Sunday, 15 January 2012

Science nay-sayers, why the rush?

I get annoyed at the repeated premature announcements that scientific breakthrough X or Y has not yielded the benefits it promised. This week's Nature Biotechnology, for example, features an editorial entitled "What happened to personalised medicine?" with the tag line:
"Personalized medicine falls a long way short of the predictive and preventative healthcare paradigm it once promised."
Notice the past tense? "It once promised." Personalised medicine as a concept has failed, apparently.

The article then says:
"In some respects, 2011 was a banner year for personalized medicine. Academic medical centers began to demonstrate the feasibility of routine clinical genotyping as a means of guiding treatment selection in oncology. The US Food and Drug Administration released its companion diagnostics draft guidance. Sanofi, Pfizer and AstraZeneca signed deals with Medco and WellPoint for access to their large databases of patient data. Cancer Research UK's Stratified Medicine Programme was launched to demonstrate how genetic tests can be used to match National Health Service cancer patients to treatments. And two new targeted oncology therapies, Roche/Genentech's Zelboraf and Pfizer's Xalkori, were approved in conjunction with companion diagnostics for BRAFV600E and structural variants of anaplastic lymphoma kinase (ALK), respectively.

All are no doubt important steps, but illustrative of a rather pedestrian form of progress in personalized care rather than a march to the future."
So, it's not that it's failing to deliver anything. It's just happening too slow. The same thing happened with the Human Genome Project (HGP). This was "completed" less than a decade ago but people have already proclaimed that it has failed to deliver because we haven't been overwhelmed with a deluge of new HGP-derived drugs. The average drug development time is 10-15 years, I think, and that's when you already understand a fair amount about the target. So, even if the genome project truly was "complete" then it is still unrealistic and unfair to have expected it to already have yielded dozens of new therapeutics, even if you ignore the fact that novel targets arising from the genome project are, by definition, going to start off with practically nothing known except the sequence.

Annotation is still ongoing but the current state is over three billion nucleotides, approx 21,000 high confidence protein-coding genes plus over 47,000 gene predictions. This is a lot of data to deal with and it is naive beyond belief to think that the "answers" are just going to magically fall out in a few years. Going back to personalised medicine, the current Ensembl release has over 45 million variants and even this is not enough data. To really make sense of the role of genetic variants, we need a lot more genomes from both patient and control populations, and these patient populations need to be sensibly stratified by, e.g. treatment response. Such data is beginning to come but it is still early days, plus we still don't really know how to analyse all this data.

Biology is flaming complicated and the more we learn, the more messy and complicated it gets. Expecting us to unlock the secrets of first "The Human Genome" and then human variability in a few years goes beyond naive or arrogant, it's ridiculous.

I'm a big believer in The Human Genome Project and it really has changed the world already, even if its "promise" in terms of new drugs etc. will take many more years to be realised. (And this realisation will probably come mostly from Academia rather tha pharma.) I'm also a big believer in the concept of personalised medicine - the tailoring of treatment to the individual based on their particular genetic background. The fact is, however, that whilst this is totally the right road to be heading down, it's going to be a very long and windy road, no doubt with a few wrong-turns and dead-ends along the way.

To be fair, the rest of the editorial does then raise some pertinent points about things that need to happen to facilitate our journey down the road towards personalised medicine. These include better incorporation of the human "microbiome" - in sheer numerical terms, we have far more bacterial cells, genes and proteins in our bodies that human ones - and increased incentives for pharma companies to develop diagnostics as well as treatments. I just wish that the whole thing hadn't been given such a negative spin from the outset. It seems that with live in a world where everything needs to be over-hyped initially and then over-criticised when it doesn't live up to the over-hyping. I say, stop that: it's silly.

21st Century Referencing

One of the new issues that I am beginning to see in undergraduate project work is uncertainty regarding how to cite various atypical sources. In my day [gets out pipe and smoking jacket], the most tricky source was a book section or occasional website. Now, though, it seems that podcasts and Youtube videos etc. are being added to list of legitimate and useful sources of information and opinion. Fortunately, help is at hand. The library staff at Anglia Ruskin University have made a really useful Harvard System of Referencing Guide [1] containing all manner of source types and the required information for citations thereof. This is the best website of this kind I have seen and well worth bookmarking if you have to deal with this stuff regularly.

1. Anglia Ruskin University, 2011. Harvard System of Referencing Guide. [online] Available at: <http://libweb.anglia.ac.uk/referencing/harvard.htm> [Accessed 14 January 2012].

Damn fine Dalmatian Dingač

Yesterday was the first tasting of the Year for the University of Southampton Wine Club. The tasting was "8 Dalmations":
"The 2012 inaugural wine tasting will bring back fond memories of summer warmth and sun-drenched picturesque shores of the south Adriatic Sea – and hopefully this setting can be recreated by tasting the wines typical of that region: Pelješac peninsula and Korčula Island. Already the ancient Greeks grew vine there and after a brief exile in established wine-making regions of the old and new world more and more wine-growers and makers return to Croatia, only to express their newly polished skills in exciting wines.

We will experience 3 white wines from the Korčula vinogorje (typical/registered region), a relatively green island with rolling hills, famous also for being the home of Marco Polo. In contrast, northern Pelješac is characterised by wind swept escarpments and small villages. Grapes barely survive what nature and the gods throws at them, but for the wine-lover the efforts of hard working small wine estates can be very rewarding, and we will taste 5 reds from the Pelješac vinogorje."
This was a great tasting that embodies all that is good about these events: good company, good nibbles and an interesting selection of wines that I would not normally have access to nor think about trying. (Too be honest, I had never heard of any of them!)

The stand-out discovery for me was my enjoyment of the Dingač red wines. We sampled two robust reds (14.3% and 15% vol!) and a dessert variety, and all three were very tasty. My personal favourite was the 2006 Matuško (right) but others favoured the 2004 Skaramuča (centre). They have an interesting flavour, with a lot more cherry versus the berries of the red wines that I normally go for. Sadly, I think they are only really available in Croatia but it is on my holiday destination wishlist, so I will just have to make a mental note and bide my time!

Thursday, 12 January 2012

A flowchart for choosing your religion

I'm not sure where this originally came from but it's a classic! (I'm not rich and insane.)

A month (or so) with iPlan

At the end of November, our iPlan energy kit arrived. With one full month under our belt, I thought it timely to give an update.

Initial experiences were a bit mixed as the website was done for quite a while but, right from the outset, the ability to monitor energy usage was really useful and reminded me to switch off lighs etc. It was also interesting to see how much energy some of our light use. (Not surprisingly (but still disappointing), the worst offenders were the brightest, most useful ones!)

Less useful at this stage is the daily target. This started off at a fairly reasonable 8.0 kWh per day (although I'm not sure how this was determined) but went down dramatically when I switched to our predicted usage from Scottish & Southern Electric (SSE). You can see this on our monthly usage chart for December, below, where the target line drops sharply on the fourth:

This is clearly nonsense, as the only days that we meet are target are those that either or both of us are away and thus (practically) nothing is being used. (The big spikes caused by extra laundry each side of trips is also clearly visible!) Having contacted SSE, I have learnt that this prediction is based on meter readings and because our reading-before-last was a massive over-estimate, our last period's usage was practically nothing. It should, I am told, sort itself out with our next meter reading later this month. Time will tell. (I still think it is a bit silly that you cannot over-ride their estimate and set your own target; you can set it for a percentage under their prediction but not over.)

Fortunately, even though we can't set a sensible target, we can still feel good about ourselves with some of the other comparisons available, such as the "LikeMe" comparison with "similar homes". It's not clear how a "similar home" is defined but I suspect, given how well we appear to be doing, it does not include a comparison of the number of occupants. (Either that, or the average couple out there are big consumers!)

You can also compare your usage with all iPlan users, although I'm not really sure how much this tells you:

Still, it makes electricity billing more interesting!

Friday, 6 January 2012

Just 24 to go until a big round-number milestone

I love geeks! Happy cartoon 1111101000, xkcd!

Oar House (inspired) cod, chorizo and potato one-pot

In December, I made the fantastic discovery that The Oar House website has a delicious-looking selection of recipes. Tonight, I tried one out - or a variant thereof, at least - and, whilst not up to the standard of the restaurant itself (a chef issue, I fancy), it was indeed delicious. Errors on my part not withstanding, it was also pretty easy.

The recipe selected was Haddock, chorizo and new potatoes, which appealed to me both because I love fish, chorizo and potatoes but also because it is done all in one pot! Due to availability when shopping, I made it with line-caught cod rather than haddock and, for matters of taste, switched the dry sherry for dry Martini. (Next time, I might use wine.)

Cooking this was easy but, at the same time, highlighted some of my failings (or "room for improvement") as a chef; one feature of the Oar House recipe is a certain absence of key instructions that an experienced chef would know, such as pan selection (it's called a sauté pan for a reason, duh!) and temperature.

First, fry the chorizo for a couple of minutes in the oil - use a sauté pan (or frying pan with a lid) rather than a saucepan (as I did). Add the spuds and 3 tbsp sherry/martini/wine, put the lid on and cook for 10-15 mins. Stir occasionally to prevent burning. (I was a bit late realising and had to replace a few bits of burnt chorizo. My pan selection also added a few extra minutes before the potatoes were tender.



Once the potatoes are tender, add the tomatoes and parsley and lay the fish on top, add another tbsp sherry/martini/wine then cover and cook for 5 mins. Because of my pan selection, this was not long enough, so I ended up flaking in the fish and giving it a couple of extra minutes to heat properly. (That was ultimate the plan for serving, anyway.)

Despite the hiccups along the way, it was delicious. Perhaps best of all, I am pretty sure that I could do it better next time!

Great Fluorescent Proteins

One of the benefits of teaching (and its ugly sibling, marking,) is exposure to interesting bits of science that I would normally not have the time and/or inclination to find out more about. One such thing is the most excellent - and Nobel Prize winning - Green Fluorescent Protein (or "GFP").

I am not a structual biologist and often find myself getting a bit bored at the minutiae of structural details that excite biochemists at lunchtime seminars but I must admit that I find the structure of GFP to be a thing of geeky beauty. GFP has what is known as a beta barrel or "can", which is comprised of a number of beta strands (a particular arrangement of protein strands that make a kind of sheet) wrapped into a tube (or barrel). Within this barrel, sits some modified amino acid residues called the "chromophore", which are responsible for the fluorescent aspect of GFP. This is then protected by caps at the top and bottom of the barrel.

I don't feel too bad about liking this - Julian Voss-Andreae liked it enough to make a sculpture!

GFP works by absorbing light of one wavelength and emitting light of another. In the case of the original GFP from jellyfish, UV or blue light is absorbed and green light is emitted, hence GFP. (The blue light itself is generated by another protein (aequorin), which is "chemiluminescent" and emits light in response to a chemical stimulus - in this case, a release of calcium in response to external stimulation. GFP and aequorin were first isolated from "squeezate", which is what you get when you pass jellyfish through some gauze!)

Other colours also exist, both in nature and as a result of tinkering by various scientists over the years. As well as enabling some fun "lab art", such as this "San Diego beach scene" created in the lab of Nobelist Roger Tsien [Artwork by Nathan Shaner, photography by Paul Steinbach] made using eight different fluorescent proteins, including a Red Fluorescent Protein (RFP) from corals that I have done a bit of work on. (I'll save that for another time.) I love the names of some of the colours too: "BFP, mTFP1, Emerald, Citrine, mOrange, mApple, mCherry and mGrape". (Mmmmmm.... Cherry.)

This diversity has led to some amazing research tools that have in turn led to some amazing discoveries, hence the Nobel prize. There are far too many to list here but one such technique that I make indirect use of in my own work is "FRET": "Fluorescent (or Förster) Resonance Energy Transfer", which is used for (among other things) detecting likely protein-protein interactions. It works a bit like the original GFP in jellyfish, using the emission of light from one protein to trigger fluorescence in the other. Unlike the jellyfish, however, FRET uses a GFP-like protein for each step. Each FP is attached to a different protein of interest and light is provided that excites the first protein. If the two proteins get close enough, such as if they interact, the emission from the first protein excites the second protein and the emission spectrum shifts, allowing the interaction (or, more accurately, proximity) to be detected.

Perhaps more fun are some of the recreational uses of the GFP family of proteins, such as these "GloFish", which demonstrate the power of genetically modification in a fun and friendly way. (Take that, Pope!)



These guys are zebrafish (shown to the right in their normal colours) that have been genetically modified to express different FPs, causing them to fluoresce under different light. (White light works but blue light is best, I think.) You can see videos of them swimming about here. The original goal was to create fish that could be used for detecting environmental pollution etc. but, given restrictions on releasing GM animals into the wild, I think that fun fluorescing pets is probaby a more practical (and lucrative) application! Other GFP'd animals (usually for scientific reasons) include mice, monkeys, cats, pigs and, of course, Alba the GFP albino rabbit, although I am always a little wary of colour enhancement for images of such things. I'd still like to have one as a pet, though!

Tuesday, 3 January 2012

Mirror Lake - yet another cracking Marlborough white

Wine this Christmas was a rather delicious New Zealand Sauvignon Blanc from Mirror Lake in the Marlborough region. Another wine that hits all the right notes for me: crisp, fruity and refreshing. Great stuff.

Monday, 2 January 2012

New Year, New Calendar?

Last year, I posted about Isaac Asimov's suggestion for a new rational calendar, freed from the idiosyncrasies of the current dominant Gregorian beast.

Since then, I have come across an even better suggestion that does not include the wholesale renaming of everything that was part of Asimov's vision. (Today would be A-1, for example, not January 1st.) This is the Hanke-Henry Permanent Calendar, described in more detail at wired.com.

Rather than getting too het up about revolutions around the Sun, this calendar focuses on being functional and consistent for users. Like the Asimov calendar, it features four equal quarters, each of 13 weeks. In the Hanke-Henry calendar, however, these quarters are subdivided into a repeating three month cycle of 30 days, 30 days and 31 days. In both cases, there is an extra day (and a quarter). Asimov adds an extra "Year Day" each year and evens the rest (I think) with Leap Years as present. The Hanke-Henry solution is, in some ways, more elegant - an "Extra Week" every 5-6 years, which covers both the extra days and the leap years.



The best thing about - and, from what I can gather, the motivation behind - the Hanke-Henry Permanent Calendar is that each day always falls on the same date every year, hence the "Permanent".
As the architects point out, this means that sports schedules and term times etc. only need to be drawn up once and can then be kept from year to year, unless their content actually changes, as opposed to the current situation where these things must be drawn up afresh.

The big question of course, is would it catch on? Would people feel happy to use it? Well. it seems that I am not alone in thinking that this kind of thing is a great idea. Although by no means scientific, the poll on the website suggests that yes, people would use it - approx. 62% of them, at least.

Will it ever happen? I doubt it. Still, a nice idea.

Sunday, 1 January 2012

Veg Every Day: Kale & Mushroom Lasagne

Due to various trips and things over the past few weeks - not to mention Christmas - we have not been eating the best of late. When I say "best", what I mean is "healthiest" - the food has been largely delicious, just a little to high in meat, fat, sugar and other yummy things. As a result, one of our newish Year's resolutions is to eat more veg.

To kick-start this endeavour, one of my Christmas presents for my wife was the River Cottage veg every day cookbook. This week, we tried one of the dishes: kale and mushroom lasagne.

The recipe itself is really easy: boil some kale for a few minutes; fry some shrooms with butter, garlic & thyme; make some bechemel sauce (milk, flour, butter, bay leaf, peppercorns, onion); layer up with lasagne sheets (bechemel - lasagne - kale+bechemel - lasagne - shrooms - lasagne - bechemel - Parmesan); cook for 30 minutes. Delicious!


The original recipe was for six but we scaled it down a bit for four and increased the shroom:kale ratio a bit too. I'd also be tempted to try it with spinach some time instead of kale, although the crunch of the kale provided great texture. The leftovers were good too!