Science blog

The first page of the letter from Caroline Herschel on display in the Treasures Gallery

Happy birthday Caroline Herschel!

Today is the 270th anniversary of the birth of the German-born British astronomer Caroline Herschel, who discovered eight comets and fourteen nebulae. She also produced an expansion and correction of the previous main British star catalogue, created in the late seventeenth and early eighteenth century by John Flamsteed, and made substantial contributions to the catalogue of nebulae and star clusters published after her death by her nephew John F W Herschel. She made heavy contributions as well to the work of her elder brother William Herschel, famous as the discoverer of Uranus.

Caroline Hershel was born in 1750 in Hannover in Germany, the daughter of a military musician. As the youngest daughter of her family, it was assumed by convention at the time that she would devote her life to helping her mother maintain the home and look after her father and elder brothers, which she resented. Her escape from this came when her brother William invited her to move to England and join him in Bath, where he was working in the family tradition as a musician. Caroline became a promising singer, but when her brother shifted his interests from music to astronomy he assumed once again that she would naturally help him in his own career. Over the years, despite this unwilling beginning, she became genuinely enthusiastic for the subject. In 1782, William was appointed Royal Astronomer by George III (not to be confused with the older position of the Astronomer Royal at Greenwich) and the pair moved to Datchet near Slough, to be closer to the royal home at Windsor. In 1787, William pursuaded the King to pay Caroline a salary in her own right, making her the first woman in Britain to be employed as a scientist.

The work was not just intellectual but physically demanding. William and Caroline had to construct their own telescopes and spend hours in the open air at night making observations. William's telescopes were some of the largest in the world at the time, being from twenty to forty feet in length. On one occasion, Caroline fell and impaled her leg on part of a telescope, losing a two ounce lump of flesh and suffering an injury which a military surgeon later told her would have entitled a soldier to six weeks spent in an infirmary.

Caroline's contributions have traditionally been undervalued due to a mixture of her personal shyness (coupled with disdain for people who she considered intellectually inferior) and her willingness to publicly depict herself as merely a submissive helpmeet to her brother, to avoid controversy, which were played up by subsequent commentators who wanted to depict her as conventionally feminine. Letters to her family which we hold here at the BL reveal her as a rather more strong-willed person, with a sardonic sense of humour.

After William's death in 1822, Caroline moved back to Hannover, where the position of her home in the centre of the city prevented her from much astronomical observation. In response, she devoted herself to compiling the catalogue of nebulae and star clusters. She died in 1848, increasingly physically frail in her later years but mentally sharp until the end.
We hold three copies of the first edition of Caroline Herschel's catalogue of stars, at the shelfmarks L.R.301.bb.2, 59.f.4, and B.265. The copy at L.R.301.bb.2 bears the bookplate of Charles Frederick Barnwell, at one time assistant keeper of antiquities at the British Museum, and is bound with a copy of the star catalogue of Francis Wollaston, another astronomer of the same era.

The letter from Caroline Herschel currently displayed in the Treasures Gallery is taken from the section of the Charles Babbage papers dealing with astronomy, Add MS 37203. It is a copy of a letter originally sent to Nevil Maskelyne, the Astronomer Royal of the era, who was one of the few friends who Caroline was comfortable enough with to make an extended visit to. Her letters to close relatives while living in Hannover, which show a more outspoken side to her, are found at Egerton MS 3761 and Egerton MS 3762. The "Egerton" refers to the fact that they were purchased by the British Museum Library with money from an endowment created specifically to acquire manuscripts in the bequest of Francis Henry Egerton, 8th Earl of Bridgewater.

Further reading:
Brock, C. The comet sweeper. Thriplow: Icon, 2007. Shelfmark YC.2008.a.3165, also available as e-book in the British Library Reading Rooms.
Hoskin, M. Herschel, Caroline Lucretia (1750-1848). In Oxford Dictionary of National Biography, 2005. https://doi.org/10.1093/ref:odnb/13100. Available online in British Library Reading Rooms.
Winterburn, E. The quiet revolution of Caroline Herschel. Stroud: The History Press, 2017. Shelfmark YK.2018.a.6511, also available as e-book in the British Library Reading Room

The 22nd of January is the birthday of the early modern lawyer, politician, and philosopher Francis Bacon, later Viscount St Alban (1561-1626). For the purposes of this blog, he is most famous for his contributions to the gradual evolution of scientific thinking, mainly expressed in his book Novum Organum, first published in Latin in 1620. We hold two copies of the first edition, published by John Bill. One is at shelfmark C.54.F.16, and has a bookplate in the name of John Bentinck, and the second is at 535.k.8.

Title page of the original 1620 edition of Novum Organum

Novum Organum was intended to be part of Bacon's life's work, The Great Instauration, which would have been a multi-volume work summarising practically all knowledge that existed during his lifetime and suggesting paths for further enquiry. He died long before completing it, although some sections of it dealing with particular subjects existed in manuscript and were published after his death. The book argues for knowledge of the natural world to be developed by collection and juxtaposition of experimental observations, refraining from forming hypotheses too early and attempting to force the information to fit them. While mature scientific method views hypotheses as more significant than Bacon did, his thought was an important reaction to earlier classical and medieval ideas about the natural world, which were based mainly on intellectual speculation.

Novum Organum is also important for its discussion of "idols", or fallacies and habits of thought which interfere with rational thought and prevent people from reaching correct conclusions. Bacon defines four types of these. "Idols of the tribe" are flaws of reasoning which are almost universal among human minds. "Idols of the cave" (an allusion to Plato's Allegory of the Cave) are biases and pre-occupations specific to each individual person. "Idols of the marketplace" are confusions created by the imprecision of language to describe the world, such as when people's understanding of the technical meaning of a word in science is confused by its everyday meaning. Finally, "Idols of the theatre" are mistaken ideas that persist because of their historic prestige and acceptance by authoritative figures.

It is not clear how much experimentation Bacon actually did. The amusing story spread by the memoirist John Aubrey that he died from pneumonia caused by an experiment to see if a chicken could be preserved by stuffing it with snow is nowadays doubted. His unfinished Utopian book New Atlantis was extremely influential in its depiction of "Saloman's House", possibly the first depiction of a scientific institute, which heavily influenced the founding of the Royal Society, just over thirty years after Bacon's death.

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

On Friday 11th October, I went to the New Scientist Live show, which is an annual event for the general public about the wonders of science. There are a series of lecture slots, and an exhibition from universities, learned societies, technology companies, commercial and charitable science "experience" organisation, and makers of science-related ornaments and clothing.

The talks I attended were all very interesting. Tom Crawford of Tom Rocks Maths described his work modelling the flows of rivers into oceans as a means of tracking plastics and other forms of pollution, to find the best places to collect them. The flows are controlled primarily by the Earth's rotation, outflow speed, and the density of the river water relevant to the sea.

Sim Singhrao of the University of Central Lancashire described her work on the possible contribution of poor oral hygiene to Alzheimer's disease. The bacterium Porphyromonas gingivalis, which contribures to gum disease, has been found in the brain of Alzheimer's patients, and it is suggested that Alzheimer's disease may be worsened by the action of the immune system in the brain, or protein fragments left behind when the bacteria feed.

Jess Wade of Imperial College, who works on organic semiconducting materials which can be used in products such as flexible displays, gave a lecture on chirality in science, from Louis Pasteur's discovery of optical isomerism in tartaric acid to biological effects, to the possible origins of chirality in polarisation of starlight due to the rotation of galaxies, to chiral selection of electron spin and the role it may play in our nervous system.

Guillermo Rein of Imperial College described the wide range of work involved in fire science, from fires aboard NASA spacecraft, to how polymers burn, to how large buildings can survive fire without structural failure, to the problem of long-lasting peat fires and the severe air pollution that they cause in South-East Asia. His work has not just been theoretical, but has included spectacularly large experiments in both the Czech Republic and Indonesia.

Finally, Ravi Gogna of BAE described work to improve information sharing between police, social workers, health care, and schools to improve child protection and allow problems to be dealth with without heavy-handed interventions. The technology was originally used to raise flags for fraud in financial institutions.

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

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

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.

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.