Livre d'Or

jack asked about Moar cool science (stuff that's obvious to you as well as stuff that's new to you). So for the old stuff I want to introduce the idea of apoptosis, because that's the thing so cool that it made up my mind I was actually going to study science to high level, when I was dithering about it in my late teens, and I do in fact work on it now. And because when I was babbling about transcription factors I clarified a few points in the comment discussion, and silveradept mentioned I had no idea there was a self-destruct button for cells, so maybe this is something other people also don't know.

And for the new stuff, I know I've been babbling about it already to some people, especially if you were at our Christmas party at the weekend, but I came across a guy recently who is basically making a piece of kit which is very nearly a Star Trek medical tricorder.

( sciiiiiience )

[December Days masterpost]

So I posted a link to one of those silly internet quizzes, this one being run as a promotion by a fairly minor scientific journal. And wow, I had forgotten how good those daft "what colour is your aura" personality quizzes are for generating conversation! I posted the type of protein one mainly because I was amused by how ridiculously over-specialist it is, but in fact people with no interest at all in protein chemistry wanted to have a go and talk about what the results meant.

And since people are interested, I might have a go at explaining the background behind the quiz, and also why I think transcription factors are cool. ( Science! )

Clear? Confusing? Over-simplified? Anyway I hope this goes some way to help you interpret your silly quiz result, and also to tell you why transcription factors are cool!

Or, what an interested lay person should know about epigenetics.

I've been promising a post about epigenetics for ages, because it's one of the most exciting things that's happened in my field in the past decade or so, and it seems like most non-biologists aren't aware of it very much.

Why is it so exciting? Well, to start with there's the older insights which led to the modern field of epigenetics: in a multicellular organism, all cells have exactly the same genome, by definition, but the cells differentiate to take on specialist structures and functions. So there must be something going on beyond (ἐπί, the Greek prefix epi) the sequence of bases forming genes and chromosomes. It turns out that something is that the cell makes a series of chemical marks on the DNA and associated proteins, which turn genes on and off. Those marks are often surprisingly long-lasting, they're not just a short-term response to circumstances, something genes can also do. So you can't take a skin cell and transplant it to the liver, its epigenetic marks make it a permanent skin cell.

It's much more recently that we started to understand that patterns of epigenetic marks don't just follow a set developmental program – they can change in response to external circumstances. And the really mind-blowing thing is that some of these changes can be inherited. This means that a female parent's life circumstances can cause measurable alterations in the genes of offspring and more distant descendants, and there's starting to be evidence for male-line transmission as well, at least in animals and probably in humans too.

The other thing that's cool about epigenetics is that we're getting to the point where we understand it well enough that we can directly manipulate the epigenetic marks. If you change epigenetics, you change the nature of the cell itself, just as much as by directly editing the gene sequence (which can be done but is massively technically difficult, and ethically questionable in humans.) Which is a possible approach for treating cancer, and that's the reason why I got into the epigenetics world, but there's an even more exciting application: we can make stem cells. We can do the thing which was regarded as paradigmatically impossible throughout the twentieth century, we can effectively reverse the direction of development. So it's become possible to take an adult's cells and turn them into the rare kind which, like the cells of an early embryo, have the potential to become any type of tissue, manipulate them more or less at will in the lab, and return them to the same person's body to repair injuries and grow new tissue. In the very last couple of years, this is actually starting to be a treatment for real humans with real diseases.

( want to know more? )

OK, this post is ridiculously long, I will post it and do one on stem cells another day. Please do ask any questions, whether it's because I've assumed knowledge and explained things with too much jargon and technicalities, or because I've simplified and glossed over something and you want more detail or want to challenge me.

forestofglory asked to hear more about how your research is going. Goodness only knows I'll take any excuse to talk shop, but I have to be a bit cautious about what I post online regarding work that's currently in progress. So I'm going to take a slightly different tack approaching this question, and instead talk for a bit about why I'm interested in what I'm interested in.

( cancer cell biology )

I am going to have to keep the exact details fairly vague, but with that caveat I'm totally happy to answer any questions. These sorts of essays always end up being both too technical and over-simplified, especially when I just type them as the thoughts occur to me, without very much planning.

Author: Jaques Monod

Details: Originally published 1970 as Le Hasard et la Nécessité; Pub Penguin books 1997; ISBN 0-14-025646-6; Translated Austryn Wainhouse; translation (c) 1971 Alfred A Knopf

Verdict: Chance and necessity is an interesting snapshot of the history of biology.

Reasons for reading it: I was interested in Monod's account of molecular biology, since he's really one of the fathers of modern genetics. I was spurred to read a book I've had lying around for a while because of attending a popular science course and wanting to look at a real example, and partly because I had somewhat run out of novels to read. (cartesiandaemon is planning to lend me a nice little pile when he gets here tomorrow, though!)

How it came into my hands: I bought it in a charity shop years ago and never quite got round to picking it up; I'm not always good at motivating myself to read non-fiction.

( detailed review )

Thank you all for being my collective conscience! I think it was the right decision to go, and the various arguments gave me lots of food for thought. That said, Watson's talk was even more pointless than I had suspected it would be.

( since everybody got involved with such gusto, you probably want to know how it went )

I cut him slack for being vague and rambly on the grounds that he's eighty. But I don't cut him slack for his sexism for that reason; he's just not old enough to remember a world where it was reasonable to assume that women are naturally incompetent and all the serious work is done by men. Female scientists were still the minority back in the 50s, but hardly unheard of; he himself mentioned that Franklin was one of a couple of dozen women in the chemistry department at King's College London. Even if has been completely unable to adapt to the changes in society in the past fifty years, there's no excuse to make comments about how you should make sure to spend time in conversation with other scientists and not waste too much energy gossiping about politics with your wife. I don't think he even intended that remark to be offensive, unlike some of his comments about "the feminists" who were so meeeeeeeeeeean to him and made a totem of Franklin just because she was a girl even though she wasn't particularly competent (sic). He just unthinkingly assumed that all scientists are men, and women only talk about trivial things. I think for someone to be too old to understand that women are people, he would have to be at least 150, which is to say, there's no excuse any more.

Anyway, the evening was much improved by an invitation to dinner with EBH, which was as usual delightful and full of interesting, intelligent conversation. Just what a Friday night should be, in fact.

We're being graced with an official visit from Bob Weinberg this week. One of the things he wanted to do was make an opportunity to meet a group of PhD students and other junior scientists. This strikes me as an excellent instinct because these vastly famous people doing their tours of honour will always have the chance to meet the other famous and important scientists at the host institution, and they will usually have a chance to be paraded for the general public, but it's quite easy for them to miss the actual working researchers. So, I signed myself up to be on the waiting list if there were any spaces for post-docs after the opportunity had been offered to the PhD students, and there were some extra spaces, so I attended the meeting yesterday.

( reactions )

One of the most exciting results in cancer biology recently is that the only cells that are capable of giving rise to tumours are adult stem cells. This means that cells that normally don't grow don't suddenly turn rogue and start growing all over the place, as used to be believed (recently enough that I was taught this model at university in the late 90s). But in fact, cancer happens when cells that normally do grow, ie stem cells, start making tumours instead of healthy tissues.

If you generalize from this, you start to wonder how far cancer cells are really normal cells in the wrong situations, rather than total aberrations. Bear in mind that all cells in the body contain exactly the same genes, but use a subset of them to perform their correct functions. Cancer cells probably have, oh, half a dozen mutations, genetic changes. But that might mean they have six altered letters out of three billion which are identical to those of normal cells. How do such tiny changes alter the whole function of the body, even fatally in many cases? What if these altered cells aren't something entirely new, they're just switching to the wrong sort of program.

There are two circumstances where cells are "supposed" to grow rapidly and relatively independently. One is when the embryo is developing, when it has only a few months to grow from a single cell one tenth of a mm wide, to a baby-sized baby 50 cm long (there are very few tumours that grow that fast!). The other is when a person is injured, and needs to rapidly make new tissue to repair the damage. Weinberg suggested that both these situations are relevant in a tumour.

So, we can argue that a tumour acts like a wound site when there is no wound. It rapidly makes new blood vessels, which act to provide oxygen and nutrients to the centre of the tumour mass, but the blood vessels don't "know" that that is their "goal". The blood vessels start to grow because the body somehow "thinks" there is a wound there that needs to be repaired. The parts of the immune system which usually deal with wounds are all present at the sites of tumours; it was previously thought that this was a response to the presence of the "foreign" tumour, but in fact this doesn't make sense because the tumour isn't really foreign in the way that bacteria or other parasites are. So another way of looking at it is that the immune system, triggered inappropriately, actually causes the tumour. The immune cells are responding to a wound that isn't there, so they send out chemicals which signal the tumour cells to grow, as they would normally signal new tissue to develop and repair an actual wound.

Weinberg also pointed out that this may mean that surgery is a really problematic way of dealing with cancer. You cut out the tumour, which obviously does need to happen. But. It's impossible to eliminate absolutely every cell, and even a single stem cell left behind can regenerate the whole tumour, because that's what stem cells do. Even worse, surgery causes an actual wound, so all the immune system gubbins which is around will go into hyperdrive, making a really ideal environment for those stem cells to get going and grow like anything.

If this were the whole story, most cancers wouldn't be fatal. A tumour that does nothing except grow inexorably bigger is usually referred to as benign (this is a relative term, of course!) A malignant tumour is much more dangerous, for two reasons. Firstly, it actively invades the surrounding tissue, breaking down healthy tissue to make room for the tumour to grow. And secondly, pieces called metastases can break off and be carried round the body in the blood stream and lymph system, and cause new tumours all over the place. These metastatic tumours often can't be removed by surgery as there are too many of them, and it's often only a matter of time before they get into vital organs and cause a total system failure, otherwise known as death.

But there are some normal cells that are meant to invade the surrounding tissue, and meant to be able to move around the body and start growth at new sites. Namely, the cells of the early embryo. Weinberg's theory is that malignant cells turn on genes that are normally turned on at the moment when the blastocyst, the ball of frog-spawn like cells, starts to turn into an actual embryo with recognizable features. These genes help the cells to move around to position themselves in the right places to form specialized tissues, and also to invade other parts of the embryo and mother's uterus as necessary. So if these genes get turned on in an adult, you can get metastatic cells.

This feels like it could be a really productive novel way of looking at cancer. And I think it's cool!

Further reading:
1. Stem cells: the real culprits in cancer?. Rather impressive Scientific American article on cancer stem cells, aimed for a popular audience.
2. Reya et al, Stem cells, cancer, and cancer stem cells is a decent review of stem cells and cancer, if you have access to Nature and want to read something at a more advanced level than SciAm.
3. Campbell & Polyak, Breast Tumor Heterogeneity: Cancer Stem Cells or Clonal Evolution? is a less good review, also written by people who are skeptical of the cancer stem cells model, but has the advantage of being free.
4. Yang et al, Exploring a New Twist on Tumor Metastasis is a recent review by Weinberg himself of some of this connection between embryo development and metastasis.

Author: Matt Ridley

Details: (c) Matt Ridley 1996; Pub Penguin Books 1997; ISBN 0-14-024404-2

Verdict: The origins of virtue overreaches and doesn't make it.

Reasons for reading it: I generally like Ridley as a science writer, and I'm interested in the topic of evolution even though I don't have much to learn from popular biology books at this point.

How it came into my hands: I don't remember; it's the sort of thing I would only have bought if I happened to find it cheaply.

( detailed review )

This reminds me that I've been meaning to post about how Screwy doesn't think that memes are a useful concept. I know he reads the blog sometimes, so if you feel like clarifying your position here, J, that would be great. I don't want to misrepresent your arguments. Anyway, what I understood from our lively discussions over Pesach is this:

The spreading of and competition between memes isn't meaningfully analogous to genetic inheritance, and trying to use biology to argue about ideas and beliefs leads to erroneous conclusions.

I think this is the thing I disagree with most; I think the ideas of evolution and natural selection are extremely powerful and they can be abstracted to things which are not inherited between parents and children. Basically, they apply anywhere where something can be replicated but imperfectly (perfect replication is about as likely as perpetual motion, so mutation is more or less a given), and where some types of individuals survive while others disappear. Both those conditions are true for memes, IMO.

The meme concept and the underlying selfish gene idea were associated with 80s, highly individualist politics, and the whole framing was created to justify that attitude.

This may be partly true, and certainly it's possible to misuse modern evolutionary ideas, just as Darwinism was misused to justify eugenics and other nasty things. But I think that kind of misuse is based on deep-rooted misunderstanding of what the theory actually says (basically, survival of the fittest doesn't mean might is right). Ridley makes an albeit imperfect argument against this kind of stupid conclusion, as do many other thinkers including Dawkins himself. In general, the fact that the idea of memetic evolution has been politically misused doesn't make the theory wrong in the first place!

There is no clear definition of what a meme is; is it the Iliad or a few words of quotation from it?

I think this is a strength, not a weakness, of the meme model. Dawkins makes it clear in The selfish gene that he isn't using "gene" to imply the sequence of DNA which encodes a single polypetide, but rather any trait which can be inherited. The power of gene selection is precisely that it can be abstracted to any level, and the same forces apply to making a particular enzyme the shape that it is, to the makeup of human society.

Calling something a meme doesn't give you any more explanatory power than simply calling it an idea. You don't need the theory of evolution to explain why the popularity of an opinion isn't a reliable guide to its rightness. The Bible and Plato were already aware of this!

This I find hardest to answer. My first point covers it partly, in that I think meme theory allows the use of a certain set of mathematical tools to reason about sociology and psychology. But I'm not sure I can come up with a convincing example where you can make a stronger argument about a meme than about an idea or a cultural artefact or whatever.

Anyway, what do you think? I think it's a very interesting challenge and one that some of you guys would have informed opinions about.

I grabbed a newspaper when I was travelling home yesterday, because I was in danger of running out of the novel I'd brought with me (Nobody's Son by Sean Stewart, which is shorter than it looks). This meant I happened to see the obituary of R John Rayner. He was a great man, one of the generation who transmitted the intellectual tradition of the former German Reform world to British Progressive Judaism after the war. He also married my parents. Blessed is the Judge of truth.

---

I have discovered that I didn't win the New Scientist essay competition I entered a while back. I am mildly disappointed but I didn't have any grand expectations. The good thing about this is that I can now make the essay public, since I'm no longer trying to publish it in the real media. So if anyone wants a basic summary of what I did for my PhD, I refer you to Death of a cellsman. Thanks to everyone who helped me write this, by the way; obviously those who were in the filter I originally used for discussing my competition entry have already read something not very different from this final version.

DNA sequencing is not magic.

Thankyou.

This comment prompted by a combination of:
– an otherwise good novel in which the simple fact of sequencing the human genome, described in mystical terms, is enough to propel the world into an SF future.
– a death penalty debate where it is suggested that now we have DNA evidence, we can execute people in good conscience.
– general frustration with scientific illiteracy.

I shall now return to my regularly scheduled thesis writing (in which sequencing DNA does not magically solve any problems, and in many cases does not in fact give any useful information about biology.)