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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,

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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.

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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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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

24 November 2018

Psychology Resources and Research Methods Workshop for Scholars

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Drawing-of-the-new-British-Library-building-from-Ossulston-Street-by-Colin-St-John-Wilson-c1991

Image source: British Library Press Images

London is blessed with a rich seam of psychology research collections represented by the British Library and the London Psychology Librarians’ Group institutions.

Together curators, reference subject specialists and psychology librarians support students, researchers and professionals in advancing our understanding the the mind, brain and behavior.

You are warmly welcome to a free workshop on Monday 3 rd December at the British Library in the afternoon, focusing on psychology research resources in London.

Monday 3 December (14.00-17.00)

This workshop, for registered Readers (and those who would find it useful to register as readers for their research needs) takes place in the Eliot Training Room in the Library’s Knowledge Centre. The workshop programme is:

Part 1: Welcome to the Library and introduction to the London Psychology Librarians Group:

  • Qualitative methods in psychology research; Christine Ozolins, Neuroscience researcher, Birkbeck College
  • Psychology collections: the London Landscape; Mura Ghosh, Research Librarian, Senate House Library

14.50-15.30 Tea break (Tea provided)

Part 2 British Library Psychology Resources and Information Literacy:

  • Information literacy for psychology research; James Soderman/Paula Funnell, Liaison Librarians, Queen Mary College
  • The post graduate psychology student voice; Holly Walton, Psychology post graduate representative
  • Psychology resources in the British Library; Paul Allchin, British Library, Reference specialist,

16.30-17.00: Question & answer session.

To find out more or to book a place, please email us at: ReferenceServicesTraining@bl.uk or speak to a member of staff at the Science Reference Desk.

The speakers will share their expertise on the what, where, and how of psychology research in London based libraries and the research needs of students and researchers generally.

BL flickr 11004937825

Image source: https://www.flickr.com/photos/britishlibrary/11004937825/

Posted by Paul Allchin - Reference Specialist, Science.

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.

PEXP_Sub_Cvr
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

15 October 2018

Stephen Hawking - the last publications

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Hawking Brief Answers
Philip represented the Library at the launch of Professor Stephen Hawking's last, posthumous, popular work, Brief Answers to the Big Questions. The book, which Hawking was writing at the time of his death, includes ten essays summarising his views on the ten questions which he was most frequently asked in interviews or at public events, such as "Is there a god?", "Is time travel possible?", and "Will we survive on Earth?".

Additionally, the launch saw discussion of Hawking's last published scholarly work, a paper dealing with the so-called "Information Paradox of Black Holes", the fact that Hawking's model of black holes, in which all information is lost when matter is sucked into a black hole contradicts a major principle of quantum mechanics, that information about a system cannot be permanently lost. Malcolm Perry and Andrew Strominger, two of Hawking's collaborators on the paper, also took part in the discussion.

A preprint of this paper is currently available on ARXIV at https://arxiv.org/abs/1810.01847, meaning that both extremes of Hawking's career are free to read online, his PhD thesis being available on the University of Cambridge's Apollo scholarly repository, at https://www.repository.cam.ac.uk/handle/1810/251038.

Posted by Philip Eagle, Subject Librarian - STM

17 August 2018

The 150th anniversary of the first observation of helium

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Saturday is the 150th anniversary of a total eclipse of the Sun that was seen across a wide band of Asia on 18th August 1868. Any total eclipse is interesting, but this one is particularly historic for chemists, as it was during this eclipse that observations were made that, with hindsight, led to the discovery of helium, the first element to be discovered in space before it was found on Earth.

NASA eclipse
Image of total solar eclipse in 2017, photographed by Carla Thomas. Copyright NASA

However, the story often told in encyclopaedias, that Pierre Janssen and Norman Lockyer discovered helium by observing the 1868 eclipse, is far too simple. In fact, Janssen, who was in India and is often credited with the discovery, was interested in completely different things, and never claimed any credit during his lifetime, Norman Pogson, who was in India and was the first person to speculate that something unusual might be happening, was forgotten, and Norman Lockyer, who is often credited as the co-discoverer and made the biggest contribution, wasn’t in India and made his discoveries without needing the eclipse.

Helium is the second-most-common element in the universe after hydrogen, but is very rare on Earth, and odd in other ways. It is one of the so-called “noble gases”, that, because they have a particular number of electrons, are uniquely happy to exist as single atoms and reluctant to react with other elements. Helium only exists on Earth because it is given off when many radioactive elements naturally decay. Once produced, because it is so light and so non-reactive, it usually flies straight out of the atmosphere and vanishes into space. It only stays on Earth if it is produced deep underground and trapped within rocks. However, helium is very common in stars, including our Sun, because the energy of most stars comes from hydrogen atoms being fused into helium, and stars’ greater gravity than the Earth keeps it in.

So how was it possible to find helium in the Sun by looking at eclipse light?

For reasons too complicated to explain here, electrons in atoms and molecules can only have certain precise amounts of energy. They can climb from one amount to a higher one by absorbing a photon of light, or drop to a lower one by emitting a photon of light. The amount of energy contained in a photon varies according to the wavelength of the light, and so this means that atoms or molecules can only absorb or emit light of very specific wavelengths. As a result, if you shine a light through a particular substance, the light that comes out will have certain wavelengths and colours of light reduced or missing (an absorption spectrum), and if you heat up a substance to the point that it starts glowing, the light produced will be mainly or only of the same specific wavelengths and colours (an emission spectrum). By studying the light absorbed or emitted by a substance, we can derive a lot of information about what it is and what its structure might be.

The first step in the story of the discovery of helium happened in 1814, when the lens-maker turned physicist Joseph Fraunhofer split sunlight using a telescope, prism, and diffraction slit to create a spectrum broad enough to notice that there were dark lines, so-called "Fraunhofer" lines, where particular wavelengths of light were simply not present. In 1834, David Brewster suggested that the Fraunhofer lines were due to light of specific wavelength being absorbed by gas either within the Sun or in the Earth's atmosphere. James D Forbes suggested that the dark lines could be proved to originate from the Sun rather than the Earth's atmosphere by observing light from the edge of the Sun's disc during an eclipse - as this passes through more of the Sun's atmosphere on its path to the observer, the lines will be stronger if they are produced by the solar atmosphere.

Physicists and chemists began studying the absorption and emission spectra of known substances and found that their characteristic lines were constant. In 1857 William Swan showed that particularly strong dark lines in the yellow region of the Sun's spectrum, known as the D lines, corresponded to the emission spectrum of sodium - something we are all familiar with now given the yellow tinge of sodium-vapour streetlights.

In 1859, Gustav Kirchhoff and Robert Bunsen (of gas burner fame), at the University of Heidelberg, were among the scientists who were making systematic studies of the spectra of different elements. When a major fire broke out in the city of Mannheim, across the valley, they playfully turned their spectroscope on the light from the flames, and were able to identify the characteristic emission spectra of strontium and barium. This experience made them realise that, if they could discover trace elements in a burning building, the Fraunhofer lines might be the key to discovering the elements present in the Sun.

The following year, the two were studying the spectrum of mineral water from a major local spa, Bad Dürkheim. They spotted two blue lines that were found in the spectrum of no known substance, and guided by this managed to prepare and purify compounds of a previously unknown element, caesium. This was the first new element to be discovered using spectroscopic methods. Within the next few years, Kirchhoff and Bunsen would discover rubidium by a similar route, and William Crookes would discover thallium.

In 1868, a total eclipse of the Sun was predicted to occur in India. The eclipse ws expected to have six minutes of totality, an extremely long time by the usual standards in which to perform observations. Spectroscopists were particularly interested in the eclipse, as with the main part of the Sun obscured from the Earth it would be possible to study the light from the Sun's outer atmosphere, potentially helping to investigate both the Sun's chemical composition and its internal structure.

The French astronomer Pierre Janssen had already made his name in the field of the solar spectrum. He had invented a much-improved astronomical spectroscope with the instrument maker Ignazio Hofmann, although the two men quickly fell out bitterly about whose contribution was greatest. In 1866 he had captured the absorption spectrum of water vapour, by a logistically challenging experiment in which he viewed the light given off by sixteen gas burners through long iron pipes filled with high-pressure steam, and verified which of the Fraunhofer lines were produced by it as sunlight passed through the Earth's atmosphere. He was selected by the French Bureau of Longitude to make a government-funded trip to India.

Science Museum spectroscope
1880 automatic spectroscope by John Browning. Image by Science Museum, released under a CC-BY-NC-SA licence

Meanwhile, the government of the British Empire, rulers of India at the time, were making their own plans for scientific observations of the eclipse. The main expedition, led by Major James F Tennant, headed for the town of Guntur in Andhra Pradesh, in Southeastern India. Meanwhile, Norman Pogson, director of the Madras Observatory, headed to Machilipatnam (then known to English-speakers as Masulipatam), closer to the coast. When Janssen arrived in India, he also considered Machilipatnam, but decided that on the coast there was too much risk of fog and cloud. He decided to go to Guntur as well, possibly because it had at one time been ruled by the French and there were still some wealthy French merchants living there. Tennant's team moved into the British government compound, while Janssen set up at the home of one Jules Lefaucheur. Janssen generously helped Tennant to set up his spectroscope and telescope.

When the eclipse occurred, all the investigators paid attention to the spectrum. Janssen did not mention anything unexpected. Tennant saw an orange line which he thought was the normal sodium D line. Only Pogson saw something unusual - a third line close to the sodium D line, but not identical with it.

Pogson report
Pogson's eclipse observations, from his printed report.

It was not until the following days that Janssen made the realisation that would be his real breakthrough of the event, and the one that popular history would later confuse with the discovery of helium. He realised that the emission spectrum of the solar atmosphere and prominences was so strong that, if one could focus the spectroscope on the precise edge of the Sun, they might be visible even without an eclipse. He experimented and found that it was entirely possible, but was easiest if you moved the spectroscope to try to find the spectrum, rather than trying to focus visually on the edge of the Sun. He excitedly wrote to his wife in a letter, "They sent me to observe the eclipse for five minutes, and I am bringing back a perpetual eclipse from India." Finally, he sent a letter to the Academy of Sciences, announcing his discoveries for the first time.

Back in London, Norman Lockyer, a civil servant and prominent amateur astronomer, with a great interest in studying the Sun, was independently realising that the spectrum of the outer atmosphere of the Sun could be viewed by accurately focussing a spectroscope, without any need for an eclipse. He also seems to have somehow got a copy of Pogson's report with its reference to a previously unidentified line in the spectrum. In October, he received a new spectroscope and managed to focus on the solar atmosphere and obtain its emission spectrum. He also noticed a new line near the D line. Among the organisations he sent preliminary reports to was the French Academy of Sciences, his letter arriving within a few days of Janssen's report from India, both being read out at the same meeting on 26th October. In 1872, to avoid a potentially ugly interpersonal and international row, the French government issued a medal featuring both Janssen and Lockyer to commemorate their solar discoveries.

By the end of the year, both Janssen and Lockyer were convinced that the yellow line near the sodium D line was new. Lockyer and the chemist Edward Frankland spent some time experimenting with the spectrum of hydrogen under different conditions, and by the end of it were convinced that the Sun consisted mostly of hydrogen, but the the yellow line could not be produced by that element. By 1871 Lockyer was convinced that the yellow line was produced by a new element never found on Earth which he named "helium", but did not make such an extreme speculation in public, only in private communications with other scientists. The first public statement of it is believed to have been in Sir William Thompson's presidential address to the British Association for the Advancement of Science in 1871. This concluded the series of events that led, in later years, to Janssen and Lockyer wrongly being jointly credited with the discovery of helium in 1868.

Why was Pogson forgotten, even though Lockyer credited him in his own brief memoir of the discovery of helium, in Nature in 1896? Although he is now remembered for his development, earlier in his career, of a scale for the apparent magnitude, or brightness of astronomical objects, his career in India was not a success. He seems to have suffered from social snobbery due to his middle-class background and lack of a university degree, but he was also a somewhat abrasive personality, as can be seen from the negative comments in his report on the "needless and lavish expenditure" on the various expeditions to view the eclipse, and the even more offensive remarks about the local Indian people in general, which I will not quote in detail here. Another item in the India Office records shows his conflict with the government and the Dutch astronomer Jean Oudemans over longitude measurements that he did not consider particularly important and delayed in analysing. Pogson's report on the eclipse was not published in a peer-reviewed journal, but in a low-profile government publication - Pogson himself complained in a letter in 1882 that it had been treated as "waste paper".

Helium was subsequently shown not just to exist in the Sun, when in 1876 the French astronmer Alfred Cornu observed it in the spectrum of a star in the Cygnus constellation. In the meantime, however, speculation on new elements in the stars had become somewhat wild and uncontrolled, developing a bad name due to multiple announcements of "new elements" that proved too frequent to be credible. (One of the most notorious was "coronium", assigned to a spectral line from sunlight at 5303 angstroms wavelength, which was eventually discovered to come from very highly-ionised iron atoms.)

In 1887, William Hillebrand discovered a mysterious gas while treating uranium ore with acid, that he suspected to be nitrogen. He noticed that its spectrum did not match that known for nitrogen, but did not realise that it was a new element, as at the time it was known that the spectrum of nitrogen could vary considerably with the conditions. In 1895, Baron Rayleigh found that nitrogen extracted from the atmosphere had a different molecular weight to chemically-produced pure nitrogen, and suspected that another element was present. He investigated further, and managed to purify a completely new element, which he named argon. William Ramsey, who was working with Rayleigh on argon, was shown Hillebrand's paper by another colleague who thought Hillebrand's gas might have been argon as well. He repeated Hillebrand's experiment with a different type of uranium ore, and discovered that the gas he produced was much lighter than argon, and had a spectrum that included the D3 line of the mysterious solar element helium. Helium had finally been discovered on Earth.

But scientific research on the Sun continues - this week NASA launched its Parker Solar Probe, to become the first human-created object to enter the Sun's outer atmosphere and observe it.

Sources and further reading:

Janssen, P J, The total solar eclipse of August 1868. Part I, Astronomical Register, 1869, 7(77), pp. 107–110. Shelfmark PP.1556 or 1755.800000
Janssen, P J, The total solar eclipse of August 1868. Part II, Astronomical Register, 1869, 7(78), pp. 131-133 Shelfmark PP.1556 or 1755.800000
Lockyer, J. N. The story of helium, Nature, 1896, 53(1371), pp.319-22. Shelfmark P.P.2011c or (P) BX 80-E(3). Also available online in BL Reading Rooms
Nath, B B. The story of helium and the birth of astrophysics. New York City: Springer, 2013. Available online in British Library Reading Rooms.
Pogson, N R. Report of the Government Astronomer upon the proceedings of the Observatory in connexion with the total eclipse of the Sun on August 18th, 1868, as observed at Masulipatam, Vunpurthy, Madras and other stations in Southern India. Madras: Madras Observatory, 1875. Shelfmark IOR/V/27/430/8.
Pogson, N. R. Letter to Captain Awdry, 10th June 1882, in Grant Duff Collection, Miscellaneous English Correspondence, pp. 96-98. Shelfmark Mss Eur F/234/67
Ramsay, W. Helium, a gaseous constituent of certain minerals, Part I Proceedings of the Royal Society, 1895, 58 pp. 80-89. Shelfmark Ac.3025/21 or (P) JA 00-E(12). Also available free online at https://www.jstor.org/stable/115763
Reddy, V., Snedegar, K.. Balasubramanian, R. K. Scaling the magnitude: the fall and rise of N. R. Pogson, Journal of the British Astronomical Association, 2007, 117(5), pp. 237-245. Shelfmark Ac.4176, (P) OT 00-E(34), or 4713.000000

Posted by Philip Eagle. Thanks to Margaret Makepeace for help in researching India Office records.

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)

30 November 2017

Digital preservation and the Anne McLaren Papers

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Today on International Digital Preservation Day we present a guest-post by Claire Mosier, Museum Librarian and Historian at American Museum of Western Art: The Anschutz Collection, concerning the digital files in the Anne McLaren Supplementary Papers (Add MS 89202) which have just been made available to researchers. As an MA student Claire worked as an intern at the British Library in 2015 helping to process digital material.

 

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Dame Anne McLaren. Copyright James Brabazon

 
The developmental biologist Dame Anne McLaren was a great proponent of scientists sharing their work with the general public, and gave many presentations to scientists as well as the general public. Some of the notes, drafts, and finished products of these presentations are on paper, and others are in digital formats. The digital files of the Anne McLaren Supplementary Papers are comprised mostly of PowerPoint presentations and images. Digital records are more of a challenge to access, and give readers access to, as they are not always readily readable in their native format. This leads to unique challenges in determining and making available the content. 
 

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‘HongKong2003Ethics.ppt’ Page from the presentation ‘Ethical, Legal and Social Considerations of Stem Cell Research’, 2003, (Add MS 89202/12/16). Copyright the estate of Anne McLaren.

 Throughout her career, McLaren gave presentations not only for educating others about her own work, but also on the social and ethical issues of scientific research. Many of her PowerPoint files are from presentations between 2002 and 2006 and cover the ethical, legal, moral, and social implications around stem cell therapy. These topics are addressed in the 2003 presentation ‘Ethical, Legal, and Social Considerations of Stem Cell Research’ (Add MS 89202/12/16), which briefly covers the historic and current stem cell research and legislation affecting it in different countries. A presentation from 2006 ‘Ethics and Science
of Stem Cell Research’ (Add MS 89202/12/160) goes into more detail, breaking ethical concerns into categories of personal, research, and social ethics. As seen in these presentations and others, Anne McLaren tried to present material in a way that would make sense to her audience, some of the presentations being introductions to a concept for the more general public, and others being very detailed on a narrower subject for those in scientific professions. 

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‘Pugwash 2006’ Page from the presentation ‘When is an Embryo not an Embryo’, 2006, (Add MS 89202/12/163). Copyright the estate of Anne McLaren.

 From looking at her PowerPoint documents it seems McLaren’s goals were to educate her audience on scientific ideas and encourage them to think critically, whether they were scientists themselves or not. However, this is hard to confirm, as the PowerPoints are only partial artefacts of her presentations, and what she said during those presentations is not captured in the collection. While she did sometimes present her own views in the slides, she presented other viewpoints as well. This is seen in the presentation for the 2006 Pugwash Conference (Add MS 89202/12/163) titled ‘When is an Embryo not an Embryo’ which presents semantic, legislative, and scientific definitions of the term embryo before a slide reveals McLaren’s own views, then goes back to legislative definitions before the slideshow ends. The Pugwash Conferences on Science and World Affairs were created to ensure the peaceful application of scientific advances, and McLaren was a council member for many years.

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Both the newly released Anne McLaren Supplementary Papers (Add MS 89202), along with the first tranche of McLaren’s papers (Add MS 83830-83981) are available to researchers via the British Library Explore Archives and Manuscripts Catalogue. Additionally one of Anne McLaren’s notebooks containing material from 1965 to 1968 (Add MS 83845) is on long-term display in the British Library’s Treasures Gallery.

10 November 2017

Using science to build international relations: a short introduction to science diplomacy

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Today, on World Science Day for Peace and Development, scientists and policymakers attending the World Science Forum in Jordan are discussing the role science can play in nurturing diplomatic relations.

Science diplomacy is an umbrella term for a wide range of activities in which science and technology are leveraged to foster ties between nations. Governments are aware that collaborating with international partners to achieve scientific goals can further their national interests. Consequently they are paying increasing attention to the idea of science as a diplomatic tool.

How is it practised? On a bilateral level diplomats co-ordinate scientific agreements which commit signatories to pooling resources by sharing knowledge and collaborating on research projects. Such agreements can open up opportunities for product development and trade deals, and are becoming an important part of the UK’s strategy to expand its research and innovation horizons post-Brexit.

Jo Johnson Ruth Garber
Jo Johnson (UK Minister of State for Universities, Science, Research and Innovation) and Judith G. Garber (U.S. Acting Assistant Secretary of State for Oceans and International Environmental and Scientific Affairs) signed the first U.S.-UK Science and Technology Agreement on 20 September 2017 in Washington, D.C. The UK is putting £65 million into the Deep Underground Neutrino Experiment (DUNE). Photo credit: STFC/FCO

Science is a global enterprise in which international collaboration is the norm. In particular multinational teams are needed to run large experimental facilities such as the European Organization for Nuclear Research (CERN) which are beyond the scope of individual countries. One of the by-products of these neutral working environments is science diplomacy. Scientists can develop long-lasting, cross-cultural relationships that sometimes help to bridge difficult political situations from the bottom up. Proposals for these huge infrastructure projects are often driven by an incentive to stimulate co-operation as much as for a need to build scientific capacity.

This was the case for the SESAME synchrotron which opened earlier this year in Jordan. The synchrotron’s powerful light source can be used to study the properties of a range of different materials, attracting researchers from across the Middle East, including Iranians, Israelis and Palestinians.

SESAME construction
Countries from across the Middle East have come together to build SESAME. Photo credit: SESAME

Science diplomacy also comes into play in resolving sensitive international disputes. When negotiations to limit Iran’s nuclear programme stalled, credit for their successful conclusion went to the two physicists, one Iranian and one US, who worked out the scientific details of the 2015 deal.

Four negotiators
The scientists and Ministers who negotiated the Iran deal: US Energy Secretary Ernest Moniz, US Secretary of State John Kerry, Iranian Foreign Minister Javad Zarif and Vice President of the Iranian Atomic Energy Organization Dr Ali Akbar Salehi. Photo credit: U.S. Mission Photo/Eric Bridiers

Scientists and diplomats also work together in addressing global issues such as climate change, antimicrobial resistance or cross-border public health crises. Using scientific evidence is fundamental when negotiating coherent responses to shared challenges, and government science advisers are seen as a key mechanism in getting science into policymaking. Gradually foreign ministries around the world are appointing their own science advisers to channel scientific research into the work of their departments.

Various strategic funding programmes, some of which focus on meeting the UN’s sustainable development goals, support the aims of science diplomacy. These international collaborative projects generate the necessary evidence to inform policymaking while also stimulating partnerships that foster trust between nations.

Climate ready rice Newton Prize
The Newton Fund project ‘Climate Ready Rice’ is being conducted by scientists from Sheffield University in the UK, Kasetsart University in Thailand and the International Rice Research Institute (IRRI) in the Philippines.Photo credit: IRRI

It is unclear how to evaluate the impact of science diplomacy activities, but participants agree that they only work when based around excellent science that generates mutual benefits.

Emmeline Ledgerwood is an AHRC collaborative student with the British Library Oral History department and the University of Leicester. She is preparing a policy briefing on science diplomacy as part of an AHRC-funded policy fellowship at the Parliamentary Office of Science & Technology (POST). The briefing will be published by POST in December 2017.

POST runs several fellowship schemes with Research Councils, learned societies and charities, through which PhD students are sponsored to spend (usually) three months working at POST. Some fellowships are also open to postdoctoral researchers in academia and industry.  

You can follow @EmmeLedgerwood and @POST_UK on Twitter.

The statements and opinions expressed in this piece are those of the author alone, not of the Parliamentary Office of Science and Technology.