Posted: 20 Aug 2008 06:46 PM CDT
Just a pointer to a great overview article of trends in medical tourism at Economist magazine. Hope the price of jet fuel doesn’t put a damper on these exciting trends.
Posted: 20 Aug 2008 05:58 PM CDT
Interesting link in Boing Boing today about a group at MIT making micro-batteries using genetically a modified virus as a construction tool. Way cool!
Posted: 20 Aug 2008 05:22 PM CDT
Anyone who has walked past a TV set over the last few days will have seen footage of the remarkable Jamaican sprinter Usain Bolt, who comfortably cruised to victory (and a world record) in the Olympic 100 metre sprint, and as I write this has just done precisely the same thing in the 200 metre sprint. The interest in Bolt stems not from the fact that he wins his races, but rather from the contemptuous ease with which he does so.
And Bolt is not the only Jamaican to impress in short distance events in Beijing: the country's women's sprint team took all three medals in their 100 metre dash.
Naturally, these performances have provoked widespread speculation about the basis of Jamaica's sprinting success, and the short-distance prowess of other populations of West African ancestry. One controversial suggestion has drawn the most headlines: that sprinting is in their genes, or rather in one gene in particular - variously referred to as "Actinen A" or "ACTN3".
This gene has been the subject of a recent rash of news stories sparked by Bolt's victories, all of which refer to comments by Jamaican academic Errol Morrison in the Jamaica Gleaner over a month ago. The Gleaner article summarised the (unpublished) results of a collaboration between Morrison and a group at the University of Glasgow:
At the base of sprint speed are the fast-twitch muscle fibres stocked with the speed protein Actinen A. And early data indicate that 70 per cent of Jamaican athletes have the gene for Actinen A. Only 30 per cent of Australian athletes studied had the gene.(The Gleaner reporter, Martin Henry, astonishingly went on to speculate that this gene may help to explain why Jamaicans are "also disproportionately aggressive and violent".)
The Daily Mail followed up on the story two weeks later with a marginally more coherent account:
What they have found - and Morrison emphasises the findings are preliminary - is that fast men have a special component called Actinen A in their fast-twitch muscles, which determine whether humans are sprinters or plodders. It is found in 70 per cent of Jamaicans. In a control study of Australians, only 30 per cent were found with it.The "preliminary" nature of the findings didn't stop the Daily Mail reporter from following this paragraph with the conclusion that this result "would seem to explain why Jamaicans punch above their weight among sprinters". Similarly definitive statements were made by other reporters continuing the story after Bolt's 100 metre victory; one rare exception was a fairly well-balanced piece in Slate.
The stories take advantage of a widespread perception - by no means totally unjustified, but nonetheless controversial - that Jamaicans and other groups of West African ancestry have a genetic advantage when it comes to raw muscle power. Having apparent scientific evidence to support this perception is a reporter's dream; the headlines write themselves.
So, how good is this scientific evidence? Does the "Actinen A" gene (whatever that is) actually influence sprinting performance? And if so, does it explain the difference in explosive power between Jamaicans and the rest of the world? The answers, as it turns out, are "probably" and "not really".
The ACTN3 gene and muscle performance
At this point I probably should confess to having a more than casual interest in this story: I was one of the authors on the first study showing an association between this gene and elite athlete status back in 2003, and this gene has been the central focus of my research for a good part of the last six years. (The opinions I express here are purely my own, by the way, and in no way are meant to represent the views of my research institute.)
The ACTN3 gene encodes a protein called α-actinin-3 ("Actinen A" is a misnomer of uncertain origin propagated by lazy reporters), which is found within the fast fibres of muscle - the cells that are required for generating rapid, forceful contraction in activities such as sprinting and weightlifting. Interestingly, the human ACTN3 gene comes in two forms in the general population: there's a normal, functional version called 577R, and a "defective" version called 577X, which contains a single base change that prevents the production of α-actinin-3. People who have two copies of the 577X version (I'll refer to them as X/X) produce absolutely no α-actinin-3 in their fast muscle fibres.
These people don't suffer from muscle disease as a result of this deficiency - in fact, there's a pretty good chance that you're one of them. The frequency of the 577X variant differs around the world, but overall somewhere between one-sixth and one-quarter of the world's population (at least a billion people worldwide) are X/X, and therefore completely deficient in α-actinin-3.
So lack of α-actinin-3 clearly doesn't destroy your muscle; however, over the last five years we and other groups have assembled evidence suggesting that it does influence how good your muscle is at generating explosive power. We first showed in 2003 that X/X individuals are significantly under-represented among elite Australian sprint/power athletes, suggesting that the absence of α-actinin-3 in X/X individuals is detrimental to optimal muscle power generation. This association has since been replicated in four separate athlete studies by groups in Europe and the US; there is also weaker but reasonably consistent evidence that α-actinin-3 deficiency results in slightly higher endurance capacity, both in human athletes and in a mouse model generated by our group. In addition, several groups have reported that X/X individuals in the general population display lower muscle strength and reduced sprint performance.
Importantly, the latter two studies suggest that the proportion of the variance in strength and sprint performance in the general population explained by the ACTN3 variant is around 2-3%. So for most of us lazy slobs this gene has a pretty trivial effect - almost completely drowned out by noise from the effects of diet, exercise levels and other genes. (Certainly there are dozens or even hundreds of other genes influencing physical performance, some of which - like the ACE gene - have been fairly well-studied, but most of which are completely unknown and uncharacterised; and environmental factors play about as large a role as genes do in traits like muscle strength and cardiorespiratory performance.)
However, even 2-3% can make a striking difference at the very elite level: of the 51 Olympic-level sprint/power athletes analysed in our original study and a follow-up analysis in Greek athletes not a single individual was X/X (compared to about 10 expected). In fact, X/X Olympian sprint athletes are unusual enough that identifying a single Spanish Olympic short-distance hurdler with α-actinin-3 deficiency was enough to warrant its own publication.
So the absence of α-actinin-3 means very little to most of us, but to a young athlete craving 100 metre Olympic superstardom it could make all the difference in the world. The same could be said of many other genetic variants, of course; Olympic sprinters, essentially, are those unlikely individuals at the vanishing edge of the probability distribution for whom nearly every genetic coin has come up heads.
Does the ACTN3 gene explain Jamaican sprinting prowess?
The underlying argument here is intuitively simple: (1) variation in the ACTN3 gene is strongly associated with elite sprint athlete status; (2) the "sprint" version of ACTN3 is more common in Jamaicans than in individuals of European ancestry; therefore (3) this variant may well play a role in the increased sprinting prowess of Jamaicans relative to Europeans. At first blush this sounds pretty convincing; however, while ACTN3 may play some role in the disproportionate success of Jamaican sprinters, I'd argue that it's likely to be a pretty small one. Here's why:
Beyond "the gene for speed"
I'm certainly not arguing here that genetics doesn't play any role in Bolt's success - or in the remarkable over-representation of West African descendents in Olympic short-distance track events, or the similarly impressive skew towards East Africans among marathon runners. In fact I think most geneticists would be staggered if this was the case, even though direct evidence for underlying genes is currently very thin on the ground.
Rather, my point is that an excessive emphasis on ACTN3 as a major explanation for Jamaican success does a grave disservice to the complex interplay of genetic and environmental factors required for top-level athletic performance. This suggestion goes against everything we've learnt about the genetics of complex traits from recent genome-wide association studies, which have revealed that quantitative traits (like height and body weight) are frequently influenced by dozens to hundreds of genes, each of small effect; if anything, it's likely that athletic performance will be even more genetically complex than these traits. The ACTN3-centred argument also dismisses the importance of Jamaica's impressive investment in the infrastructure and training system required to identify and nurture elite track athletes, the effects of a culture that idolises local track heroes, and the powerful desire of young Jamaicans to use athletic success to lift themselves and their families out of poverty.
It is almost certainly true that Usain Bolt carries at least one of the "sprint" variants of the ACTN3 gene, but then so do I (along with around five billion other humans worldwide). Indeed, I'm fortunate enough to be lugging around two "sprint" copies - but that doesn't mean you'll see me in the 100 metre final in London in 2012. Unfortunately for me, it takes a lot more than one lucky gene to create an Olympian.
(Usain Bolt photo by Phil McElhinney, used under a Creative Commons license.)
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Posted: 20 Aug 2008 02:01 PM CDT
So I had the chance over the weekend to try a new fruit advertised as "dinosaur egg". The vendor claimed that it was a nectarine/plum hybrid. Yeah right I thought, nectarines and plums seem like very different fruits to me, and it's not like people are still inventing fruits right, it's just probably a plum variety with a taste similar to a nectarine. wrong.
Turns out it's a pluot, an interspecific hybrid fruit with 3/4 plum and 1/4 apricot, and there are several varieties of pluots to boot (13 according to wikipedia). How is that possible. Well they are derived from a 1:1 hybrid of plum and apricot, the plumcot, which was generated simply by cross-pollination. The plumcot can then be crossed back to either an apricot or a plum tree to get different percentage contribution (which you could probably track by QTL analysis).
In fact you can do this with apricot, plum, cherry, peach and almond trees. For example the peacotum is a peach/apricot/plum hybrid which tastes just like fruit punch. Zaiger's Genetic from California holds the patent and trademarks to pretty much all these hybrids.
People sometimes mistake nectarines as a cross between plum and peach, but in fact nectarines are just a cultivar of peaches with a recessive mutation. The fuzziness of peaches is a dominant trait.
So there you go, we are still inventing new fruits, and there is still room for innovation by using simple crosses. Who knew those fruit trees were related enough to be crossed, and that the hybrids would be fertile. Now if one of them mutha uckas fruit vendors could make me a grapple, we would be in business...
Posted: 20 Aug 2008 01:15 PM CDT
Just heard about this particular cancer therapeutic on the Science Magazine Podcast (link to mp3 of episode), called Blinatumomab. It is made by a US company called Micromet, who has a patent on this class of engineered proteins called BiTE antibodies. These proteins are a single polypeptide containing the variable regions from two antibodies with different specificities. BiTE stands for bi-specific T-cell engagers and are named such becuause one of the antibodies specificities is for CD3, a compentent of the T-cell receptor, while the other is specific for a tumour specific antigen. The idea is that these molecules attach to cells expressing the tumour antigen and then recuit Tcells (nonspecifically as they all have CD3) to kill these target cells. The mechanism of exactly how this works eludes me as the T-cells are not being activated in the conventional mechanism that I understand. However it is therefore suggested that the cancer cells would be more suseptable to this mechanism as they have managed so far to escape conventional immune control.
Check out the Micromet company backgrounder on BiTE antibodies. (pdf)
What makes these molecules Science magazine worthy is that Blinatumomab has demonstrated some impressive efficacy against non–Hodgkin's B cell lymphoma (NHL). Check out the publication from Science.
Posted: 20 Aug 2008 11:53 AM CDT
Opponents of human embryonic stem cell research have been screaming about this for years, but it never really gets the press it deserves. Researchers have found that embryonic stem cells cause rejection (because they come from a different human being) just like with organ donation. From Scientific American:
The answer is iPS, or induced pluripotent stem cells. This procedure would take the patient's adult cells and reprogram them back to a pluripotent state, no eggs needed and no embryo created, and best of all, the stem cells would be a true exact genetic match.
But even with iPS there are many more hurdles to overcome. A realistic outlook is very important. Dr. Joesph Wu, co-author of the study, agrees:
Posted: 20 Aug 2008 11:48 AM CDT
Posted: 20 Aug 2008 11:15 AM CDT
The august issue of Nature Methods seems very appetizing for any reporter-genomist. The following is only a personal cherry-picking from the table of contents.
A time stamp for proteins (doi:10.1038/nmeth0808-662a)
Posted: 20 Aug 2008 10:11 AM CDT
Posted: 20 Aug 2008 09:30 AM CDT
After spending two weeks in Britain, I intended to blog about the genomics issues I read and heard about in the British Press. Then I get home and the first thing I see on my homepage when I start up my computer is a link to a newspaper article on analysing Bigfoot DNA. Wow! I thought nothing I saw in Britain could compare to this.
Turns out that the DNA indicated the Bigfoot to be 96% Possum and the remainder human. I guess they didn’t even need to do the DNA test, there was a Bigfoot body. Examination of the body proved it to be a rubber gorilla suit.
I did wonder though, how would we know if indeed we had Bigfoot DNA.
Posted: 20 Aug 2008 09:00 AM CDT
Posted: 20 Aug 2008 07:00 AM CDT
Apparently, scientific thought needs rekindling, seemingly it has run out of kindle and needs a new flame if it is to burn brighter. In steps Terence Witt with the concept of null physics. Witt has now self-published a hefty tome by the name of Our Undiscovered Universe.
According to the press blurb that came with my review copy of the book, he’s a visiting scientist at Florida Institute of Technology. Now, I can find FIT on the web, but I cannot find Witt at FIT. Anyway, he puts forward an intriguing, if not entirely original, idea that modern physics requires a paradigm shift back to common sense thinking and a logical reconnection between observation and theory.
There is, Witt says, a disconnect between the two in our current Big Bang theory of the origins of the universe. In Our Undiscovered Universe, Witt puts forward the hypothesis that the universe is static and not expanding, and rouses various equations to explain away the red shift of distant cosmic objects and concepts such as dark matter and dark energy. Likewise there is a disconnect between the purportedly irrational quantum world and the reality we observe.
Perhaps there are almost as many loopholes in modern physics as there are wormholes and maybe it is possible to tangle up any scientific model with enough string to fill a universe. But, Witt’s is too comfortable a conclusion, that the universe does not rely on any unknowable precursors in the untestable past and will not grow old, collapse or die, but is an unimaginably large cosmic engine. Moreover, his null hypothesis suggests that “our universe actually is, the only thing it could possibly be: the internal structure of nothingness.”
So, you might ask, what is Witt’s evidence for this concept? He explains that evidence of the Null Axiom is everywhere:
I put a few questions to Witt on behalf of Sciencebase readers. First off, I asked him to describe null physics briefly.
Null physics is a bottom-up theory built upon the solution to the ontological dilemma: why does the universe exist [instead of nothing]? The solution - that our universe is composed of nothing - leads directly to the four-dimensional geometry of which energy and space are composed. Null physics is the study and quantification of this geometry and its larger ramifications. In contrast to modern physics’ top-down, heuristic approach, which uses measurements and mathematical symmetries to build models that conform to empirical reality, null physics derives empirical reality, such as the magnitude of unit elementary charge and the range and strength of the strong force, through calculations applied to the topology of a fully known underlying geometry.
I put it to Witt that because his theory is a blend of philosophy and science, that might be a double-edged sword?
Not at all. What we currently call physics originally began as natural philosophy. Physics replaced natural philosophy because it provided an accurate mathematical description of the macroscopic scale of the physical world. This set the stage for untold advances in engineering and technology, but many of the foundational questions that natural philosophy confronted, such as why the universe exists and why matter is composed of discrete particles, were lost in this transition, leaving us with empty mathematical models. Null physics is the best of both worlds, fusing a deep understanding of physical reality (as geometry) with empirical validation. The geometry used in Null physics is derived using logic and reasoning similar to that employed by natural philosophy, but has no philosophical component in its final geometric formulation.
Of course, there are other theories around that suggest the universe did not begin with the Big Bang, I asked Witt, what makes his stand out among them?
Sweeping unification and empirical validation. Unlike other non-Big Bang theories, null cosmology is falsifiable, provides testable predictions, and gives a full accounting of the many nuanced properties of the intergalactic redshift and CMB. It also, unlike any cosmology before it (including the Big Bang), provides a logical reason for the universe's existence and a clear framework that unifies a wide variety of known galactic properties with the large-scale universe. And in keeping with true scientific progress, the unification provided by null cosmology illuminates a number of currently unknown galactic properties, such as the vortical motion of a galaxy’s disk material.
Finally, I was still curious about the philosophical implications and asked about what this theory can tell us of our place in the universe.
It tells us everything about our place in the universe. It tells us why and how we exist on a finite scale that, because of space's intrinsic symmetry, must exist precisely midway between infinite largeness and smallness. It tells us that the universe is, through causality and sheer size, large enough to contain its own history. In fact the universe must contain its own history, because each and every moment of our lives is integral to ultra-large-scale structure. Perhaps most importantly, null physics demonstrates that our existence is neither accident nor design - it is inevitable.
His theory has an additional redeeming feature for people hoping to eradicate the ultimate irrational explanation in that it closes the door on a designer. If the universe has always existed and always will exist, then how could a creator have any role to play at all? My cynical brain suspects that this could be one of the motives for the resurrection of the static universe theories that are springing up at regular intervals. Witt is not the first to try to defuse the Big Bang. In the final, and I use the word lightly, given that apparently there is no final, Witt’s conclusion could be summed up with the naive parent’s riposte to the childish question: Why are we here? Because we’re here!
Posted: 20 Aug 2008 05:28 AM CDT
Last Thursday’s post on the animal rights firebombing in Santa Cruz earned me a couple outraged comments, so I suppose I did something right. I’m sure they don’t realize it, but they’re comments reflect what I was saying.
That is, commenter Connee said, “[Animal Rights] people value ALL life but have NO problem with destroying the property of people who commit acts of violence against sentient beings.” That would be the words from a supporter of terrorism - “I will hurt you if you get in the way of my extremist ideology.”
People like these implicitly condone violence over the use of animals in biomedical research - including the use of fruit flies and nematodes in research. That’s right - they threaten violence to save the lives of flies and worms for crying out loud. They care not that the welfare and ethical treatment of research animals is looked after, but that they are studied at all. I wonder why these people aren’t bombing livestock farms, pet shelters, pet stores, and generally anyone who owns an animal cage.
No, as has been implied, I do not think that supporters of animal welfare are terrorists - I count myself among them. But animal “liberators” are nuts, and the members of some animal liberation groups (e.g. ALF) are terrorists and terrorist supporters.
Even for the mammals that they get upset over, animal rights terrorists deny the indisposable service that mammalian models of disease perform for medicine, including for veterinarians helping the animals that they value above human life. Speaking of - I would love to know what the SPCA thinks of terrorist groups like ALF. Of course I support bans on the use of animals for cosmetic testing, fashion, etc. Even the SPCA supports this. But no one in their right mind wants biomedical research to come to a screeching halt.
But I digress - as I have said, I urge them and everyone to stop this nonsense, and renounce the use of violence as a political tool. In fact, take it one step further - support biomedical research and encourage informants of these violent acts to come forward to the proper authorities.
More related blog posts on Animal Rights terrorists:
Posted: 20 Aug 2008 03:27 AM CDT
Sorry about the long blogging break - we have been keeping busy here at CLC getting ready for the upcoming release of Genomics Workbench 2.0 . These days we are preparing the final test rounds and fine polishing the code. Besides being busy coding, one of our NGS specialists has been busy preparing a presentation for [...]
Posted: 20 Aug 2008 02:58 AM CDT
Yes, my drug is for treating genomitis, chromosome inflammation and DNA fever…
You name your drug, customize it’s features and get this:
Posted: 19 Aug 2008 11:39 PM CDT
In Our Friend the Atom, one of my favorite books as a kid, I remember two chapters (I forget the exact titles); Why is the Atom so Small, and Why is the Atom So Big.
The point is that while the atom is pretty small, much of the atom is empty space, so relative to the size of it’s components it’s pretty darn big. I’ve been thinking about that a lot lately, in a different context, biological data and information.
We are at the beginning of a new era, petabytes of sequence data will be collected as part of the 1000 genomes project and many other efforts. But the thing that keeps gnawing at me is this. We have so much data, but in reality, we have such little information. Our knowledge of human biology, of what all the data we are collecting tells us is still so sparse relative to all the data we have. There is an expectation that microarrays and next-gen sequencing should be revolutionizing our knowledge, and to a degree they are, but we are a long way from bringing all of this together, to make sense of the data. Quite frankly to build a complete picture, we don’t quite have enough data, with the multiple measured datapoints and different levels of information content that will allow us to get there.
This is also the crux of my argument against statistical correlations driving the fundamentals of science. microRNA, epigenetics, etc are real, not statistics. How they correlate with certain factors might be analyzed statistically (or as I prefer, using probabilistic models), but I maintain that in the long run that is an interim step, since we are working with relatively sparse information sets that leave too many wholes. We must eventually figure out the mechanisms and start designing on the basis of these mechanisms, whether it is new drugs, or engineering in new functions into organisms to produce fuels, etc.
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