̽��ֱ�� of Cambridge - history of science

̽��ֱ��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.

Yes

Astrolabe reveals Islamic–Jewish scientific exchange

ta385 — Mon, 04 Mar 2024 06:30:00 +0000

̽��ֱ��identification of an eleventh-century Islamic astrolabe bearing both Arabic and Hebrew inscriptions makes it one of the oldest examples ever discovered and one of only a handful known in the world. ̽��ֱ��astronomical instrument was adapted, translated and corrected for centuries by Muslim, Jewish and Christian users in Spain, North Africa and Italy.

Magdalene College discovers a treasure trove of women’s intellectual history

ta385 — Mon, 08 Mar 2021 09:20:00 +0000

̽��ֱ��collection comprises 47 books and pamphlets owned and annotated by the philosopher Mary Astell (1666–1731), viewed by many as “the first English feminist”. Her hand-written notes reveal, for the first time, that Astell engaged with complex natural philosophy including the ideas of René Descartes.

COVID-19: ̽��ֱ��long view

ta385 — Fri, 22 May 2020 12:00:00 +0000

̽��ֱ��COVID-19 pandemic should only present a short-term interruption to 250 years of improving life expectancy, argues historian Leigh Shaw-Taylor.

Opinion: Patient zero: why it's such a toxic term

fpjl2 — Wed, 01 Apr 2020 15:14:09 +0000

Dr Richard McKay traces the history of the 'patient zero' idea through epidemics such as HIV and typhoid, and the return of this trope with COVID-19.

An instrumental collection

ta385 — Thu, 24 Oct 2019 09:00:00 +0000

Hundreds of scientific treasures are going on display as the Whipple Museum marks the 75th anniversary of a remarkable donation to the ̽��ֱ�� of Cambridge.

Sir Isaac Newton’s Cambridge papers added to UNESCO’s Memory of the World Register

sjr81 — Fri, 01 Dec 2017 09:36:33 +0000

Held at Cambridge ̽��ֱ�� Library, Newton’s scientific and mathematical papers represent one of the most important archives of scientific and intellectual work on universal phenomena. They document the development of his thought on gravity, calculus and optics, and reveal ideas worked out through painstaking experiments, calculations, correspondence and revisions.

In combination with alchemical papers at King’s College, Cambridge and his notebooks and correspondence at Trinity College, Cambridge and the Fitzwilliam Museum, this represents the largest and most important collection of Newton’s papers worldwide.

Katrina Dean, Curator of Scientific Collections at Cambridge ̽��ֱ�� Library said: “Newton’s papers are among the world’s most important collections in the western scientific tradition and are one of the Library’s most treasured collections. They were the first items to be digitised and added to the Cambridge Digital Library in 2011 and featured in our 600th anniversary exhibition Lines of Thought last year. In 2017, their addition to the UNESCO International Memory of the World Register recognises their unquestionable international importance.”

̽��ֱ��Memory of the World Project is an international initiative to safeguard the documentary heritage of humanity against collective amnesia, neglect, the ravages of time and climatic conditions, and wilful and deliberate destruction. It calls for the preservation of valuable archival, library and private collections all over the world, as well as the reconstitution of dispersed or displaced documentary heritage, and the increased accessibility to and dissemination of these items.

Newton’s Cambridge papers, and those at the Royal Society, now join the archive of Winston Churchill, held at Cambridge ̽��ֱ��’s Churchill Archives Centre, on the UNESCO Register. They also join Newton’s theological and alchemical papers at the National Library of Israel, which were added in 2015.

̽��ֱ��chief attractions in the Cambridge collection are Newton’s own copies of the first edition of the Principia (1687), covered with his corrections, revisions and additions for the second edition.

̽��ֱ��Cambridge papers also include significant correspondence with natural philosophers and mathematicians including Henry Oldenberg, Secretary of the Royal Society, Edmond Halley, the Astronomer Royal who persuaded Newton to publish Principia, Richard Bentley, the Master of Trinity College, and John Collins, mathematician and fellow of the Royal Society who became an important collector of Newton’s works.

Added Dean: “One striking illustration of Newton’s experimental approach is in his ‘Laboratory Notebook’, which includes details of his investigations into light and optics in order to understand the nature of colour. His essay ‘Of Colours’ includes a diagram that illustrates the experiment in which he inserted a bodkin into his eye socket to put pressure on the eyeball to try to replicate the sensation of colour in normal sight.”

Another important item is Newton’s so-called ‘Waste Book’, a large notebook inherited from his stepfather. From 1664, he used the blank pages for optical and mathematical calculations and gradually mastered the analysis of curved lines, surfaces and solids. By 1665, he had invented the method of calculus. Newton later used the dated, documentary evidence provided by the Waste Book to argue his case in the priority dispute with Gottfried Wilhelm Leibniz over the invention of the calculus.

Cambridge ̽��ֱ�� Librarian Jess Gardner said: “Newton’s work and life continue to attract wonder and new perspectives on our place in the Universe. Cambridge ̽��ֱ�� Library will continue to work with scholars and curators worldwide to make Newton’s papers accessible now and for future generations.”

Isaac Newton entered Trinity College as an undergraduate in 1661 and became a Fellow in 1667. In 1669, he became Lucasian Professor of Mathematics at Cambridge ̽��ֱ��, a position he held until 1701.

Among the more personal items in the Cambridge collections are Newton’s daily concerns as recorded in an undergraduate notebook which records Newton’s expenditure on white wine, wafers, shoe-strings and ‘a paire of stockings’, along with a guide to Latin pronunciation.

A notebook of 1662-1669 records Newton’s sins before and after Whitsunday of 1662, written in a coded shorthand and first deciphered between 1872 and 1888. Among them are ‘Eating an apple at Thy house’, ‘Robbing my mothers box of plums and sugar’ along with the more serious ‘Wishing death and hoping it to some’ before a list of his expenses. These included chemicals, two furnaces and a recent edition of one of the most comprehensive compilations of alchemical writings in the western tradition Theatrum chemicum, edited by the publisher Lazarus Zetzner.

Cambridge ̽��ֱ�� Library is also hosting a series of talks open to the public by Sarah Dry and Patricia Fara on Newton’s manuscripts and Newton’s role in Enlightenment culture and polite society on December 7 and December 14 respectively. For details and bookings, see: http://www.lib.cam.ac.uk/using-library/whats

̽��ֱ��Cambridge papers of Sir Isaac Newton, including early drafts and Newton’s annotated copies of Principia Mathematica – a work that changed the history of science – have been added to UNESCO’s International Memory of the World Register.

Newton’s papers are among the world’s most important collections in the western scientific tradition and are one of the Library’s most treasured collections.

Katrina Dean

Cambridge ̽��ֱ�� Library

Image from Newton’s own annotated copy of Principia Mathematica

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

Yes

Licence type:

Attribution-Noncommercial-ShareAlike

Research reveals accidental making of ‘Patient Zero’ myth during 1980s AIDS crisis

fpjl2 — Wed, 26 Oct 2016 17:02:10 +0000

A new study proves that a flight attendant who became notorious as the human epicentre of the US AIDS crisis of the 1980s – and the first person to be labeled the ‘Patient Zero’ of any epidemic – was simply one of many thousands infected in the years before HIV was recognised.

Research by a historian from the ̽��ֱ�� of Cambridge and the genetic testing of decades-old blood samples by a team of US scientists has demonstrated that Gaétan Dugas, a French-Canadian gay man posthumously blamed by the media for spreading HIV across North America, was not the epidemic’s ‘Patient Zero’.

In fact, work by Dr Richard McKay, a Wellcome Trust Research Fellow from Cambridge’s Department of History and Philosophy of Science, reveals how the very term ‘Patient Zero’ – still used today in press coverage of outbreaks from Ebola to swine flu to describe the first known case – was created inadvertently in the earliest years of investigating AIDS.

Before he died, Dugas provided investigators with a significant amount of personal information to assist with studies into whether AIDS was caused by a sexually transmitted agent. McKay’s research suggests that this, combined with confusion between a letter and a number, contributed to the invention of ‘Patient Zero’ and the global defamation of Dugas.

Dr McKay’s work has added important contextual information to the latest study, led by Dr Michael Worobey from the ̽��ֱ�� of Arizona and published today in the journal Nature, which has compared a new analysis of Dugas’s blood with eight other archived serum samples dating back to the late 1970s.

“Gaétan Dugas is one of the most demonised patients in history, and one of a long line of individuals and groups vilified in the belief that they somehow fuelled epidemics with malicious intent,” says McKay.

While his wider research traces this impulse to blame back several centuries, for the Nature paper McKay located the immediate roots of the term “Patient Zero” in an early ‘cluster study’ of US AIDS patients.

Mistaken for zero

Reports emerged in early 1982 of historical sexual links between several gay men with AIDS in Los Angeles, and investigators from the Centers for Disease Control (CDC) undertook a study to interview these men for the names of their sexual contacts.

They uncovered more links across southern California, but one connection was named several times despite not residing in the state: Case 057, a widely travelled airline employee. Investigators found that his sexual contacts included men in New York City, and some of his sexual partners developed symptoms of AIDS after he did.

CDC investigators employed a coding system to identify the study’s patients, numbering each city’s cases linked to the cluster in the sequence their symptoms appeared (LA 1, LA 2, NY 1, NY 2, etc.). However, within the CDC, Case 057 became known as ‘Out(side)-of-California’ – his new nickname abbreviated with the letter ‘O.’

Because other cases were numbered, it was here that the accidental coining of a new term took place. “Some researchers discussing the investigation began interpreting the ambiguous oval as a digit, and referring to Patient O as Patient 0,” says McKay. “‘Zero’ is a capacious word. It can mean nothing. But it can also mean the absolute beginning.”

̽��ֱ��LA study expanded, due in no small part to information provided by Case 057. Over 65% of men in the cluster reported more than 1,000 partners in their lifetimes, over 75% more than 50 in the past year. But most could offer only a handful of names of those partners.

As well as donating plasma for analysis, Case 057 managed to provide 72 names of the roughly 750 partners he’d had in the previous three years. Also, his distinctive name may have been easier for other men to remember, says McKay. “ ̽��ֱ��fact that Dugas provided the most names, and had a more memorable name himself, likely contributed to his perceived centrality in this sexual network.”

By the time the expanded study was published in 1984, the same year Dugas died of his illness, the cluster showed dozens of cases connecting several North American cities. Near the very centre of an accompanying diagram is a floating case that links both coasts, the itinerant Dugas. Case 057, the ‘Out-of-California’ case, had been rechristened simply as “Patient 0” – causing much speculation in the media.

‘Casting’ an epidemic

̽��ֱ��journalist Randy Shilts would use the LA cluster study as an important thread in his bestselling book on the AIDS crisis, And the Band Played On. During the book’s research, he became fascinated by the study’s ‘Patient 0’.

Motivated to find out more about this man, Shilts eventually learned his name in 1986. ̽��ֱ��journalist tracked down his friends and colleagues for interviews, and, as “Patient Zero,” made him one of the more memorable villains in his book.

To call attention to the crisis, Shilts set out to “humanise the disease”, says McKay, who discovered that an early outline for the book actually listed ‘ ̽��ֱ��Epidemic’ itself among the cast of characters. “To Shilts, Dugas as Patient Zero came to represent the disease itself.”

̽��ֱ��1982 study had initially suggested to investigators that the period between infection and the appearance of AIDS symptoms might be several months.

By the time Shilts’s book was published in 1987, however, it was known that an infected individual might not display symptoms for several years, and that the study was unlikely to have revealed a network of infection. Yet Shilts uncritically resurrected the story of the Los Angeles cluster study and its ‘Patient 0,’ with long-standing consequences.

̽��ֱ��journalist’s decision provoked immediate criticism from AIDS activists in lesbian and gay communities across North America and the UK. Some of their works of protest are cited in the Nature study, and explored in greater detail in McKay’s own forthcoming book and in a 2014 article he published in the Bulletin of the History of Medicine.

“In many ways, the historical evidence has been pointing to the fallacy of Patient Zero for decades,” explains McKay. “We now have additional phylogenetic evidence that helps to consolidate this position.”

McKay describes the very phrase ‘Patient Zero’ as “infectious.” “Long before the AIDS epidemic there was interest in locating the earliest known cases of disease outbreaks. Yet the phrases ‘first case,’ ‘primary case,’ and ‘index case’ didn’t carry the same punch.

“With the CDC’s accidental coining of this term, and Shilts’s well-honed storytelling instincts, you can see the consolidation of an ‘infectious’ formula that would become central to the way many would make sense of later epidemics.”

Blaming ‘others’

Now, almost 30 years since Shilts’s book, analysis of the HIV-1 genome taken from Dugas’s 1983 blood sample, contextualised through McKay’s historical research, has shown that he was not even a base case for HIV strains at the time, and that a trail of error and hype led to his condemnation as the so-called Patient Zero.

̽��ֱ��researchers say it may be naïve to expect Patient Zero’s legendary status, or the popular impulse to attribute blame for disease outbreaks, to ever disappear.

“Blaming ‘others’ – whether the foreign, the poor, or the wicked – has often served to establish a notional safe distance between the majority and groups or individuals identified as threats,” says McKay.

“In many ways, the US AIDS crisis was no different – as the vilification of Patient Zero shows. It is important to remember that, in the 1970s, as now, the epidemic was driven by individuals going about their lives unaware they were contracting, and sometimes transmitting, a deadly infection.

“We hope this research will give researchers, journalists and the public pause before using the term Patient Zero. ̽��ֱ��phrase carries many meanings and a freighted history, and has seldom pointed to what its users have intended.”

A combination of historical and genetic research reveals the error and hype that led to the coining of the term ‘Patient Zero’ and the blaming of one man for the spread of HIV across North America.

We hope this research will give researchers, journalists and the public pause before using the term Patient Zero

Richard McKay

Harry Reasoner introduces the 60 Minutes program featuring ‘Patient Zero’ and the American AIDS crisis, broadcast on CBS in November 1987.

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

Yes