THE BRITISH LIBRARY

Science blog

11 posts categorized "Research collaboration"

21 June 2019

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

Add comment

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.

Chart showing influences of the environment and genetics on development cycle
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).

Fig-2
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).

Handwritten pages of notes on scientific experiments
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).

Fig-4
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).

Newspaper column heading with headline "Brave New Mice"
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.

14 March 2019

From Cauliflowers to Chimaeras: A New Window onto Development

Add comment

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. 

The logo of British Science Week

 

The Flight of the Hoverfly

Add comment

“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

The logo of British Science Week

 

08 March 2019

How Embryologists See: Anne McLaren’s Mouse Models

Add comment

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.

Logo of British Science Week

13 March 2018

Did Man Get Here by Evolution or by Creation?

Add comment

In 1967, Jehovah's Witnesses publish a little blue volume asking Did Man Get Here by Evolution or by Creation? Half a century later, a copy shows up in the British Library, in a box of books left as part of the John Maynard Smith Archive.

John Maynard Smith (1920-2004) was a British evolutionary biologist and no supporter of Jehovah's Witnesses in any form. Rather, he had been an atheist ever since discovering the writings of population geneticist J.B.S. Haldane at the age of 15 – and a 'semi-conscious atheist before that'. Going into Eton's school library, he found Haldane's essay collection Possible Worlds and its 'mixture of extreme rational science, blasphemy and imagination, was a way of thinking that I had never encountered before'. It inspired Maynard Smith to read up on evolution and eventually – after a detour into aircraft engineering – to study it with Haldane and turn it into a successful career. So how did he come to own such a curious little book?

We have to go back to 1967 again. In October of that year, a Mrs Daphne Taylor of Sheffield packs up the book and posts it to Sussex University. 'Dear Professor,' she writes, 'Please find enclosed a small gift which I hope you will accept and enjoy reading.' Why send it to Maynard Smith? Has she sent it to any other evolutionary biologists? We don't know, but her motivation becomes quite clear as she goes on to say that she knows several people 'including teachers interested in evolution' who 'have found it most enlightening.' She wonders if Maynard Smith would let her know his views 'on any of the points brought out in the book'? There is, unfortunately, no record of any reply.

But is it telling that he kept both the book and, folded inside it, the accompanying letter? We do know that Maynard Smith had a continued interest in religion and creation(ism). The archives contain a short manuscript from his later years on "The Evolution of Religion" (co-authored with David Harper); in the 1960s he discussed science and religion on the radio and in 1986, following an invitation by the Oxford Union, debated the motion "That the Doctrine of Creation is more valid than the Theory of Evolution" (198 noes, 115 [or 150; the recording is unclear] ayes).

01-MS-Image-1
Proof for an intelligent designer? From "Did Man Get Here By Evolution Or By Creation?", p.71. Copyright © Watch Tower Bible & Tract Society of Pennsylvania.

 

What do the Jehovah's Witnesses ask and affirm in their volume? Evolutionary teaching saturates everything, even religion. But 'what do you personally know of the evidence for or against the belief in evolution? Does it really harmonize with the facts of science? We invite your careful examination of this matter, as it has a direct bearing on your life and your future.' The running argument is one that had been first used by William Paley in his 1802 book Natural Theology: or, Evidences of the Existence and Attributes of the Deity – nature is too complex for there not to have been an intelligent designer or creator. Paley famously used the analogy of a watchmaker: suppose you were to find a watch on the heath, and upon examining it and its complexity, would you not suppose there has to have been a watchmaker? Similarly, the Jehovah's Witnesses argue that 'what is made requires a maker'. Liking DNA to 'complex blueprints for future development', they wonder: 'And when we see blueprints responsible for the building of beautiful bridges, buildings and machines, do we ever contend they came into being without an intelligent designer?' What is more, there is not enough evidence for evolution (while all the existing evidence is compatible with the Bible), it's all just a theory based on conjecture and wishful thinking, unsupported by fact, and, really, not proper science at all.

The conclusion? The truly 'honest seekers after truth must acknowledge that the evidence is overwhelming that man got here, not as a result of evolution, but by means of creation by God.'

The question of evolution or creation is of course not new – Paley's watchmaker analogy may be familiar, but more will have heard (of) the story of the 1860 debate between Thomas Huxley ("Darwin's bulldog") and Bishop Samuel Wilberforce: are you descended from monkeys on your grandmother's or your grandfather's side? (The story itself has been highly sensationalised: contemporary accounts suggest that it was much less dramatic.) But organised creationism, in the sense in which it is most commonly understood today, is very much shaped by American Evangelical Christians and emerged in the 20th century. Stephen Jay Gould referred to it as a 'local, indigenous, American bizarrity' – but it has in fact not been confined to America. In Britain, especially recently, creationism has been discussed mostly in the context of education (free schools). Maynard Smith, while obviously not involved in those recent debates, discussed whether there is a conflict between science and religion in a serious of radio broadcasts aimed at school audiences in 1964. He concluded that there are cases and ways in which they do contradict each other but agreed with Christians in so far as to say that there seems to be something remarkable – but not necessarily unique! – about human intelligence in comparison to animals. He debated creationists, once together with Richard Dawkins – famously or infamously, one of the most outspoken critics of creationism and religion. Dawkins remembers that in the 1986 debate, Maynard Smith 'was, of course, easily able to destroy the creationist's case, and in his good-natured way he soon had the audience roaring with appreciative laughter at its expense.' Interviewed by the British Humanist Association – who are actively lobbying against creationist influences – in 2001, Maynard Smith finally summarised his views on religion as follows:

'I think there are two views you can have about religion. You can be tolerant of it and say, I don't believe in this but I don’t mind if other people do, or you can say, I not only don't believe in it but I think it is dangerous and damaging for other people to believe in it and they should be persuaded that they are mistaken. I fluctuate between the two. I am tolerant because religious institutions facilitate some very important work that would not get done otherwise, but then I look around and see what an incredible amount of damage religion is doing.'

So how did man get here? Obviously, Maynard Smith's answer would have been very resounding, "by evolution"!

02-JMS-1965
John Maynard Smith c. 1965. Copyright © University of Sussex.

 

Posted by Helen Piel. Helen Piel is a PhD student at the University of Leeds and the British Library. She is part of the AHRC's Collaborative Doctoral Partnership scheme and working on the John Maynard Smith Archive, exploring the working life of a British evolutionary biologist in the post-war period.

This post forms part of a series on our Science and Untold Lives blogs highlighting some of the British Library’s science collections as part of British Science Week 2018.

Further reading:

The book and letter are now catalogued and can be found in the John Maynard Smith Archive (Add MS 86839 C)

Krasnodebski, M. (2014). Constructing creationists: French and British narratives and policies in the wake of the resurgence of anti-evolution movements. Studies in History and Philosophy of Biological and Biomedical Sciences 47, 35-44.

Numbers, R. (2013). Creationism. In M. Ruse (ed.). The Cambridge Encyclopedia of Darwin and Evolutionary Thought. Cambridge [etc.]: Cambridge University Press.

Pallen, M. (2009). The Rough Guide to Evolution. London: Rough Guides Ltd.

Watch Tower Bible & Tract Society of Pennsylvania (1967). Did Man Get Here by Evolution or by Creation? Watch Tower Bible & Tract Society of New York, Inc. & International Bible Students Association Brooklyn: New York.

 

30 November 2017

Digital preservation and the Anne McLaren Papers

Add comment

IDPD17_Logo_small
Today on International Digital Preservation Day we present a guest-post by Claire Mosier, Museum Librarian and Historian at American Museum of Western Art: The Anschutz Collection, concerning the digital files in the Anne McLaren Supplementary Papers (Add MS 89202) which have just been made available to researchers. As an MA student Claire worked as an intern at the British Library in 2015 helping to process digital material.

 

AM30NovImage 1
Dame Anne McLaren. Copyright James Brabazon

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

AM30NovImage 2
‘HongKong2003Ethics.ppt’ Page from the presentation ‘Ethical, Legal and Social Considerations of Stem Cell Research’, 2003, (Add MS 89202/12/16). Copyright the estate of Anne McLaren.

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

AM30NovImage 3
‘Pugwash 2006’ Page from the presentation ‘When is an Embryo not an Embryo’, 2006, (Add MS 89202/12/163). Copyright the estate of Anne McLaren.

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

***

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

10 November 2017

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

Add comment

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

You can follow @EmmeLedgerwood and @POST_UK on Twitter.

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

05 July 2017

A tribute to Anne McLaren

Add comment

Dame_Anne_McLaren_©_James_Brabazon
Dame Anne McLaren. Copyright © James Brabazon

 

To publicise the upcoming event: Anne McLaren: Science, Ethics and the Archive, to be held at the British Library on 20 July, 6.30-8.00 pm, we present a guest-post by Professor Marilyn Monk, UCL Emeritus Professor of Molecular Embryology, with her personal recollections of Anne McLaren.

       
It is a great honour to have this opportunity to give my own personal tribute to Anne McLaren. Anne was my role model and my mentor over so many years. Not only in my scientific life - although her influence here was huge - but she was such a tower of strength and support for me over many difficult times. ‘Water under the bridge Marilyn. Water under the bridge’, she would say, encouraging me to move on.

I worked closely with Anne in her Medical Research Council Mammalian Development Unit for 18 years from 1974 to 1992 and I remained in contact with her thereafter. I would often email or phone Anne – ‘what do you think of this Anne?’ – questions about science, about life, about new ideas. And she would always respond with words of wisdom and support.

Right from the beginning Anne accepted me unconditionally. My first encounter with Anne was my phone call to her in Edinburgh in 1974. At that time, Anne was in Animal Genetics at Kings Buildings in Edinburgh and I was in the Molecular Biology Department working on DNA replication and repair in bacteria and on slime mould aggregation. But, in 1974, our MRC unit in Molecular Biology in Edinburgh closed with the retirement of our director, Bill Hayes. The MRC told me that I could relocate to another MRC unit that interested me and that would have me. I visited many MRC units and talked to various people who were encouraging but nothing seemed to be right for the interests and expertise in research I had at the time. Then Harry Harris at the Galton Laboratory suggested I contact Anne McLaren as she was just about to move from Edinburgh to London to start up a new MRC Mammalian Development Unit at the Galton. I knew nothing at all about development - let alone mammalian development. A move to mice and their embryos would be a huge leap both intellectually and technically.

In any case, I plucked up courage to phone Anne in Edinburgh in 1974. I remember everything about that moment when I phoned Anne because I was holding onto my last hopes of continuing as a scientist. I introduced myself, told her my problems, and asked her if she would consider taking me on in her new MRC Unit in London. I told her I knew nothing about mice – I had only worked with bacteria, viruses and amoebae. She said, ‘Yes of course you can join me. You must!’ I was flabbergasted. So overjoyed I could not speak. She did not even know me. She didn’t ask to meet me. But she had no reservations. She’d give me a chance. But this says it all about Anne - a tower of strength and support, particularly for women scientists (in my experience, it can still be difficult, even today to be a woman in science).

But as well as being a tower of strength, Anne was patient, tolerant, allowing, and very wise. And of course - very intelligent. I would prefer to talk about science and life and new ideas with Anne than anyone else I know. And Anne was a great listener. She always liked my ‘What if’ ideas and 'Why' questions. She thought that some of them were 'whacky' (her word) but always interesting.

Another great quality of Anne’s was her wicked sense of humour and sense of fun. Over the years, she would only have to raise one eyebrow in my direction over some happening, or strange remark from an unsuspecting visitor, and it would be difficult for me not to collapse in giggles. I always knew what she meant by the raised eyebrow. I felt privileged to be a secret accomplice to the raised eyebrow.

I know there are so many others who will have had the same wonderful experiences of Anne and will be feeling the way that I do. In the days and weeks after Anne died, so many people shared that they had just been in touch with her about this or that – about meeting soon for a meal and a talk about science and about life, or asking her advice on various issues, or arranging some new initiative. I have realised that Anne was looking after all of us pretty much all of the time. She made each one of us feel special.

Her energy and engagement with life and people was phenomenal. In addition she had extra-ordinary self-discipline and I had a lot to learn from her here. I never once saw Anne nod off in a seminar. She listened carefully to everything everyone said and her responses were always measured, incisive and invariably ‘spot on’. She never said a bad word about anybody that I can remember. She never complained.

When I joined Anne’s Unit, I was already a molecular biologist of some 15 years. But as such, I was used to working with millions of cells, bacteria or amoeba. We used to call it bucket biochemistry. The huge challenge was to bring molecular biology to the few cells of the embryo and even to the single cell. And we did it. I guess the hallmark of my research with Anne was to make the molecular techniques a million times more sensitive so we could look at specific enzyme activity, specific gene expression, and specific gene mutation or modification in just a few cells, and even a single cell, of the embryo. Once these single-cell molecular technologies were established, we could apply them to different developmental and biological questions and many insights into mammalian development followed during the years I was at the Galton. We began with establishing the cycle of X chromosome activation and inactivation as a model for gene expression and its regulation in early development. From there, we made many new discoveries such as the late origin of the germ line (anti Weissman doctrine). differential methylation of the active and inactive X chromosomes (beginning of mechanisms of epigenetics), imprinting and transgenerational inheritance of acquired characteristics (Lamarkian inheritance) and the discovery of methylation erasure in early development and again in the germ line thus bringing development back to tabula rasa - totipotency. Clinically we applied our single cell molecular biology to pioneering experiments for preimplantation diagnosis of genetic disease. My colleagues and co-workers during these years in Anne's Mammalian Development Unit were Mary Harper, Asangla Ao, Andrew McMahon, Mandy Fosten, Susan Lindsay, Maurizio Zuccotti, Mark Grant, Michael Boubelik.and Cathy Holding. Anne always gave me a completely free rein and encouraged me in whatever I wanted to do. I still miss her.

Marilyn Monk
UCL Emeritus Professor of Molecular Embryology


Both the Anne McLaren and Marilyn Monk papers are available to readers through the British Library Explore Archive and Manuscripts catalogue. The Mclaren papers can be found at Add MS 83830-83981 and Add MS 89202 and the Monk papers are available at Add MS 89158.

17 March 2017

Old issues in new guises: Dame Anne McLaren and the embryo research debate

Add comment

Following the birth of the world’s first baby by In Vitro Fertilisation (IVF), Louise Brown, in 1978, the research on human embryos that had made this possible became the subject of scrutiny and unease from both the public and politicians. This led the government to task Dame Mary Warnock with the chairing of a committee consisting of medics, social workers, lawyers and clerics in 1982, to set out a guideline for the legislation on IVF and embryo research in the UK. The report was enacted in the 1990 Human Fertilisation and Embryology Act. One of the report’s most lasting and controversial recommendations was a limit on research on human embryos in vitro beyond fourteen-days – the so-called ’fourteen-day rule’.

McLaren-image-1
Detail of the letter to Anne McLaren inviting her to take part in the Warnock Committee. (1982). (Add MS 89202/8/1). Crown Copyright/estate of Anne McLaren.

This law has been in force for more than twenty-five years. For scientists, there had been no need to contest it, since scientists had not come close to culturing an embryo anywhere near to the fourteen-day limit. The equilibrium was only disrupted at the end of last year, when a research group at Cambridge University led by Magdalena Zernicka-Goetz claimed to have developed a method of culturing live human embryos for thirteen days, only stopping their experiment at this point to comply with the fourteen-day rule. This possibility has recharged the debates over the desirability of embryo research and the extent to which it should be regulated.

In the face of these reopened debates on the ethics of embryo research, it is important to understand the premises and arguments that shaped the current legislation. These arguments, at first glance, appear to be predominantly scientific.

Developmental biologist Dame Anne McLaren (1927-2007) was the only research scientist serving on the Warnock Committee, and played an important role in providing the lay-committee with a scientific understanding of the processes of embryo development that proved definitive in the committee’s efforts to convince ministers of the validity of the fourteen-day rule. McLaren made the case for the rule by arguing that the fourteenth day was a clearly distinguishable step towards individuation in the development of the embryo. Fourteen days, for example, sees the onset of gastrulation, a point at which the embryo can no longer divide into identical twins. Fourteen days also falls well before the beginnings of what will become the central nervous system, and so there is no chance that the embryo could experience pain. 

McLaren-image-2
Title page of Anne McLaren’s draft for ‘Comments on the use of donated eggs fertlilized specifically for research purposes’. (c. 1982). (Add MS 89202/8/1) Copyright the estate of Anne McLaren.

Yet, as Lady Warnock has stressed, fourteen days is by no means a landmark set in stone. McLaren could have made a well-substantiated scientific argument for a different cut-off point- the embryo, for example, is just as incapable of experiencing pain at twenty-eight days. As Lady Warnock stated at a 2016 Progress Educational Trust conference on the topic, it was merely important to set a time limit, to provide clarity through law, so that the public would feel reassured that research would not progress untethered. The fourteen-day rule did therefore not express a moral distinction for the human embryo based on biological facts, but emphasised a specific part of the biological process in order to make a practical compromise – as Warnock writes in the committee’s report: ‘What is legally permissible may be thought of as the minimum requirement for a tolerable society’ (1985, p.3). 

Understanding the arguments McLaren made in the 1980s will shed light on what is required of legislation today—that it should take into account the current political climate and public sentiment, perhaps before making arguments about the ethics of research based on biological facts. 

The Anne McLaren papers at the British Library consist of letters, notes, notebooks and offprints. There is currently one tranche (Add MS 83830-83981) available to readers through the British Library Explore Archives and Manuscripts catalogue with a second tranche (Add MS 89202) planned for release at the end of April 2017. Additionally one of Anne McLaren’s notebooks containing material from 1953 to 1956 (Add MS 83843) is on long-term display in the British Library’s Treasures Gallery. 

Anne McLaren’s scientific publications and books, along with an oral history interview conducted in February 2007, are available to readers via the British Library Explore catalogue.

 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 2017.

Posted by Marieke Bigg. Marieke is an MPhil student in sociology at the University of Cambridge and works under the supervision of Prof. Sarah Franklin. Marieke’s MPhil dissertation and PhD will both explore the contributions made by Dr Anne McLaren to the debate over human fertilisation and embryology in the 1980s.

15 March 2017

Local Heroes: John Maynard Smith: (1920-2004): A good "puzzle-solver" with an "accidental career"

Add comment

 

JMS-1965
John Maynard Smith c:1965. Copyright University of Sussex

Maynard Smith was born in London, though after his father’s death in 1928, the family moved to the countryside. There, Maynard Smith deepened his love for natural history – already manifest in his insistence to repeatedly visit the Zoo and Natural History Museum in London – while bird-watching and beetle-collecting during the holidays in Exmoor. His family was generally not scientifically inclined, and there were expectations for him to join his grandfather’s stockbroking firm. However, during one Sunday lunch he declared that he would not do so. What was he going to do then? Remembering a lecture on the building of the Sydney Harbour Bridge, he decided, rather spontaneously, to become an engineer. And so, after graduating from Eton in 1938, he went on to read engineering at Cambridge.

Maynard Smith is known for not having liked his time at boarding school very much – the atmosphere, he felt, was ‘really anti-intellectual’, ‘snobbish’ and ‘arrogant’ – but he credited Eton with teaching him mathematics and giving him the freedom to explore the natural sciences on his own, mostly by reading popular science books. Cambridge, in a way, did less for him academically than Eton. ‘This time, however, the fault was partly mine and partly Hitler’s. It was hard, in 1938, to take either academic work, or one’s own future, seriously.’ He joined the Communist Party, influenced by a visit of Nazi Germany in the summer of 1938 from which he returned ‘in a state of complete confusion, convinced that my pacifism was wrong’. Communists were those ‘saying we have got to unite and oppose Fascism’, and he spent more time being politically active than studying. Soon after joining, Maynard Smith met Sheila Matthew, his future wife, at a Communist Camp. They were to marry in 1941, making Maynard Smith one of the first married undergraduate students at Trinity College. Their first son, Anthony, would be born in 1944, their daughter Carol in 1946, and their youngest, Julian, in 1949.

In 1941, Maynard Smith graduated with a second-class honours degree in mechanical engineering. After graduation, he worked as an aircraft stressman which, importantly, ‘taught him to trust models, a lesson that would become fundamental in his work as a scientist.’ Moreover, ‘and for obvious reasons, Maynard Smith formed the valuable habit of not making mistakes in computations.’ However, when the war was over, he began to reconsider his career choices. He decided to return to his first love and started a second degree in zoology at University College London. Maynard Smith knew JBS Haldane was teaching there, whose work he had sought out already at Eton because several teachers seemed to particularly hate this man – so he couldn’t be ‘all bad’.

During his years as an undergraduate at UCL Maynard Smith became less and less active politically. He was much more involved in his studies than he ever was at Cambridge. In addition, Lysenkoism reached its peak in 1948. Trofim Lysenko was a Soviet biologist and Lamarckist supported by the Soviet government. Maynard Smith was not so much averse to Lysenkoism as ‘disgusted’ by the comrades who were ignorant of genetics but who were nonetheless telling him what to believe. He lost faith in the Communist Party, became disillusioned with communist politics and – though to a lesser extent – with Marxist philosophy. In 1956, after the Soviet Invasion of Hungary, he finally left the Party yet retained his leftist political outlook.

JMS-1984
John Maynard Smith c:1984. Copyright University of Sussex

In the year before his death, Animal Signals, his last book, co-written with David Harper, was published. The book was one of several; Maynard Smith published both textbooks and popular science – his ‘little Penguin’, The Theory of Evolution, was published as early as 1958. Indeed, he was convinced that science is a social activity: he had a ‘desire to embed discoveries in the discourse of a community as broad as possible.’ So next to writing books, reviews, and essays he also appeared on both radio and television.

The John Maynard Smith Archive at the British Library documents over half a century of John Maynard Smith's work as an evolutionary biologist, covering the years 1948 to 2004 (with an emphasis on the 1970s to 1990s). It contains letters, notes, computer printouts, draft manuscripts, lecture notes and offprints as well as artefacts and digital files. The archive is available to readers through the British Library Explore Archives and Manuscripts catalogue (Add MS 86569-86840), excepting the digital material which is in the process of being catalogued.

Maynard Smith's books and scientific papers, along with two interviews (one on camera), can be found via the British Library Explore catalogue.

This post forms part of a series on our Science and Untold Lives blogs highlighting some of the British Library’s science collections as part of British Science Week 2017.

 

Sources and Further Reading:

Charlesworth, B. and Harvey, P. (2005). John Maynard Smith. Biographical Memoirs of Fellows of the Royal Society 51, 254-265.

Kohn, M. (2004). A Reason for Everything: Natural Selection and the English Imagination. London: Faber and Faber, esp. pp.197-255.

‘Making it formal.’ (1988). In: Wolpert, L. and Richards, A. (eds.). A Passion for Science (pp.122-137). Oxford [etc.]: Oxford University Press.

Maynard Smith, J. (1985). In Haldane's Footsteps. In: Dewsbury, D.A. (ed.). Leaders in the Study of Animal Behavior: Autobiographical Perspectives (pp.347-354). Lewisburg, PA: Bucknell University Press.

Posted by Helen Piel. Helen Piel is a PhD student at the University of Leeds and the British Library. She is part of the AHRC's Collaborative Doctoral Partnership scheme and working on the John Maynard Smith Archive, exploring the working life of a British evolutionary biologist in the post-war period.