̽��ֱ�� of Cambridge - Nick Hopwood

̽��ֱ��rise, fall and revival of research on human development

Anonymous — Fri, 02 Aug 2024 09:23:47 +0000

Analysing the past sheds light on the present resurgence of research on human development. That’s the lesson of a new study by Professor Nick Hopwood, from the Department of History and Philosophy of Science, that is published in the Journal of the History of Biology. ̽��ֱ��paper discusses the flourishing of human embryology a century ago, its drop in popularity after World War II, and especially its revival since the late twentieth century.

“Every journal article and news story about human development includes a bit of history, but it’s often narrow, rarely informative and not always accurate”, Hopwood says. “I wanted to stand back and see a bigger picture, then dig down to find out how and why there has been such a surge of attention. Working in Cambridge made that easier.”

̽��ֱ�� ̽��ֱ�� has been at the forefront of innovation, from the first test-tube baby to the extended culture of early embryos, organoids and other stem-cell models. ̽��ֱ��networking through Cambridge Reproduction of expertise in science and medicine, humanities and social sciences helped Hopwood reconstruct the genesis of these advances. This took a combination of research in libraries and archives and interactions with scientists, including interviews, sharing of documents, attending conferences and giving talks, here and elsewhere.

“Human development has long been of special interest as evidence of our origins and for its medical relevance, but is hard to study”, Hopwood explains. “Historically there have been two main approaches. Either deciding that it’s too difficult to research human embryos because they’re usually hidden in pregnant bodies, so we should study other animals and hope results will transfer. That’s an indirect approach. Or trying for the best possible results from the few human specimens that can be obtained. That’s a direct approach. My article analyses the rise of research directly on human material as part of the changing politics of choosing a species to study. I explore how researchers distanced themselves from work on animal models but even human studies depended on this.”

Interest in human embryos grew in the later 19th century, following debates about evolution. Darwinists pointed to the similarity of humans and other animals at early stages as evidence of common descent. Critical anatomists responded by setting up networks of physicians to collect material, mainly from women’s pregnancy losses. New techniques such as serial sectioning and wax modelling from the slices made details of internal structure visible in 3-D.

This led to a watershed moment: the establishment by the Carnegie Institution of Washington of a Department of Embryology at Johns Hopkins ̽��ֱ�� in Baltimore. Founded in 1914, the first research institution devoted specifically to embryology focused on human embryos, now also increasingly recovered from aseptic operations for various conditions. Important discoveries include elucidation of the timing of ovulation in the menstrual cycle, initially in rhesus macaques. Human embryos from the first two weeks after fertilization were described for the first time.

Flies, frogs and chicks

After World War II human embryology ran out of steam. A new field, developmental biology, focused on model organisms, such as flies, frogs, chicks and, as the exemplary mammal, mice.

“To make progress, the argument went, it was necessary to work on species where more could be done more easily”, Hopwood explains. “That meant micromanipulation, enough material to do biochemistry and molecular biology, and genetic tools.” This approach demonstrated its power in the 1980s, when mechanisms of development were found to be more conserved across the animal kingdom than researchers had imagined. Yet from around the same time interest revived in using human material.

“There was not a steadily rising curve of research on human development through the twentieth century”, Hopwood contends. “Instead, human embryos have gone through cycles of attention and neglect. As opportunities opened up and the balance of power shifted between researchers invested in different organisms, so the politics of species choice have changed. Over the last four decades we’ve seen a renewal of research directly on human development. This is in the first place because of changes in supply and demand.”

̽��ֱ��achievement of human in-vitro fertilisation, with a live birth in 1978, gave access to embryos before implantation in the uterus. After much debate the UK Human Fertilisation and Embryology Act 1990 permitted donated embryos to be kept in vitro, under strict regulations, for up to 14 days from fertilization. Though only in 2016 was that limit approached. Meanwhile, biobanks, notably the Human Developmental Biology Resource in Newcastle and London, provided ethical supplies of post-implantation stages from terminations of pregnancy.

There has been opposition from anti-abortion activists, and many fewer embryos are donated for research than scientists (and some patients) would like. But the field was transformed. As in the years around 1900, new technologies eased the study of human embryos. Only now the advances were in digital communication, molecular analysis and imaging methods. Optical slices and computer graphics replaced microscope slides and wax models.

Beyond mice

To obtain human embryos with permission and funding to study them, researchers had to make the case for studying our own species. They stimulated demand by arguing that it would no longer do simply to extrapolate from mice. Knowledge and skills from the mouse model could be applied, but the differences as well as the similarities had to be explored. That was crucial before clinical application, as in fertility treatments. It was also desirable in discovering what makes us human—or at least not mice. Funders were keen to support medically relevant research or “translational science”.

In the last fifteen years another kind of model has transformed the politics of species choice. Subject to ongoing ethical negotiations, stem-cell-based embryo models have enabled fresh kinds of experiment on human development. Some researchers even argue that, for investigating fundamentals of vertebrate development, these human systems are now the model. Mice remain a crucial resource, with almost every innovation made on them first. But since their development is rather peculiar, other laboratories are promoting comparisons with species that develop more like humans.

Around ten years ago, all this inspired the organization of a new sub-field, human developmental biology, not least through a series of conferences. Major research programmes, such as the Human Developmental Biology Initiative, bring together scientists working, in different ways, on various aspects of embryogenesis.

Questions remain. Hopwood’s historical research concentrated on the USA and the UK, with nods to continental Europe and Japan. It would be good to explore other countries’ histories, he suggests, especially since differences in reproductive politics and infrastructure mean that access to material is uneven.

More generally, Hopwood argues, “history can contribute by showing how we got here and clarifying the arguments that have been used”. “It helps stakeholders see why there are now such opportunities for research on human development, and that, because arrangements are fragile, it will take work to gain and keep public support.” So a long-term perspective can assist researchers and funders in thinking about what might happen next.

“Interest in human development has risen and fallen and risen again. Are we now going through another cycle of attention, or could interest be maintained? Will the balance shift back to animal models or will we see an ever greater focus on humans, at least in the form of stem-cell models? How might present actions shape choice of species in the future?”

̽��ֱ��research was part-funded by a Major Research Fellowship from the Leverhulme Trust. Story by Edward Grierson from the School of Humanities and Social Sciences communications team.

A new study takes a tour of the history of research into human embryology and development to show the "cycles of attention" that led to major scientific breakthroughs.

Carnegie Science

Photos of embryos of horizon XVII, published in Contributions to Embryology in 1948 and still in use as Carnegie Stage 17.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Giving life to research

zs332 — Fri, 19 Mar 2021 09:24:32 +0000

A special online symposium will celebrate the archive of IVF pioneer, Sir Robert Edwards, and seek ways that this extraordinary archive can be used by researchers of today.

"Reproduction matters to us all": latest issue of Horizons magazine

lw355 — Fri, 20 Nov 2020 11:26:45 +0000

Professor Kathy Niakan talks about why it’s vital to take a multidisciplined approach to understanding the urgent challenges posed by reproduction today – and introduces our Spotlight on some of this work, highlighted in the latest issue of Cambridge's Horizons magazine.

Remedies for infertility: how performative rituals entered early medical literature

amb206 — Sun, 24 Jan 2016 09:00:00 +0000

̽��ֱ��medicalisation of life’s beginnings and endings has not diminished the human need for ritual. Earlier this month a photograph of a newborn baby still attached to his mother’s placenta, with the umbilical cord arranged to spell the word ‘love’, was posted on the web. ̽��ֱ��image, by an Australian photographer, went viral. ̽��ֱ��online discussion drew attention to the age-old Maori tradition of returning the placenta to the land and to the many rituals still associated with childbirth around the world.

While many birthing traditions are passed on orally, others entered the realms of literature well before the advent of printing. One of the many treasures among the manuscripts belonging to Pembroke College, Cambridge is a compendium of medical and surgical knowledge written by Gilbertus Anglicus (Gilbert the Englishman) around the middle of the 13th century. ̽��ֱ��text is titled Compendium medicine and is written in a near contemporary hand in two columns, probably by a scribe from the south of France.

Later in the same century, this manuscript (now kept in Cambridge ̽��ֱ�� Library) found its way to England. We know this because there are notes made by an owner writing in an English hand. ̽��ֱ��Latin text of Gilbertus’s Compendium medicine was the first great survey of medical knowledge to have been assembled after the arrival of Greek and Arabic texts in Western Europe, and was tremendously popular. It represents a key source for historians of medical knowledge in the Middle Ages.

Particularly fascinating for historians interested in the communication of practical medical knowledge are additions to the text written in the margins of the Pembroke manuscript (MS 169). Some of these “postscripts” are valuable evidence for how orally transmitted traditions gradually entered written records – and became embedded in later copies of medical texts.

At the bottom of a page of the manuscript is an empericum (remedy) neatly written in the margin, perhaps even by Gilbertus himself, soon after the original text was compiled. It sets out, in considerable detail, a prescription for the treatment of sterility that “never fails” (“qui numquam fallit”). This personal witness to the remedy’s success (“through this treatment by our hand many who were thought to be sterile conceived”) inspired someone to add the remedy in the margin of a manuscript written at some expense by a professional scribe.

Other entries in the margins of Compendium medicine credit remedies to “a soldier”, or “a Saracen”, but scholars don’t know who told Gilbertus this particular empericum.

To summarise the remedy: a man aged 20 years or more should, at a precisely designated hour and while reciting the Lord’s prayer, pull from the ground two plants (comfrey and daisy) and extract their juices. These juices should be used to inscribe the words of a well-known directive from Genesis (“ ̽��ֱ��Lord said: Increase and multiply and fill the earth”), together with some magical names, on an amulet to be worn during sexual intercourse. If the verse is worn by the man, the union will produce a boy, if by the woman, a girl.

In subsequent copies of Gilbertus’s Compendium medicine, the same prescription appears in the main body of the author’s text, and so it found its way into print in the 16th century. Its later readers would have had no idea that this remedy was not part of the original version and may have first circulated by word of mouth.

In an article published in a special issue of the Bulletin of the History of Medicine, Peter Murray Jones and Lea Olsan (Department of History and Philosophy of Science) draw on dozens of examples from manuscripts circulating in England between 900 and 1500 to show how medieval men and women used performative rituals to negotiate the dangers and difficulties of conception and childbirth.

Charms, prayers, amulets and prayer-rolls played important roles within the sphere of human reproduction at a time when male impotence or infertility, and the perils of childbirth, were not just matters of personal anxiety but vitally affected the legality of marriage and the inheritance of land or noble status.

Jones and Olsan illustrate, through their analysis of surviving documentation, the ways in which performative rituals combine spoken words and actions which drew on Christian liturgy, the intercession of saints, as well as occult symbols and powers to protect mothers and children or to ensure fertility. Repeated use of the rituals added to their force. Some were extremely long-lived, but at different times might involve different actors – monks, priests, or friars as well as local healers, midwives, doctors or the lay owners of remedy books.

One of the earliest and most important of the sources for these rituals is the Trotula collection of texts – a compendium of women’s medicine dating from the 12th century when it was collated in Salerno (Italy), and later assumed to have been written by a female physician.

Drawing on a detailed study of this collection by historian Monica Green, Jones and Olsan cite three rituals to facilitate a delayed birth or expel a dead fetus. One such remedy, for difficult birth, requires the woman to eat the sator arepo tenet opera rotas palindrome (a phrase that could be written out as a magic square of letters) written in butter or cheese. A second specifies a string of letters, this time to be drunk with the milk of another woman. A third ritual employs the skin of a snake as a birthing girdle, to be tied around the mother-to-be.

This special issue of the Bulletin of the History of Medicine was edited by members of the Department of History and Philosophy of Science in Cambridge (Nick Hopwood, Peter Murray Jones, Lauren Kassell and Jim Secord).Their introduction explains how important the whole business of communication has been to the history of reproduction. ̽��ֱ��other articles in the issue explore communication and reproduction from a variety of angles and in different periods. See the Q&A at the JHU Press blog.

̽��ֱ��special issue springs from a larger Cambridge project that looks at the long-term shifts in understandings and practices of reproduction. Funded by a Wellcome Trust Strategic Award, the historians involved in this ‘Generation to Reproduction’ programme are offering fresh perspectives on issues ranging from ancient fertility rites to IVF. They are thus reassessing the history of reproduction over the long term.

A study of one of the most important medieval texts devoted to women’s medicine has opened a window into the many rituals associated with conception and childbirth. Research into the shifting communication of knowledge contributes to a wider project looking at the history of reproduction from ‘magical’ practices right through to IVF.

By permission of the Master and Fellows of Pembroke College, Cambridge

̽��ֱ��"empericum that never fails" in the margin of the Compendium of Gilbertus Anglicus. ̽��ֱ��instructions are for making and applying an amulet for conception.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Haeckel’s embryos: the images that would not go away

amb206 — Mon, 06 Jul 2015 08:00:00 +0000

Some of the best-known illustrations in biology were challenged as forgeries soon after their publication 140 years ago in books by the German Darwinist, Ernst Haeckel. Hundreds of attacks placed them among the most controversial scientific images, but textbooks nevertheless copied and recopied them through the 20th century. Though recently forced out by new scientific criticism, and by creationist advocates of so-called intelligent design, some biologists defend them still. They make striking examples of how standard pictures represent knowledge over the long term.

In Haeckel’s Embryos: Images, Evolution and Fraud, published by the ̽��ֱ�� of Chicago Press, Dr Nick Hopwood tells the full story for the first time. He tracks the drawings and the charges against them from their genesis in the 19th century to the present day. He recaptures the shocking novelty of pictures that enthralled schoolchildren and outraged priests, and highlights the remarkable ways these images continued to shape knowledge as they aged.

Ernst Haeckel was a passionate and pugnacious advocate of evolution. An accomplished artist, he drew provocative illustrations for books that, from 1868 onwards, caught the public imagination with their message that human beings are not divinely created but evolved from humble beginnings. ̽��ֱ��similarity of human to other vertebrate embryos provided Haeckel’s strongest evidence for common descent, but he lacked vivid comparative pictures.

He designed some by lining up human development alongside equivalent stages in the development of turtle, chick and dog, and later of many other species. For their first two months in the womb, this liberal roared, even those aristocrats who fancied that blue blood flowed in their veins were indistinguishable from dogs. ̽��ֱ��plates further supported Haeckel’s view that “ontogeny recapitulates phylogeny”: we climb our evolutionary tree in the womb. But expert critics accused Haeckel of drawing the embryos more alike than they really are, and thus of playing fast and loose with the truth.

̽��ֱ��usual approach to Haeckel’s embryos has been to try him for fraud and assess the implications for the theory of evolution. Hopwood answers these questions: Haeckel drew recklessly compared with his peers, but there is no evidence of dishonest intent and he had little to gain from deception. ̽��ֱ��discovery of molecular homologies between species evidences evolution more persuasively than Haeckel ever could.

Hopwood argues, however, that it is more interesting to use the case to explore how images succeed or fail, how they come to be taken for granted or cause trouble. Haeckel’s pictures became so controversial because they were viewed simultaneously by specialists fighting his approach and by readers who had never seen an embryo before. Education was still the preserve of a privileged few and science was hardly taught, but Haeckel promised to reveal the mysteries of life.

He lampooned “the so-called educated”, those products of the classical grammar schools who did not believe that humans come from eggs and recoiled in disgust when shown images representing their own becoming. He worked to create a mass audience for science and to make embryonic development a process we can see, compare and discuss.

Supporters mostly accepted Haeckel’s defence that his pictures of embryos were ordinary schematics like his colleagues used in classrooms every day, but theologians exploited the forgery charges to discredit the “German Darwin”. Wave after wave of attacks rained down on his head.

On the eve of the First World War, by which time he was the most famous living evolutionist in the world, new enemies rewarmed the allegations and added more.

̽��ֱ��embryos were copied nevertheless, now especially into textbooks in the US, where authors were often unaware of the fuss. Until 1997, that is, when a British biologist accused Haeckel again and creationists waged an iconoclastic campaign. But these apostles of “intelligent design” also tried to turn the pictures into icons of infamy. This combined with the take-off of the internet to make them, ironically, more accessible than ever before.

Haeckel’s Embryos shows how the most controversial images in the history of science became some of the most widely seen. Hopwood suggests that the novel grid structure gave them persuasive power, but that they did not just express Haeckel’s recapitulation theory.

̽��ֱ��pictures favoured the idea of a conserved stage, but otherwise remained open to different interpretations. Texts even reproduced them, attributed to a secondary source, on the same pages that explained Haeckel was wrong.

Hopwood investigates copying as the way an image gains a life of its own and becomes embedded in a field. This case demonstrates how creative, consequential and contested the process can be.

Trouble started when Haeckel was accused, among other things, of miscopying standard figures. Then copying released the images from his books and, from many variants, selected one canonical form. Controversy sparked when the copying of the pictures intersected with the repetition of the forgery charges.

̽��ֱ��pictures and the charges usually circulated independently, but clashed in small-scale disputes. A religion teacher would catch a pupil reading one of Haeckel’s books under the desk and denounce the illustrations as frauds. A priest would challenge an itinerant freethinker during a slide lecture. Or parents would warn their daughters that books with such horrible illustrations were unsuitable for girls. ̽��ֱ��big controversies started, during periods of intense debate over Darwinism, when such objections reached the press.

̽��ֱ��product of more than a decade of work, Haeckel’s Embryos is published in a large format and lavishly illustrated with colour illustrations that range from fine engravings to cartoons and wax models to websites. These allow the argument to proceed in pictures as much as in words. ̽��ֱ��book is the most comprehensive history of a scientific image ever undertaken – and that history is not over yet.

“ ̽��ֱ��shock of the copy”, as Hopwood calls it, is not simply that the pictures were reproduced for so long. ̽��ֱ��real surprise is that they are still involved in innovation over a century after they were first published. In 2010, in the wake of the recent controversy, Haeckel’s grid appeared in the unusual form of a mosaic of stained fruit-fly embryos on the cover of the leading science journal Nature, where it signalled that genomic methods confirmed the existence of a conserved embryonic stage.

While most images make a brief appearance, only to be forgotten quickly, others become so entrenched that it is almost impossible to wave them goodbye.

Nick Hopwood is Reader in History of Science and Medicine in the Department of History and Philosophy of Science, ̽��ֱ�� of Cambridge. Haeckel’s Embryos: Images, Evolution and Fraud is published by the ̽��ֱ�� of Chicago Press. ̽��ֱ��research was supported by the Wellcome Trust as part of the Generation to Reproduction programme.

Inset images: A bewildered listener representing “the so-called educated” flees Haeckel’s lecture, his mind blown by the embryological illustrations, and rushes to an inn (Illustration by Fritz Steub from Moritz Reymond, Fünf Bücher Haeckel [1882], 1:102); Still from the 2007 Discovery Institute video Hoax of Dodos – an advocate of “intelligent design” shows a sceptic Haeckel-style drawings in a recent biology book; A grid of shark, snake, chick and human embryos, modelled on Haeckel’s but more accurate and much less successful (from Richard Hesse, Abstammungslehre und Darwinismus (1902), 21).

A new book tells, for the first time in full, the extraordinary story of drawings of embryos initially published in 1868. ̽��ֱ��artist was accused of fraud – but, copied and recopied, his images gained iconic status as evidence of evolution.

Education was still the preserve of a privileged few and science was hardly taught, but Haeckel promised to reveal the mysteries of life

Lithograph from Haeckel, Anthropogenie (1874), plates IV–V.

Comparison of embryos of fish, salamander, turtle, chick, pig, cow, rabbit and human embryos at three different stages of development.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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