore, using mass spectroscopy, they found peptides whose sequences reflected the RNA variant sequences rather than the original DNA sequences. What all of this suggests is that the DNA-RNA-Protein relationship is not as strict as previously thought. The DNA sequence of a gene might not dictate the exact composition of it's gene product after all. 
(M. Li et al. "Widespread RNA and DNA sequence differences in the human transcriptome". 2011. Science. doi:10.1126/science.1207018)
  •  Extinction rates may be overestimated - Estimating extinction rates is an important part of ecological conservation, but unfortunately, there is really no reliable way of directly determining such rates. Instead, researchers often rely on indirect methods, but this can run into problems. One popular indirect method is to observe the number of different species found as your area of study gets larger (called a species-area accumulation curve), and then extrapolating backwards to successively smaller and smaller areas to determine the rate at which species number decreases. A new paper in Nature by Fangliang He and Stephen Hubbell argue that this method routinely overestimates extinction rates (sometimes by as much as 160%!). This comes as both good news and bad news; it means that species loss due to habitat destruction in some areas might not be as high as previously estimated, but it also means a more accurate method for estimating extinction rates needs to be devised in order to develop optimal conservation projects. 
(F. He and S. Hubbell. "Species-area relationships always overestimate extinction rates from habitat loss". 2011. Nature 473: 368-371. doi:10.1038/nature09985)

1. Yeah, I am aware I'm posting this a little late. So sue me.

    Saturday, 14 May 2011

    From Embryo to Adult: Body Plan Patterning in Drosophila - Part I

    Take a look at a fly and it won't be long until you realize that even such a relatively simple creature is quite complex. This issue of complexity is a talking point for creationist rhetoric; "How can such complex structures just come together to create a fully formed individual?" they muse, "It must be the work of a divine creator!" Unfortunately for them, the process of development is well known and thoroughly understood. In a series of posts, I'll attempt to dispel this myth, and show just how a complex life form can arise from a single simple cell by entirely natural means. In this first part, I will introduce the concept of maternal effect genes, and one of the most important such gene, bicoid.

    The development from a single egg to a full adult fly is a long one, but the process begins long before fertilization ever occurs. Consider, for a moment, the process of fertilization in humans. In humans, the egg cell is monstrous in size compared to the relatively diminutive sperm cell. There is much more cytoplasm in an egg than in sperm, and that cytoplasm is full of mRNA, mitochondria and other cytoplasmic factors. These are ultimately donated to the embryo upon fertilization: the fertilized embryo contains nuclear genetic information from both parents, but contains cytoplasmic factors from the mother alone.

    Drosophila are no different. The unfertilized egg is not just a storage container for nuclear DNA, but it contains mitochondria and mRNA which will ultimately become part of the embryo after fertilization. Many of those mRNA transcripts belong to a class of genes that is very important to the development of the body plan: maternal effect genes.

    Maternal effect genes get their name from the fact that they are expressed in the mother, and not in the embryo. During oogenesis, the tissues in the ovary express these genes, and the transcripts are packaged into the embryo. This is in contrast to zygotic genes, which are expressed in the nuclei of the embryo itself. One thing that makes maternal effect genes so interesting is that individual females that are mutant in such genes are phenotypically normal: the phenotype shows up in the progeny instead1. There are about 50 maternal effect genes that play a role in the development of the Drosophila body plan, and they set up the basic framework for the zygotic genes that come later (which I will describe in a later part). Perhaps the biggest role they play, though, is in setting up the body plan axes.

    The Drosophila embryo has two axes: the anterior-posterior axis, and the dorsal-ventral axis (see Figure 1). If the the adult body plan is to be laid out in the developing embryo, it is important to make sure the embryo knows which side is which (you don't want the head to end up on the wrong end, for instance), and this is the primary goal for many maternal effect genes. The first of such genes that comes into play is called bicoid, and it works to determine the anterior-posterior axis of the egg. It does this through morphogenic gradients, a concept that you'll see used extensively throughout development.

    Early on in the investigation of body plan development, it was noted that those mothers who are bicoid mutants give rise to progeny without properly differentiated anterior ends (they lack a head or thorax). This fact was interesting itself, but a series of experiments made the fact all the more striking. If you take an unfertilized Drosophila egg and poke the anterior end with a needle, allowing some of the cytoplasm to leak out, they end up developing into embryos that resemble those from bicoid mutants. Furthermore, if you were to transfer cytoplasm from the anterior end of a wild-type egg to the anterior end of a bicoid mutant egg, the embryos would develop normally2. It was also found that if the cytoplasm from the anterior end of a wild-type egg were transferred to the middle of a bicoid mutant egg, the embryos would develop a head right in the middle. This immediately suggested that there was some cytoplasmic factor in the anterior end of the egg that was lacking in bicoid mutant eggs, and this factor was responsible for establishing which end of the embryo became the anterior end.

    If you were to look at the distribution of bicoid mRNA in the unfertilized egg, you would see just that (Figure 2). Before fertilization, bicoid mRNA is concentrated in anterior end. It remains untranslated until fertilization occurs. Upon fertilization, translation begins, and Bicoid protein diffuses through the embryo. Bicoid, then, forms a gradient, with high concentrations at the anterior end and low concentrations at the posterior end. Regions with a high concentration of Bicoid protein develop anterior structures, and the regions with a low concentration of Bicoid protein develop into posterior structures. The precise function of Bicoid will be explained in a later post, but for the moment, it is sufficient to know that bicoid activates particular zygotic genes in a concentration-dependant manner. Different zygotic genes have different threshold levels for activation, so the concentration of Bicoid across the embryo will determine which zygotic genes get activated, and in turn, determines what each region of the embryo develops into. This is the key principal behind a morphogenic gradient.

    But bicoid isn't the only maternal effect gene that plays a role in setting up the anterior-posterior axis. In the next part to this series, I will discuss three more important maternal effect genes: nanos, caudal, and hunchback.

    1. If this seems confusing, remember that the genes are expressed in the mother, but the transcripts, and ultimately, the gene products, are packaged in the egg. If a maternal effect gene is mutated, the mother will be fine, but her progeny will not, because it is the eggs that are receiving the defective gene products.

    2. This type of experiment is called a "rescue experiment", because it allows one to "rescue" the mutant embryos and allow them to develop normally.

    From Embryo to Adult: Body Plan Patterning in Drosophila

    How a fully formed organism develops from a single fertilized egg cell is a complex process. That process is no less complex in inverterbrates than in verterbrates, and much is known about just how development occurs in Drosophila. In the following series of posts, I'll detail the just how you can get a complete fly from a simple cell.

    (Links will be available as I write and post each individual part)

    Part II: Setting up the Anterior - Posterior Axis: Hunchback, Nanos & Caudal
    Part III: The Terminators
    Part IV: Setting up the Dorsal-Ventral Axis: Spätzle, Toll and Dorsal
    Part V: Zygotic Gene Expression along the D-V Axis
    Part VI: Gap-gene Expression
    Part VII: TBD

    Friday, 13 May 2011

    This Week in Science! (May 13, 2011)

    This week has seen the publication of quite a few interesting research articles. Here is a list of some that have piqued my interest:
    • New Lizard Species Created in Lab – Many species of lizards in the genus Aspidoscelis have an interesting life history. There are a dozen species of Aspidoscelis that live in New Mexico, and about half of these species reproduce by way of parthenogenesis. Among those parthenogenic species, some have triploid genomes (that is, they have three complete sets of chromosomes), while others are diploid (two sets of chromosomes). A team of researchers lead by Peter Baumann, however, has created a new species of Aspidoscelis – one that is tetraploid. Their paper, published in the Proceedings of the National Academy of Sciences, details how they crossed females of the species Aspidoscelis exsanguis – a parthenogenic triploid species – with sexually-reproducing diploid Aspidoscelis inornata males. The matings resulted in hybrid daughters that, upon karyotyping, were found to be tetraploid. These offspring went on to reproduce asexually, giving birth to daughters that were also tetraploid. This continued for multiple generations, effectively establishing multiple lineages of a brand new species!
      (Baumann et al. "Laboratory synthesis of an independently reproducing vertebrate species". Proc. Natl. Acad. Sci.: doi/10.1073/pnas.1102811108)  
    • Ribosomes Do More than Make Proteins – Every biology student is taught that ribosomes are complex ribozymes that are the "protein factories" of the cell. But new research published in Cell indicates that ribosomes are actually involved in regulating genes as well. Maria Barna's team at UCSF took a look at Ts, Tss and Rbt mice – strains of mice that all have the similar phenotypes of short, kinked tails and an extra rib. These defects mapped to the distal region of Chromosome 11, and after cloning this region in Ts mice, they found that the Rpl38 gene was deleted. Sequencing the region in Tss and Rbt mice showed similar problems in the Rpl38 gene (a frameshift mutation due to a single nucleotide deletion, resulting in a stop codon and a truncated, nonfunctional protein in the case of Tss mice; and a dinucleotide insertion at the Intron 2/Exon 3 splice site, causing a frameshift leading to a truncated protein in Rbt mice). Ribosomes are complexes of nucleic acid and proteins, and RPL38 is one such protein. It was immediately obvious that RPL38 – and by extension, the ribosome - was involved in proper development of the body plan, a process controlled by Hox genes. One question remained: how? Interestingly, when they looked at the expression of the Hox genes, the transcript levels were unchanged, so RPL38 does not provide transcriptional regulation. Rather, they found that a subset of Hox gene transcripts was not being translated by the ribosome in Rpl38 defective mice. In normal mice, RPL38 acts to facilitate the formation of the 80S ribosomal complex on these select Hox transcripts; in Rpl38 defective mice, this does not occur, the Hox genes are not translated, and the mice are born with gross physical abnormalities. Looks like ribosomes just got a little bit cooler.
      (Barna et al. "Ribosome-Mediated Specificity in Hox mRNA Translation and Vertebrate Tissue Patterning". Cell: doi/10.1016/j.cell.2011.03.028)
    • Fascinating Fungi FindNature this week published an article about an interesting mycological find that may have implications regarding the evolution of fungi. A team of researchers at the University of Exeter in the UK began by analyzing the genomes of microbes found in a local pond. Using the sequence data obtained from these samples, they constructed a phylogenic tree by comparing the sample data with that of known species of fungi. What they found was a set of unknown sequences that was basal to the known species. They then compared these unknown sequences to those obtained from samples collected in a large variety of environments, and discovered that the fungi were almost ubiquitous. Since they appeared to be found everywhere, but had not been previously discovered, the team named the fungi cryptomycota (or 'hidden fungi'). Intrigued, they designed fluorescently labeled DNA probes that were specific to cryptomycota DNA. This allowed them to visualize which cells in the sample belonged to their newly discovered fungi. They found that cryptomycota cells were very tiny (3-5 microns in diameter) ovoid in shape. But the truly interesting part was what they lacked: a cell wall made of chitin. A chitinous cell wall is considered the defining aspect of fungal species, so cryptomycota must represent a lineage that diverged very early on in fungal evolution.
      (Jones, M. D. M. et al. "Discovery of novel intermediate forms redefines the fungal tree of life". Nature: doi:10.1038/nature09984)  
    • Another Step Towards an HIV Vaccine – also published in Nature this week is a report by Picker et al on a novel SIV vaccine. SIV (simian immunodeficiency virus) is a very close relative to HIV that infects monkeys. The researchers administered the vaccine – which consisted of SIV-antigen expressing cassettes inserted into a vector made from an avirulent cytomegalovirus – to a group of 24 rhesus monkeys. 59 weeks after immunization, the monkeys were given the SIV virus. When they monitored the infection in the monkeys, they found that 13 of the 24 showed continually diminishing viral loads, and by 52 weeks, the virus was rarely detected at all. Undoubtedly, it remains to be seen if the vaccine will remain effecting in preventing SIV infection over longer spans of time, but this development is nonetheless a groundbreaking step towards an effective vaccine for HIV.
      (Picker et al. "Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine". Nature: doi:10.1038/nature10003)

    Tuesday, 10 May 2011

    Gee, why didn't I think of that?

    "According to mainstream scientists and chronologists, based on uranium-lead series radiometric dating of moon rocks the Earth is only 4.6 billion years old therefore years did not exist before that because the Earth wasn't orbiting the Sun." [emphasis added]
      I really wish I had a witty retort here, but I'm dumbstruck at the sheer ignorance.

    Sunday, 8 May 2011

    Nephy's Nylonase Nonsense

    Oh, Nephilimfree, you've done it again. You went and dragged genetics through the mud again, and I won't stand for it.

    At this point, having dedicated a few posts to his inane ramblings, debunking Nephy's claims is beginning to feel like picking on the fat kid at the playground. He's a slow, lumbering target, and all the other kids on the playground keep picking on him because he's easy prey. But Nephy is so ripe with nonsense, so overflowing with vacuous crap like a bountiful cornucopia of bullshit, that it's hard to resist tearing his arguments apart when I'm looking for something to write about. And his silly website [Edit: 06/11/11: Looks like Nephy has let his registration of his domain lapse, so that link doesn't work any more. I tried to find an archived version, but had no luck] has no shortage of fodder for a creationist asskicking.

    This week, I took a look at this article he wrote about the enzyme nylonase. You've probably heard about nylonase before, as it is often given as a great example of an evolutionary adaptation that has occurred in recent history. In 1975, a team of researchers from Osaka University in Japan got the idea to try and culture sludge obtained from the waste water outside of nylon factories1. The samples they collected were used as inocula, and added to cultures which contained a form of nylon (6-aminohexanoic acid cyclic dimer) as the sole carbon and nitrogen source. Any bacteria that grew would have to rely on metabolizing nylon to survive. And grow they did. They designated the strain as KI72, and after isolating the bacteria, they identified it as a strain of Achromobacter guttatus, although later work by the same team reclassified the species as a strain of Flavobacterium2. A few years later, the researchers identified two novel enzymes which allow the bacterium to metabolize nylon: 6-aminohexanoic acid cyclic dimer hydrolase and 6-aminohexanoixc linear oligomer hydrolase (6-AHA CDH and 6-AHA LOH, respectively)3,4. Since nylon production began in the 1930s, these enzymes had to have originated in the time since then. After all, it doesn't make much sense for a bacterium to  have produced enzymes to specifically degrade nylon before nylon itself was invented. These genes, then, represent an example of a novel adaptation arising outside of the lab and within the past century.

    But Nephy disagrees. He states, 
    "Because the bacteria encountered nylon and developed an ability to digest it does not provide evidence of any kind of evolutionary change. This ability does not effect the form and structure (morphology) of the bacteria by introducing any new structural feature, nor does it transform any existing structural feature of the bacteria into a new kind of structure with a new physiological function."
    Two paragraphs in, and he's already run into a major problem. He seems to have this odd idea that unless a change results in gross morphological alterations, it cannot be an evolutionary change. He simply discredits novel biochemical adaptation out of hand without any sort of justification. He simply wishes to define evolution as changes in "form and structure" and ONLY changes in "form and structure" - any other kind of change he refuses to acknowledge as evolutionary change. In essence, he's defining evolution in his own incredibly narrow terms, so that any actual evolutionary change can be shrugged off as "not evolution". If we were to narrowly define creationism as "the spontaneous formation of aardvarks from forest detritus", it would be pretty easy to discredit, too.

    But beyond that, it is simply silly to only accept large changes in morphology as the only kind of evolutionary change. Morphological alterations cannot occur all at once. Any modification to an organism's body plan would require many not-so-obvious biochemical changes to occur first - the very type of changes that Nephy does not accept as "evolution". Evolution can only work with what it has available. No organism is going to mutate and grow wings de novo all in one shot, even if it would be advantageous. Such changes would require modifying the existing body plan, and this would require extensive biochemical changes to happen first.

    Nevertheless, the discovery of novel nylon-degrading enzymes is indisputable. Musing over the origins of these enzymes, Nephy declares that these proteins, or any protein, could not have simply evolved. No, he says, statistical analysis says otherwise:
    "The field of sicence [sic] called Statistical Ananlysis [sic] which is employed to determine probability in various fields of science, has determined that the formation of proteins by random molecular interactions is on the order of 10^950, which is 1 to a number for which no name exists; a number greater than all of the paticles [sic] of matter in the speculated universe. In other words, according to science itself, the chance of a single, medium-sized protien [sic] arising by purely materialistic molecular interactions is considered impossible to science because it is considered impossible times impossible times impossible. The evolutionist would have you believe that random mutation is capable of producing novel protiens [sic] which have specific function, but this is not only unfounded but exceedingly irrational."
    This is a typical creationist talking point: whipping out statistics to churn out large numbers and proclaim "See! It's statistically impossible for evolution to occur!"  It is also typical, as Nephy demonstrates quite well, for creationists not to cite the source of these statistical calculations. The problem with Nephy's argument is that he does not take into account the process of selection during evolution. Forming a protein "randomly" and all at once is incredibly unlikely (though not entirely impossible), but if you factor selection into the equation, it becomes an incredibly likely phenomenon. Richard Dawkins illustrates this beautifully in his book The Blind Watchmaker, where he likens evolution to monkeys banging away at typewriters. If you were to wait for a monkey to type out the sentence "Methinks it is like a weasel", you'd be waiting for eons for it to "randomly" happen. But suppose you were to use cumulative selection to pick and keep the letters that work. Dawkins wrote a computer program to do just this (as computer programs are much cheaper and easier to work with than hordes of monkeys). Starting with a string of gibberish and then changing one letter per generation, the computer program "evolved" the correct sentence is about 40 generations5. It took only a few minutes for the computer program to complete this task, whereas single-step selection (waiting for the correct sentence to happen randomly, and all at once) would have taken the computer "a million million million million million years"6. Obviously, selection gets past the staggering statistical improbability that creationists argue.

    But Nephy continues. He tells us that it was discovered that the nylonase genes originated from a frameshift mutation, resulting in an alternate reading frame which produced a novel enzyme7. This may be true, but recent work by Negoro et al indicates that the origin of the genes might be due to base substitutions after an ancestral gene duplication8. Nephy proceeds to tell us that there are only two ways that such a frameshift can occur: a random mutation or by a "Programmed Translational Frameshift Mutation".

    At last, we come to the crux of Nehpy's argument. According to him, random frameshift mutations are invariably bad and the idea of a random frameshift mutation is a cop-out employed by "evolutionists" to ignore the reality of intelligent design. The origin of nylonase must be due to "Programmed Translational Frameshift Mutation", a process, he claims, is divinely inspired..

    At this point I feel I should clear something up. Nephy, I hope you're reading. There is no such thing as "Programmed Translational Frameshift Mutation". Programmed Translational Frameshift (PTF) is a very real process, but it is not a mutation. PTF actually describes a variety of complex, but similar, processes. The essence of the idea is this: under normal circumstances, a protein is produced when a ribosome translates a strand of mRNA. Usually, the ribosome translates in a linear fashion, starting at the 5' end of the strand and reading the length of the strand until it comes to a stop codon at the 3' end. But in certain cases, the ribosome can be induced to "skip" or "hop" over a number of nucleotides in the sequence. The result is that the ribosome is shifted out of frame, and the resulting gene product is unlike the original9. With PTF, one gene sequence can produce multiple gene products: the original, unshifted, product and the second, shifted, gene product. This process is not a mutation. Mutations are changes to the genetic sequence itself, and such changes do not occur during PTF.

    Perhaps Nephy's mistake stems from him being unable to comprehend the scientific literature. In his article, he describes PTF as "the modification of the arrangement of amino acids in a chain caused by information in the DNA which programs the event to occur", which is inaccurate, to say the least. This is further evidenced by the fact that he chooses to illustrate PTF with a diagram of alternative splicing, which is an entirely different process altogether! These errors would indicate that he simply did not understand what PTF is. I get the feeling that Nephy just skims through paper abstracts, pulling out words to form misshapen ideas, rather than taking the time to actually read any scientific papers.

    But, regardless of whether or not PTF counts as mutation, Nephy's argument that nylonase originated due to PTF, rather than a simple frameshift mutation, doesn't hold much water. What we know about nylonase - the gene's sequence, how it is regulated, etc - would indicate that PTF is NOT at play here. As mentioned above, PTF occurs when a single transcript is read in two different reading frames, resulting in two different gene products. But in the case of nylonase, there is only ONE reading frame. It is always read by the ribosome in the same fashion. At no point is the ribosome prompted to switch to a new reading frame during translation - a hallmark of PTF. In many cases, this switch is induced by particular sequence elements, but the nylonase gene does not contain any such sequence elements. All evidence points to an ancestral gene that underwent a frameshift mutation that permanently altered it's reading frame, rather than two different and active reading frames from a single sequence. The original frameshift alteration was likely transcriptional in nature rather than translational.

    Nephy's claim that random frameshift mutations are always harmful is nonsense as well.  In any case where a mutation is deleterious, creationists are quick to say "See! Random mutations are bad!"; any case where a mutation proves to be beneficial, they shout "That didn't count! That was Intelligent Design!". This amounts to little more than special pleading. Nephy does not see it this way. He states 
    "The problem for evolutionists is that we have discovered that random frameshift mutations produce novel proteins which do not have a function in the cell, and when produced in great numbers, are causes of diseases such as Alzheimers and Tay-Sachs."
    But how are deleterious mutations and non-functional proteins a problem for evolution? On the contrary, they are a huge problem for Creationists! After all, why would God allow for non-functional proteins to cause deadly conditions? Why would God allow for mutations to begin with? Pretty sloppy work for a Creator who is supposedly "perfect".

    Another issue with his argument is how he ascribes PTF as an "intelligent design process". What evidence does he have that PTF is not a naturally occurring process? Why does he call it intelligent design? He gives no reason. He simply slaps the ID label on and announces "Hah! PTF proves intelligent design!" with no justification whatsoever. One could just as easily label espresso brewing "intelligent design" and proclaim that Starbucks baristas are evidence of divine creation. It is nonsensical. 

    Nephy proceeds with a few paragraphs of rambling spew about DNA being a "computer code". I have already talked at length about why DNA is not a code, so I will not go into it here. Needless to say, it makes little sense.

    So what it all comes down to is this: the nylonase gene is a product of a frameshift mutation and not programmed translational frameshift; programmed translational frameshift is not a mutation, nor is it evidence of Intelligent Design; biochemical adaptations do count as evolution; and nylonase still illustrates a wonderful example of evolution occurring within recent memory.  Once again, Nephilimfree abuses genetics to form a murky mire of distorted truth, and once again, his claims do not stand up to the scrutiny of critical thought.

    1. Kinoshita, S.; Kageyama, S., Iba, K., Yamada, Y. and Okada, H. (1975). "Utilization of a cyclic dimer and linear oligomers of e-aminocaproic acid by Achromobacter guttatus". Agricultural & Biological Chemistry 39(6): 1219−23

    2. Negoro, S.; Shinagawa, H.; Nakata, A.; Kinoshita, s.; Hatozaki, T. and Okada, H. (1980). "Plasmid control of 6-aminohexanoic acid cyclic dimer degradation enzymes of Flavobacterium sp. KI72".  Journal of Bacteriology 43(1): 238-245

    3. Kinoshita, S.; Negoro, S.; Murayama, M.; Bisaria, V. S.; Sawada, S. amd Okada, H. (1977). "6-aminohexanoic acid cyclic dimer hydrolase . A new cyclic amide hydrolase produced by Achronobacter guttatus KI72" European Journal of Biochemistry. 80: 489-495.

    4.  Kinoshita, S.; Terada, T.; Taniguchi, T.; Takene, Y.; Masuda, S.; Matsunaga, N. and Okada, H. (1981). "Purification and characterization of 6-aminohexanoic-acid-oligimer hydrolase of Flavobacterium sp. KI72". European Journal of Biochemistry. 116(3): 547-551

    5. Dawkins, R. (1986). The Blind Watchmaker, p. 48

    6. Ibid. p. 49

    7. Ohno, S. (1984). "Birth of a unique enzyme from an alternate reading frame of the preexisted, internally repititious coding sequence".  Proceedings of the National Academy of Sciences. 81: 2421-2425

    8. Negoro, S.; Ohki, T.; Shibata, N.; Sasa, K.; Hayashi, H.; Nakano, H.; Yasuhira, K.; Kato, D; Takeo, M. and Higuchi, Y. (2007). "Nylon-oligomer degrading enzyme/substrate complex: catalytic mechanism of 6-aminohexanoate-dimer hydrolase". Journal of Molecular Biology. 370: 142-156

    9. Farabaugh, P. (1996) "Programmed Translational Frameshifting". Microbiological Reviews. 60(1): 103-134