Tag: biology

Feb 10 2011

Book review: The Immortal Life of Henrietta Lacks by Rebecca Skloot

HenriettaLacksThe Immortal Life of Henrietta Lacks by Rebecca Skloot is an unusual book. It is part cell biology: the story of cell-lines kept alive perpetually in the laboratory; it is part story of Henrietta Lacks and her family from whom the first of these cell-lines (called HeLa) was derived; it is the story of how medical ethics has evolved over the last 60 years and it is part story of the story.

Henrietta Lacks’ cells were taken at the Johns Hopkins Hospital in Baltimore in 1951 and cultured by George Gey during her treatment for an aggressive cervical cancer from which she subsequently died at the age of thirty-one, later that year. Gey, with the help of Lacks’ cells, was the first person to successfully maintain a cell-line. The cells cultured are cancer cells rather than normal cells. Following his work a wide range of other cell-lines were cultured from a variety of organs and species, however it subsequently turned out that many of these were actually the HeLa cell-line which turned out to be particularly pernicious. Researchers would start with a culture of different cells, but they would die to be replaced by HeLa cell “contaminants”.

Once Gey had started the cell-line he gave them away freely to other researchers, however it was not very long before the HeLa cells were being sold commercially. An early application of the HeLa cell-line was in testing the newly developed Salk vaccine for polio, the first of many, many applications. More dubiously Chester Southam injected the cancerous cells into prisoners, and subsequently into many patients. This was with the view to seeing if they developed within the body, the problem was that the patients were not informed that the cells were cancerous. This practice ended when three young Jewish doctors aware of the Nuremburg Code, proposed as a result of post-war trials of Nazi doctors responsible for horrific human experimentation, refused to take part in the experiments.

To my mind the unique part of the book is the in depth coverage of Henrietta Lacks’ family through to the present day. Rebecca Skloot tells in detail the long persistent trail to talk to them, an African-American family who certainly have good reason to be suspicious of white people asking about Henrietta. The Lacks’ were never a model family but then there is no reason for them so to be. Race and medicine have a poor history in the US. The Tuskagee Syphilis experiments perhaps being the lowest point, in which African-Americans were denied effective treatment for the disease so the full course of its symptoms could be observed. Other racism is less direct, as relatively poor Americans the Lacks family have reduced access to the treatments arising from the cells of their ancestor. If she were a white child, Elsie Lacks, Henrietta’s mentally disabled daughter would not have died at the Crownsville State Hospital, certainly not in such terrible circumstances.

In 2011 the cell lines derived from Henrietta Lacks would not have been called HeLa. Possibly her cells would not have been collected at all, requiring full informed consent. Her name would have become known to all including the family. The family would not have learned of the gruesome details of her death at the “hands” of an aggressive cervical cancer via a book whose author had been given Henrietta Lacks medical records.

To my mind the real shortcomings of the scientists were not in what they did in the first instance but how they failed to support the Lacks’ not with money but with information. Until Skloot and Christoph Lengauer showed them and spoke to them, no-one had explained exactly what cells had been taken, what had been done with them, the significance of Henrietta Lacks to science or the specific knowledge of her condition did or did not have to their health in terms which they could understand; giving them a book on cell biology was not enough.

Skloot relates three stories of discoveries arising from a specific persons’ cells: the Lacks story and those of Ted Slavin and John Moore. Slavin was born a haemophiliac and as a result of the blood transfusions that he had to receive as a result of his condition he contracted Hepatitis B, however he did not succumb to this disease, he was immune. His doctor told him that this made him special, and that his blood was valuable and he subsequently profited from this knowledge by selling samples of his blood. John Moore, on the other hand, had hairy-cell leukemia and only discovered his blood was valuable after his doctor had patented his cell-line, he was subsequently involved in lengthy legal action to regain some control of his cells.

As a scientist whose work once touched, peripherally on human tissue culture and who recently had surgery from which such tissue was taken this is a somewhat uncomfortable story. In the project I worked on a postdoc was tasked with organising consent forms for, I think, blood vessels removed during a procedure i.e. they were a by-product. In this instance the specifics of the cells were not important – they were destined for frequently unsuccessful experiments. From our point of view the best possible outcome would been that the materials we had synthesised proved to be a congenial home for blood vessel wall cells. In this case nothing of monetary value is derived directly from the donors cells.

For my own part: I have no problem with researchers using my medical offcuts, I do feel unhappy with the idea that my specific cells might be valuable and that I might not get a proportion of that value.

Dec 30 2010

Book review: Mutants by Armand Marie Leroi

Mutants Armand Marie LeroiChristmas is a time for reading, so in addition to Rolt’s Brunel biography I have also read “Mutants: On the form, varieties & errors of the human body” by Armand Marie Leroi.

This is a story of developmental biology told through the medium of mutants, people for whom development doesn’t go quite to standard plan.

The book runs through a sequence of distinct mutations: Siamese twinning, deformities to arms and legs, skeletal defects, dwarfs and giants, various sexual variations, albinism and hairiness, and finally ageing. His approach does not revel in the freak show aspects of human mutants rather makes a brief reference to the historical recognition of such mutations and uses this as a jumping off point for discussion of modern biological understanding.

Mutations have long been an area for scientific study because it was realised that studying malfunction would provide clues to the mechanisms of normal development.

The marvel of developmental biology is that it is a method of construction completely at odds to the human way of making complex devices. Rather than a complex entity assembling pieces to a plan, biology starts with an instruction set which builds order out of chaos with no external help. It is self-organisation, creation from (nearly) nothing with no supporting infrastructure. There are non-biological self-organising systems and we make use of some of them industrially, but there is nothing that matches the complexity, the heterogeneity that biology can achieve.

The fundamentals of development biology are genes coding for proteins that tell you where you are in the developing embryo and trigger growth or differentiation on that basis i.e. “I find myself in the presence of proteins A, B, and C at these particular concentrations, therefore I must make a leg”. As an example, the proteins noggin and bone morphogenetic protein 4 (BMP4) define the top and bottom of the growing embryo – in simple terms noggin stimulates the growth of the brain. Whimsical naming of a protein may seem like a good idea in the lab but I imagine it makes discussions with parents about the problems of their perhaps-dead child difficult.

An intriguing point is the frequent robustness of developmental mechanisms, often as not molecular biologists have identified a “critical” protein, created a “knock-out” mouse lacking that protein and discovered that the mouse developed relatively well – other developmental systems having compensated for the loss.

The diverse effects of mutations can be surprising, for example there is a condition called Kartagener’s Syndrome whereby the internal organs of the body are flipped left-right – the heart, rather than lying slightly on the left of the body lies on the right and so forth. People with this syndrome have respiratory problems, a diminished sense of smell and sterility. The cause of these apparently disparate problems is a faulty cilia motor, cilia are small hairs on the surface of a cell that move. In the lungs and nose they whip about to move mucus around, in men the cilia motor drives the tail of sperm, and in the developing embryo the whipping of cilia break the left-right symmetry. Hence failure of the cilia motor proteins leads to a diverse set of impacts.

In addition to proteins which induce specific behaviours, there are proteins which have a more overarching impacts, such as those produced in the pituitary gland, malfunctions of which can lead to dwarfism or gigantism.

As usual my butterfly mind has fixed on some less relevant portions of the book. Plato giving voice to Aristophanes in The Symposium posited that sexual desire can be explained because man and woman were once combined: in fact three pairings existed man-man, man-woman and woman-woman. These creatures were physically joined, having four arms and legs, two heads and two “privy members”. However, they were troublesome (cartwheeling on their eight limbs is explicitly mentioned) – so Zeus separated them into the men and women. And now everyone seeks to find their original partner thus explaining homo- and hetero-sexuality. There’s some suggestion that Plato was making a little fun of Greek myth here!

Thanks to this book I have learned that the male scrotum is the homologous structure to the female labia, the two halves have fused to form a handy sack. The development of sexual organs finds the male really as something that has failed to become female.

Leroi finishes with signposts to a couple of open areas in developmental biology, one is race: people have a moderate ability to identify racial groups and tie them to countries but current genetics cannot match this ability often finding much bigger variations within populations. As Leroi highlights, this is a fraught area in social terms but it is interesting that differences obvious to people are not obvious to genetics. Secondly he mentions beauty: does beauty tell us something about genetic fitness?

This book highlights the huge gap between knowing the base pair sequence of DNA and understanding how the organisms arise from that sequence. At times the language gets technical a little too quickly and it could really have done with some explanatory diagrams.

Jun 24 2010

Book review: Botany of Desire by Michael Pollan

Yet another in my erratic series of book reviews cum notes. This time I’m reading “The Botany of Desire:A Plant’s-eye View of the World” by Michael Pollan.

The introduction lays out the land of the book, sections on apples, tulips, marijuana and potatoes and the central thesis: that it’s a useful idea to consider that not only do we domesticate plants but that in a sense plants naturalise us. As stated in the introduction this thesis felt a bit hardline, grating a little for my taste but once into the reading this feeling receded since the illustrative stories are enticing and nicely written.

First up, are is the story of apples in American and the folk hero, Johnny Appleseed, who travelled the mid-West, setting up ad hoc orchards from seeds, a little way in front of the settler-wave, and sold them trees as they moved into the area.

The point about apples is that they don’t grow true from seed, take a fine apple and plant its seed and what you get is a lucky dip. This is a recurring theme, plants amenable to domestication appear quite often to be those amenable to quickly producing a wide variety. To grow “true” from an apple you need to graft from the parent onto a root stock. It’s always struck me as something of a miracle that grafting works and that people managed to discover it.

Apples were significant to the early settlers since they offered sweetness (sugar would not have been very available), a sense of order when planted in neat orchards and cider. It seems cider played a big part in the popularity of Johnny Appleseed during his life, since the apples grown from seed were most often best suited to cider-making rather than eating. After he died the temperance movement gained strength in the US, and this aspect of apple cultivation was pushed into the background.

Despite the focus on Johnny Appleseed (and comparisons to Dionysus) the thing that will remain with me from this section is the descriptions of the wild apple forests around Alma-ata in Kazakhstan. You can get a flavour of the place from the fabulous images here, in an article in Orion Magazine and here, on the BBC website. These wild trees are important because they represent massive genetic diversity. The drawback of grafted plants is that they are genetically identical to their parents, so over time they become more and more susceptible to pests and diseases which evolve freely to take advantage of their stasis.

After the apples come the tulips, and Tulip Mania amongst the unlikeliest of enthusiasts: the Dutch. Tulips are a relatively recent addition to the pantheon of flowers, unlike the rose and the lily which appear in the Bible, tulips appear to have been introduced to Europe from Turkey in around 1550.

Interesting thought from this section: flowers became beautiful before there were ever humans to appreciate them – in a sense flowers are the result of the aesthetic decisions of bees (and other pollinating insects).

Tulip Mania was a speculative bubble in the Netherlands slightly before the middle of the 17th century wherein the prices paid for tulip bulbs skyrocketed, a single bulb fetching the equivalent of a acres of land or a fine townhouse, only to crash thereafter.

The flower in the picture to the left is Semper Augustus, emblematic of the most valued of the tulips during tulip mania. The interesting thing is that the most prized of these flowers – those that had “broken”  – were actually suffering the effects of a virus from which their line would eventually weaken and die. “Broken” refers to the variegated appearance with a dark colour, appearing in streaks on a lighter background. The modern Rembrandt tulips are similar in colouring but, according to Pollan, less impressive than the best of the virus “broken”.

A common theme through all these stories is the large variability of the species from which the domesticated cultivars are drawn and the vulnerability of the much more uniform varieties once domesticated.

The third section is devoted to marijuana, clearly a plant for which the author has some fondness. Marijuana has long been cultivated for two reasons: one for fibre as hemp, and one for drugs. Since the early 80’s and the American “War on drugs” marijuana production has been pushed underground, or rather indoors. Pollan recounts the story of the recent cultivation of marijuana by Dutch and American growers. The plant has undergone fairly rapid change in the last few years with the crossing of the large, traditional cannabis sativa and the more compact, frost resistant cannabis indicas. A substantial amount of work and horticultural ingenuity has gone into this process, leading to plants that can produce high yields of the active material in small, indoor spaces. The prize being the $13,000 that a hundred plants grown on a 6 foot square table can yield in a couple of months.

For Pollan there is an element of horticultural challenge in this process, he clearly grows a wide range of plants  in his own gardens (from each of the sections of this book) valuing the challenge and the diversity. The garden at SomeBeans Towers is similar: more a plantswoman’s garden than a designer’s garden.

He digresses at length on purpose of intoxication and whether drug taking really does open the doors of perception, or just lead to inane blithering, falling eventually for the former. There’s an interesting section on the neuroscience of cannabis.

The book finishes with a chapter on potatoes, in particular on a genetically modified potato called NewLeaf which was developed by Monsanto to express the pesticide from the Bacillus thuringiensis bacteria (Bt). Organic certification schemes allow the limited ‘manual’ application of the Bt pesticide. In this chapter he visits various potato growers, spanning the ultra-technological to the organic. He highlights the dilemma that he finds GM potatoes more palatable than the non-organic equivalent when presented with the choice, in large part because the level of inputs, in particular fungicides and insecticides, to conventionally grown potatoes is very high.  His visit to an organic highlights something from the organic movement in which I’m in favour: which is a willingness to explore different methods of cultivation (and a wider range of cultivars), where I part company is where they say “There must be no X” where X is a somewhat arbitrarily drawn list, enforced with religious fervour.

The section also covers the history of the cultivation of the potato, from the wide variety in the mountain gardens of its native Peru, to its introduction into Europe as a favoured staple crop. Prior to the introduction of the potato bread was the staple food in Europe; wheat is somewhat fussy in its growing conditions particularly in Northern Europe and getting bread from wheat is quite an involved process. Potatoes, on the other hand, are less fussy on growing conditions and exceedingly simple to prepare for eating (stick in fire and wait, or if feeling extravagant: boil in water).

Overall I enjoyed this book, each section seemed to divide into two unlabelled parts one largely factual and one rather more philosophical – I preferred the more factual sections but appreciated the philosophical too.

Nov 26 2009

Wonderful Life

You might have noticed I’m happy to go off into areas of science which are not my own with gleeful abandon, applying a physicist’s mind to what I find. This week I’m off to see the biologists, Mrs SomeBeans is a zoologist – so in a sense, I sleep with the enemy. Twitter puts me in touch with so many more of the biological persuasion.

Animals are very well covered in TV documentaries but their view is somewhat partial, favouring the furry and cute, but there’s so much more.

I think my appreciation for the wonders of the tree of life was first stimulated by “Wonderful Life” by Stephen Jay Gould. This book describes the fossils uncovered in the Burgess Shale a collection of fossils, from almost the very earliest life in the record – 500 million years ago. Gould is making two key points in his book, the first is that the so-called Cambrian explosion of species threw up a very diverse range of body plans; his second point is that the ones that survived did so almost by chance, there wasn’t anything obviously superior about them. Richard Dawkin’s book, “The Ancestor’s Tale” is also well worth a read.

I should explain body plan: this is the overall layout of the animal. So for the tetrapods (including mammals, reptiles, amphibians, birds) you get four appendages. Insects: the plan is six legs, three body parts and an exoskeleton. I’m reliably informed that snakes are tetrapods, although I’m struggling with this particularly since one of my advisers previously tried to persuade me that mohair came from mo’s. Basic rule seems to be that you can lose bones, fuse bones but not gain bones.

Once you appreciate this body plan stuff you start to get offended by representations of mythical beasts like angels and centaurs: they are clearly mammalian so angels can either have wings or they can have arms, they can’t have both! Similarly centaurs can either have two pairs of horsey legs and no arms or a pair of horsey legs and a pair of arms, what they can’t have is two pairs of horsey legs and two arms. The only reason I’m letting off the fairies is that I suspect they might be insects.

As a physicist, I really like this approach. Physicists basically have poor memories which shapes their approach to science, they like nice simple rules that encapsulate as much information as possible. You also spot them looking for “the simplest possible” model. So being freed from the requirement to learn lots of animal names by the simple expedient of calling them all ‘tetrapods’ is great. It’s true that the tree of life is more complicated than that but the principle is there. If you want to go into this in more depth, the technical name for this study is phylogenetics… *time passes as I get completely distracted*

At this point I originally made my usual error by referring to other living animals as being further down the tree of life: they’re not, we’re all leaves on the surface of the tree. A good way to wind up a biologist is to refer to another currently living species as ‘primitive’. They don’t like this because, as they point out, they’ve been evolving for just as long as us! So, rather than referring to them as ‘primitive’ here are a couple of distant leaves: Hagfish are the only vertebrates to have a skull, but not a spinal column. They evade capture by covering themselves in slime. And as for tunicates, they start with a notochord (a precursor to a spinal cord) as larva but give it up as adults which indicates a certain bloody-mindedness that I admire. (it’s a tunicate that decorates this post, at the top).

Rather more interesting than yet another furry animal…