Science blog

Wise Festival - Celebrating the International Day of Women and Girls in Science

Dr Rachel Edwards-Stuart is a renowned Food Scientist and Flavour Expert. She runs a selection of unique and bespoke events around the Science of Flavour and Gastronomy. Since graduating from Cambridge University, Rachel has trained as a chef in Paris, gained a PhD sponsored by Heston Blumenthal, lectured around Europe, appeared on TV and in the national press, set up the London Gastronomy Seminars, taught science to chefs, developed over 100 gluten free products, and helped to stabilise a 5 tonne chocolate waterfall. (To read more about Rachel, see about)

In her break-out session Rachel demonstrates how what you see, hear, touch, smell and taste affects flavour. Learn about the science of the senses, and discover more about how you taste in this interactive journey through flavour perception.

Join us next time to find out more about Back to the Future.

WISE (WOMEN IN SCIENCE EVENTS) Festival, British Library 11 February 2020.

The British Library is joining in the International Day of Women and Girls in Science, celebrating and raising the voices of women in science with a one day mini festival.  Our events and talks will encourage you to laugh, sing and think.  Every few days this blog will look in more detail at the participants and their involvement with the event.

https://www.bl.uk/events/wise-festival

Wise Festival - Celebrating the International Day of Women and Girls in Science

The WISE Festival is in particularly excited to announce Professor Sunetra Gupta as its closing speaker. We will be drawing on Sunetra’s unique perspective combining her scientific work on the evolution of pathogens with her experience as an award winning novelist and translator, to discuss science as a part of our culture and not something that is separate, reserved only for scientists and independent of other human endeavour.  How can we create new links and ways of thinking that can enrich our lives beyond the perceived boundaries of science and arts? Do scientific and literary narratives have anything in common? Can science be beautiful? A perfect reflection at the British Library where different fields of knowledge sit alongside each other, ready for new connections to be made by anyone curious and creative.

Sunetra is an acclaimed novelist, essayist and scientist. In October 2012 her fifth novel, So Good in Black, was longlisted for the DSC Prize for South Asian Literature. In 2009 she was named as the winner of the Royal Society Rosalind Franklin Award for her scientific achievements. Sunetra is Professor of Theoretical Epidemiology at Oxford University's Department of Zoology, having graduated in 1987 from Princeton University and received her PhD from the University of London in 1992. Sunetra was born in Calcutta in 1965 and wrote her first works of fiction in Bengali. She is an accomplished translator of the poetry of Rabindranath Tagore.

See more about Sunetra

Join us next time to find out more about our second plenary speaker Danielle George.

WISE (WOMEN IN SCIENCE EVENTS) Festival, British Library 11 February 2020

The British Library is joining in the International Day of Women and Girls in Science, celebrating and raising the voices of women in science with a one day mini festival.  Our events and talks will encourage you to laugh, sing and think.  Every few days this blog will look in more detail at the participants and their involvement with the event.

https://www.bl.uk/events/wise-festival

The British Library is happy to help promote the CILIP Health Libraries Group annual conference, which will be held at Aviemore in Scotland on 23rd and 24th July 2020. The conference is one of the main events of the year for healthcare librarians, and is aimed at librarians in healthcare organisations and universities, as well as anyone else with a connection to the health sector. Accomodation is included in the booking and an early bird discount is available until 27th March.

The British Library is joining in the International Day of Women and Girls in Science, celebrating and raising the voices of women in science with a one day mini festival. Our events and talks will encourage you to laugh, sing and think. Every few days this blog will look in more detail at the participants and their involvement with the event.

From 1pm drop in to our free Entrance Hall sessions, including fun scientific presentations, hands-on activities and a chance to create your own (bio)selfie using the bacteria swabbed from your cheek. There’s something for all ages and levels of science knowledge. See the full list of activities here.Then join us for an evening of talks to hear from women about their experiences of working in the sciences. This is a ticketed event and tickets can be purchased from our website.

The British Library holds one of the most comprehensive national science collections in the world, ranging from ancient manuscripts grappling to understand different aspects of the world, prior to the development of science as we know it today, to the latest scientific publications deposited at the Library through the electronic legal deposit every day. The British Library preserves the UK scientific record, supports scientific research and enables access to science for all, which includes supporting equality and diversity in science. During 2020 the Library’s exhibition Unfinished Business: The Fight for Women's Rights will be looking into the struggle for women’s rights in all walks of life which includes an ongoing struggle for equality in all areas of science, technology and engineering. The WISE Festival is an opportunity to start our reflection on women’s rights and to celebrate the achievements of women in science in a way that we hope will be fun, inspirational and thought-provoking.

Join us next time to find out more about Sunetra Gupta.

WISE (WOMEN IN SCIENCE EVENTS) Festival, British Library 11 February 2020.
www.bl.uk/events/wise-festival

To replace the Leonardo da Vinci items that are usually in our Treasures gallery, but are now in the stand-alone "A Mind in Motion" exhibition, our Manuscripts and Incunabula curators have selected some less well-known but very interesting items dealing with the connection between art and science in the Renaissance. On the pure art side are some works by Albrecht Dürer and Michelangelo, but this post is about three volumes of Renaissance science. They sum up the way that humanists during the Renaissance sought to synthesise the existing knowledge of medieval Europeans with rediscovered Classical texts, many of which had been lost in Europe but preserved by Arabic scholars, and further advances that had been made in the Arabic world.

Depiction of edelweiss from the Codex Bellunensis.

The first item, shelfmark Add MS 41623, is the "Codex Bellunensis", a bound manuscript of herbal material in Latin with some Italian notes. Much of the content is based on De Materia Medica by Pedanius Dioscorides, a famous Greek physician of the first century CE. De Materia Medica was the single most important herbal text in Europe from its writing until the nineteenth century. "Bellunensis" refers to the town of Belluno in Italy, north of Venice, where the manuscript may have been created. The page to which the manuscript is opened in the display shows what is thought to be the first artistic representation of edelweiss, used to treat abdominal and respiratory diseases. The other herbs shown on this spread are valerian, an early sedative, eupatorium, and agrimony. The whole manuscript can be read free online .

The second item, shelfmark Royal MS 12 G VII, is a fifteenth-century Latin copy of Kitab al-Manazir, or "Optics", and another short work, by the great Arab scientist Hasan Ibn al-Haytham, known in Renaissance Europe as Alhazen. The pages on display deal with binocular vision and how the visual axes of the eyes intersect. The book was the first to empirically demonstrate that sight occurs when light reflected from an object enters the eye. Many early classical thinkers had believed that vision worked by the eye emitting some kind of "ray of sight". The book also includes "Alhazen's problem", a geometrical problem involving finding the point on a spherical mirror that a light ray from a given location must strike to be reflected to a second given location. This would not be completely solved algebraically until 1965. The copy on display comes from the Royal Manuscripts collection, a collection of manuscripts and printed books donated by King George II to the British Museum (not to be confused with the King's Library collection housed in the centre of the building, which was donated later by George IV).

Illustration from the Phaenomena

The third of these items, shelfmark Add MS 15819,  is a manuscript copy of the Phaenomena by Aratus of Soli, a Greek poet of the early third century BCE. This is a long poem with one section describing the constellations of the stars, and a shorter second section on weather forecasting based on observations of the heavenly bodies and animal behaviour. You can read a public domain English prose translation of the poem at the Theoi Project, although we have two copies of the most recent English translation by Douglas Kidd in our collections. Our copy is a manuscript of the Latin translation of the poem by the Roman general Germanicus Julius Caesar, the nephew of the emperor Tiberius and father of Caligula. Our manuscript dates from the fifteenth century and once belonged to, and was probably written for, Francesco Sassetti, a senior manager in the Medici Bank.

Posted by Philip Eagle, with thanks to Eleanor Jackson, Curator of Illuminated Manuscripts, and Karen Limper-Herz, Lead Curator Incunabula and Sixteenth-Century Books.

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.

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).

Handwritten diary heading giving location and date

.
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).

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).

Hand-drawn "tree of life" diagram

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).

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.

From Lloyd's List 13th January 1883, shelfmark LOU.LD21

Among the exhibits in our Writing: Making Your Mark exhibition is this advertisement for a "Remington Perfected Typewriter". Guest blogger James Inglis, from the University of St Andrews and the National Museum of Scotland, wrote this guest post for us on how far it was from "perfected".

In 1878, American sewing machine and gun manufacturers E. Remington and Sons released the Remington Standard No. 2. Often regarded as the first commercially successful writing machine, the No. 2 Typewriter incorporated many features of typewriters that we are familiar with today. The No. 2 was the first machine to use a shift mechanism; based on patents by Lucian S. Crandall and Byron Brooks in 1875, this allowed the user to change between upper and lower-case letters. The No. 2 also showcased a QWERTYUIOP keyboard, which was first introduced on Remington’s Sholes and Glidden Type-Writer released in 1874. Today the QWERTY keyboard is ubiquitous across computers and smart devices.

The No. 2 Typewriter was followed by the Perfected No. 2 Typewriter in 1879, which ironed out some of the technical bugs with the original design. Adverts for the Remington Perfected Typewriter proudly stated that “it is to the pen what the sewing machine is to the needle”, reinforcing Remington’s role in the development of sewing machines and typewriters. The No. 2 Typewriter was so successful that Remington continued manufacture for 16 years. By the time the No. 2 typewriter was withdrawn in 1894 almost 100,000 machines had been sold: it was easily the most successful typewriter up to that point. 

Yet for all its success, there was one glaring problem with the Remington Perfected Typewriter. This was a drawback that beset all Remington typewriters in the late 19th and early 20th centuries. The No. 2 was a blind writing typewriter. In other words, the writing was not visible as you were typing it!
To understand the blind writing typewriter design, the images below show a No. 2 Typewriter from the National Museum of Scotland’s collection. The carriage of the No. 2 Typewriter is raised to reveal the circular arrangement of typebars known as the typebasket. At the end of each typebar are letters, numbers or symbols cast in relief. Each typebar carries two characters which are selected by using the shift key. Upon pressing a particular key, a system of wires pulls the corresponding typebar upwards, out of the typebasket so that it comes into contact with the inked ribbon directly beneath the underside of the platen (the roller around which the paper is wrapped). The pressure of the typebar through the ribbon leaves an imprint on the paper and the character is formed!

Remington No. 2 Typewriter manufactured c. 1887. Held at National Museum of Scotland’s Collection Centre. Object reference T.1960.34.

The problem is that when the carriage is lowered the typebars are concealed. The characters are formed on the underside of the platen, out of the operator’s sight. The typist can only see what is written three or four lines later, once the platen has rotated around enough to reveal their previous work.

Remington No. 2 with carriage raised revealing the inked ribbon and type-bar basket. Object reference, T.1960.34

View from above showing how the typebars strike the ribbon from below

The video below show how pressing the keys lifts the typebars out of the typebasket and brings them into contact with the ribbon.

For inexperienced typists the amusing results of this drawback were illustrated in the article ‘The Type-Writer and Type-Writing’ published in The Girl’s Own Paper on August 18th, 1888. The article describes how, “During the first week or two the learner’s attempts will probably be something like the following”:  

Type sample of an inexperienced typist, from an article in The Girl’s Own Paper, Saturday, August 18, 1888, BL shelfmark P.P.5993.w.

The fourth line is particularly bemusing and is caused by the operator typing straight over the previous sentence. Clearly, the typist did not return the carriage correctly in order to start a new line. These kinds of mistakes went unnoticed because the text was completely out of sight.
Yet the common argument was that a properly trained typist shouldn’t need to be able to see their work. A contemporary account of typewriters from Encyclopedia Britannica insisted:

Doubtless the novice who is learning the keyboard finds a natural satisfaction in being able to see at a glance that he has struck the key he was aiming at, but to the practical operator it is not a matter of great moment whether the writing is always in view or whether it is only to be seen by moving the carriage, for he should little need to test the accuracy of his performance by constant inspection as the piano player needs to look at the notes to discover whether he has struck the right one.

The reality of course was somewhat different, and typists of all levels found ways of getting around the problems with blind writing typewriters. The most popular solution was to stop and check on the progress of writing. Typewriters like the No. 2 came with carriages that could be raised and lowered on a hinge for basic operations such as loading the paper and changing the ribbon.
 
The film below, courtesy of British Pathé, shows a typing pool from around 1905. The typists regularly lift the carriage on the typewriters to check on their work.

Raising and lowering the carriage to check what was typed became a routine part of a typist’s work. While this got around the problem of writing visibility this technique was highly inefficient. As typewriter chronicler and inventor Henry Charles Jenkins commented in a paper to the Society of Arts in 1894:  

The Remington, Caligraph, Smith-Premier, Densmore, and Yost machines all have means by which the paper carrier or holder can be turned over upon some kind of hinge, and the writing, which has been performed under and out of sight, is brought into view. Operators get used to this, that they scarcely know how often they do it, but it must consume much time.

Unsurprisingly, rival typewriter manufacturers developed machines where the writing was always visible. The first visible writing typewriter was the Horton released in 1883. A circular introducing the Horton announced: “In the Horton Typewriter has been fully attained… the invaluable object of having all the writing, to the last word, visible to the eye of the operator”. Of the many individuals this will benefit the advert claimed:

It will especially commend itself to those, such as clergymen, journalists and writers generally, who use writing machines in original composition. In the use of machines in which the writing is out of sight much time is necessarily lost in turning up the printing cylinder to get at the run of a sentence construction of which has escaped from the memory; and then, when this has been ascertained and the printing cylinder turned down again, the last word is perhaps forgotten before the rest of the sentence has been formed in the mind, so that the printing cylinder has to be turned up a second time before the writer is able to make any further progress.

Preliminary circular for the Horton typewriter c. 1885

Despite these benefits, the Horton achieved very little success and it was not until the 1890s that visible writing typewriters gained much popularity. One particularly successful machine was the Oliver. The Oliver used U-shaped typebars that struck down on the paper from the right and the left. The video below shows an Oliver Visible No. 3 manufactured in 1904.

The machine that changed the state of the play more than any other was the Underwood. Invented by Franz Xavier Wagner in 1892, and manufactured by the Wagner Typewriter Company, this machine has been described as “the first truly modern typewriter”. In 1895, the patent rights were bought by John T. Underwood, marking the birth of the Underwood Typewriter Company. The Underwood was a front-strike typewriter. That is, the typebars hit the front of the platen leaving the text in full view of the operator.

Underwood Typewriter manufactured c. 1905. Held at the National Museum of Scotland’s Collection Centre. Object reference, T.1934.212

Finally, in 1908 Remington brought out its own front-strike, fully visible typewriter: the Remington Model 10.  The perfected, Perfected Typewriter you might say.

In an advertising pamphlet titled ‘Miss Remington Explains the New Model No. 10’, Miss Remington assures readers: “Yes, I am using one of the new No. 10 Remington Models, and I never supposed that it would be possible to combine so many good things in one machine.”

‘Miss Remington explains the New Model No. 10 Typewriter’ c. 1908. An advertising pamphlet held at the National Museum of Scotland’s Collection Centre.

Yet Miss Remington makes no mention of the move from the blind writing, up-strike design of the Remington no. 9; to the front-strike visible writing set-up of the Model 10, which was arguably the biggest change in design since the introduction of the shift key 30 years earlier. Instead, Miss Remington makes vague comments such as “It has all the splendid points that my old Remington had and a dozen others that no writing machine has ever had.”

By 1908, the Remington Typewriter Company had been supporting their blind writing typewriter design for over a quarter of a century. While market pressures forced the company to change to the new and more popular visible writing system, it was too much of a climb down for Remington to admit that the old blind writing typewriters they had promoted and sold for so long, were far from perfect!

Sources
Michael H. Adler, The Writing Machine. London: Allen & Unwin, 1973. BL shelfmark X.620/7108
https://www.antikeychop.com/

James Inglis, The University of St Andrews and the National Museum of Scotland

Posted by Philip Eagle, Subject Librarian STM

Copyright James Inglis, posted by the British Library under a Creative Commons CC-BY-NC license. All illustrations are copyright James Inglis or public domain.

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,

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. 

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: 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.

Strange cauliflower shapes. Detail from Anne McLaren’s ‘UCL Embryo Transfer’ laboratory notebook, 1953-1956. Copyright estate of Anne McLaren (Add MS 83843).

‘Ghosts’, or disappearing, eggs. Detail from Anne McLaren’s ‘UCL Embryo Transfer’ laboratory notebook, 1953-1956. Copyright estate of Anne McLaren (Add MS 83843).

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.