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Biological Reasoning: why biological translation is a sociological art

Earlier this year in January, Katie Dow and I went in search of the missing early Warnock files that we had never found either in the Burnley, Lancashire holdings of the Department of Health Repository, or in the National Archives at Kew. Although it was a wonderful surprise to discover a complete set of freshly declassified files of this famous Committee of Inquiry into Human Fertilisation and Embryology waiting for us on our arrival, the visit ended with one major disappointment, which was that the crucial paper I have been looking for since 2010 was not in any of the places it should have been, and is apparently not in the new files.

Sarah Franklin, September '16 - available to download as a PDF.

Earlier this year in January, Katie Dow and I went in search of the missing early Warnock files that we had never found either in the Burnley, Lancashire holdings of the Department of Health Repository, or in the National Archives at Kew. Although it was a wonderful surprise to discover a complete set of freshly declassified files of this famous Committee of Inquiry into Human Fertilisation and Embryology waiting for us on our arrival, the visit ended with one major disappointment, which was that the crucial paper I have been looking for since 2010 was not in any of the places it should have been, and is apparently not in the new files. Anne McLaren’s paper ‘Where to Draw the Line?’ was arguably the most important single document of the entire Warnock Inquiry. It was tabled at the Committee’s 11th meeting in October 1983, for discussion at their next meeting on November 9th – a day that would be wholly devoted to the single issue of embryo research. McLaren’s paper laid the basis for what became the 14-day rule, allowing embryo research up to 14 days, subject to strict regulation, in order that the benefits of such research to both biomedicine and bioscience could be most fully realised.

 

 

 

The files from the Warnock Committee include a wide range of papers, memos, agendas, minutes and correspondence from many branches of gov’t and dating back to the formation of the committee. Many of them were closed for 25 years until 2016.

 

 

 

From the new files it is possible to develop a nuanced picture of what went on at the Warnock Committee meetings, which were meticulously planned in advance, and supported by several members of the Secretariat, who kept detailed confidential records of what went on, and what they thought, in memos, meeting synopses, and briefings to the Chair. In preparation for the 9 November meeting, a briefing note to Warnock, from her Secretary, Jenny Croft, summarised the ‘Organisation of the Day’s Business’  and anticipated some of the possible outcomes: ‘As agreed at the last meeting [13 October 1983], the whole of Wednesday is to be devoted to a discussion of experiments on embryos.... We had thought in terms of allowing the morning for the more general discussion, and turning to the matters requiring decisions after lunch.’ 

She continued: 

It may be that we cannot get answers to all the questions at the meeting, but I think we agreed we might need more than one meeting on the subject [as] it is a topic where it is important that the inquiry feel satisfied with the position they eventually take.  If it would be helpful, we could draw together the lines of discussion on Wednesday, and any decisions which are reached into a connected piece of narrative for the next meeting [in December], so that members could consider whether this indeed represents their views.

It’s clear the first major item for discussion in the old DHSS Headquarters in Elephant and Castle on the morning of 9 November 1983 was a single page document circulated before the meeting with the Agenda and other papers. In a neat numeric table summarising correspondence received by the Inquiry was a rather sobering set of sum totals for the 16 members of the Inquiry assembled around the table in Hannibal House to digest.  Against the 8 letters written in support of IVF, 123 letters had been received by the Inquiry opposing either IVF or surrogacy, while yet another 284 letters specifically objected to experiments on embryos. Letters written in opposition to IVF, surrogacy and embryo experiments consequently outnumbered those in favour of IVF by a daunting ratio of 50 to 1. 

 

 

 

Members of the Committee of Inquiry into Human Fertilisation and Embryology chaired by Mary Warnock

 

 

 

It is difficult to imagine a document more unlikely to have opened a meeting that would lay the groundwork for the most comprehensive and progressive legislation supporting reproductive biomedicine and embryo research ever enacted. As a starting point for the discussion of what was arguably their most challenging topic, on which, as Warnock later wrote, ‘there is bound to be criticism that we have gone too far, or not far enough’ (1985:vii), such a large ‘no vote’ must have felt like a shot across the bows. Especially since only a small minority of members would have been inclined to support a total ban on IVF and embryo research, the placement of this document at the top of the agenda would have signalled a call to action. Indeed, this inauspicious forecast may have been a deliberate warning to the members of the Inquiry, or even a red flag? Was it a line in the sand?

Many people have described the Warnock Committee as the Warnock and McLaren Committee – so significant was Anne’s role not only as a scientific advisor but as a strategist and co-author of the final report. Warnock herself has long been effusive in her praise of Anne’s ‘genius as a teacher’ and ‘spellbinding powers of exposition and explanation’ (2001: 488, 490), which she and many others relied upon extensively both during and after the Inquiry, as the Warnock Committee recommendations passed very gradually, but steadily, and with minimal modification, into law. Moreover, it is specifically Anne’s role as a skilled communicator whose ‘impeccable clarity’, ‘infinite patience’, and ‘unruffled amiability’ enabled ‘the developmental story of the fertilisation and post-fertilisation development of the embryo’ to become the basis for the famous 14-day rule that has been described as the secret of Warnock’s success. 

In the article I am writing at the moment about this single day in the history of the Warnock Committee’s deliberations, and Anne’s missing paper, I suggest that there are many translational lessons exemplified by the meeting on 9 November 1983 – as well as a translational paradox. Translational medicine today relies precisely on the kind of practice McLaren exemplified with her ‘excellent diagrams’ and ‘non-intimidating manner which made the science available... to the wider public’ (Warnock 2001:488). She managed to combine the highest level of expert scientific authority with both an exceptional ability to translate basic science and a generosity toward her audiences that communicated a level playing field. Like many scientists today, who have learned to value a more two-way conversation with the general public, and to build such conversations into their routine practice as scientific professionals, McLaren understood the importance of language and communication, of inclusivity and openness, and of the need to reach out and bring people in to the scientific way of thinking.

Despite its success, however, the collaboration between Warnock and McLaren has also been the source of much lasting criticism – and often for exactly the same reasons it is praised. The fourteen day rule, based as it is on the appearance of the primitive streak approximately 2 weeks after fertilisation, which is seen to mark the emergence of a distinct embryonic individual, immediately became one of the most controversial features of the Warnock proposals. One of the most common accusations about the fourteen-day rule, and in particular the distinction between the ‘embryo proper’ and the ‘pre-embryo’ which was later used to distinguish between the period before and after the ‘embryo proper’ or ‘definitive embryo’ had developed, was that it was ‘arbitrary’. John Biggers (1990), one of Anne’s long-term collaborators, wrote a scathing denunciation of ‘arbitrary partitions’ in the leading journal Human Reproduction. In October 1986, comparing scientists to Humpty Dumpty, MP Kenneth Hargreaves described the 14-day distinction as a barbaric attempt to manipulate the public in order ‘to diminish the status of the newly conceived embryo in the minds of the public’ (21 October 1986, HC cs. 971-3).

McLaren was admittedly equivocal on this point. At one level she admits the 14-day distinction is arbitrary – just as any line through a continuous process is arbitrary: the 14-day period ‘may be fairly arbitrary’, she admitted in a paper she gave in Edinburgh shortly after the Warnock Report was published, having inserted a hand-written qualification above the line in brackets ‘but not entirely arbitrary’. McLaren uses a range of descriptions, referring to ‘certain ethically significant attributes in development’ and the emergence of a ‘coherent entity with a self-contained set of lineages’ (ibid.). She frequently uses the term ‘developmental landmark’ instead of the more administrative ‘cut-off point’ favoured by the Medical Secretary to the Inquiry, Jeremy Metters.

What is interesting about this debate, in which very precise definitions of biological phenomena become translational platforms for deliberation and consultation about much larger issues – such as morality and the law, or utilitarianism vs. deontology -- is the inherent paradox of translation it exemplifies.  For if ‘maximally translational’ research initiatives must mobilise, as Dan O’Connor of the Wellcome Trust recently put it, ‘the full ecosystem of knowledges’ in order to deliver effective health improvements, then the distinction between what biology is and what biology means can no longer be absolutely maintained. The accusation of ‘arbitrariness’ misses the point that the social life of biological facts is inevitably plural. Moreover, it crucially overlooks the social, ethical and political reality that what biology means will directly shape what it becomes. This is exactly the principle the Warnock Report confirms: as a result of their interpretation of embryology, a new set of biological understandings, a new array of biological technologies, and new biological facts have come into being since 1984. By not banning embryo research, many new biological people, techniques and research trajectories were born in Britain over the past 3 decades, which have in turn changed how we understand phenomena such as stem cells, cloning, and cellular regeneration. As both McLaren and Warnock wisely and presciently recognised, biology is not just a set of facts, models, concepts, principles and theories. Biology is also a form of reasoning. Indeed what we might call ‘biological reasoning’ is how biology – as both a science and a popular idiom – is normally used. 

The question of whether a biological fact is true or false can only be answered if we overlook the context of reasoning in which it is being deployed. Biological claims about gender and sexuality are excellent places to observe the way biological reasoning can be employed to reach a wide range of factual conclusions. We see in these and other examples the way in which biological reasoning has a contradictory or equivocal element. Like many Americans, my born-again cousins from Illinois reject Darwin’s model of evolution root and branch: they believe humans must have alien ancestry. However when it comes to their pride in the pigs they farm by the thousands, whom they praise to the skies for their intelligence, cleanliness, grace, athleticism, orderliness, and longevity, their accumulated breeding acumen is so detailed you are certain they could turn a pig into a pigeon. Biological reasoning, like biology itself, takes many forms and often benefits from hybridity. 

Anne McLaren understood that biology was not the only concern of the people in the room on 9 November 1983. Their biological reasoning would have to take in much else besides, and that is exactly what she helped them to achieve by charting a biological sequence that could be appended to other agendas, and could accommodate entirely non-biological concerns. By breaking her biology down into manageable building blocks, she all but put in front of them the policy edifice that might be built. ‘Where to Draw the Line?’ offered a map based on a form of biological reasoning as close to biological science as possible, but with an ear to other possibilities. We can all but reassemble this paper word for word from the many versions of biological development McLaren published elsewhere, not least in the essential paragraphs 11.2 – 11.5 of the Warnock Report itself, which Anne drafted:

11.2 At fertilisation, the egg and sperm unite to become a single

cell. The nucleus of this cell contains the chromosomes derived

from both parents. This single cell is totipotential, as from it

develop all the types of tissue and organs that make up the human

body, as well as the tissues that become the placenta and fetal

membranes during intra-uterine development. In vivo, fertilisation

takes place in the upper portion of the fallopian tube and the

fertilised egg then passes down the fallopian tube into the cavity

of the uterus over a period of four to five days. At first when it

reaches the cavity of the uterus, it remains free-floating until it

begins to attach to the uterine wall at the start of implantation. This

is considered to begin on the sixth day following fertilisation.

During implantation, which occurs over a period of six to seven

days, the embryo enters the endometrium, the lining of the uterus.

At the eleventh to thirteenth day after fertilisation implantation is

complete.

 

11.3 While the fertilised egg is still in the upper portion of the

fallopian tube, it begins to divide into first two, then four, then eight,

then sixteen smaller cells, and so on by a process called cleavage.

At the start of cleavage, in a two or four-cell embryo, each cell

retains its totipotential capacity. Thus if separation occurs at the

two-cell stage each may develop to form a separate embryo. Such

a separation could lead to identical twins.

 

11.4 When sixteen or more cells have resulted from cleavage

the cells hang together in a loosely packed configuration, similar

to that of a blackberry, called a morula. The morula stage is

reached at about the same time as the embryo in vivo reaches the

uterine cavity. At about the same time a fluid-filled space begins

to form in an eccentric position within the substance of the morula.

Once this accumulation of fluid had occurred, the embryo is

described as a blastocyst. Within the blastocyst a thicker section

of the cyst wall becomes identifiable as the inner cell mass; it is

within this mass that the embryo proper, eventually to become the

fetus, develops. The remaining cells of the thin walled portion of

the blastocyst develop to become part of the placenta and fetal

membranes. At about the time that the blastocyst begins to

implant, a second fluid-filled space, the amniotic cavity, also

appears within the inner cell mass. Between the two cystic spaces

within the blastocyst, a plate of cells is formed. This is described

as the embryonic disc; within it the first recognisable features of

the embryo proper will appear.

 

11.5 The first of these features is the primitive streak, which

appears as the heaping up of cells at one end of the embryonic

disc on the fourteenth or fifteenth day after fertilisation. Two

primitive streaks may form in a single embryonic disc. This is the

latest stage at which identical twins can occur. The primitive

streak is the first of several identifiable features which develop in

and from the embryonic disc during the succeeding days, a period

of rapid change in the embryonic configuration. By the seventeenth

day, the neural groove appears and by the twenty-second

to twenty-third day this had developed to become the neural folds,

which in turn start to fuse and form the recognisable antecedent

of the spinal cord.

 

This short, four paragraph, account of embryological development in the Warnock Report clearly describes a continuous biological process while dividing it into three separate stages proceeding from the fertilised egg to the morula to the blastocyst. Similarly, within the blastocyst stage, McLaren describes four distinct developmental events, namely the formation of the embryonic disc, the primitive streak, the neural groove and later the neural folds. Like the three developmental stages, these four visibly transitional embryological events are named, so that the overall impression is of touring a well-known landscape which is navigable via a set of prominent and distinctive landmarks. Along the way, however, McLaren has inserted a new term that augers a new way of looking at this familiar process in order that a new division can be introduced between the ‘embryo’ and what McLaren calls ‘the embryo proper’. Later, this distinction will evolve into the 14-day rule, and still later into the distinction between the ‘embryo’ and the ‘pre-embryo’ (a term that was not used in the Warnock report, but introduced shortly afterwards – notably in an article by McLaren in 1986). 

This distinction between the ‘embryo proper’ and the ‘embryo’ is undoubtedly confusing, and has remained so. To a certain extent all scientific terms are arbitrary: past a certain point, it is obvious the differences between a fertilised egg, conceptus and zygote, for example, are blurred, overlapping and contextual. But what the accusation of ‘arbitrary’ has often been used to imply is that a purposeful distortion of scientific fact was imposed in order to achieve, by somewhat deceptive means, a desired political end. In this context ‘arbitrary’ does not mean ‘random’ or ‘haphazard’ or ‘serendipitous’. Critics such as Kenneth Hargreaves pointed not only to the deliberate and purposeful nature of the introduction of a new distinction between the ‘embryo’ and the ‘embryo proper’ – or ‘pre-embryo’: he argued such a use of words was undemocratic and implied it sought to disguise the interest of the scientific community beneath a veneer of objective fact.

However, Anne McLaren and Mary Warnock’s goal was both pragmatic and translational, and their use of words was far from arbitrary. They sought a combination of language, reason, evidence and analysis that would persuade the general public to follow their recommendations, which, they frequently emphasised, required a substantial degree of compromise. Warnock’s description of her goal in the introduction to the published version of her report was to provide a ‘reasoned discussion of the issues which...will contribute to a high standard of public debate on matters which are of deep concern to the public’ and to provide ‘a coherent set of proposals for how public policy...should respond’ (1985: vii). Part of this reasoning was by definition biological, but it also had to be many other things including morally defensible, procedurally viable, and acceptable to a large enough constituency to become politically feasible. ‘Translation’ in such a context thus involved developing a framework for legislation that would encompass ‘as many viewpoints as possible’ (1985:vi). 

At some point in the future I am hoping to locate the elusive document I have been seeking, and which is mysteriously missing from the Warnock files. In the meantime, I am preparing short paper for the Progress Educational Trust Annual Conference organised for 7 December 2016 on the topic of the 14-Day Rule and the recent calls for it to be extended by leading scientists such as Azim Surani at Cambridge. This in turn will be part of a larger project in the form of an extended article recreating the scene at the table on 9 November 1983 where Anne McLaren’s paper was the subject of a key transitional discussion among the members of the Warnock Committee 33 years ago. 

After the meeting on 9 November Jenny Croft wrote a summary of the day’s discussion in an internal memo circulated to the other members of the Secretariat.

Yesterday’s meeting of the Warnock Inquiry proved to be extremely successful. Certainly it was the most constructive meeting we have had. This was all the more surprising given the subject matter, research on human embryos, where we had expected considerable difficulty and sharp differences of view. To date this has not surfaced, though I am sure there are differences of position between members. The quality of the debate was unusually high, with an evenness of contribution from members which we have not previously seen and with all bar one making a contribution. The tone was uniformly constructive, with a marked desire to be comprehensive and not evade the issues. Progress was slow but rather more certain than on other occasions. (J Croft, memo from folder FPS 15/1). 

 

 

 

 

 

 

 

 

 

 

 As we saw earlier, it was the same Secretary, Jenny Croft, who had described the embryo research discussion as one ‘where it is important that the inquiry feel satisfied with the position they eventually take’. She was hoping that it might be possible to ‘draw together the lines of discussion on Wednesday, and any decisions which are reached into a connected piece of narrative for the next meeting’.

It appears that ‘Where to Draw the Line?’ was indeed a means of drawing the lines of discussion together, into the beginnings of a position with which enough of the members could feel satisfied to make a decision and form a recommendation. The ability to turn a conversation ‘where we had expected considerable difficulty and sharp differences of view’ into one in which ‘the tone was universally constructive’ and ‘the quality of the debate was unusually high’ reflecting ‘an evenness of contribution from members which we have not previously seen’ marked a turning point in the life of the Inquiry. From this point on the birth of the 14-day rule was only a matter of time. ‘Drawing the lines together’ into ‘a connected piece of narrative’ are phrases that describe several levels of this debate, in which the ability to tell a coherent biological story enabled the implementation of a coherent piece of legislation. They remind us that both biological translation and translational biological science do indeed require as inclusive, open and generous a conversation as possible. Paradoxically they also remind us that even the most literal biological facts are hybrid entities, and that handling them in public requires specific kinds of social skills. Many of these translational skills have been very successfully developed and implemented in the context of a series of debates over embryo research in the UK over the past three decades. In these debates biology is never just biology, and embryos are never only embryos: indeed they have convincingly shown that sound biological reasoning is best practiced as a sociological art.

 

References

Biggers, John (1990) ‘Arbitrary Partitions of Prenatal Life’ Human Reproduction 5:1:1-6

McLaren nd (1985?), ‘Early Human Development: Do we need research?’, Lecture delivered in Edinburgh,  Anne McLaren Papers, Box 83842, British Library

McLaren, Anne (1986) ‘Why Study Early Human Development?’ New Scientist 24 April pp 49-51

Warnock, Mary (1985) A Question of Life Oxford: Basil Blackwell

Warnock, Mary (2001) ‘Anne McLaren as Teacher’ International Journal of Developmental Biology 45:487-490.

The Reproductive Sociology Research Group supports research and teaching on the social and cultural implications of new reproductive technologies. ReproSoc is part of an expanding concentration of Reproductive Studies at Cambridge, is led by Professor Sarah Franklin and has funding from the Wellcome Trust, British Academy, ESRC, ERC, and Office of the Vice Chanccelloer, as well as several other funding bodies.

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