Monday, 21 December 2015

Elgar, soul, and neuroscience

Sir Edward Elgar did not follow conventional religious practices and his biographer, Michael Kennedy [1], remarks that:

He expressed a wish that he should be buried at the confluence of Severn and Teme, without religious ceremony. He had for many years avoided going to church and while dying and still lucid refused to see a priest.

Raised a Roman Catholic, Elgar certainly knew well the concept of soul – it is no wonder that Cardinal Newman's poem The Dream of Gerontius had such an attraction for him, forming the basis of one of his greatest compositions. He was a complex man and his music reflected that, extending from State ceremonial, through religious oratorio, to the pastoral. It is the reflective, soulful Elgar that has always had the most appeal for me and his source of inspiration came from his feelings for people and a passion for landscape and the natural world. His loyal friend, W. H. (Billy) Reed [2] tells us of visits to Elgar:

Elgar was intensely fond of the country. Like William Morris, he was in love with the earth. He seemed to know every inch of Worcestershire (his own county), Herefordshire and the Malverns, Gloucestershire, and the Severn and Wye Rivers. He never tired of talking of them, exploring and re-exploring them if only to see again all the things he knew to be there; and his great joy was to have a kindred spirit with him to share in these pleasures, and to see his own joy reflected in the face of another.

Reed was the leader of the London Symphony Orchestra and provides us with another insight into the inner Elgar when he wrote:

I remember once when we were rehearsing the First Symphony, and the passage at Fig. 66 in the second movement was being played in too matter-of-fact a manner to please him, he stopped and said, "Don't play it like that: play it like" – then he hesitated, and added under his breath before he could stop himself – "like something we hear down by the river"..

It is soul – an inner self, moulded by emotional wounds and triumphs – that Elgar portrays so well in his music. Some people listening to pieces such as Sospiri or the Violin Concerto will be unmoved and find them rather slow and meaningless, but, for me, these pieces cut through everyday things into something much deeper. Here are recordings of the two:

Both works have a link to Billy Reed as he helped Elgar, himself a competent violinist, with fingering and other technical aspects of the solo part of the Concerto. He was not only a very fine violinist, but his nature was quite different to that of Elgar's [3]:

Reed was valuable as a technical adviser and indispensible as a warm-hearted companion, his sympathy, wit, and gay charm being antidotal to Elgar's frequent melancholy.

A photograph of the two men in later years is shown below (from the cover of Reed's book) and something of their relationship comes across in it. Reed was the dedicatee of Sospiri and this was a wonderful gesture by Elgar, reflecting the help that Reed had given the composer four years earlier. 

On the manuscript of the Violin Concerto is written "Aquí está encerrada el alma de ....." (Herein is enshrined the soul of .....), something that has engaged many Elgar scholars, in attempting to identify the person represented by "....." Not being a scholar, I have nothing to add there. What is clear, however, is that the piece does contain what Elgar himself described as his "insidest inside" [1,3]. He was pleased with the Violin Concerto and, during its composition, wrote to a friend [3]:

I have the Concerto well in hand & have played (?) it thro' on the p.f. & it's good! awfully emotional! too emotional but I love it..

I do not get an affecting and moving response when I see the notes of Sospiri or the Violin Concerto written down – I have to hear them (they are music after all). At the risk of trivialising the wonderful sensations that result from listening to the pieces, I wonder how the music would be interpreted by a neuroscientist? Firstly, each instrument in the orchestra is creating sound waves and the complex of sounds is transmitted through the air to be picked up by the ears of the listener, then passing down the auditory canals to vibrate the eardrums and the small bones of the middle ear. The complex of sounds is then translated into electrochemical signals that pass along the auditory nerve to the brain where they are interpreted. Recent studies indicate that there is a special area of the brain that is used to process signals that are generated by music [4], but this is only part of the story. Once received, the signals produce responses in other parts of the brain dealing with pleasure, memory and a host of other activities related to soul. 

In closing, I would like to return to Elgar the man rather than the composer, although both are, of course, interlinked. Above is a picture of Elgar shortly after he had cycled over to his father's home (Mr Elgar was, by then, a widower, living with his daughter, Polly). The composer had just learned of his Knighthood and the reaction of old Mr Elgar also expresses a very special kind of emotion; the handkerchief being used for much blowing of the nose and mopping of the eyes. Elgar stands behind him in "nobilmente" pose, showing a very different part of his soul from that which generated Sospiri and the Violin Concerto. He would no doubt been impressed by the extraordinary achievements of contemporary neuroscience (he was an enthusiast for both chemistry and technology), even though its findings only lead to a rudimentary understanding of the complexities of musical appreciation. If we ever understand the neuroscience of soul, and I doubt that we will, the next question would be: how did soul evolve?

[1] Michael Kennedy (1968) Portrait of Elgar. Oxford, Oxford University Press.

[2] W. H. Reed (1936) Elgar as I knew him. London, Victor Gollancz.

[3] Percy M. Young (1956) Letters of Edward Elgar and other writings. London, Geoffrey Bles.

Wednesday, 16 December 2015

Where is Biology heading?

Nearly 20 years ago, I attended a reception for Francis Crick, after he had given a lecture at UCL on consciousness in animals. There was no opportunity for a conversation, but, like everyone else in the room, I was aware that this was Crick of Watson and Crick, who, with Wilkins and Franklin, were responsible one of the most important discoveries in Biology – the structure of DNA. There was a feeling of awe that here was someone whose name would go down in history, alongside Darwin, Newton and a few others.

Since the discovery of DNA, we have found ways of cutting DNA strands, so that we can not only identify what each gene codes, but also manipulate the genetic material of an individual to change gene expression. The recent development of CRISPR brings a cheap and readily available technique for changing the genetics of organisms, something that excites both scientists and the media [1].

As we find out more and more about which genes code which chemicals, we also discover how these affect biological processes within the body. The eventual aim is to be able to understand how life functions as an immensely complicated series of chemical reactions. Computers provide a means of storing all the information that we acquire about each gene, and computing power enables us to model the possible interactions of chemicals. Many studies are required to gain information and these form the basis of research projects that are routine and, dare I say it, dull.

Recently, I received an e-mail from someone advertising a talk at a leading University in the UK. It said:

X is a very exciting speaker with a very refreshing perspective on cell biology. It goes well beyond the standard approach of spending 4 years studying one modification on one variant of one protein in one type of tissue culture cell.

That, surely, is almost a definition of something dull and it is clear that the purpose of all these investigations is to train students in the use of techniques to gain information that forms a tiny part of a giant jigsaw. There is no knowing whether we will ever be able to complete the jigsaw and it will certainly not answer questions about thought processes, aesthetics and what drives emotions. We might discover the components of individuals, but will we have any clue as to how those individuals live, especially as only a small proportion of the total DNA appears to be "used" [2]?  There are those that think that it will, and the media also build expectancy, and show little restraint, in reporting each discovery that may lead to eradicating a disease, or transformation of a farm animal, or food crop. Scientists go along with this because they like the publicity and it aids recognition of their work, perhaps enhancing the chance of success in the next round of grant awards.

Taking a step back, what is happening to Biology as a result of the revolution in genetics? Certainly there have been great discoveries, with more to come, but there is also a large amount of humdrum recording for the jigsaw puzzle. The Biology that so entranced me, based on Natural History and the environment, is becoming lost in the worlds of chemistry, physics and mathematics. Perhaps I should just move with the times?

During my research career I looked largely at populations of insects and the way that they transformed organic matter. It could loosely be categorised as Ecology but that subject, too, has become dominated by deterministic approaches and models. For example, one set of models that has been developed over many years explains the interaction of predators and prey, and the way they affect each other's population density. Having conducted some experiments, I found that some predators killed more prey than others and only ate some, and this wasn't the result of a difference in life stage or in anything else I could measure. Now, where do these killers fit into a model that treats all predators as being equal? Clearly there is a need to allow some variable, or stochastic, component that makes the solution of the models much more complex, but brings them closer to the real situation.  

I think Biology has passed a crossroads. I don't join in all the excitement over determinism and can even see that it might lead to a new Dark Ages where we cease to question. In an earlier Dark Age in Christian Europe, we were constrained by a belief system, while Islamic scholars were encouraged to acquire knowledge and use it in advancing ideas. During the time of Al-Mamun, there was great respect for knowledge of all types [3] and it was accorded high status: blue-sky research was a means of advancing human achievement, quite unlike the way it is currently regarded as the poor relation of technology and applied science. Of course, the deterministic approach of Biomedicine is invaluable in proving us with novel treatments that are beneficial, but we must recognise that most biomedical research programmes only produce small pieces of jigsaw and they might not even be doing that. How much better to have a balance, with a return to the excitement of Natural History that so marked the Nineteenth Century, with the discoveries of Charles Darwin and others? These Natural Historians knew that we are dealing with a great deal of complexity and were filled with awe at just how complex the World seems. They probably knew that we would never get as many answers as we would questions.

In supporting a return to Natural History, I am not advocating only the study of plants and animals, but also of the extraordinary world of single-celled organisms. We have the tools to make many new discoveries across a wide range of environments; from hostile regions of land masses through to the deep oceans. Discoveries that enhance our knowledge of the World we live in and not just those that are perceived as being potentially useful, or threatening, to humans. Natural History, like the Arts, brings pleasure and purpose to life and that is as important as all the advances in Biomedicine.

[3] Jim Al-Khalili (2012) Pathfinders: The Golden Age of Arabic Science. London, Penguin Books.

Wednesday, 2 December 2015

Barnacles from space?

Part of a space rocket has been recovered from the Atlantic Ocean near the Scilly Isles. It was from a launch vehicle carrying cargo to the International Space Station and large chunks fell to Earth after the rocket exploded [1]. The pieces that were recovered had coverings of goose barnacles (above and also below left) and those with a very fanciful imagination may conclude that these were carried back to Earth from somewhere in the planet's atmosphere, or beyond. However, the story of their colonisation is not the stuff of science fiction, but nonetheless fascinating.

We are all familiar with acorn barnacles (above right) from our walks along coasts. Millions of the crustaceans coat the surface of rocks, often giving them a creamy-white appearance, but fewer people have seen their relatives, the stalked goose barnacles, like those found on the pieces of space rocket. They can be seen on many shores during low spring tides and they are familiar to those who own boats and ships, where their presence causes a reduction in performance, so that hulls need to be cleaned of barnacles from time to time. To prevent such colonisation, the hull may be treated with anti-fouling paints containing metals that deter the attachment of barnacles, or even have a covering of copper sheets that fulfils the same purpose. The latter was a feature of the fastest tea clipper ships.

Barnacles do not colonise surfaces as adults, but as larvae. The adults are hermaphrodite and shed both sperm and eggs into the sea where fertilisation occurs. The first stage larva that hatches from the fertilised egg is called a nauplius (A, above) and this transforms into a cypris larvae (B, above). Both stages are free-swimming and are carried by currents, often very far from the adults that produced them. The oceans contain enormous numbers of larval stages of many familiar creatures, in addition to barnacle larvae, yet most of us would be hard pressed to identify them as they are so unlike the adults. Limbs are used both for locomotion and feeding and barnacle larvae capture tiny particles of various kinds that are then passed to the mouthparts and swallowed.

If cypris larvae are washed on to a shore, or to any other solid surface, a remarkable series of events takes place. The first is that the larva cements itself to the substratum (different types of adhesive being used across the spectrum of barnacle taxa [2]) and calcareous plates are secreted to begin the process of conversion to the familiar adult form. The process of transformation has been described by Calman [3]:

..after a series of nauplius stages the larva passes suddenly, at a single moult, into a stage in which the body and limbs are enclosed in a bivalved shell.. ..this is known as the cypris stage. Through the valves of the shell a large pair of compounds eyes can be seen, as well as six pairs of two-branched swimming feet, while in front a pair of antennules projects between the valves. On each antennule is a sucker-like disc by means of which the larva, after swimming freely for some time, attaches itself to a stone or some other object, where it remains fixed for the rest of its life. A cementing substance produced by a gland at the base of the antennules attaches the front part of the head firmly to the support; the valves of the shell are cast off, and replaced by rudimentary valves of the adult shell; the six pairs of swimming feet grow out into tendril-like cirri; the compound eyes disappear, and the animal assumes the structure of the adult.

Acorn barnacles and goose barnacles feed using the cirri on their legs, these limbs no longer being required for swimming. Acorn barnacles use the legs to sweep the cirri through an aperture between the shell plates and captured particles of a wide variety are then transferred to the mouthparts, in a similar way to that employed by the larvae. In goose barnacles, the cirri are static, or nearly so, and feeding is from currents or, in the case of moving objects, the water that passes over them. Unlike their smaller relatives, goose barnacles also capture small planktonic animals and the cirri close around these to prevent their escape. To enhance access to currents, goose barnacles have developed a peduncle, or stalk, that is muscular and covered with a strong cuticle. It grows intermittently [4] and those familiar with the cuisine of Portugal will know the structure well after eating a plateful of percebes (see recipe here [5]) and below a video from Gordon Ramsay:  

Goose barnacles are not able to exist for long out of water but acorn barnacles certainly can, as they have calcareous plates that close off the aperture of the "shell" when the cirri are withdrawn. That is why we see them so readily on the shore when the tide is out. Some forms are so high on the shore that they only become submerged at the highest tides, remaining exposed to the air for days, showing how effective the closing plates are at preventing water loss. Altogether, barnacles are most remarkable animals and it is little wonder that they so intrigued Charles Darwin [6].

The basis for the structure and complex life history of these crustaceans is encoded in the barnacle's genes. Repeating a question here that I often asked students: "How do you think the structure and development evolved?" Anyone like to venture a guess as to the stages in the evolution of the life history of barnacles and their way of life?

[2] Jaimie-Leigh Jonker, Liam Morrison, Edward P. Lynch, Ingo Grunwald, Janek von Byern and Anne Marie Power. (2015) The chemistry of stalked barnacle adhesive (Lepas anatifera). Interface Focus 5:20140062.

[3] W. T. Calman (1911) The Life of Crustacea. London, Methuen & Co.

[4] John Chaffee and Cynthia Arey Lewis (1988) Pedunculate barnacle stalk growth. Journal of Experimental Marine Biology and Ecology 124:145-162

Thursday, 19 November 2015

The Dark Ages and Islamic Medicine

Like millions of others, I have visited the Alhambra in Granada to marvel at the Islamic architecture and decoration of the buildings. We admire the achievements of the craftsmen who made them and it is wonderful that the site exists and has been restored. The Alhambra gives us an insight into the period from the 9th Century to the 14th Century CE and, if we are not able to visit, we can become familiar with the palaces by an abundance of pictures on the Internet. The achievements of Islamic scientists, and medical practitioners are less familiar, and much less publicised, and this is partly the result of a lack of interest in the history of these subjects, compared to up-to-the-moment practice and discoveries.

In an interview with Kaleen Hussain [1], Professor Rabie E Abdel-Halim advocates that Universities teaching Medicine should have Departments for studying the history of the subject. It is a point that applies also to Science and I always appreciated being taught History of Science as an undergraduate. It opened my eyes to an awareness of significant discoveries, when they were made, and how ideas change through time; it also instilled a respect for the achievements of Greek Philosophers, especially Democritus and Aristotle, that I have retained. All contemporary thinking has its roots in history, yet we interpret history subjectively on occasions.

Charles Singer's A Short History of Biology [2] was a recommended book for my course and, while this concentrates on Biology rather than Medicine, it does consider the contributions made by Hippocrates (ca. 460 – ca 370 BCE) and Galen (130-200 CE), both of whom were interested primarily in the anatomy, physiology and diseases of humans. Singer's book contains an interesting section on The Dark Ages (A.D. 200-1200) that includes the following:

After Galen.. ..we encounter no biological activity for many centuries.. .. While the knowledge and intelligence [?] of men in Western Europe steadily deteriorated, there was one part of the world where the old traditions lingered. After the fall of ancient science, the most civilized part of the world was the Near East. In Syria, in Asia Minor, in Constantinople, men still read Greek scientific works. Then in the seventh century came the great movement of Islam. It established Arabic as a literary language and the face of the world was changed. Intellectual leadership thus passed, by the ninth century, to people of Arabic speech. It remained with them till the thirteenth century. The science of these Arabic-speaking peoples was based on translations of the Greek works into Arabic.. .. The movement for the translation of Arabic works into Latin began in the eleventh century. Such versions did not, however, become common until the beginning of the thirteenth century.

The impression is thus given that Islamic scholars were concerned just with translations of Greek texts, rather than being important contributors to the development of the discipline. This view is still held and it is instructive to listen to the BBC programmes by Andrew Cunningham on The Making of Modern Medicine. In the first of these [3], Cunningham introduces us to the ideas of Hippocrates and Galen, with the core of Greek practice being adopted by the Arabs [sic.] and then by mediaeval Western practice. No mention is made of any contributions made by Islamic scholars to the development of the discipline, whether important or not. Then, in the second of the programmes [4], Cunningham discusses hospitals and states that the need for hospitals "started from Christ's description of The Last Judgement" and they are "a quintessential Christian Institution" taking care of the needy as well as the sick and with benefactors who gain benefit from their charity. That being the case, one would expect to find hospitals only in regions of the Mediaeval World where Christianity was practised.

We obtain a rather different perspective in Cumston's The History of Medicine first published in 1927 [5]. These are excerpts:

For a long time it was maintained that the Arabs [sic.] were merely servile copyists of the Greeks, and even that they caused a delay in the evolution of medical science. This is a mistaken opinion. At the time when the Arabs appeared in the Orient, Greek science was in complete decadence, and the practice of magic reigned supreme. Not only did the Arabs save the Greek treasures from the irredeemable loss to which but for them they had been doomed, but they developed the taste for scientific studies, both in the East and in the West, by popularizing and commenting upon the Greek works. Had they merely been content with collecting Greek science and transmitting it to Europeans, that would alone have been a great glory to them. But they did better still, for in the arts, as in the sciences, they did original work..

..There is no question.. ..that the Islamic physicians beneficially influenced the progress of surgery and of medicine..

..The experimental method enabled the Islamic physicians to introduce a large number of new drugs and to determine the exact therapeutic indications of old ones derived from the Greeks and, into the bargain, to find new properties in them..

..From the IXth to the XVth century the teaching of medicine was very well organized in the schools of Bagdad, Damascus, Cairo and Cordova, which were usually connected with a hospital so that theoretical teaching was completed by clinical instruction at the bedside. After a certain time a kind of diploma (Ijaza) was given to students as a certificate of complete study..

All this seems rather different from the views expressed earlier in this blog post, with the translations of Greek texts being used as a basis for further detailed enquiries and with experimentation to explore the most effective treatments. Medicine was also linked to hospitals (not a Christian invention, then) and with a training, and certification, programme for aspiring physicians and surgeons. It is something that I am learning about on a course organised by Paul Ranford for the WEA and entitled The Light Ages. The course is inspiring. 

Some specific achievements of Islamic medical practice can be given, with the author of the works describing them in parentheses:

- the drawbacks of excessive obesity are understood (Ibn Sina Canons in Medicine [6])

- there should be opposition to charlatanism and the exaggerated importance of examining urine  (Al-Razi Liber Continens [7])

- physicians should  work next to surgeons and help with pain relief (Ibn El Quff Al-Omda Fi Sinaat Al-Jarrah [7])

- a rational approach to diagnosis is based on recording, interpreting and classifying clinical and experimental [my underlining] observations (Al-Razi Liber Continens [8])

- a control group was used when testing the effects of bloodletting as a treatment for meningitis (some patients not receiving venesection) (Al-Razi Liber Continens [8])

- the effects of mercury were tested on monkeys to assess its safety for human consumption (Al-Razi Liber Continens [8])

- the safe use of tracheotomy was employed (Ibn Sina Canons in Medicine [7], Al-Razi Liber Continens [8], Al-Zahrawi Al-Tasrif [1])

- drugs should be tested carefully by experimentation to assess their potency (Ibn Sina Canons in Medicine [8])

- haemophilia is described as an inherited disease (Al Zahrawi [Al Tasrif] [9])

- catgut [preparations from the intestine of cows] can be used for internal sutures in surgery (Al Zahrawi [Al Tasrif] [9])

This is a very small sample of the approaches found in the Middle East and Islamic Europe around the end of the first Millennium, yet these are mostly ignored by Historians of Medicine. It is a point that has been made well by Paul Ranford as he leads our course through Islamic contributions to Philosophy, Mathematics, Astronomy, Physics and Chemistry, as well as to Medicine.

During the period referred to as The Dark Ages in Western History there was conflict between Christians and supporters of Islam (think of the Crusades) and this continued until the Islamic caliphs were overthrown. There is no question that the practice of Medicine, and the foundation of hospitals, were linked closely to Islamic belief and there was thus an inbuilt resistance among Catholic scholars to recognise the contributions made in Baghdad, Cordoba and elsewhere. Galen, however, was considered acceptable and in the Middle Ages it was believed that he had converted to Christianity, having written about characters in the Holy Bible and believing in one God [2], rather than the polytheism of most Greeks. The lack of recognition of the achievements of Islamic Medicine thus appears to be the result of an opposing religious standpoint.

While the practice of Islam at the end of the first millennium supported charity and care for individuals, it was not tolerant when it came to the acquisition, and defence, of territories and there were also battles over successions within caliphates. Nevertheless, there was recognition that both Christians and Jews could live alongside followers of Islam and, indeed, many Jews were valued for their skills as translators, thus allowing access to more knowledge, something that was considered to be of great importance.

It is clear that beliefs have been corrupted over time by the practitioners of religions and we see the evidence of that only too clearly today. During our present era, some followers of Islam are gaining a bad reputation for the great majority that do not follow their dogmatic and illiberal views, such a contrast to those when Islam was still a young religion. Having champions of Islamic Science and Medicine like Paul Ranford, Rabie E Abdel-Halim, Jim Al-Khalili and others does something to redress the balance, and I close with a quote from the Prophet Muhammad that is given Jim Al-Khalili's excellent review [10]:

The ink of the scholar is more sacred than the blood of the martyr.

[2] Charles Singer (1931) A Short History of Biology: A General Introduction to the Study of Living Things. Oxford, The Clarendon Press.

[5] Charles Greene Cumston (1987) An Introduction to the History of Medicine: From the time of the Pharaohs to the end of the XVIIIth Century. New York, Dorset Press. [Reprint of the 1927 book]

[6] Rabie E Abdel-Halim (2005) Obesity: 1000 years ago. The Lancet 366: 204

[7] Rabie E Abdel-Halim (2006) Clinical methods and teamwork. The American Journal of Surgery 191: 289-290

[8] Rabie E Abdel-Halim (2011) Experimental medicine 1000 years ago. Urology Annals 3: 55-63

[9] Paul Ranford (2015) Notes for the WEA course on The Light Ages

[10] Jim Al-Khalili (2012) Pathfinders: The Golden Age of Arabic Science. London, Penguin Books.