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3 posts from March 2019

14 March 2019

From Cauliflowers to Chimaeras: A New Window onto Development

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

 In my previous blog  we saw how, as she conducted her embryo transfer experiments, Dr Anne McLaren was already looking for ways of more directly influencing the environment of the embryo, in order to test what effect this would have on the embryo itself. This was part of her project to illuminate the interactions between genes and their environment in the development of the embryo. She found her answer in the in vitro dish:

In my laboratory we culture… very early mouse embryos in little plastic dishes, under a layer of liquid paraffin. Drops of culture medium are added, just a simple salt solution, with some glucose and some protein, and some antibiotics to stop bacteria growing; the mouse embryos, which are just too small to be seen with the naked eye at this stage, are then added, several to each drop, and the dish is put in an incubator, in the right temperature and gas conditions.

Now McLaren no longer had to influence embryos and cells in the earliest stages of development through the environment but could directly manipulate them, change the conditions under which they were put, and see what effect this had on subsequent development. One way in which she changed the environment of the embryo was by making what she called ‘Chimaeras’. In Homeric legend, the chimaera described a strange hybrid animal that had “the body of a she-goat, the head of a lion, and the tail of a serpent”, and throughout the literature of antiquity many other strange combinations are found. McLaren picked up on this, as she explained in Mammalian Chimaeras (1976):

…the six-limbed centaur, half man, half horse; the harpy, a bird of prey with the head and breasts of a woman; the griffon, with eagle’s head and legs, and the body of a lion; the beats of the Apocalypse, like a seven-headed leopard with the mouths of a lion and the feet of a bear; the Apocalyptic locusts, horse-shaped with men’s faces, women’s hair, lion’s teeth and scorpions’ tails. All bear witness to the ambition of Man to combine outstanding qualities of different animals into a single creature of surpassing power.

IMAGE 2-1 : Etruscan Chimaera, 4th Century BC, National Archaeological Museum, Florence, Italy. With kind permission from Steven Zucker CC BY-NC-SA 2.0

A bronze sculpture of a chimera, a mythological beast with the appearance of a lion, with a goat's head emerging from its back and a snake's head at the end of its tail.

Sexual reproduction is also a way of forming a composite, of selecting traits from two different animals, two parents, and recombining them in a given environment to form an organism that carries forth the traits of both into a next generation. The method is anything but certain. McLaren’s transfer experiments showed that a lot can go wrong, the results are unpredictable, and the method can only be used within a species or it will produce infertile offspring. Nonetheless,

Biology as well as mythology provides examples of strange and often intimate associations between different species. Alga and fungus form a partnership so close we refer to it by a single name, ‘lichen’; the hermit crab collects stinging sea anemones to guard its shell; the sea slug (Aeolis pilata) accumulates nematocysts from the hybroid that it eats, and positions them in its epidermis as a defence. Even some subcellular organelles, like chloroplasts and mitochondria, are now thought to have originated as independent organisms existing in symbiotic relationship to a host cell.

A clump of grey lichen growing around a broken Y-shaped branch.

IMAGE 2-2:  Lichen, a composite of alga and fungus. Photo courtesy of Hans Braxmeier. Pixabay License

There are thus lots of examples in nature of chimaeras. In experimental embryology, the term has a slightly more specific meaning, and is used to refer to a “composite animal or plant in which the different cell populations are derived from more than one fertilized egg, or the union of more than two gametes”. McLaren showed with her collaborator Dr John Biggers in 1958 that if you take two 8-cell mouse eggs and push them together, they’ll stick, and the total 16 cells will develop as a normal embryo and that, when transferred to another female mouse, the cells will grow up into “a muddled but otherwise normal mouse”. This mouse would thus be described as a chimaera.

So why would McLaren want to interfere with mouse embryo development in this way? What would this tell her about gene-environment interactions? After all, she wasn’t so much changing the culture environment in the dish which had replaced the maternal uterus, as the cells of the embryo themselves. In Chimaeras in Mouse and Man (1970), she explains,

How do genes link up with chimaeras? Well, one of the subjects that has always fascinated me as a geneticist is the interaction of genes and environment, the old Nature-Nurture dichotomy. A gene on its own cannot determine a single feature of an organism. It's only a meaningful concept in interaction with a particular environment, and the same gene in different environments may produce quite different effects. In mammals, an important part of the environment may experienced by the developing embryo is provided by the mother, before birth. Some years ago my colleague Donald Michie and myself studied how mice of the same genotype reacted differently in different uterine environments, that is in different mothers. In a chimaera one is studying a still more intimate interaction between genotype and environment, because each of the two cell populations is developing in an environment largely made up not only of its own type, as would be the case in any normal animal, but in the most intimate interaction with cells of the other type…this can produce unexpected effects.

So what kind of experiments did this new research technique lead to? One of the problems this method allowed her to investigate was the development of sex. What happens when you create a chimaera that is half male and half female? What is the effect of this altered cellular environment on the phenotypic [the traits expressed] sex of the mouse? If two male embryos are fused, or two females, McLaren showed, their sexual development presents no problems, or no special problems at least. When, however, male and female cells are fused, you would expect them to develop into hermaphrodites with special combinations of male and female organs.

What she found, however, was that in a sample of randomly aggregated male-female chimaeras, the proportion of hermaphrodites was nowhere near 50%, which is what you would statistically expect when mixing half male and half females. The proportion was closer to 10%. The reason turned out to be that the mice which are made up of both male and female cells develop as perfectly normal males. The proportion of male and female cells in the body of these chimaeras also varies even though half of each were used initially to form the chimaeras. This is because, when the eggs are fused and the two types of cells get mixed together, sometimes more female cells will get into the outer layer of the embryo, which is the layer that goes on to develop into extraembryonic structures, such as the placenta and membranes, and sometimes more will get into the inner part, in which case female dells will predominate in the baby mouse itself.

The experiments eventually showed, in combination with work done by Dr Chris Tarkowski who was working in Poland, that normal female development only occurs if virtually all the cells in the body are female. If there are a small proportion of male cells present, then the mouse develops abnormally, as a hermaphrodite. However, if the proportion of male cells approaches 50% or more, the animal develops as a normal male, and the fact that it has a lot of female cells scattered throughout the body does not seem to upset the overall phenotype or make it less male.

These experiments thus showed that sex is not only or directly determined by the XX or XY chromosome, that the overall phenotype results from regulation at the level of the whole animal, and that means that the interaction between cells determines what sex the embryo has. In this sense, the mouse chimera is not like the mythological chimera at all, because, even when composed of different parts it will still function as a coherent whole. There is often nothing outwardly ‘unusual’ about a chimera, in fact we are always composed of two distinct genotypes coming together, although this isn’t included in the biological definition of the chimera, it proposes the same biological conundrum. The interesting question in biology is how different parts come to function as a unity. No monsters here, only lots of composite individuals.

Marieke Bigg

Ph.D candidate, University of Cambridge

Further reading:

McLaren, Anne. 1968. The Developing Egg.

McLaren, Anne. 1970. Chimaeras in Mouse and Man.

McLaren, Anne. 1976. Mammalian Chimaeras. Cambridge, London, New York and Melbourne: Cambridge University Press.

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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The Flight of the Hoverfly

“According to classical aerodynamics, it is impossible for a bumblebee to fly!” said the Doctor once, around 1971, standing in the Wiltshire countryside. (Doctor who? THE Doctor. The Third one.)

But years earlier, in the 1950s, John Maynard Smith – not a doctor then or ever, except when people misaddressed him – had in fact glued one to a pin and showed why and how they could.

Well, to be honest, he had glued a hoverfly to a pin, not a bumblebee. Although he and M.J. Davies, fellow undergrad at University College London, had tried bees. But the bees were unwilling to fly when tethered, so hoverflies had to serve as stand-ins.

Their reason was so nicely summed up by the Doctor: science could not only not explain how bumblebees managed to fly, according to science – aerodynamics to be precise – they shouldn’t be able to fly at all. This idea had got hold of people’s minds because they took aerodynamics as applied to helicopters and rotating disks and then applied it to the wings of bees and large flies. Thinking like that, they concluded that these insects shouldn’t be able to get enough lift to fly.

So Maynard Smith and Davies etherised flies and glued them onto a pin before they surrounded them with, essentially, fluff (metaldehyde particles, to be exact) and flash photographed them, timing the length of exposure. ‘The resulting photographs,’ Maynard Smith remembered in 1990, ‘were fairly awful by modern standards, but were good enough to show that the velocity of the air in the jet was about one-third of the theoretical values, and the area of the jet correspondingly greater.’ Below is a surviving photograph from the experiments, numbered 11. The large white shape roughly in the centre is the fly, the white smudges around it the traces left by the fluff, indicating the air movement created by the beating wings.

A photograph showing a fly attached to a pin and beating its wings, with particles flying away from it.IMAGE 1: Photograph: Insect Flight, c 1950. Copyright estate of John Maynard Smith. (Add MS 86626)

To put the results differently, insects like bumblebees, bees and hoverflies can fly because of the air’s viscosity. Viscosity is the resistance to a change in shape, or the movement of neighbouring portions relative to one another. This means that when a large insect beats its wings, the wings drag along more air than just the air directly affected by the wing. This additional volume of air - ‘about ten times more air than you’d think’ - is large enough to provide lift for the insect; the downward jet of air supports its weight: it flies.

Why? Scale proved to be important: helicopters and bees operate on rather different ones. ‘It’s a very small scale, and the viscosity of the air means that not only the air that’s actually gone past the wings is going into a jet below the bee but a great mass of the air from all around is being sucked in by viscosity. […] We tried to publish that and never could. I was [...] cross about that.’

While they didn’t manage to publish in a scientific journal (the Journal of Experimental Biology rejected it around 1950), Maynard Smith did present his and Davies’ findings at a meeting on insect flight at the Zoological Laboratory in Cambridge during the summer of 1953. The meetings were the result of ‘attempts to bring together a group of persons with a special interest in the flight of insects.’ The meeting notes stress that the experiment had been developed independently by Maynard Smith and Davies. This was important because it was similar to one described by F.S.J. Hollick, who had, for example, published on the flight of the fly Muscina stabulans in 1940.

IMAGE 2: F. S. J. Hollick. (1940). The flight of the dipterous fly Muscina stabulans fallén. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 230(572), 357-390. Reproduced by kind permission of the Royal Society.

A drawing of a fly attached to a pin and the tools used in the process.

 

(The report also gives us the exact formula used by Maynard Smith and Davies: ‘The mass of air passing through the wings per second (m) was then calculated by using the expression W = mv, where W is the weight of the insect, and v the velocity of the air. Power was then calculated from the expression P = 1/2m.v2, and the average value determined for several species was 0.009 h.p. per lb. of flight muscle. Using Wigglesworth’s figures for the rate of sugar consumption in Drosophila, the efficiency was estimated at between 1 and 2 per cent.’)

The experiment and ‘fairly awful’ photograph saved in Maynard Smith’s archive are fascinating not only as an example of 1950s research tools. It also illustrates Maynard Smith's transition from aircraft engineer to biologist. He had a first degree from Cambridge, then worked as an aircraft engineer during the Second World War, and only in the late 1940s switched careers by going back to university to study biology. In studying the mechanics and efficiency of flight, both in insects and in birds, his engineering background and knowledge of aerodynamics, mathematics and equations proved invaluable.

Second, it is an example of Maynard Smith’s early trouble in getting papers published. His research and results were from hard to impossible to get past mathematically ignorant biologist reviewers. A comment on one of his papers on the evolution of flight even claimed that the author had no knowledge of aerodynamics!

‘Now this did slightly annoy me,’ Maynard Smith commented. ‘If they had rejected it on the grounds that I didn’t know anything about animals I wouldn’t have minded so much, ‘cause it was probably true. But, you know, test pilots had been trusting their lives to the fact that I knew some aerodynamics for a number of years; I felt a bit cross.’

IMAGE 3: Maynard Smith, J. (1953). Birds as aeroplanes. New Biology 14, 64-81. Copyright Penguin Random House UK.

A drawing showing a fly in mid air with arrows showing the airflow descending from it.

Maynard Smith did manage to publish that particular paper eventually, in 1952, but his work with Davies on hoverflies proved impossible to publish in a scientific journal. His contacts at Oxford saved him. David Lack, author of The Life of the Robin and Darwin’s Finches, introduced Maynard Smith to Michael Abercrombie and M.L. Johnson, a husband-and-wife team of biologists at the University of Birmingham. They were editing the popular biology journal New Biology, published by Penguin. The journal aimed to reach the educated layman and schools, explaining and presenting biological research. Maynard Smith published “Birds as Aeroplanes” with them in 1953. All the things he had trouble getting into professional journals, he included: his research with Davies and mathematics. The above figure from that article translates the photograph into a more easily interpretable illustration. This article marks the start of Maynard Smith’s successful third “career” as a science communicator, which he continued to do next to his research for almost half a century.

Lastly, the photograph shows Maynard Smith in the role of the experimental biologist, a role that he later abandoned for theoretical biology. As a postgraduate he worked in the laboratory on the genetics of the European fruit fly Drosophila subobscura and largely ignored theoretical problems. This wasn’t due to theoretical incompetence but rather due to the fact that J.B.S. Haldane, one of the founding fathers of population genetics, was working down the hallway. Maynard Smith later commented that their was no point in doing theory because Haldane would find the solutions before anyone else. The switch to theory happened around the time Maynard Smith accepted a deanship at the University of Sussex in 1965. Not only had Haldane left the UK for India previously, but Maynard Smith's new duties didn’t leave much time for fruit fly farming and experiments.

It remains to clear the Doctor of any possible misapprehension that he was ignorant of insect flight. He likely knew exactly how and why bumblebees fly. He’s the Doctor. But he needed to make a point to a rather incredulous sergeant who was about to build an instrument with the Doctor’s instructions.

OSGOOD: What’s the principle, sir?

DOCTOR: Negative diathermy, Sergeant. Buffer the molecular movement of the air with the reverse phase short waves. It’s quite simple.

OSGOOD: Simple? It’s impossible.

DOCTOR: Yes, well, according to classical aerodynamics, it is impossible for a bumblebee to fly!

This blog was written for British Science Week. As part of this ten-day celebration of science, the John Maynard Smith Archive will also feature in an event on 15 March 2019: ‘Dear John: The Kin Selection Controversy’.

Helen Piel
Collaborative Doctoral Partnership (CDP) PhD student, University of Leeds and the British Library

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08 March 2019

How Embryologists See: Anne McLaren’s Mouse Models

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,

The stages of human embryo development from ovum to foetus.
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. 

 

‘This image has been removed due to expiry of the copyright licence. '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.

Sketch showing an ovum being influenced by either its genotype or the environment.
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.

Image of written lines in a notebook
Strange cauliflower shapes. Detail from Anne McLaren’s ‘UCL Embryo Transfer’ laboratory notebook, 1953-1956. Copyright estate of Anne McLaren (Add MS 83843).
Image of written lines in a notebook
‘Ghosts’, or disappearing, eggs. Detail from Anne McLaren’s ‘UCL Embryo Transfer’ laboratory notebook, 1953-1956. Copyright estate of Anne McLaren (Add MS 83843).
Image of written lines in a notebook.
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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