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.

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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.

Remember that discussion where I was trying to explain why Screwy doesn't believe in memes? Well, he showed up to put his own point of view. If you're at all interested in philosophy of biology, go and read it.

While I'm on the subject of my clever sibs, P'tite Soeur recently graduated from Nottingham with a 2:1 in French and Latin, so many congratulations to her. That's all four of us through higher education at long last (Screwy is supposed to finish his Masters at some point around now, but I haven't heard an official announcement yet). So between us we have just under 50 GCSEs, nearly 20 A Levels and 20 cumulative years of tertiary education. None of us has a steady job yet, mind you, but we're working on it in various ways.

It is midnight (which means I should be in bed) at the summer solstice, 60 degrees north. You don't quite get midnight sun here, but it is un-dark, with the sky sort of pinkish.

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.

Both our internal information people and the local press are getting very excited because some Karolinska people have made some pretty good progress towards developing a test that will predict dementia 20 years ahead. [Press release, with links to the original article] It's cool science, no doubt about it, but I can't help wondering, would you want to take a test at the age of 50 that might predict that you had a high chance of being senile by the time you were 70? I guess it's the same problem as with any predictive medical testing: in the absence of a cure or even sensible prevention, what's the point of knowing?

I think it's the timescale that bothers me, in part; I don't have the same objection to, say, cervical smears which tell me whether I might be at risk for cancer in the coming few years. That allows me to do something about it in terms of possibly readjusting my life plans. But I can't plan on the basis of some terrible thing that might happen in 20 years' time; I'd just have to live with the knowledge that this was likely to happen to me, which I don't think would be good psychologically.

It's true that almost everybody expects to be mortal (the exceptions are a few religious people and a few quasi-religious geeks who think the Singularity is going to cure death). So you always have to run your life on the basis that you have a few decades at best and possibly even less. But I'd still rather not know the probable time and manner of my demise more than a few years in advance, I think.

In non-morbid news: Stockholm is full of magicians and flamboyantly gay people with rainbow banners at the moment. I find this very cool, it's a bit like living in the Paul Gallico novel The man who was magic.

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.

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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.

Author: Olivia Judson

Details: (c) 2002 Olivia Judson; Pub Metropolitan Books 2002; ISBN 0-8050-6331-5

Verdict: Dr Tatiana's sex advice to all creation is a really impressive popular science book.

Reasons for reading it: I'd been vaguely curious about the concept, though I was afraid it would be gimmicky. Then I happened to find it cheap enough to tempt my curiosity. It's more of a dipping book than a read straight through from start to finish book, so I've been reading it in odd moments when for whatever reason I can't concentrate enough to get involved in a novel.

How it came into my hands: A cool book stall in Central Park.

( detailed review )

linley is here. Yay. I may not have all that much online time until Sunday evening, though.

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.)