Archive for the ‘books’ Category

Poincaré, chaos and the limits of predictability

March 5, 2017

In the past I was surprised that there seemed to be no biography of Henri Poincaré. I recently noticed that a biography of him had appeared in 2013. The title is ‘Henri Poincaré. A scientific biography’ and the author is Jeremy Gray. At the moment I have read 390 of the 590 pages. I have learned interesting things from the book but in general I found it rather disappointing. One of the reasons is hinted at by the subtitle ‘A scientific biography’. Compared to what I might have hoped for the book concentrates too much on the science and too little on the man. Perhaps Poincaré kept his private life very much to himself and thus it was not possible to discuss these aspects more but if this is so then I would have found it natural that the book should emphasize this point. I have not noticed anything like that. I also found the discussion of the scientific topics of Poincaré’s work too technical in many places. I would have preferred a presentation of the essential ideas and their significance on a higher level. There are other biographies of great mathematicians which made a better impression on me. I am thinking of the biography of Hilbert by Constance Reid and even of the slim volumes (100 pages each) on Gauss and Klein written in East Germany.

On important discovery of Poincaré was chaos. He discovered it in the context of his work on celestial mechanics and indeed that work was closely connected to his founding the subject of dynamical systems as a new way of approaching ordinary differential equations, emphasizing qualitative and geometric properties in contrast to the combination of complex analysis and algebra which had dominated the subject up to that point. The existence of chaos places limits on predictability and it is remarkable that these do not affect our ability to do science more than they do. For instance it is known that there are chaotic phenomena in the motion of objects belonging to the solar system. This nevertheless does not prevent us from computing the trajectories of the planets and those of space probes sent to the other end of the solar system with high accuracy. These space probes do have control systems which can make small corrections but I nevertheless find it remarkable how much can be computed a priori, although the system as a whole includes chaos.

This issue is part of a bigger question. When we try to obtain a scientific understanding of certain phenomena we are forced to neglect many effects. This is in particular true when setting up a mathematical model. If I model something using ODE then I am, in particular, neglecting spatial effects (which would require partial differential equations) and the fact that often the aim is not to model one particular object but a population of similar objects and I neglect the variation between these objects which I do not have under control and for whose description a stochastic model would be necessary. And of course quantum phenomena are very often neglected. Here I will not try to address these wider issues but I will concentrate on the following more specific question. Suppose I have a system of ODE which is a good description of the real-world situation I want to describe. The evolution of solutions of this system is uniquely determined by initial data. There remains the problem of sensitive dependence on initial data. To be able to make a prediction I would like to know that if I make a small change in the initial data the change in some predicted quantity should be small. What ‘small’ means in practice is fixed by the application. A concrete example is the weather forecast whose essential limits are illustrated mathematically by the Lorenz system, which is one of the icons of chaos. Here the effective limit is a quantitative one: we can get a reasonable weather forecast for a couple of days but not more. More importantly, this time limit is not set by our technology (amount of observational data collected, size of the computer used, sophistication of the numerical programs used) but by the system itself. This time limit will not be relaxed at any time in the future. Thus one way of getting around the effects of chaos is just to restrict the questions we ask by limits on the time scales involved.

Another aspect of this question is that even when we are in a regime where a system of ODE is fully chaotic there will be some aspects of its behaviour which will be predictable. This is why is is possible to talk of ‘chaos theory’- I know too little about this subject to say more about it here. One thing I find intriguing is the question of model reduction. Often it is the case that starting from a system of ODE describing something we can reduce it to an effective model with less variables which still includes essential aspects of the behaviour. If the dimension of the reduced model is one or two then chaos is lost. If there was chaos in the original model how can this be? Has there been some kind of effective averaging? Or have we restricted to a regime (subset of phase space) where chaos is absent? Are the questions we tend to study somehow restricted to chaos-free regions? If the systems being modelled are biological is the prevalence of chaos influenced by the fact that biological systems have evolved? I have seen statements to the effect that biological systems are often ‘on the edge of chaos’, whatever that means.

This post contains many questions and few answers. I just felt the need to bring them up.

In the beginning was the worm

September 29, 2016

In a previous post I mentioned the book by Andrew Brown whose title I have used here. I came across it in a second hand bookshop in Berkeley when I was spending time at MSRI in 2009. I read it with pleasure then and now I have read it again. It contains the story of how the worm Caenorhabditis elegans became an important model organism. This came about because Sydney Brenner deliberately searched for an organism with favourable properties and promoted it very effectively once he had found it. It is transparent so that it is possible to see what is going on inside it and it is easy to keep in the lab and reproduces fast enough in order to allow genetic research to be done rapidly. The organism sought was supposed to have a suitable sexual system. C. elegans is normally hermaphrodite but does also have males and so it is acceptable from that point of view. One further important fact about C. elegans is that it has a nervous system, albeit a relatively simple one. (More precisely, it has two nervous systems but I have not looked into the details of that issue.) Brenner was looking to understand how genetics determines behaviour and C. elegans gave him an opportunity to make an attack on this problem in two steps. First understand how to get from genes to neurons and then understand how to get from neurons to behaviour. C. elegans has a total of 302 neurons. It has 959 cells in total, not including eggs and sperm. Among the remarkable things known about the worm are the complete developmental history of each of its cells and the wiring diagram of its neurons. There are about 6400 synapses but the exact number, unlike the number of cells or neurons, is dependent on the individual. For orientation note that C. elegans is a eukaryotic organism (in contrast to phages or E. coli) which is multicellular (in contrast to Saccharomyces cerevisiae) and it is an animal (in contrast to Arabidopsis thaliana). Otherwise, among the class of model organisms, it is as simple and fast reproducing as possible. In particular it is simpler than Drosophila, which was traditionally the favourite multicellular model organism of the geneticists.

In this blog I have previously mentioned Sydney Brenner and expressed my admiration for him. I have twice met him personally when he was giving talks in Berlin and I have also watched a number of videos of him which are available on the web and read various texts he has written. In this way I have experienced a little of the magnetism which allowed him to inspire gifted and risk-taking young scientists to work on the worm. Brenner spent 20 years at the Laboratory of Molecular Biology in Cambridge, a large part of it as director of that organization. In the pioneering days of molecular biology the lab was producing Nobel prizes in series. He had to wait until 2002 for his own Nobel prize (for physiology or medicine), shared with John Sulston and Robert Horvitz. In his Nobel speech Brenner said that he felt there was a fourth prizewinner, C. elegans, which, however, did not get a share of the money. My other favourite quote from that speech is his description of the (then) present state of molecular biology, ‘drowning in a sea of data, starving for knowledge’. Since then that problem has only got worse.

Now I will collect some ‘firsts’ associated with C. elegans. It was the first multicellular organism to have its whole genome sequenced, in 1998. This can also be seen as the point of departure for the human genome project. Here the worm people overtook the drosophilists and the Drosophila genome was only finished in 2000. Sulston played a central role in the public project to sequence the human genome and the struggle with the commercial project of Craig Venter. It was only the link between the worm genome project and the human one which allowed enough money to be raised to finish the worm sequence. According to the book Sulston was more interested in the worm project since he wanted to properly finish what he had started. Martin Chalfie, coming from the worm community introduced GFP (green fluorescent protein) into molecular biology. He first expressed it in E. coli and C. elegans. He got a Nobel prize for that in 2008. microRNA (miRNA) was first found in C. elegans. It is the basis of RNA interference (RNAi), also first found in C. elegans. This earned a Nobel prize in 2006. The genetics of the process of apoptosis (programmed cell death) was understood by studying C. elegans. When Sulston was investigated the cell lineage he saw that certain cells had to die as part of the developmental process. Exactly 131 cells die during this process.

To conclude I mention a couple of features of C. elegans going beyond the time covered by the book. I asked myself what we can learn about the immune system from C. elegans. Presumably every living organism needs an immune system to survive in a hostile environment. The adaptive immune system in the form known in humans only exists in vertebrates and hence, in particular, not in the worm. Some related comments can be found here. It seems that C. elegans has no adaptive immune system at all but it does have innate immunity. It has cells called coelomocytes which have at least some resemblance to immune cells. It has six of them in total. Compare this with more than 10^9 immune cells per litre in our blood. C. elegans eats bacteria. These days the human gut flora is a fashionable topic. A couple of weeks ago I heard a talk by Giulia Enders, the author of the book ‘Darm mit Charme’ which sold a million copies in 2014. I had bought and read the book and found it interesting although I was not really enthusiastic about it. Now TV advertising includes products aimed at the gut flora of cats. So what about C. elegans? Does it have an interesting gut flora? The answer seems to be yes. See for instance the 2013 article ‘Worms need microbes too’ in EMBO Mol. Med. 5, 1300.

Rereading ‘To the Lighthouse’

August 23, 2015

There are some statements I started to believe at a certain distant time in my life and which I have continued to accept without further examination ever since. One of these is ‘the English-language author who I admire most is Virginia Woolf’. Another is obtained by replacing ‘English-language author’ by ‘author in any language’ and ‘Virginia Woolf’ by ‘Marcel Proust’. At one point in her diary Virginia Woolf writes that she has just finished reading the latest volume of ‘A la Recherche du Temps Perdu’ which had recently been published. Then she writes (I am quoting from memory here) that she despairs of ever being able to write as well as Proust. Perhaps she was being too modest at that point. Until very recently it was a long time since I had read anything by Woolf. I was now stimulated to do so again by the fact that Eva and I were planning a trip to southern England, including a visit to St. Ives. For me that town is closely associated with Woolf and it is because of the connection to her that I was motivated to visit St. Ives when I spent some time in Cornwall several years ago. (Here I rapidly pass over the fact, without further comment, that the author with the widest popular success whose books have an association with St. Ives is Rosamunde Pilcher.) The other aspect of my first trip to Cornwall which is most distinct in my memory is missing the last bus in Land’s End and having to walk all the way back to Penzance where I was staying. We visited Land’s End again this time but since I did not want miss the bus again I did not have time to visit the ‘Shaun the Sheep Experience’ which is running there at the moment. As a consolation, during a later visit to Shaun’s birthplace, Bristol, I saw parts of the artistic event ‘Shaun in the City’ and had my photograph taken with some of the sculptures of Shaun.

When I go on a holiday trip somewhere I often like to take a book with me which has some special connection to the place I am going. Often I have little time to actually read the book during the holiday but that does not matter. For Cornwall and, in particular, St. Ives the natural choice was ‘To the Lighthouse’. That novel is set in the Isle of Skye but it is well known that the real-life setting which inspired it (and the lighthouse of the title) was in St. Ives. This lighthouse, Godrevy Lighthouse, cost a little over seven thousand pounds to build, being finished in 1859. In 1892, on one of two visits there, the ten year old Virginia signed the visitors book. The book was sold for over ten thousand pounds in 2011. So in a sense the little girl’s signature ended up being worth more money than the lighthouse she was visiting. Of course, due to inflation, this is not a fair comparison. Looking on my bookshelves at home I was surprised to find that I do not own a copy of ‘To the Lighthouse’. On those shelves I find ‘The Voyage Out’, ‘Jacob’s Room’, ‘Moments of Being’ and ‘Between the Acts’ but neither ‘To the Lighthouse’ nor ‘The Waves’. Perhaps I never owned them and only borrowed them from libraries. I have a fairly clear memory of having borrowed ‘To the Lighthouse’ from the Kirkwall public library. I do not remember why I did so. Perhaps it was just that at that time I was omnivorously consuming almost everything I found in the literature section in that library. Or perhaps it had to do with the fact that lighthouses always had a special attraction for me. An alternative explanation for the fact I do not own the book myself could be that I parted with it when I left behind the majority of the books I owned when I moved from Aberdeen to Munich after finishing my PhD. This was due the practical constraint that I only took as many belongings with me as I could carry: two large suitcases and one large rucksack. I crossed the English Channel on a ferry and I remember how hard it was to carry that luggage up the gangway due to the fact that the tide was high.

I find reading ‘To the Lighthouse’ now a very positive experience. Just a few paragraphs put me in a frame of mind I like. I have the feeling that I am a very different person than what I was the first time I read it but after more than thirty years that is hardly surprising. I also feel that I am reading it in a different way from what I did then. I find it difficult to give an objective account of what it is that I like about the book. Perhaps it is the voice of the author. I feel that if I could have had the chance to talk to her I would certainly have enjoyed it even if she was perhaps not always the easiest of people to deal with. Curiously I have the impression that although I would have found it extremely interesting to meet Proust I am not sure I would have found it pleasant. So why do I think that I may be appreciating aspects of the book now which I did not last time? A concrete example is the passage where Mrs Ramsay is thinking about two things at the same time, the story she is reading to her son and the couple who are late coming home. The possibility of this is explained wonderfully by comparing it to ‘the bass … which now and then ran up unexpectedly into the melody’. I feel, although of course I cannot prove it, that I would not have paid much attention to that passage during my first reading. The differences may also be connected to the fact that I am now married. Often when I am reading a book it is as if my wife was reading it with me, over my shoulder, and this causes me to pay more attention to things which would interest her. A contrasting example is the story about Hume getting stuck in a bog. I am sure I paid attention to that during my first reading and it now conjured up a picture of how I was then, perhaps eighteen years old and still keen on philosophy. After a little thought following the encounter with the story it occurred to me that I knew more of the story about Hume, that he was allegedly forced to say that he believed in God in order to persuade an old woman to pull him out. This extended version is also something I knew in that phase of my life, perhaps through my membership in the Aberdeen University philosophy society. On the other hand this story does come up (at least) two more times in the book and it is a little different from what I remember. What the woman forced him to do was to say the Lord’s Prayer.

I came back from England yesterday and although I did not have much time for reading the book while there I am on page 236 due to the head start I had by reading it before I went on the trip. The day we went to St. Ives started out rainy but the weather cleared up during the morning so that about one o’ clock I was able to see Godrevy lighthouse and look at it through through my binoculars. They also allowed me to enjoy good views of passing gannets and kittiwakes but I think I would have been disappointed if I had made that trip without seeing the lighthouse.

‘There but for the’ by Ali Smith

November 13, 2014

In a previous post I said that I might write something about my impressions of Ali Smith’s novels. Since I just finished reading ‘There but for the’ I thought that this was a good opportunity to do so. The other novels of hers which I have read (both a very long time ago) are ‘Like’ and ‘Hotel World’. I liked the first of these a lot and the second less. I no longer have many concrete memories of the contents of these books and I just want to mention one thing which sticks in my mind from ‘Like’. I am telling this story from memory and I did not go back to check the details. In one episode a young girl growing up in Scotland is alone at home when a woman comes to the door. This woman is of the exotic type called ‘English’. The girl asks her if she would like tea, according to the usual code of hospitality in that social context, which is the one I grew up in. The woman asks her what kinds of tea she has. This confuses the girl completely and would have confused me just as much in the same situation. For us drinking tea was very important and tea was tea. We knew nothing about herbal tea, fruit tea, green tea or special kinds of black tea. I only encountered Earl Grey, for example, as a student. In this context I remember one other experience I had while I was at university. I used to spend the summer holidays with my family. In general our dinner at home, the main meal of the day, always included potatoes. These potatoes grew on our farm and I was involved with planting and picking them as well as eating them. (I mentioned in a previous post how this encouraged my interest in metaphysics.) My grandmother, who lived with the family, loved eating potatoes, in particular potato soup, and towards the end of her life she sometimes said that that she would be quite happy to eat nothing else. The specific memory I wanted to mention is a comment she made on the eccentric habits I had picked up at university. She said, in the context of potatoes, ‘O, Alan he eats rice and pasta and ‘yin dirt’ (standard English translation ‘that rubbish’).

Now let me finally come to ‘There but for the’, I enjoyed reading it a lot and it had the effect of a good novel of somehow modifying my feelings and mood in everyday life. Being confronted with and made to think about certain ideas helps with getting out of certain ruts. I have to say that I cannot recommend the book as bedside reading. I found that when I read it before going to bed it had the effect that my thoughts had such a momentum that they could not easily slow down. I would not advise reading it in public either, unless you are a real extrovert. At any rate I could end up laughing so much that it would make me embarrassed to do so in public.

The book is very up to date in the sense that it features a lot of aspects of our daily life which are very new. There are some things which can creep up on us so that they become familiar without our ever really being conscious that they are there. The book helps to reveal these hidden companions. It is full of humour and wordplay, much of which I appreciated. I imagine that I also missed a lot. I have lived outside Britain and even outside English-speaking countries for many years now and this is bound to mean that various jokes and references were lost on me. Many of the things in the book could be taken as comments on society but the interesting thing is that these comments come from inside. We receive them through a portrayal of the thoughts of individual characters including a young girl (who plays a central role) and an old woman approaching death. We also receive them by hearing the conversation between very different characters and seeing the misunderstandings which limit communication between them. In the end, while I appreciated the text ‘locally’ I was left  with the feeling that I did not understand its global structure. I could see that the snake bites its tail, the end connecting to the beginning, but I felt as if I was left facing a question mark. Was this the author’s intention? Or did I miss something essential? Whatever the answers to these questions I feel that the time I spent reading the book was time well spent.

Thoughts on Helen Keller

October 19, 2014

I must have seen something about Helen Keller on TV when I was a child. I do not exactly remember what it was and when her name recently came into my mind I could not remember what the story was. I just knew that she had an unusual handicap. Wikipedia confirmed my vague memory that she was deaf and blind. I saw that her autobiography is available online and I started to read it. I got hooked and having been reading a bit each evening I have now finished it. Actually the text is not just the autobiography itself but also has other parts such as some of her letters and text by her teacher Anne Sullivan.

Helen Keller, born in 1880, was left deaf and blind by an illness (it does not seem to be clear what, perhaps meningitis or scarlet fever) at the age of 19 months. Being cut off to such an extent from communication she lost some of the abilities she had already acquired as a small child, although she did invent her own personal sign language. The development was only turned around by the arrival her teacher in 1887. Anne Sullivan was not happy with the way in which people exaggerated when writing about the achievements of Helen and herself. She rightly remarked that what Helen did did not require extra embroidery – the plain truth was remarkable enough. It was claimed that she (Anne) had become Helen’s teacher as a selfless act. She writes that in fact she did so because she needed the money. She had herself been blind for some time before regaining her sight. On the other hand what she did for her pupil was in the end very remarkable. The first route of communication for Helen was through her teacher spelling into her hand. Later on Helen learned to type and read Braille, to write on paper (although in the latter form she could not read what she had written) and to speak (in several languages). She got a college degree despite the special difficulties involved. For instance in mathematics, which was not her favourite subject, there were difficulties for her to be able to understand the examination questions which were presented in a special form of Braille which she was not very familiar with.

I think that the story of Helen Keller can be an inspiration for the majority of us, those who do not have to struggle with the immense difficulties she was confronted with. If we compare then we may complain less of our own problems. Of course she did have one or two advantages. Her family must have been quite well off so as to pay for personal tuition so that she was freed from certain practical difficulties. She had great intellectual gifts which could develop vigorously once a sufficiently good channel of communication to the outside world (and, very importantly, to the world of books) had been established. The prose in her autobiography is of high quality. When she is describing some experience she often describes it as if she had seen and heard everything. This makes a strange impression when you realize that this had to be reconstructed from things her teacher had communicated to her, direct sensations such as smells and vibrations and memories from things she remembered from books. She seems to have had a remarkable talent for integrating all this information. I can only suppose that this integration was done not just for her writing but to create parts of her day to day experience.

The book was published in 1903 and so only contains information about Helen Keller’s life until about the turn of the century. She lived until 1968, was later a prominent public figure and wrote many books. Perhaps in the future accounts of her later life will cross my path.

Harald zur Hausen and the human papilloma virus

September 27, 2014

I just finished reading the autobiography ‘Gegen Krebs’ [Against Cancer] by Harald zur Hausen. I am not aware that this book has been translated into English. Perhaps it should rather be called a semi-autobiography since zur Hausen wrote it together with the journalist Katja Reuter. If I had made scientific discoveries as important as those of zur Hausen, and if I decided to write a book about it, the last thing I would do would be to write it with someone else. He made a different choice and the book also includes reminiscences by colleagues, even by some with whom he had controversies and who have a very different view of what happened. I have the impression that the amount of material on conflicts with colleagues is rather large compared to the amount of science. I think that many successful scientists tend to selectively forget the conflicts, even if these have taken place, and concentrate more on the substance of their work. Thus I ask myself if this slant in the book comes directly from zur Hausen, or if it comes from his coauthor, or if he himself really tended to get into conflicts more often than other comparable figures. In any case, this aspect tended to make me enjoy the book less than, for instance, the book of Blumberg I read recently.

Let me now come to the central theme of the book. Harald zur Hausen discovered that a type of viruses causing warts, the human papilloma virus (HPV), also cause the majority of cases of cervical cancer. He was also involved in the development of the vaccine against these viruses which can be seen as the second major cancer vaccine, following the vaccine against hepatitis B. For this work he got a Nobel prize in 2008. He pursued the idea that this class of viruses could cause cervical cancer single-mindedly for a long time while few people believed it could be true. The picture in the book is that while there were a number of people thinking about a viral cause for the disease they were fixated either on herpes viruses or retroviruses. Herpes viruses were popular in this context because the first human virus known to be associated with cancer was the Epstein-Barr virus (EBV) related to Burkitt’s lymphoma and EBV is a herpes virus. Early in his career zur Hausen worked in the laboratory of Werner and Gertrude Henle in Philadelphia. I studied (among other things) zoology in my first year at university and part of that, which appealed to me, was learning about anatomical structures and their names. From that time I remember the ‘loop of Henle’, a structure in the kidney. The Henle of the loop, Jakob Henle, was the grandfather of Werner. As I learned from a footnote in Blumberg’s book, the elder Henle was also the mentor of Robert Koch. Incidentally, Blumberg worked in Philadelphia starting in 1964 while zur Hausen went there in 1966. I did not notice any personal cross references between the two men in their books.

It seems that Gertrude Henle ruled with a strong hand. Once when a laboratory technician was ill for a few days she put on so much pressure that the young woman came into the lab one day just to show how ill she was. She did look convincingly ill and while she was there a blood sample was taken. This turned out to be a stroke of luck. Everyone in the lab had been tested for EBV as part of the research being done there and the technician was one of the few who had tested negative. After her illness she tested positive. In this way it was discovered that glandular fever, the illness she had, is caused by EBV. At that point it is natural to ask why EBV causes a relatively harmless disease in developed countries and cancer in parts of Africa. I have not gone into the background of this but I read that the areas where Burkitt’s lymphoma occurs tend to coincide with areas where malaria is endemic, suggesting a possible connection between the two.

One of the key insights which led to progress in the research on HPV was the recognition that this was not just one virus but a large family of related viruses. Those which turned out to be the biggest cause of cervical cancer are numbers 16 and 18. (After some initial arguments the viruses were named in the order of their discovery.) To obtain this insight it was necessary to have sufficiently good techniques for analysing DNA. The book gives a clear idea of how the progress in understanding in this field was intimately linked to the development of new techniques in molecular biology.

When zur Hausen won the Nobel prize it seemed that the German press and parts of the medical establishment had nothing better to do than to attack him, instead of celebrating his success. From the beginning it was suggested that he only got the prize because a member of the prize committee was on the board of one of the companies producing the vaccine and so would have a personal advantage from the publicity. It was also suggested that the vaccine was ineffective and/or dangerous. (The latter point actually led to a decrease in the number of people getting vaccinated and so, presumably, will mean that in the future many women will get a cancer that could have been prevented.) I do not believe that there was any justification for any of the criticism. So why did it happen? The explanation which occurs to me is the (latent or openly expressed) negative attitudes to science and technology which seem rather widespread in the German press and in German society. I find this surprising for a country which has contributed so much to science and technology and derives so much economic benefit from it.

After finishing the book I decided to try to get a small personal impression of Harald zur Hausen by watching the video of his Nobel lecture. It is untypical for such a lecture in that it contains relatively little about the work the prize was given for and instead concentrates on future research directions. According to the book zur Hausen’s co-laureate Luc Montagnier was suprised by that. The subject is zur Hausen’s lasting theme, the relation between infection and cancer. I found a lot of interesting ideas in it which were new to me. I mention just one. It is well known that there are statistics relating to a possible increase in the incidence of leukemia near nuclear power plants. Whether or not you find this data a convincing argument that there is an increased incidence it is fairly certain that you will link the increase in leukemia in this case (if any) to the effects of radiation. I was no exception to the tendency to make this connection. In his talk zur Hausen says that there are similar statistics showing an increase in leukemia near oil drilling platforms. So how does that fit together? If you cannot think of an answer and you would like to know then watch the video!

My connection to literature

September 23, 2014

When I was at school I had mixed feelings about the English class. One of the things we had to do was to write essays, which was enjoyable for me. Another was to study Shakespeare plays and I got nothing positive out of that. The teacher once asked in class who did not like Shakespeare. I was the one who was brave enough to stand up and say that I did not like it. I am sure I was not the only one who thought so. More generally I had no interest in ‘literature’. The person I have to thank for changing that is Vivia Leslie, my English teacher in my last year at school. In that year each of us was supposed to choose an author and read some of their books and write about them. At that time my main fictional reading was science fiction and so I wanted to choose a writer of that kind, such as Isaac Asimov. Mrs Leslie was rightly not prepared to allow that and in the end the compromise we found was Aldous Huxley. After all, ‘Brave New World’ is a kind of science fiction. When I then came to read other novels of Huxley it was strange at first and difficult to appreciate. With time this changed and Huxley became the first ‘serious author’ who I liked. In the following years I read more or less all of his novels and became a fan. One thing led to another and at the end of my time in school I was reading a lot of classical literature. When I went to university I had much better access to books and I spent a lot of my time reading the classics.

The one modern foreign language I studied at school was French and I liked that a lot. The system was that at the age of sixteen everyone chose between sciences and languages. I could not give up science and so I had to give up French after four years. At least officially. In my fifth and last year of secondary school I used to spend my lunch breaks with two girls, Ingrid and Joy, who were still studying French. Since I had been relatively far advanced I could help them with their homework and this naturally caused me to continue learning some more French. Apart from an intrinsic appreciation for the beauty of the French language which I already had then the association with spending time with two attractive girls certainly increased my interest further. After I went to university I started reading French literature and getting more and more into that. The culmination of this was ‘A la recherche du temps perdu’ and since then Proust has always been the author I appreciate most. Over the years I read the whole novel twice and parts of it more often. I would like to read it again but at some time (a long time ago now) I decided to put that off until my retirement.

At university I was a member of the Creative Writing Group. I wrote some poetry and short pieces of prose but nothing has remained of that. It was a chance to meet interesting people. For certain periods Bernard MacLaverty was writer in residence and part of the duties associated with that was to take part in the Creative Writing Group and give the students advice. I remember him arriving to meet us for the first time with a bottle of Scotch whisky as a present. Among the members of the group were Alison Smith and Alison Lumsden (commonly referred to by us as Ali Smith and Ali Lum). I recently saw that Alison Lumsden has gone back to Aberdeen University (where we studied) as professor of English. As for Ali Smith, she was clearly the most talented writer in the group and later she became a successful novelist. I last saw her quite a few years ago at a reading she gave in Berlin. Perhaps I will write something about my impressions of her novels in a later post. I recently remembered a story associated to another member of the group, Colin Donati. I was once visiting him in his flat in Aberdeen and I found a single loose page of a novel lying on the floor. Of course I was curious to read it and see if I could identify the author. It was not something I had read before but I thought I recognized the style as that of one of my favourite authors. Despite that I would not have been certain if it had not been for one specific subject mentioned on the page which appeared to me conclusive: rooks. These birds occur in several places in the writings of Virginia Woolf (the errant page was from her novel ‘Jacob’s room’), notably in ‘To the Lighthouse’. At the moment I am living in a small furnished flat until our house is built and the final move to Mainz can take place. Near that flat there is a roost of Jackdaws and Rooks and I enjoy hearing them through the open window in the evenings. It occurres to me that I will probably miss those pleasant companions when I move to the house.

These days I do not find much time for reading novels. The last one I can remember reading which I really liked is ‘Ungeduld des Herzens’ by Stefan Zweig. That was about a year ago. Perhaps I should take some time again for reading beyond the confines of science.

Baruch Blumberg and Hepatitis B

August 6, 2014

This year, at my own suggestion, I got the book ‘Hepatitis B. The hunt for a killer virus.’ by Baruch Blumberg as a birthday present. Blumberg was the central figure in the discovery of the hepatitis B virus and was rewarded for his achievements by a Nobel prize in 1976. The principal content of the book is an account of the story leading up to the discovery. In fact the subtitle is a bit misleading since Blumberg was not hunting for a virus when he started the research which eventually led to it being found. He was interested in polymorphisms, differences in humans (and animals) which lead them to have different susceptibilities to certain diseases. Nowadays this would be done by comparing genes but at that time, before the modern developments in molecular biology, it was necessary to compare proteins. This was done by observing that antibodies in the blood of some individuals reacted with proteins in the blood of others. This is a mild version of what happens when someone gets a transfusion with an incompatible blood group.

Blumberg did a lot of work with blood coming from people living in unusual or extreme conditions. For this he travelled to exotic places such as Suriname, northern Alaska and remote parts of Nigeria. He seems to have had a great appetite for exciting travel and a corresponding dose of courage. He has plenty of adventures to relate. The second protein he found he names the ‘Australia antigen’ since it was common among aborigines. A good source of antibodies was the blood of people who had had many blood transfusions since their immune systems had been confronted with many antigens. In particular they often carried the Australia antigen.

Pursuing the nature of the Australia antigen led  to the realization that it was part of the hepatitis B virus, a virus which causes liver disease and can be spread by blood contact, in particular blood transfusions. The transfusion recipients had become infected with hepatitis B and had produced antibodies to it. Hepatitis B was the first hepatitis virus to be discovered and so why is it labelled ‘B’? In fact people had noticed cases of hepatitis after tranfusions and suspected two viruses, ‘A’ transmitted by contaminated food or water and ‘B’ transmitted by blood contact. There were researchers who had been ‘hunting’ intensively for these viruses and many of them were understandibly not happy when an outsider beat them to it.

For many years Blumberg worked at the Fox Chase Cancer Center in Philadelphia. It was generously funded and the fact that his research had little obvious relation to cancer was not a problem. Once the director of the institute warned that a serious funding cut might be coming. This led Blumberg and colleagues to the idea of developing a vaccine against hepatitis B as a way of making money. Just as Blumberg had not been a virologist when he discovered the virus he was not an expert on vaccines when he developed the vaccine. At that time the need for a vaccine did not seem so urgent since hepatitis B was known as an acute disease which was rarely life-threatening. Later the vaccine acquired a very different significance. There are very many chronic carriers (hundreds of millions worldwide) and a significant proportion of these develop liver cancer after many years. Thus, surprisingly, the hepatitis B vaccine has attained the status of an ‘anti-cancer vaccine’ and has had a huge medical impact.

This book has a very different flavour from the book of Francois Jacob I wrote about in a previous post. Blumberg gives the impression of being a highly cultured person but more than that of an adventurer and man of action. (Along the way he was Master of Balliol College Oxford and director of the NASA Astrobiology Institute.) Jacob also had enough adventures but appears to belong to a more intellectual type, concentrating more on his inner life. In his book Blumberg does not reveal too much which is really personal and always maintains a certain distance to the reader.



The life of François Jacob

August 19, 2011

I have just read the autobiography ‘La statue intérieure’ by François Jacob. I find that this is a book of high literary quality. An indication of this going beyond my personal judgement is that after the book came out Jacob was invited to talk about it by Bernard Pivot on his TV programme ‘Apostrophes’. I understand that at the time when Pivot was active an invitation from him was a kind of certificate of quality for any new book which appeared in French. Jacob is best known as a biologist but this book convinces me that he is also a very gifted writer. The book is not a monumental work, but rather a collection of anecdotes which illuminate many aspects of Jacob’s life and, more generally, many aspects of the human condition. I find it difficult to say what makes up the charm of his writing – I can only suggest reading the book in order to experience it at first hand.

The first three quarters of the book describe the part of his life before he began his career as a scientific researcher in his late twenties. He had started out studying medicine with the aim of becoming a surgeon. After less than two years this was interrupted by the outbreak of the second world war. Jacob, who is Jewish, fled France and joined the French army in exile led by de Gaulle. He spent a large part of the war in Africa. Shortly after his return to France he was very seriously wounded. This made it impossible for him to become a surgeon and left him somewhat at a loss what to do. An interesting point, which he does not emphasize in the book, is that in a sense his being wounded in this case was a result of a decision of his own. He was tending to an officer who had just been wounded when the group was bombed again. The officer could not be moved and begged Jacob not to leave him alone. Jacob could not do anything to protect the man but he nevertheless stayed with him instead of taking cover. As a result of this he was almost killed himself. His decision was very honourable but maybe not very reasonable. In any case, he ended up spending many difficult months in hospital.

Jacob’s way into research was quite indirect and dependent on a lot of chance factors. For some time he worked in an institute which was supposed to produce penicillin in France but never came close to doing so. He became involved in developing and marketing an antibiotic called tyrothricin. Somewhat later he was able to enter the research group of André Lwoff at the Institut Pasteur. This paved the way for the work for which he was awarded the Nobel prize for medicine with Lwoff and Jacques Monod. He describes how each year to commemorate the anniversary of Pasteur’s death everyone working at the institute (not just the scientists) would make a formal visit to the tomb of Pasteur in the basement of one of the buildings. This was made more vivid for me by the fact that I had visited this tomb myself a couple of years ago. I was at the Pasteur museum quite late in the afternoon when not many visitors were there. I was shown the tomb by a very friendly employee of the museum. It is an impressive structure with lots of marble. I remarked to her that Robert Koch did not have such an impressive mausoleum. She replied that the Germans do not honour their great scientists in the way the French do. I am not sure how true this is but it is at least food for thought.

A large part of the last quarter of the book is a description of the work with Monod. There are also a lot of general reflections on the way in which science is done and how the process by which scientific ideas are developed contrasts with the final product as found in research papers and textbooks. It also gives a good picture of who did what in this collaboration. A key mechanism was the interaction between what Jacob was doing on prophages and what Monod was doing on the lac operon. From a certain point on they were always looking for analogies between the two. This part of the book gives a vivid portrait of the early days of the discipline of molecular biology. It includes a description of Jacob working feverishly with Sydney Brenner at Caltech to establish the existence of messenger RNA, in an atmosphere of general scepticism. The narrative ends after the completion of the project with Monod. What happened afterwards in Jacob’s (scientific) life? According to the book ‘In the beginning was the worm’ by Andrew Brown, Jacob tried to work on Caenorhabditis elegans but without success and he failed to get funding to set up an ‘Institut de la Souris’. Jacob later wrote a book called ‘La souris, la mouche et l’homme’ and perhaps I will read that sometime. But since my summer holiday is at an end it will not be very soon.

The immortal Henrietta Lacks, part 2

January 12, 2011

I now read the book about Henrietta Lacks mentioned in a previous post. This book has perhaps three main aspects. One is the history of a scientific development. The second is the information about the family of Henrietta Lacks and the effects on them of her unusual type of fame. The third is a discussion (and some history) of medical ethics. My own bias is that I was most interested in the first point and less in the other two. Having read some reviews of the book I was not sure if I would like it. I was afraid that it might be too political in a direction I would not like, with overemphasis on polemical criticism of racism and hostility to the medical community. Fortunately my fears were not confirmed. In my opinion the intellectual quality of the book is a lot higher than that typical of the reviews I had read. The book tells many interesting stories and I recommend it to anyone with an inquiring mind.

One of the themes I found most interesting was that of contamination of human cell cultures by HeLa cells. This problem has been much more extreme in the past than I had known or expected. I did not get a picture of how it is today and I would like to read up on that sometime. The situation at one time was that it was uncovered that many cell cultures allegedly coming from different tissues and individuals had actually been colonized and taken over by HeLa cells. Embarrassingly, many papers had been published reporting experiments on the differences between the properties of cells coming from these ‘different’ cultures. I was struck by the horror story of a doctor who injected patients with HeLa cells to see if they would produce tumours. Sometimes they did. Sometimes these tumours were eventually eliminated by the patient’s immune system but sometimes they were not.

Another thing I would like to know more about after reading the book is what it is that makes HeLa cells so special. It is known that they have been genetically modified by one of the HPV, the viruses known to cause cervical cancer. What I did not see is what is known the status of these cells. How unique are they? Are there many other comparable human cell lines these days? If not, why not? As well as teaching me many facts the book has left me with a list of questions which I will try to keep in mind whenever I encounter information about human cell culture in the future.