Not sheepish, but individ-ewe-al

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.

Someone asked me what exactly Weinberg is so famous for: basically he did the original work to prove that you can turn a normal cell into a cancer cell by blocking a couple of genes and injecting another couple, and what the minimum set of genes is. And he’s by no means a one-hit wonder, he’s been doing lots of exciting stuff in the quarter century since that landmark achievement. It’s actually quite surprising that this was the first time I’d heard him speak; I’d have expected to run across him at conferences by now.

His talk was mixed; I could clearly see why he is so respected both as a scientist and as a communicator, and indeed I’m writing this post because I’m excited about what he had to say. But at the same time he didn’t live up to his towering reputation. He talked down to the group quite badly; this may well be because his expectations of PhD students are based on the American system where a new PhD student has only had a science “major” and is still very much learning. So his talk was pitched at the wrong level for European PhD students who have completed an entire degree in their specialist subject, and are used to being treated as professional scientists albeit at an early stage of their training. He also admitted half way through the talk that he was sleep deprived and in a really horrible mood, and apologized for being unusually grumpy as a result (he was really thrown by some annoying computer problems at the beginning, when it took nearly 20 minutes to get the system set up to display his Powerpoint slides).

Both his grumpiness and his slight tendency to patronize caused me to behave rather abrasively, which I’m not particularly proud of. He started out by saying that he expected to be interrupted with lots of questions, so I took him at his word. But instead of asking questions which show how intelligent and engaged with his ideas I am, I found myself jumping on apparent flaws or omissions in his arguments and generally being a bit arsey. I doubt he was offended, but I also doubt I made a glowingly positive impression.

He started off by making what I thought was a really odd argument about cancer epidemiology. He showed some figures that point out that pretty much the only thing correlated with cancer incidence is access to screening and diagnosis. So ok, there’s huge reporting bias in how we track the prevalence of types of cancer in populations or over time. I didn’t find this as surprising or significant as he seemed think it was. I think the point was supposed to be that in spite of huge changes (usually alarming increases) in the reported incidence of various kinds of cancer, the (age-adjusted) death rates didn’t really change between 1930 and 1990, or between different countries studied. So he postulated that one way to read these figures is that human intervention basically has no effect on cancer mortality; a certain proportion of people with a given type of cancer die no matter what anyone does, and a certain proportion survive because they were destined to survive anyway, (though they are likely to attribute it to some kind of faith healing or quackery).

OK, 1990 to the present there has actually been a measurable decline in mortality from breast cancer and a couple of types of leukaemia. So it’s not all fatalism; medical advances are making a really profound difference here. He said that part of the decline in breast cancer mortality is explained by awareness of the risks of HRT so that it is no longer pushed at women as it was a generation ago. I wasn’t convinced by that, because it is really only in the US that every middle aged woman took HRT, and then everyone stopped because of the breast cancer scare. According to Weinberg screening programmes and knowledge of some of the major genetic factors haven’t made much difference, but he didn’t really justify dismissing those factors. Breast cancer does also benefit from two of the only three new drugs that unquestionably outperform any therapy attempted since the 30s: tamoxifen and its friends, and the antibody-based therapy herceptin. The third unquestionably successful drug is Gleevec for a certain type of leukaemia. That gives really stunning results, like improving the 5 year survival rate from about 20% to about 95%, but it is only useful in one particular relatively rare type of leukaemia, so it doesn’t register as a blip in overall population statistics.

If the glass is half-empty, it’s depressing that humanity spent 60 years and unimaginable sums of money without making any measurable progress. If the glass is half-full, there have been three genuine breakthroughs in the past 15 years, so it could be that we’re finally on the right track. (Also, no measurable progress might mean that the survival rate is improved from 5% to 10%, meaning thousands of people are alive who otherwise wouldn’t be, or it might mean that patients get a year of decent quality of life rather than 6 months of misery, but of course would still count as mortality statistics.) FWIW, my old boss, who is not as famous as Weinberg but pretty famous, reckons that cancer will be a curable disease in our lifetime.

This stuff is more or less what all famous cancer researchers say. Some of you probably don’t get as many chances to hear famous cancer researchers giving their spiel as I do, so I’m writing it here because I think it might be of interest. The really exciting bit was the second part of the talk though:

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.

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.

A random passer-by contacted me to ask: Is it difficult to reconcile science and religion? The flippant answer is: in my world, they never really quarrelled. But I thought I might expand a bit on that, especially as a few people expressed interest in seeing my thoughts on the topic when I alluded to it.

I think asking this kind of question relies on certain (often unstated) assumptions about both science and religion. So let me have a go at defining why I am not religious in the sense that some random stranger probably assumes, and also why science is different from the conception of it I think the questioner holds.

I can’t remember who it was that said we shouldn’t assume that a certain strand of Fundamentalist American Protestantism represents all religion. (I also suspect that the media portrayal even of that sort of religion is an unfair caricature, but I’m no expert.) My religion, Reform Judaism, is closer to that assumed model than many; we’re working from a similar founding principle of monotheism, and we have one major text, the Old Testament, more or less in common. So we’re using some of the same metaphors. But I do think the differences between my religious approach and that stereotype is more profound than just, I’m nice and tolerant and emphatically non-proselytizing whereas they are mean old fundamentalists who hate gay people and want most of the world to go to Hell.

So what does religion mean to me? I will admit I am somewhat embarrassed about talking about my personal beliefs and religious understanding (you’ll get a readier answer if you ask personal questions about, say, sexuality, for sure). But I’ll have a go, and if you want to ask further questions, I’ll do my best to answer them.

The starting point of my religion is monotheism: God is One, and almost everything else is up for grabs, but not that. God is so utterly unique that it is not possible to describe or define God, because God can not be compared to any material thing. There is some relationship between the nature of God and the nature of the universe and existence, which for a limited human understanding is partially approximated by talking of God as the Creator.

So far so deist; I suppose where religion comes in is that I believe that this God has, so to speak, chosen to enter into a relationship with human beings. Revelation, not creation, strikes me as the real miracle. By revelation I don’t necessarily mean that a particular set of texts were dictated word for word by God, but that God has given people some means by which they can try to relate to the Divine, however paradoxical this may be for a God who is so utterly unique and undefinable. I’m sorry if this is couched in rather abstract terms, but that’s the best I can manage for an explanation.

Claiming to know how revelation works would be like claiming to know how God works, which I emphatically don’t (to me, that is essentially idolatry). But it seems to me that part of it is living within and exploring the system defined by centuries of religious thought. And part of it is looking for God within God’s creation. Believing that God created everything we can observe (and probably a whole load of things beyond what we can observe too) doesn’t at all seem incompatible with wanting to know exactly how the universe works. In fact, I would go so far as to say that my belief in a Divine Creator encourages me to study creation in as much detail as I am able.

Science, to put it very simply, seems like one of the best tools available for doing this. To me, science is definitely a tool, a method, not a collection of facts. The only way science can be seen as being in conflict with religion is if science makes one set of assertions which conflict with the assertions made by a particular religion. I don’t think science is about making assertions anyway; it’s about making deductions from experiments to construct falsifiable hypotheses. And my religion is not making the kinds of assertions that conflict with empirical evidence either; I don’t hold it as an article of faith that the world was created in 7 days 6000 years ago. This isn’t because I have rejected that belief in favour of scientifically derived facts about the history of the universe, but because my religion never asserted that in the first place.

I am aware that to certain people at certain times, science has meant rational positivism or dogmatic materialism. If science is seen as being atheist by definition, then it’s pretty circular to point out that it is in conflict with theistic religions! But that’s not what science means to me. Equally, I am aware that some religious people, including a minority of Jews, believe that the Bible is literally true and discusses actual historical facts. That belief does require one to deny some empirically derived models of things like cosmology, evolution, and what happened several thousand years ago. I don’t think that denying those models is to reject science altogether, because science is not a dogma, but it is very likely to lead to rejecting science.

Anyway, that is not my attitude to the Bible; my religious tradition has a very creative relationship with sacred texts. They are spiritual and moral guides, and they give people an insight, as far as it is possible for finite human beings to have such insight (see above about the miracle of revelation) into the nature of God. My religion has no problem with telling God to butt out of discussions of Biblical interpretation, since God gave the text to us and our human perspective. And it has no problem with making interpretations such as from creating an imagined dialogue between Jonah and the whale about theology and eschatology, to creating an elaborate legal and practical system of separating meat products from dairy products based on the injunction not to boil a young animal in its mother’s milk. So it’s a long way from being a literalist tradition!

Science is a good tool for understanding how the material world works, and the latter is a religious duty for me personally, as I understand these things. Science is not a good tool for probing the question of whether there is anything out there which is metaphysical, whether God or anything else. Because by definition if metaphysical entities do exist, they are not susceptible to empirical analysis. God who can’t be defined is also God who can’t be measured or tested or analysed. Science is not a tool at all for defining moral values, because it isn’t really even possible to frame the right questions in a scientific way. But science may well be a good tool for working out the practical consequences of moral values once defined.

So, primarily I see science as a religious value because as a scientist, I am devoting a great part of my life to studying an aspect of how God’s creation works. It’s also a religious value because using science to know more about how the world works helps people to create technology to improve the human condition. This is not an essay about technology and religion, but if you are curious, I am (from a religious standpoint) absolutely pro technology. My religion does not give value to leaving God’s creation in its so-called “natural” state; we are specifically enjoined to have dominion over the earth, and later tradition has built on this to regard people as God’s partners in creation. The world is not perfect; to regard it as such is pretty insulting. I don’t claim to know why God decided to create an imperfect world, but I see it as a core religious value to try to improve and repair it.

As it happens I have ended up in a quasi-medical field. It’s easy to justify that helping to find better cancer treatments is a good thing for a religious person to be doing, but I am very suspicious of the attitude that directly medical research is somehow worthier than any other kind. Primarily, I think what I do is morally good because it adds to human knowledge, and that’s true of much less directly applied scientific research. I also think it’s religiously good to try to maximize one’s potential as a human being, and science is something that I happen to be good at so it seems morally right for me to put effort into that area.

I was at a cancer conference the other week. One of the talks was about the developments we can expect to see in cancer medicine in the next few years. One of the things he was getting excited about was a vaccine against HPV, which is currently at quite an advanced stage of development.

HPV is the virus which causes cervical cancer. The virus is sexually transmitted; a clear majority of sexually active people carry the virus, although it doesn’t always cause cancer. But it does cause cancer in about 3000 women per year in the UK; most of them are between the ages of 30 and 60. It’s treatable if caught in the very early stages (that’s why there are widespread screening programmes by means of the cervical smear test), but in the advanced stages it’s incurable. The virus can also cause fertility problems, and genital warts in both sexes.

A vaccine is within reach. There’s a good chance that in a few years’ time, a routine injection at the start of secondary school could be saving thousands of women’s lives, and preventing huge amounts of suffering. That’s a pretty significant medical breakthrough, and all the evidence so far is looking positive.

But this vaccine has been blocked at every stage, the initial research, the clinical testing, and now the larger scale testing preceding setting up a national vaccination programme. Why? Because some busybodies are offended by the idea of vaccinating young teenaged girls against a sexually transmitted disease. Erosion of family values! Green light for promiscuity! Corrupting the innocent!

Well, fuck you, lobbyists. I hope you are haunted for the rest of your life by all the women who die unnecessarily and in horrible pain as a result of your stupidity. I hope that your smug self-righteousness gives you exactly no comfort when you come face to face with people who have lost friends, wives, mothers and daughters because you are a bunch of fucking prudes. I don’t hope that you end up among the unfortunate people who get cervical cancer, though, because that I wouldn’t wish on anybody.

How can anyone seriously believe that people dying of cancer is preferable to providing decent sex education and contraception and making the most of major medical breakthroughs like this one? Which, incidentally, are the results of years of work costing huge amounts of money. And it’s not a few weirdos who think like this, it’s people who have a significant influence on funding policy and laws which determine which experiments and trials are allowed to go ahead. Ugh!

Sorry to rant, people. I’d sort of like other people to get angry about this kind of idiocy, but more importantly, I want all my friends to look after yourselves. Eat a sensible diet (including plenty of fruit and veg), do a reasonable amount of exercise, cut down on smoking as much as possible, be responsible about sex, that kind of thing. Oh, and if you’re female, keep up to date with your smear tests.

That’s all.