Tuesday, 30 April 2013

Charles Darwin, the gentleman scientist

Yesterday, we went to Down House, the home of Charles Darwin, with a friend from the US. I've been meaning to go for a while and, as an evolutionary biologist, I guess it is something of a Pilgrimage. (Somehow fitting, therefore, that my Tom Tom Sat Nav decided to direct via all the country backroads, including Pilgrim's Way.) The house is now looked after by English Heritage and features some great exhibits and insights into the great man's life.

As I am reading the blog of Darwin's Beagle diaries, I was initially most interested in the material from that time of his life, including the reconstruction of his cabin on the Beagle. Perhaps what struck me most, though, was Darwin the man, not Darwin the scientist.

Darwin was a gentleman in every sense. It is true that he was independently wealthy and never had to work for his money, being the son of a very successful doctor and financier. Although he did not eschew this inheritance (honestly, who would?!) it is clear that he did not take his fortune for granted. I have already seen glimpses of his opposition to slavery in his journal comments but it was clear from Darwin House that he was also a kind employer to those paid to serve on his staff. His butler, Joseph Parslow, for example was described on his headstone as "Faithful servant and friend of Charles Darwin" and used to play billiards with Darwin. One of Charles Darwin's sons, Frances, wrote (quote taken from TwoJays):
"“As a master of servants he was much loved and respected; he always spoke to them with politeness, using the expression "would you be so good" in asking for anything. And he was considerate in giving them trouble, one little thing I remember, how he used to reprove one for using a useless number of spoons because it gave so much more trouble in cleaning."
On the subject of Darwin's children, the other thing that really came across from the house and the quotes taken from letters etc. was how much he cared for his family. Not only was Darwin a keen lover of nature, he was a loving husband and a doting father. It is not hard to imagine Down House and its gardens as the site of happiness and fun as well as some of the most influential science of the modern age.

Critics of Darwin often try to make him out as some kind of monster, as if discrediting the man can discredit the science. Of course, this is nonsense on many levels. Newton, it seems, was a pretty nasty piece of work but his scientific genius remains. In Darwin's case, not only has the science stood the test of time but the character of the man himself deserves respect, whether you accept the scientific truth of evolution by Natural Selection or not.

Sunday, 28 April 2013

Are anti-vaxxers worse than Homeopaths?

Vaccination has hit the news again recently following an outbreak of Measles in Swansea. Sadly, indications are that this might be the direct result of successful lies and scaremongering by the fraudulent Mr Andrew Wakefield (not "Dr", since he got struck off “dishonest, unethical and callous” behaviour) at the end of the '90s, which caused a lot of parents to avoid giving the MMR jab to their kids. (And he's not finished.)

I don't generally go in for naming-and-shaming on this blog but if you are not familiar with Mr Wakefield's awful behaviour - and he still somehow seems to have supporters - I suggest you read this informative infographic by Darryl Cunningham, "The Facts In The Case Of Dr. Andrew Wakefield", or the more in depth expose by journalist Brian Deer. Not only did Wakefield fabricate data but he also had direct financial interests in seeing the MMR vaccine withdrawn. Bizarrely, far from being disowned by the anti-vax and alternative health community as a fraud and a miscreant, he has been embraced as a champion and hero of the cause.

Anti-vaxxers come in three main flavours, as far as I can tell. First, there are the snake-oil salesmen, who are actively trying to raise funds and/or sell alternative medicine through their scaremongering. These are the worst of the set because they pretend to be campaigning for truth when really they are putting people at risk by spreading lies to line their own pockets.

Second, there are the conspiracy theorists. These are deluded - often by the snake-oil salesman - into thinking that there is some giant conspiracy across science and healthcare professionals to lie to the public because we're all in the pocket of big pharma companies. (It is particularly ironic when these people support the likes of Andrew Wakefield, who was paid to discredit the MMR vaccine!) The tragedy here is that I suspect they are occasionally right about specific cases but, like the boy who cried wolf, who is going listen to them when blanket opposition to vaccination is so patently absurd? (I suspect this group also includes those who have been unfortunate enough to have a child suffer a rare condition or reaction and are looking for something more sinister than bad luck to blame.)

Lastly, there are those who are in favour of living a more "natural" lifestyle and who have sadly been suckered in by the more militant anti-vaxxers in online forums and the like. They may not fully buy into the whole "vaccines are evil" conspiracy, but they have been sufficiently brainwashed regarding the perceived dangers of tried-and-tested vaccines - and dulled to the very real dangers of not being vaccinated - that they avoid vaccinating their own children. This last camp includes the author of the recent "Comment is free" column in the Guardian, "Why I wish my daughter had been vaccinated". I hope more people read it. The evidence is clear. Vaccination is one of the most important medical innovations in history and has saved countless lives. As the article points out, people can only afford to be so complacent about it in the 21st Century because it has been so successful.

It is true that not all vaccines are 100% safe for 100% of people, and some of the stabilisers and adjuvants (immunity boosters) can have risks associated with them - which is why all new vaccines go through intensive testing, clinical trials and monitoring (as MMR has). These are not generally what the scaremongers are talking about, however, as they are generally not just opposed to new and unproven vaccines (indeed, they often promote their own unproven remedies) but instead trot out the same set of busted myths as a basis for opposing vaccination in general. These common myths are explained in "Six myths about vaccination – and why they’re wrong" from a great Australian site that I will be visiting again, The Conversation. (But you will still find them repeated.)

There is a small but genuine minority of people for whom vaccination is not possible, usually due to an allergy or immune deficiency of some kind. These people - along with the other small minority for whom vaccination fails - are wholly dependent on "herd immunity" to keep those nasty diseases at bay. This is the very real phenomenon where a sufficient proportion of the population is immune such that the disease is unable to take hold and spread.

By refusing to get their children vaccinated and discouraging others from doing so, anti-vaxxers are weakening the effects of "herd immunity" and out-breaks such as the current (and frankly embarrassing) UK measles outbreak in Wales are the result. You are not just endangering your own children, you put the children of others at risk, and that is just not fair. It's a bit like people who think that speed limits or the Highway Code do not apply to them. You can get away with such behaviour for a while so long as everyone else is following the rules because they are keeping you safe with their diligence. Whether born of ignorance or not, it's selfish, pure and simple.

But what if you are worried that you are one of those - or might be - with a genuine bad reaction to vaccination? Don't you have the right to avoid that risk?

No. First, bad reactions to vaccines are both rare and even more rarely as bad as getting the disease you are being vaccinated against. We tend to forget that because, ironically, vaccination has been so successful that incidents of these nasty diseases are themselves rare. Yes, you might be the unlucky one to experience a bad reaction - but you might equally be the unlucky one to get the life-threatening disease if there is a lack of herd immunity. Second, because of herd immunity, people with known bad reactions to vaccination should be even more pro-vaccination! Without the ability to get protection themselves, they are relying on the civil responsibility of others.

I've blogged a few times about Homeopathy, a sham treatment of sugar pills or water with no scientific basis nor evidence for efficacy that (shamefully) is still offered on the NHS in some places. Most homeopathic treatments are targeted at fairly innocuous conditions and are usually sold alongside real medicine, so the main damage done is to your finances (and maybe your pride once you realise you've been scammed). Apart from the diversion of funds from legitimate treatments, however, the damage done to third parties by Homeopaths is minimal.
"First, do no harm."
These words, attributed to Hippocrates, nicely sum up the essence of the "Hippocratic Oath" that (ethical) practitioners of medicine generally swear to. Anti-vaxxers, in contrast, put innocents at risk, including those who have not embraced their twisted and deviant message of lies. For that reason I think, yes, they are worse than Homeopaths - at least if you buy into the hogwash of Homeopathy, you are usually only harming yourself. (Sadly, that's not always the case and reliance on homeopathic treatment can kill children too. I think the effects on society are smaller, though. That said, the lesser of two evils is still evil.)

Saturday, 27 April 2013

Mastering Wildlife Conservation with Marwell Zoo and the University of Southampton

Although it's not quite formalised yet, Southampton has just announced an new Masters in Research course to start in October 2013. The MRes Wildlife Conservation is a joint venture between the University of Southampton and Marwell zoo, and represents a pretty unique opportunity (in the UK at least) to work closely with an active conservation organisation in the UK or Africa.

Result!         [Photos from my September 2010 Marwell Zoo album.]

Friday, 26 April 2013

Happy DNA Day!

It's 60 years to the day since the trio of Nature papers about the structure of DNA were published, including the famous 1953 Watson & Crick paper. The double helix has to be one of the most elegant and beautiful of all natural phenomena. The Exploratorium website has an annotated version of the Watson and Crick paper if you fancy a read. It's pretty short and contains one (or two) of the biggest understatements in biological history:
"This structure has novel features which are of considerable biological interest. ... It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."
Indeed!

Monday, 22 April 2013

Young Darwin at Cold Spring Harbor Laboratory


Observant folks will have noticed a statue of a young Darwin outside the Luke Building in my earlier post about Cold Spring Harbor Laboratory. I like it. Normally, Darwin statues (such as at the Oxford University Museum of Natural History) are of the old Darwin, balding and beardy. I have been reading Darwin's Beagle Diary blog and so it's great to see a statue of the young Darwin striding forward into the unknown. (The 2nd voyage of HMS Beagle die not go via North America, so it's not commemorating an actual visit to Cold Spring Harbor.)

In reading the diaries, I've been captured by the enthusiasm for nature that Darwin exhibits. A few quotes from his time in Bahia, Brazil in February/March 1832 give good examples.

29th February 1832:
"The day has passed delightfully: delight is however a weak term for such transports of pleasure: I have been wandering by myself in a Brazilian forest: amongst the multitude it is hard to say what set of objects is most striking; the general luxuriance of the vegetation bears the victory, the elegance of the grasses, the novelty of the parasitical plants, the beauty of the flowers — the glossy green of the foliage, all tend to this end. — A most paradoxical mixture of sound and silence pervades the shady parts of the wood, the noise from the insects is so loud that in the evening it can be heard even in a vessel anchored several hundred yards from the shore. Yet within the recesses of the forest when in the midst of it a universal stillness appears to reign. To a person fond of natural history such a day as this brings with it pleasure more acute than he ever may again experience."
1st March 1832:
"I can only add raptures to the former raptures. I walked with the two Mids a few miles into the interior. The country is composed of small hills & each new valley is more beautiful than the last. — I collected a great number of brilliantly coloured flowers, enough to make a florist go wild. — Brazilian scenery is nothing more nor less than a view in the Arabian Nights, with the advantage of reality. — The air is deliriously cool & soft; full of enjoyment one fervently desires to live in retirement in this new & grander world."
5th Mar 1832:
"It is a new & pleasant thing for me to be conscious that naturalizing is doing my duty, & that if I neglected that duty I should at same time neglect what has for some years given me so much pleasure."
This is a side of Darwin's character that often seems to be forgotten when discussing his accomplishments with regards to evolution and it's good to have reminders from time to time. He was not just a great Scientist, he was a lover of Nature.

Saturday, 20 April 2013

Nature launches "pastcasts" with 1953 DNA papers - and unsung hero of the story, Raymond Gosling

The Nature Podcast has added a new series: the Nature Pastcast, which revisits key papers from the Nature archives. The first episode looks at the famous 1953 Watson & Crick paper and the other two DNA papers from the same issue.

Watson and Crick are rightly famous for the discovery of the structure of DNA. Maurice Wilkins, who was senior authors on one of the other papers in the issue and showed Watson the famous X-Ray diffraction image of "B DNA" ("Photograph 51" [image, above right, from Wikipedia]) shared the Nobel prize with Watson and Crick.

Everyone also seems to know about Rosalind Franklin, whose group took the X-Ray image (but did not appreciate its significance) and many people was cheated of a Nobel prize because it is not awarded posthumously. There was another key player that I had never heard of until today, though, Raymond Gosling.

Having listened to the podcast, if anyone should have shared the glory of the discovery it was Gosling. It was he who took the famous Photograph 51 and he who gave it to Wilkins, who in turn showed it to Watson. Franklin, it seems, was primarily interested in solving the "A" form of DNA, of which this was not an image. You can hear more of his story in his own words in a Nature Podcast Extra interview. Interesting stuff.

Wednesday, 17 April 2013

How to read a phylogenetic tree

This week I have been preparing my last phylogenetics lectures and practical of the year. Something that is quite clear when marking student work is that many students have no idea how to read a phylogenetic tree and identify the key features about it that aid interpretation. To help combat this, here is my basic guide of "How to read a phylogenetic tree".

Topology

The first and possibly most important thing about any tree is the topology - the branching order. It's easy to get distracted by the direction or style of the tree (e.g. curved branches versus straight) but none of these things matter for the topology. The key thing here is the path taken from one node to the other and how the species (or molecules but I will just refer to species here for clarity) cluster together. The "direction" of the tree and whether the (terminal) "leaf" nodes are at the top, bottom, left or right is not important. (I'll come back to this below, for "rooting") Likewise, the vertical ordering of nodes is not inherently important - whether a particular node appears at the top, bottom or somewhere in the middle of the tree is largely a matter of preference that will depend on the purpose of the tree and the story you are using it to tell.

In fact, it is easier to look at the branches in a tree, as nodes can be rearranged in a way that can at first appear confusing. These four trees, for example, all have the same topology:

Each branch can be thought of as dividing the tree in two and splitting the species into two accordingly. If two trees share a topology, their branches will make the same splits, even if their (in this case) vertical ordering is different. Trace, for example, the path from A to D. This is easiest first in the top left tree. The branch leading directly to A splits the tree into A:BCDE. The next splits AB from CDE. (This has the root, which I will come to, below.) Now, moving back out from the root to the tip, we travel along a branch that splits ABE:CD before finally the branch leading only to D and splitting it from ABCE. Tracing the path of A to D in any of the other three trees will take exactly the same route. Any other tip to tip journeys will likewise be the same in these four trees.

This is particularly important when comparing trees, particularly big ones. I have seen people invest a lot of time and effort (and sometimes manuscript space) speculating about the differences between two particular trees when, in fact, they were really the same tree and there was no difference. Alternatively, the topology might be the same but the differences might just be due to where the tree was rooted, which I will return to.

Branch Lengths

Once the topology is clear, the next things to look at are the branch lengths, as these can give key insights into how the tree can be interpreted and, sometimes, even the methods behind the tree. There are two key things to look at in this respect: (1) the distance between (not necessarily connected) internal nodes, shown with the red arrows below, and (2) the root-to-tip distances for each terminal node, shown by the coloured arrows in the figure below:

If the spacing is even (i.e. all the red arrows are the same length) then it is highly likely that branch lengths are not being shown and the tree is only displaying the toplogy. This can be confirmed by (a) the lack of a scale bar, and (b) a bias towards internal nodes towards the tips. (In the left tree, the node joining AB is aligned with that joining CD, not the deeper CDE ancestor.) If the spacing is not even then branch lengths are being shown. These should really be accompanied by a scale bar (although the figure about does not have any).

If branch lengths are being shown, the next thing to look at is the total root-to-tip distance for each terminal node. (The coloured arrows in the figure above.) If these are all the same length, as in the right-hand tree, it is highly likely that a molecular clock has been assumed (if it's a molecular phylogeny). If it hasn't been assumed - and the methods should provide enough details to know - then the molecule in question is just evolving in an incredibly clock-like fashion. More usually, these root-to-tip distances will not all be the same. If the tree is topology-only, as in the left-hand tree, the equal root-to-tip distances do not mean anything and no conclusions about rates can be reached.

Rooting

Evolutionary trees are (almost) always starting with an ancestor and then dividing, so you can always identify the root (if there is one) as the point where all the branches converge. Historically, it was drawn at the bottom like a real tree (as with the great Molluscan tree in OUMNH and the OneZoom Tree of Life Explorer). These days, it is usually drawn on the left as in these diagrams but I have seen trees with the root at the top, bottom or even on the right. (The latter is usually only used when mirroring another tree.) I have posted before on how to root a phylogenetic tree, so I won't go over that again here. The rooting method should be given in the methods but, when it is missing, you can often guess from the shape of the tree and using the root-to-tip branch lengths again:

Unrooted trees are pretty obvious when shown in the "radiation" style. If the tree is rooted, it is almost certainly either midpoint rooted or outgroup rooted (see "how to root a phylogenetic tree"). Midpoint rooting can be identified by virtue of the fact that the two longest root-to-tip distances will (a) be the same length and (b) be either side of the root. If either of these conditions is broken, it is not midpoint rooted and is probably outgroup rooted. (Note that if both conditions are met, it is still possible that the tree is outgroup rooted. Indeed, if the evolutionary rates are fairly consistent, outgroup rooting and midpoint rooting should be the same.)

Ideally, a rooted tree should have the root marked. Sometimes, however, it is left off, as in the bottom left. This can be confusing as tree visualising programs will often display trees in the "traditional" style even when they are not rooted. This is particularly a problem when branch lengths are not shown as it will not be at all obvious when the tree is rooted or not. The time that I see this catch people out most is when making a Maximum Parsimony tree using the popular software, MEGA - these trees are displayed randomly rooted and without branch lengths by default.

Reliability and Confidence Metrics

It is always important to consider how reliable the rooting method used is likely to be if conclusions are being reached regarding the direction of particular evolutionary events. Despite this, it's pretty rare for the root position to have a direct confidence measure associated with it (although I am sure there are ways to do it). What is common, however, is to have confidence metrics for the internal branches, which are usually placed above (or sometimes below) the branch next to the descendant node (in red, below). (Branch lengths, when shown, are normally below and nearer the middle of the branch.)

Bayesian and Maximum Likelihood methods quite often produce branch probabilities as part of the method but otherwise the most common method is "bootstrapping", which is a random sampling method. I will save bootstrapping and branch tests for future posts. My one tip for now: always remember that bootstrap values are associated with branches and not nodes.

Phylogenetic checklist

In summary, my checklist for reading a phylogenetic tree: topology ⇒ branch lengths? ⇒ molecular clock? ⇒ rooting ⇒ branch confidence metrics.

Tuesday, 16 April 2013

Something to cure the Monday Blues

I'm not sure why I find nature's blues so appealing. I suspect it is because blue creatures are clearly there to stand out - it is unlikely to be camouflage - and therefore usually also somewhat flamboyant. This is combined with the fact that my mild red-green colour deficiency reduces the equivalent wow-factor of reds. Anyway, whatever the reason, here are a couple of great blue animals. The first is Homarus americanus, the American lobster, which is featuring in an undergrad practical I am running next week - or, at least, some DNA sequences are. (Picture from World Register of Marine Species.)

The second is even more spectacular: a close-up of a blue damselfly, which is part of a set of amazing photos in an item at The Telegraph website, Bug-eyed: macro photographs of insects by Ireneusz Irass Waledzik. Isn't it adorable‽ It's well worth checking out the complete set.

Tuesday, 9 April 2013

Evidence-based medicine needs your help!

This is turning into a week of petitions, with another important cause that needs more signatories. This time, is not rhino horn or pangolin scale quackery that's the target, though, it's real evidence-based medicine.

I've blogged before about Ben Goldacre's book, Bad Pharma, and how legal loopholes allow big drug companies to get away with heinous crimes of data massage and selective reporting of clinical trial results. The AllTrials campaign to make clinical trial data more available and transparent is in full swing and has the backing of hundreds of organisations including big names like the MRC, NHS and, encouraging, GSK. This is a big one, not just because the issue at stake is so important to all of us but also because it stands a real chance of success.

They have tens of thousands of signatures at the moment but want to break a million and get support from more international companies and professional bodies. If you haven't signed already, please do. If you have, please encourage others to do likewise. As Ben Goldacre and Tracey Brown wrote in an email recently:
"We are on the threshold of significant change, but we now urgently need help from all of you to make this a reality."

Monday, 8 April 2013

Save the Pangolins!

The picture on the right is a pretty shoddy one I took in the Royal Ontario Museum in Toronto (more on that later) to remind me to write a post about pangolins because I think they're great. (There's a better Wikipedia photo by Valerius Tygart, below, of a tree pangolin). This is not really what I had in mind but it will do until I get to write a proper one, as there is currently a Care2 petition to the Prime Minister of Vietnam to crack down on the illegal trade in pangolins. It's not just rhinos that are endangered due to the supposed healing qualities of their body parts. (Pangolin scales, like rhino horns, are nothing more exotic than keratin - like finger nails.)

I'm not sure how much good these things do but the Thai Prime Minister vowed to end the ivory trade last month following a large WWF campaign, so it can't do any harm. Look at this guy and tell me that the world wouldn't be diminished without him* - then sign the petition:

*In the interests of full disclosure: (a) the tree pangolin shown is not one of the two threatened species - the Sundra pangolin and the Chinese pangolin - in Vietnam, and (b) I don't know if it's a he.

Saturday, 6 April 2013

Geek architecture at Cold Spring Harbor Laboratory

As well as the geeky sculptures, the Cold Spring Harbor Laboratory has some good geeky architecture. The tower of the Beckman Laboratory (above) stood out to me as a geneticist, with the four nucleotide abbreviations (g, a, t, c) on its four faces. There was a bit of a missed opportunity with the staircase in the middle, though, which is just a spiral up a central column rather than a double helix (right). Oh well.

As it happens, the conference was too engaging to do much exploration, so I'm not sure if it's a repeating theme across campus. If I get to go back, I will have to find out. Even if there isn't, though, it's a charming place to wander about. Apparently, it used to be a whaling station and many of the labs are in what look like large colonial houses, such as the Luke Building (below).

Wednesday, 3 April 2013

Aboriginal-style stegosaurus


Another ArtStudio creation, this is an attempt to combine two of my favourite things - Aboriginal art and dinosaurs! Given that I am not Aboriginal, I can't really call it Aboriginal art but I don't know what the technical name for this style is.