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46 posts categorized "Bioscience"

21 June 2019

Influencing Environments: Material, Socio-political, and Ethical Environments in Anne McLaren’s Work

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Anne McLaren (1927-2007) was a leading mammalian developmental biologist who worked primarily with mice and contributed to many fields, including most famously the development of in vitro fertilization (IVF). As McLaren often put it, she was interested in ‘everything involved in getting from one generation to the next’, and in particular, she emphasized the ways in which an individual is always connected to, and a part of, its many environments. Taking a cue from McLaren, then, this post considers how environments—understood materially, socially, and ethically—shaped McLaren’s work.

Scientific Environments

For McLaren, environmental effects are never incidental—not for cells, not for science, and not for the scientist in society—and even her earliest experiments probed deeply into the effects of various environments. Some of the environmental effects she studied are more familiar, like the effect of ambient temperature on population variance, and others are more surprising, like the genetic effect that a mother’s uterus, and not just the material contained within the egg, has on the development of an embryo.

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Figure 1. Slide from McLaren’s thumbnail sheet (Add MS 89202/2/20). Copyright © Estate of Anne McLaren.

While McLaren’s research showed how interconnected our very cells are with our environments, she showed an acute awareness for how this interconnectivity proves equally true for science itself. For example, McLaren knew that science needed diverse perspectives to grow, and so she actively fostered collaborative working environments. She was also highly attuned to socio-political issues, including the changing interests of funding bodies; structural gaps, like the lack of accessible childcare, that limit the participation of women in science; and the rise of new social concerns, including those surrounding ‘designer babies’ as embryonic research progressed. She knew that each of these issues materially shaped what scientific questions got asked and by whom (McLaren).
But McLaren did not stop with simply acknowledging the ways in which science was affected by its environment. She also held the reciprocal to be true: scientists affect their own physical, socio-political, and ethical environments. She therefore worked throughout her life to uphold what she saw as the duty of scientists, namely, to share research widely and to work with the public in ensuring that science progresses ethically and in the best interests of society.

Working Environments

But how did McLaren’s own research environments affect her actual work? The path that led to her 1958 breakthrough with John Biggers (1924-2001) on successfully transplanting fertilized mouse embryos cultured in vitro (in glass) to surrogate mothers proves an illuminating example.
From 1952-1959, McLaren and her then-husband Donald Michie (1923-2007) worked together on embryo transfer experiments. They first worked at University College London, but when they ran out of space for their mice in 1955, they undertook what proved to be a fortuitous move into the larger facilities at the Royal Veterinary College, London. There, they had room to grow and, as an added bonus, enjoyed relative autonomy from a specific department while doing their work (McLaren).

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Figure 2. Note recording the move to the Royal Veterinary College. (Add MS 83844) Copyright © Estate of Anne McLaren

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McLaren and Michie’s experiments went through more than just a change of scenery though. Across their work, they tested a variety of processes for ovary transplants, specimen preservation methods, and embryo transfers from a donor mouse to a surrogate mother. They also experimented with superovulation and superpregnancy, or hormonally triggered ovulation cycles and artificially increased litter sizes respectively, in order to consider, for example, what factors might hinder an embryo’s chance of survival, such as uterine crowding. They asked as many questions as they could and perfected a method of transferring embryos in vivo (directly from the donor to the surrogate), while also proving that the surrogate mother’s uterus passed on genetic effects to the transplanted offspring, tracked in the case of their experiments through the number of lumbar vertebrae (McLaren and Michie).

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Figure 3. Pages from McLaren's Embryo Transfer Experiments Notebook, 1955-1959 (Add MS 83844). Copyright © Estate of Anne McLaren.


In the midst of this flurry of work, McLaren and Michie met Biggers. Their research interests overlapped, and, with him, McLaren and Michie undertook even more parallel experiments. One such experiment considered the effect of temperature on population variance, mentioned above, which was inspired in part because they had access to three different temperature rooms at the Vet Collage. Biggers, McLaren, and Michie also briefly considered the relationship between the length of a mouse’s tail—a major site of heat loss—and its ability to regulate temperature, although Biggers reports that they never fully explored that project (Biggers).

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Figure 4. Charles Darwin's On the Origin of Species diagram, public domain

This rich, collaborative, and multi-tasked environment can be likened to a Darwinian tree of research ideas with many offshoots. As a product of this environment, a seemingly small experiment took place over about two months in the summer of 1958. Using the techniques McLaren had perfected with Michie, she and Biggers cultured 249 fertilized embryos for 48 hours in vitro before transplanting them into eight female mice (McLaren and Biggers). Nineteen days later, these transplants resulted in the live birth of two mice, or as McLaren called them, ‘bottled babies’, which were the first mammals ever cultured outside of a uterine environment pre-implantation (Biggers).

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Figure 5. Anthony Smith, ‘Brave New Mice.’ Daily Telegraph, 6 October 1958, p. 11.

This experiment, dubbed by the press as producing ‘Brave New Mice’, justifiably received much scientific and public attention, while also laying the ground work for IVF in humans only 20 years later. Yet, as we see, the experiment itself was but a single offshoot in a much larger web of experiments, in which IVF as such was not specifically McLaren’s focus. This incredible range of McLaren’s impact is due in no small part to the efficient way in which she used the environments, people, and resources around her to their fullest potential, asking as much as she could from and through them in order to learn and give back.


Bridget Moynihan
PhD student, University of Edinburgh

As a PhD student at the University of Edinburgh, Bridget Moynihan’s research focuses on archival ephemera and digital humanities. These same interests led Bridget to undertake a British Library internship, researching the notebooks of Anne McLaren.

Further reading in the British Library

    1. For more on the temperature experiments, consult Add MS 83846, Add MS 83847, and Add MS 83848 for laboratory notebooks documenting these experiments, and Add MS 83972, which contains some of McLaren’s relevant published papers, such as 'The growth and development of mice in three climatic environments'. See also Add MS 89202/6/26, which includes tail length data.
    2. For more on the uterine effect experiments, consult Add MS 83843, Add MS 83844, and Add MS 83845 for laboratory notebooks documenting these experiments, Add MS 83830 for conference papers presented by McLaren, including ‘An Effect of the Uterine Environment upon an Inherited Skeletal Character in the Mouse’, and Add MS 83972 for some of McLaren’s relevant published papers, such as ‘Factors Affecting Vertebral Variation in Mice. 4: Experimental Proof of the Uterine Basis of a Maternal Effect’.
    3. For more on the in vitro mice, consult Add MS 89202/2/10 for McLaren and Biggers’ article ‘‘Test-Tube’ Animals. The Culture and Transfer of Early Mammalian Embryos’.

References

Biggers, JD. ‘Research in the canine block.’ Int J Dev Biol. 2001; 45:469–76.
McLaren, A. and Michie, D. ‘Factors affecting vertebral variation in mice. 4: Experimental proof of the uterine basis of a maternal effect.’ JEEM 6, 1958: 645-659.
McLaren, A. and Biggers, JD. ‘Successful Development and Birth of Mice Cultivated in vitro as Early Embryos.’ Nature 182, 1958: 877-878.
McLaren, A. ‘Professor Dame Anne McLaren interviewed by Martin Johnson and Sarah Franklin.’ 2007, oral history recording at the British Library.

08 March 2019

How Embryologists See: Anne McLaren’s Mouse Models

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This post forms part of a series on our Science blog highlighting some of the British Library’s science collections as part of British Science Week 2019.

What does an embryo look like? You’ve probably seen pictures –photos of clumps of tiny little cells, most likely taken of a petri dish in a lab. But embryologists face many barriers when bringing these miniscule cells into vision. The developmental biologist Dr Anne McLaren found ways around some of these problems starting with her work in the 1950s.   

In 1952, the mammalian developmental biologist Dr Anne McLaren moved to UCL to begin conducting a series of experiments intended to transplant mouse embryos from the uterus of one mother to the uterus of another, foster, mother – a technique called embryo transfer. There were several reasons for her wanting to do this, but the central one was a problem of vision. She wanted to make the embryos visible. As she explained in 1960,

Experimental embryology in mammals starts with a grave and obvious disadvantage compared to experimental embryology in, say, frogs or sea-urchins - namely the relative inaccessibility of the mammalian embryo. On the other hand it is a subject of particular interest, not only because man himself, and most of his domesticated animals, are mammals, but also because the mammalian embryo goes through almost all the critical stages of development in the most intimate contact with a genetically different organism, its mother.

This intimate relationship between the embryo and its mother in the very early stages of implantation, and the potential applicability of these insights to other mammals, like humans, made this an important area of study. This relationship also represented a prime example of McLaren’s central research interest, namely how the gene and environment interact in development. In the mammal, the maternal uterus crucially provides the environment in which the genes have to exert their effects. This is why maternal effects on inherited characters are of particular interest to McLaren.


At school we are often taught that development looks something like this,

Image-1-1
Illustration: human fertilization and embryogenesis. With kind permission of Gaurab Karki, at www.onlinebiologynotes.com


McLaren saw things differently. Although the embryo could indeed develop into a foetus and a baby, this was only under particular circumstances, in a given environment. McLaren wanted to better understand what was required of this environment for the embryo to develop into a healthy mouse. Development could also go wrong, and it was certainly not as simple as the expression of a set of genes against a neutral backdrop. In fact, she believed that the whole concept of a gene meant fairly little without an adequate account of the environment through which they were expressed. 

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‘The Bucket Model and When Causes Interact,’ are from The Mirage of a Space Between Nature and Nurture, Evelyn Keller Fox, pp. 8-9, Copyright, 2010, Duke University Press. All rights reserved. Republished by permission of the copyright holder. www.dukeupress.edu



But the problem of being able to see this environment remained. Although she could not look directly inside the womb, McLaren realised that instead she could make the interactions taking place between the embryo and the uterus visible. This was made possible by a phenomenon that had been noticed with the number of lumbar vertebrae, the vertebra starting after the last rib attachment and running down to the last vertebra not sacralised, in the offspring of reciprocal crosses between two strains of mouse. In Problems of Egg Transfer in Mice (1955), she explained,

We suspect the existence of a maternal effect whenever reciprocal crosses are made between two genetically differing strains or varieties, if the progeny differs according to which strain was taken as the maternal parent, and which the paternal. …In species hybrids between the horse and the donkey, the mule, which has a horse mother and a donkey father, differs in a number of respects from the hinny, which has the donkey mother and the horse father. One difference lies in the number of lumbar vertebrae that the animals have. Most mules have 6 lumbar vertebrae, like their mothers; while most hinnies have 5 lumbar vertebrae, again like their mothers.

Another example of this effect observed in mules by John Hammond and Arthur Walton in 1938, was the case of lumbar vertebrae in mice. E. L. Green and W. L. Russel, working at Bar Harbor in New York in 1943, noticed such a phenomenon, a suspected maternal effect on lumbar vertebrae in mice, but their experiments had been stopped short by a fire in their laboratory. The effect presented McLaren with an observable trait that was definitely not just due to chromosomal sex linkage, because the difference also appeared in female progeny of the crossed strains, who of course carry two of the same X chromosome. Even through the trait was not sex-linked, it could still be determined either by the cytoplasm of the egg or the uterine environment that the mother provides. The case thus provided a specific instance of the question of the respective roles of gene and environment in the inheritance of an observable trait. The best way of distinguishing between these contributions, she decided, would be by transferring eggs between females of the two strains, “since such eggs would have the cytoplasm of one strain but the uterine environment of the other” (Research Talk, 1953). If the influence was exerted through the cytoplasm, the young would be unaltered in phenotype by the transfer; but if it was exerted through the uterine environment, the reciprocal difference would be reversed.

Image-1-4
Image: Is it the uterus or the egg affecting the number of vertebrae of the mice? Copyright estate of Anne McLaren MS89202/12


Embryo transfer techniques had been around for a while – in fact, the pioneer of the technique, Walter Heape had used the technique as early as 1890, to show the exact opposite of what McLaren suspected was the case with lumbar vertebrae – namely that the uterus had absolutely no effect on the developing embryo. As their experiments progressed, McLaren and her then husband and collaborator Donald Michie showed that the uterus, in the case of lumbar vertebrae, did exert an effect on the embryo. The mice in the surrogate uterus expressed the trait of the surrogate, not the genetic mother.  There was something in the maternal uterus, not the cytoplasm, that effected the number of lumbar vertebrae. By the end of the experiment she was not able to determine exactly how  this effect was exerted but, she reflected in 1985, the message of the experiment was clear,

As to how this influence is exerted, from the physiological point of view, we are so far in complete ignorance. But the general moral for the geneticist, I think, is clear: that is, when we are dealing with mammals we must be prepared to extend our picture of the genetic control of morphogenetic processes, to envisage their regulation not only by the action of the embryo's genes, but also by the action of the genes of the maternal organism in which the embryo is gestated

Turning cauliflowers into mice: mouse model growing pains 

As might be expected with such a new technique, it took a while to perfect it, to be able to produce standardised results. In the process, McLaren began to see some unusual things. Indeed, during the early days of the experiments, McLaren and Michie were worried about the appearance of some the fertilised ova being produced by the donor female after they’d administered the hormones to induce ovulation. In a research talk from 1953, McLaren recounts,

During the Summer of last year, we were using two-day eggs only; and one day, actually the day we were rejoicing because for the first time we’d got transferred eggs to develop into mice, our 2-day eggs, instead of looking like normal mouse eggs with 4 or 8 distinct spherical blastomeres, suddenly began to look like cauliflowers. The blastomeres coalesced, and the eggs looked awful.

She goes on,

From that day onward, all their eggs looked like that, and as it seemed obvious that something looking like a cauliflower couldn’t develop into a mouse, we didn’t even bother to transplant many of them, but spent much fruitless effort trying to find the cause of the trouble. However, we’ve now got over this difficulty, partly because by using 3-day eggs, which look quite normal, as well as 2-day eggs; partly because this Summer only some of our 2-day eggs looked like cauliflowers; and partly because we’ve got some evidence that cauliflowers can in fact develop into mice.

These pages from McLaren’s lab notebooks show how she tested different variables, like the PH of the medium in the dish before transfer to the foster mother, or the daylight to which embryos were being exposed. She obtained some strange shapes in the process.

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Strange cauliflower shapes. Detail from Anne McLaren’s ‘UCL Embryo Transfer’ laboratory notebook, 1953-1956. Copyright estate of Anne McLaren (Add MS 83843).
 
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‘Ghosts’, or disappearing, eggs. Detail from Anne McLaren’s ‘UCL Embryo Transfer’ laboratory notebook, 1953-1956. Copyright estate of Anne McLaren (Add MS 83843).
 
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A healthy blastocyst (Cells differentiated into cell layers, preceding the embryo stage) –‘hooray’! Detail from Anne McLaren’s ‘UCL Embryo Transfer’ laboratory notebook, 1953-1956. Copyright estate of Anne McLaren (Add MS 83843).

McLaren was discovering new things about the ways in which embryos could develop, and she didn’t always understand what was going on. The appearance of these cauliflowers in development point to the limited view she was getting. It remained difficult to visualise what was going on at these early stages inside the maternal uterus, and the best the embryologist could do was to set up an limited model of the process, to bring to the fore some of the phenomena she was interested in. But biological models, unlike the ones we draw or build out of inanimate material, don’t always comply. Moreover, the view was always partial, and in this case especially limited because all she could do was move her embryos between uteri –about which she knew very little. The only way of knowing more about the uterus would be by intervening in this environment, changing it in some ways and observing the effects this had on the developing embryo which was impossible while the womb remained inaccessible.  As we shall see, McLaren soon went on to develop another window that would allow her to visualise more directly the forces acting on the embryo during development. 

From wombs to dishes

As far as her interest in making the interactions between uterus and embryo visible was concerned, McLaren had definitely succeeded. She had done this by intervening in the biological process of gestation, by moving an embryo from one mother to another and observing the effects it had on the developing embryo. As we have just seen, this technique threw up obstacles and limitations. The cauliflower effect was just one example of a malformation that McLaren was unable to explain because she had little idea about what the uterine environment was made of. She could not figure out the exact mechanisms by which the uterus acted on the embryo because, in order to do this, she would have to play around with them like she had with the medium in the dish prior to transfer, to isolate different variables until she could figure out what factors were at work. She would have to manipulate to be able to see. At the same time, however, McLaren was developing a very promising technique that could provide the solution – the technique of embryo culture. Writing in 1958, she mentioned a method by which egg transfer enables the experiment to influence the environment of the early mouse embryo directly, instead of through the medium of the mother or the other embryos. In collaboration with Dr. Biggers, I have been culturing 8-16 cell mouse embryos according to the technique of Whitten, on Krebs bicarbonate with glucose and bovine plasma albumen added. In two days at 37 [symbol: degrees], nearly 100% of such embryos reach the blastocyst stage, a development which in vivo takes only one day. I then transferred these blastocysts to the uteri of pregnant female recipients, and found that their viability relative to that of control blastocysts had been in no way impaired by the culture treatment….So far we have done no more than demonstrate the feasibility of the technique; but it seems to me that a study of the effects upon subsequent development of variation in the conditions of culture and the constitution of the culture medium, might provide yet another means to overcome the inaccessibility of the mammalian embryo…

Embryos in dishes would allow McLaren to figure out the conditions needed for normal embryonic development. When she and John Biggers (1958) later showed that a mouse embryo after being cultured outside the womb for over 24 hours, could be replaced in the uterus of a mouse mother and develop into a normal healthy mouse, they had pathed the way for In Vitro Fertilisation in humans that would become a reality 20 years later. IVF, a technique that changed the field of embryology as well as society at large, was just one of the offshoots of McLaren’s explorations of gene-environment interactions.

Marieke Bigg
Ph.D candidate, University of Cambridge

Further reading:

McLaren, Anne, and J. D. Biggers. 1958. ‘Successful Development and Birth of Mice Cultivated in Vitro as Early Embryos.’ Nature 182 (September): 877.
McLaren, Anne. 1958, 1960. Experimental studies on the effect of the prenatal environment. 
McLaren, Anne. 1985. An effect of the uterine environment. 

Marieke Bigg is a Ph.D candidate at the University of Cambridge. After completing a B.A. Honors in comparative literature at the University of Amsterdam, she obtained an M.Phil in sociology from the University of Cambridge. In her current PhD research, which she conducts under the supervision of Professor Sarah Franklin, she draws on the biography of Anne McLaren to map the debates on human embryo research in Britain in the 1980s, and proposes new models for policy-making in the area of human fertilisation and embryology today. She is funded by the Wellcome Trust.

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28 February 2019

A visit to the Joint Library of Ophthalmology at Moorfields Eye Hospital

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Conjunctiva
Eye painting by an unknown artist from the Moorfields collection, digitised by UCL. Used under a CC-BY Creative Commons license.


Yesterday Philip went on a CILIP-sponsored visit to the Joint Library of Ophthalmology at Moorfields Eye Hospital.

The library is joint between the NHS trust responsible for Moorfields and the UCL Institute for Ophthalmology. The hospital was opened in 1805 in Charterhouse Square as the Dispensary for Curing Diseases of the Eye and Ear. The driving reason for this was the number of soldiers who were returning from the Napoleonic wars in North Africa with what was known as “Egyptian Ophthalmia”, now recognised as trachoma. The founders were John Cunningham Saunders and Dr. John Richard Farre. In 1810 a medical school was opened and alumni were responsible for opening ophthalmic hospitals in other parts of the world. In 1821 the hospital was moved to Lower Moorfields near what is now the Broadgate office complex and renamed the London Ophthalmic Infirmary, although it quickly became popularly known as “Moorfields”. In 1837 it achieved royal patronage and became known as the Royal London Ophthalmic Hospital. In 1897 the hospital moved to its current site in City Road after the Moorfields site became overcrowded. In 1947 the hospital merged with the Royal Westminster Ophthalmic Hospital and Central London Ophthalmic Hospital, and the name officially became Moorfields. A green line is painted on the pavement from Old Street tube station to the hospital main entrance, to help partially-sighted people find their way.

The Institute of Ophthalmology was founded in 1948, initially on the site of the former Central London Ophthalmic Hospital in Judd Street. It became part of UCL in 1995.

The library now includes items from all the predecessor organisations, and as it is considered a national subject collection no material is disposed of. Much of the journal collection was donated in exchange for the content being indexed in either the British Journal of Ophthalmology or Ophthalmic Literature. There are 7000 books, 63 currently subscribed journals, and 250 journals which are no longer published. There are over 280 CDs or DVDs. The library currently keeps paper subscriptions when possible due to concerns about loss of access due to subscription cancellation or technical obsolescence – many of the CDs or DVDs cannot be used due to outdated software requirements. Most of the material is on open shelf apart from the rarer collections. The rarer material consists of 1500 books and pamphlets, many of which have been digitised by the Wellcome Institute and are included in the Wellcome online digital library. There is also a unique collection of 1700 painted images of healthy and pathological eyes. Many of the earlier eye paintings were by the sisters Mary and Alicia Boole, who were daughters of George Boole of Boolean logic fame. They were mathematicians in their own right and many of their siblings and the following generation had notable achievements in science and art. Later twentieth century paintings were created by the talented medical artist Terry Tarrant. The paintings have been digitised by UCL .The rare books include copies of John Dalrymple’s 1834 “Anatomy of the Human Eye”, the first ophthalmic textbook in English, and the “Atlas of Ophthalmoscopy” by Richard Liebreich, inventor of the ophthalmoscope.

There is a photographic collection of patients and their conditions, often “before and after” treatment. This includes an interesting dimension in terms of Victorian attitudes to privacy and personal identification – many poorer patients had their full names given, while more middle or upper-class patients are identified only by given names or initials. There is also a collection of bound notes on patients back to 1877.

Finally, there is a “museum” collection of artifacts. Many of them are originally from the Institute of Ophthalmology. They include eye testing equipment, ophthalmoscopes, surgical instruments and microscopes. Particularly unusual exhibits include an ivory leech holder used to apply leeches to the area around the eye to treat glaucoma, and a pair of prism spectacles that redirect the vision downwards through ninety degrees, to allow patients forced to lie flat on their backs to read more easily.

The library still serves an audience of predominantly medical students and practitioners. They do a lot of training on databases and library inductions. They lend the majority of the material and there are self-service lending/returning terminals. They also do inter-library loan.

Other activities include doing systematic reviews and helping people with basic IT skills.

There are 32 satellite sites with electronic resources only.

Last year the library achieves Platinum status in the Green Impact scheme for environmentalism in libraries, based around recycling and saving energy.

The whole institution is intended to move in a few years time to a new site in the St Pancras area.

23 January 2019

Lab notebooks - handwriting at the core of science

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McLaren notebook
Page from Anne McLaren's notebook (shelfmark Add MS 83844) covering embryo transfer experiments in mice, 1950s. (Copyright estate of Anne McLaren)


Today is World Handwriting Day, and we thought we’d pay our respects to the most important role handwriting plays in science, one which you might not have heard of if you aren’t a practicing scientist. This is the “lab notebook”, a scientist’s daily diary of all their experiments, thoughts, and other scientific activities. Until relatively recently, these were always handwritten, as they were meant to record what, in detail, someone was doing as they did it. Waiting to create them until work was finished caused too much risk of forgetting or distorting something.


Lab notebooks grew out of the personal diaries and notebooks of individual researchers. Some notebooks by well-known scientists have become Library treasures in their own right. One of the most famous works in our Treasures of the British Library exhibition is the Codex Arundel, a collection of notes written by Leonardo da Vinci (although probably not in the order they were bound) in the sixteenth century. At the other extreme of history, the Treasures Gallery currently displays the biologist Anne McLaren's lab book on embryo transfer in mice. Outside the BL, most of the lifelong field and theoretical notebook collections of Charles Darwin are digitised and available online, as are some of Albert Einstein's most significant theoretical notebooks. At the other end of accessibility, some of the lab notebooks of Marie and Pierre Curie, held by the National Library of France, are reported to still be so radioactive that they are not safe to handle without protective clothing.


Laboratory notebooks later became an even more important record of exactly what was done, as lone researchers were replaced by academic and private-sector research groups, science and technology became ever-more important to society, and scientists were expected to describe their methods in detail so that they could be replicated and turned into innovative technologies, materials and treatments. Additionally, until quite recently, American patent law worked on a “first to invent” basis whereby the person who could prove that they had the idea for an invention first, or their employer, had the right to a patent. Laboratory notebooks were the main source of evidence for this. In recent years, scientific misconduct has become a higher-profile issue, as scientists worry about a “replicability crisis” where too many uncertain or exaggerated results have been published. Lab books help prove that the work was done as the researchers claim, or the detail expected in them make discrepancies easier to recognise. And the notebooks of eminent scientists are a rich source for scientific historians.


By the latter part of the twentieth century, some organisations had very detailed instructions for how laboratory notebooks should be completed and stored. Lab books had to be written exactly as the work was carried out, or as soon as possible – no jotting notes on scraps of paper and writing them up at the end of the day. Notebooks were considered the property of the employer or the university, and could not be removed from the lab. And they had to be clearly paginated with no chance of pages being removed or replaced.


Many laboratories still use paper notebooks, due to the ease of simply writing notes down as you go. In many types of science, electronic devices are at risk of being exposed to spillages or damaging electromagnetic conditions, or are simply unwieldy. Some researchers also like to keep their detailed records to themselves instead of sharing them with a group. Some research groups and organisations are now moving to electronic recording, but the lifetime of electronic data can be questionable due to failure to back up and the lifespan of media. Specifically-designed electronic laboratory data systems are more secure. They are more common in industry than academia, as academics are more independent and less likely to respond to top-down orders, and academic institutions can be less able to afford the necessary software and hardware. The advantages of electronic research notes systems are that you can save large amounts of original data directly into the system without retyping or printing it, clone records from earlier experiments to save time, search your records more easily, share data within the group easily, and track the history of records. Now data is often electronically recorded and can be directly copied into a laboratory system without a transcription stage. It is possible to use general project and collaboration software packages such as Evernote, SharePoint, or GoogleDrive but specifically-designed software is now available. 


In 2011, Gregory Lang and David Botstein published a scanned copy of the entire lab notebook covering the research leading to a paper on yeast genetics, as an attachment to their e-journal article.


Modern lab books rarely find their way into the British Library collection, but our most famous example is the collection of Alexander Fleming, the discoverer of penicillin (also including records of earlier experiments by his mentor Sir Almroth Wright). As well as the material by Anne McLaren mentioned earlier, we also have some material from the photography pioneer Henry Fox Talbot, electrical inventor David Edward Hughes, and biologist Marilyn Monk.

Sources and further reading:
Barker, K, At the bench: a laboratory navigator, Cold Spring Harbor: Cold Spring Harbor Press, 2005. pp. 89-99. Shelfmark YK.2005.b.1888
Baykoucheva, S. Managing scientific information and research data, Oxford: Chandos Publishing, 2015. Available electronically in British Library reading rooms.
Bird, CL, Willoughby, C and Frey JG, "Laboratory notebooks in the digital era: the role of ELNs in record keeping for chemistry and other sciences", Chemical Society reviews, 2013, 42(20), pp. 8157-8175. Shelfmark (P) JB 00-E(105) or 3151.550000.
Elliott, CA, "Experimental data as a source for the history of science", The American archivist, 1974, 37(1), pp. 27-35. Shelfmark Ac. 1668 or 0810.390000, also available electronically in British Library reading rooms.
Holmes, FL, "Laboratory notebooks: can the daily record illuminate the broader picture", Proceedings of the American Philosophical Society, 1990, 134(4), pp.349-366. Shelfmark Ac. 1830 or 6630.500000, also available electronically in British Library reading rooms.
Stanley, JT and Lewandowski, HJ, "Lab notebooks as scientific communication: investigating development from undergraduate courses to graduate research", Physical review: physics education research, 2016, 12, 020129, freely available online at https://journals.aps.org/prper/pdf/10.1103/PhysRevPhysEducRes.12.020129.
Williams, M, Bozyczko-Coyne, D, Dorsey, B and Larsen, S, "Appendix 2: Laboratory notebooks and data storage", in Gallager, SR and Wiley, EA, Eds. Current protocols essential laboratory techniques, Hoboken: John Wiley & Sons, 2008. Shelfmark YK.2008.b.6299 or m09/.30081

18 December 2018

Arabic science manuscripts from the British Library

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Kitab al sirah
The beginning of Kitāb al-sīrah al-falsafīyah, an autobiographical treatise by the physician and philosopher Abū Bakr Muḥammad ibn Zakarīyā al-Rāzī (Add MS 7473, f. 1v)


Today is World Arabic Language Day, so here's a reminder of the scientific content in our Qatar Digital Library digitisation project. Our friends on the Asian and African Studies blog created two lists of major scientific works digitised in the collection, including Arabic versions of classical scientific texts, some of which were lost from Western European culture until the Renaissance, and original works by great early scientists of the Arabic-speaking world, such as Quṭb al-Dīn al-Shīrāzī, Ibn Sīnā (Avicenna), Ibn Haytham (Alhazen), and Abū Bakr Muḥammad ibn Zakarīyā al-Rāzī (Rhazes).

13 November 2018

The centenary of the 1918 flu pandemic

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2 Nov Contagion
A dancer in "Contagion", a piece memorialising the pandemic presented at the British Library earlier in November


This November sees not just the centenary of the end of the First World War, but the centenary of the peak of the influenza epidemic that came at its end. The 1918 flu epidemic may have killed fifty million people or more worldwide, over three times the number of people killed in the war. It is thought to have been the third worst disease epidemic ever in Europe, after the fourteenth-century Black Death and the sixth-century Plague of Justinian. 228,000 people died in the UK, with as many as a third of the population infected, although the death rate among those who fell ill was around 2.5%. 1918 was the first year since official records began that deaths in Britain outnumbered births. Epidemiological studies have shown that children whose mothers suffered flu during pregnancy suffered lifelong negative effects on their health and employment histories.

 The flu is still sometimes known as the Spanish Flu, although this is a misnomer that, even at the time, seriously upset the Spaniards. It was associated with Spain because Spain, being neutral in the war, had less media censorship than other European countries, so that the epidemic was more honestly reported. The first unambiguous cases of the pandemic broke out at a US Army base in Kansas in March 1918. The first worldwide wave continued through the spring and summer, but appeared to be no more problematic than ordinary flu. The second, far more lethal wave, occurred in September to December 1918, while a third, less serious wave took place in the first half of 1919.

However, some people have suggested that earlier outbreaks of disease may have been unrecognised early stages of the flu pandemic. Particular suspicion has been cast on an outbreak of a lung disease called at the time "purulent bronchities" which struck the Allied Powers' huge military camp at Etaples in France in early 1917, and a lethal epidemic of lung infection which hit the region of Shansi in China in the winter of 1917-8, although that was believed by local authorities at the time, and many scientists to this day, to have been pneumonic plague.

A major question, especially given the possibility of further flu pandemics in the future, is what made the 1918 virus so lethal. As well as the sheer number of fatalities, it was unusual in killing young and healthy people in large numbers, rather than those who were elderly or frail. Some people have blamed the physical and psychological stresses of the war, and in particular the long-term effects of chemical warfare, for this, but young people also died in countries which were barely affected by the war. It has been suggested that healthy people died because of a phenomenon known as "cytokine storm", where the influenza infection causes the immune system to go into such a state of extreme activity that it itself causes fatal damage to the lungs. This is more likely to happen in people with healthier immune systems, although recent work has suggested that it might be more likely in people with a specific genetic condition in which the first stage of immune response, involving the production of interferon, is unusually weak.

In 2005, the genetic code of the 1918 virus was sequenced from samples taken from the body of a woman buried in Alaska, which had been partly preserved by the cold climate. This indicated that the 1918 virus was a member of the "H1" type of flue virii. That gave rise to a new theory about the higher death rate among young people - for the previous thirty years the majority of influenza circulating worldwide had been of the "H3" type, so older people may have been more likely to have encountered H1 influenza before and had more immunity to it.

Another mystery is why the 1918 pandemic had so little apparent cultural impact at the time. The most famous deaths from the virus were the poet Guillaume Apollinaire, the artist Egon Schiele (along with his wife Edith, who was pregnant with their first child), and John McCrae, author of one of the most famous poems of WWI remembrance, "In Flanders Fields". It also had a wider historical impact. Some military historians argue that the last major German offensive in 1918 failed only because of flu among the soldiers. The British prime minister David Lloyd George nearly died, although this was covered up at the time. The Versailles Treaty might potentially have been less harsh on Germany, reducing the chances of WWII, if the US President, Woodrow Wilson, had not been incapacitated with the flu during the later part of the negotiations. And the death of the leading USSR politician and administrator Yakov Sverdlov has been said to have opened up an opportunity for Josef Stalin to begin his rise to power. Some suggest that the influenza was not seen by people in general as a separate catastrophe from the war, while others have argued that, despite the death toll, it was seen as "just the flu" in an era when death from infectious disease was still much more common than it is today.

Further reading:

Honigsbaum, M. Living with Enza. London: Macmillan: 2009. Shelfmark YC.2009.a.3229 or m08/.36952
Johnson, N. Britain and the 1918-19 influenza pandemic (Routledge studies in the social history of medicine no. 23). Abingdon: Routledge, 2006. Shelfmark YC.2007.a.11206 or 8026.519925 no. 23
Ministry of Health. Report of the pandemic of influenza 1918-19, Reports on public health and medical subjects, 1920, No. 4. Shelfmarks B.S. 17/1, (P) HF 00-E(18), or 7665.590000
Spinney, L. Pale rider. London: Jonathan Cape, 2017. Shelfmark YC.2018.a.7038, or available in British Library Reading Rooms as Legal Deposit e-Book.

Posted by Philip Eagle

12 November 2018

New psychology and nature databases on trial at the BL

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Starting today, users in the British Library Reading Rooms can use two new databases from Alexander Street, which are on trial until mid-January 2019. The usage figures in the next two months will determine whether we take the databases permanently.

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Psychological Experiments Online has information on some of the most famous (or notorious, given the dark conclusions of some of them) experiments in psychology since 1900, with articles, archive material, sound or video interviews with researchers and participants, and even recordings of the experiments themselves when available.

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The BBC Landmark Video Collection has complete episodes of some of the BBC's most significant nature documentary series from the last fifteen years. All of them have full subtitles and searchable transcripts.

Note that to use these databases you will have to use our desk PCs within the Reading Rooms. For the full effect of sound and video material, you will need to use a PC with headphones, although most of those in the Science reading rooms are now fitted with them.

Please can you give any feedback to the enquiry desk staff, or to science@bl.uk

Posted by Philip Eagle, Subject Librarian - STM

10 October 2018

Andreas Vesalius - The most famous Belgian you have never heard of

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This week, the episode of Sky Arts’ Treasures of the British Library featuring the actor Jim Carter, who you might remember as Mr. Carson in Downton Abbey or, if you are a bit older, Philip Marlow’s father in The Singing Detective, was broadcast. One section covered Jim’s interest in anatomy, and among the items we showed him was one of our copies of Andreas Vesalius’s paradigm-shifting anatomy textbook, Atlas of the Human Body, the first truly scientific anatomical work. The copy shown in the programme is our copy of the book's first edition, which was owned by Hans Sloane, a famous eighteenth-century doctor and collector whose collections of books, antiques and curiosities formed the original core of both the British Museum and the British Library. I showed the book to Jim in the programme, and here is some more information on Vesalius.

It is a standing joke, much to the annoyance of Belgians, that it is difficult to name great descendants of their proud kingdom in Western Europe. Mentions of Tintin and Poirot (fictional characters) or Jean Claude Van Damme (The muscles from Brussels) may just accentuate their irritancy. However, one of their greatest sons, one Andreas Van Wiesel, who would adopt the more impressive Latinised name of Vesalius, changed anatomy and medicine forever and he really did know about muscles. His magnum opus De Humani Corporis Fabrica, published in 1543, was both a paradigm shift for the study of human anatomy and also a work of the finest aesthetic beauty.

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Andreas Vesalius, a portrait included in "De Humani Corporis Fabrica"

 Vesalius chooses his parents well and is born into a family of physicians in 1514 in Brussels, then part of the Holy Roman Empire. Initially studying at the University of Louvain, he completes his doctorate in Padua in 1537 and becomes the chair of anatomy and surgery at the tender age of 23; however, this was not considered an especially important branch of medicine compared to the more exciting emerging areas of lotions and potions.

His big break comes when a local judge, impressed with his work, permits use of corpses of executed criminals thus enabling him to perform comparative dissection of the human form. Such opportunity was denied to the great Galen of the second century who despite being physician to the stars such as the gladiators and emperors, only ever worked on animals due to the religious dogma of the time.

Vesalius quickly realised that Galen had simply extrapolated his findings to humans and consequently had made a huge number of glaringly embarrassing assumptions and errors.

Most notably Galen thought that blood was made in the liver and then used for fuelling muscles, and he also thought there were holes in the septum, allowing blood flow from one side of the heart to the other. Galen incorrectly described the human jawbone as being made of two bones, like that of a canine and he was completely wrong about the shape of the human liver. Vesalius was also able to demonstrate that males and females have identical numbers of ribs, the biblical orthodoxy was that men had one less because God made Eve from Adam’s rib.

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The frontispiece of the book, showing Vesalius dissecting a body in allegorical surroundings

 

Vesalius then pulls another masterstroke as he goes about publishing this great work, which is essentially the human anatomy in seven books. He employs an artist out of the school of Titian to do the illustrations. These stunningly beautiful drawings of figures striking theatrical poses in classical landscapes grab the limelight, and they will be for ever be known as the muscle men. Vesalius stock rises and he becomes physician at the imperial court of Charles V and later to his son Philip II of Spain. Vesalius is aged 29 and at the height of his powers, 1543 is his annus mirabilis.

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One of the "muscle man" images from the book

The frontispiece of De Fabrica shows Vesalius performing a dissection, centre stage playing to a packed house; it is literally standing room only and an entirely allegorical scene. Three large robed figures loom imposingly at the front, surely a nod to the ancient wisdom of Galen, Socrates and Hippocrates. Right at the epicentre stands Vesalius one hand on the corpse and the other pointing towards the heavens, a good move to be acknowledging God is on his team also.

Then in 1564, he has his annus horribilis and for the man with the surgical Midas touch, it all appears to go wrong. One story suggests he dissected a corpse who wasn’t quite as dead as he might have been and possibly as a form of penance he was advised to do a tour of the Holy Land; a journey from which he would never return. A second possibility is that he fell foul of the Inquisition, causing this empirical man of science to find making the pilgrimage a good idea.

He dies in the same year aged 50 in mysterious circumstances on the Greek island of Zakynthos, his burial site and grave remain unknown. Unlike his working life, which is referenced with earth shattering evidence based medicine; his final year is shrouded in mystery. No monument or memorial depicts his final resting place. Perhaps the only epitaph needed is de humani corporis fabrica. Anatomy and medicine changed forever, his legacy lives even if his name and accomplishments have been lost to most.

By Matt Hunt, Head of Research User Services

07 June 2018

The sixtieth birthday of obstetric ultrasound

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Ultrasound image
Ultrasound image by mylissa, CC-BY-SA

Today is the sixtieth anniversary of the publication in The Lancet of the first scholarly article on medical ultrasound by the obstetricians Ian Donald and John MacVicar, and the engineer Tom Brown. While earlier groups had experimented with ultrasound, it was Donald and Brown who achieved real diagnostic success with it, and popularised it in the medical profession. They initially applied it to distinguish uterine cysts from solid tumours such as fibroids, and later developed it for other important tasks, such as diagnosing placenta praevia (a potentially lethal condition during pregnancy in which the placenta attaches too low down in the womb) and directly observing foetuses. It is thanks to their work that ultrasound has become routine in pregnancy and many peoples' first view of their children. 

Donald had become interested in the potential of ultrasound for medicine thanks to his experience with both radar and sonar while serving in the RAF during World War II. Much of his success was because he happened to work for the University of Glasgow, in a city with a large-scale shipbuilding industry which used ultrasonic techniques to test for flaws in metal parts. It was also the home of Kelvin and Hughes, one of the main manufacturers of ultrasonic testing equipment, for which company Brown worked.

There was also a particular perceived need at the time for a safer method of examining foetuses in the womb, as epidemiological studies had discovered that X-ray examinations during pregnancy led to a higher risk of leukaemia and other cancers in the early lives of the children.

Donald subsequently became a celebrity not just for his scientific and medical skills, but as a prominent medical campaigner against abortion. He frequently stated that his observations of foetuses in the womb had confirmed him in his belief that they qualified as human beings from conception, although unlike some religious pro-life campaigners he morally accepted abortion when the foetus was clearly unlikely to survive childbirth or where the child would be very severely disabled. Brown's career effectively ended with the failure of an attempt to start a business producing medical ultrasound equipment, and he felt later in life that much of the media neglected his vital technological contributions to the development of the idea, although Donald always acknowledged them in public.

Further reading:

Brown, T G. Personal recollections. 1999. Available free online at http://www.ob-ultrasound.net/brown-on-ultrasound.html
Craig, M. Craig's Essentials of Sonography and patient care, Baltimore: Saunders, 2018. Available as an ebook in the British Library reading rooms.
Donald, I, MacVicar, J, and Brown, T G. Investigation of abdominal masses by pulsed ultrasound, The Lancet, 1958, 271(7032), pp. 1188-1195. Available at (P) GP 00 - E(14) and also electronically in the British Library reading rooms.
Nicholson, M and Fleming, J E E. Imaging and imagining the foetus. Baltimore: Johns Hopkins University Press, 2014. Available at YK.2014.a.7586.
Norton, M E. Callen's Ultrasonography in obstetrics and gynecology, Elsevier, 2016. Available as an ebook in the British Library reading rooms.

03 April 2018

Augmented reality - it isn't just for catching mons.

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The most recent GREATforImagination post covered an augmented reality app created by Nexus Studios for the US Presidential administration in 2016. Augmented reality is a halfway point towards the more famous virtual reality, in which CGI elements are added to a real-time image of the user's surroundings, using either a mobile device screen or virtual reality goggles. The most well-known applications at the moment are for entertainment, such as the famous game Pokemon Go, or our own use of it in our Harry Potter exhibition.

 

However, there are some more practical uses for augmented reality in the worlds of science and engineering.

The construction industry still largely uses 2-D documents to indicate what should be built. However, why not create augmented reality images of objects in situ for people to copy? Or why not help utilities workers "see" underground pipes before they start digging holes?

An obvious application is in the world of chemistry, where physical 3-D models of large molecules have been familiar for decades, but can take a long time to build. Digital models can be created much more quickly, and AR equipment allows scientists to interact with them with increasing realism. There's a freeware program to try it yourself, if you have some chemistry and computing knowledge.

AR can also be used in surgery, either for training purposes or to allow surgeons to "see" what they are doing during minimally invasive surgery.

(All the articles linked are open access, so you don't have to come to the Library to read them)