Book Review: The Dance of Life: Symmetry, cells and how we become human

The Dance of Life: Symmetry, Cells and How We Become Human

By Professor Magdalena Zernicka-Goetz and Dr Roger Highfield

Published by WH Allen

ISBN-10: 0753552922, ISBN-13: 978-0753552926

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The Dance of Life: Symmetry, Cells and How We Become Human is the autobiography of the developmental biologist Professor Magdalena Zernicka-Goetz, written with the unobtrusive but unerring support of a master science writer, Dr Roger Highfield. The titular dance is not only that of early embryonic life, but of Magdalena herself, whose life and work 'locked together' when advised that her unborn baby was likely to have an additional chromosome. So begins Magdalena's 'journey to find' her 'own scientific voice'.

Until she was four, her home was her father's laboratory in Warsaw, her family having lost everything to the Nazis. Struggling with reading (she would be diagnosed dyslexic at 17), her father advised her to forget about homework, enroling her in a professional tennis club. She seemed destined to become a tennis professional until a back injury intervened.

An embryology lecture changed everything. Joining Andrzej Tarkowski's lab in the late 1980s, she learnt to use crude equipment creatively, undertook a year's fellowship at Oxford, eventually joining Martin Evans' Cambridge lab in 1995. Working on the polarity of eight-cell embryos, she saw evidence that seemed to conflict with a curious embryological dogma. In principle, a fertilised egg should simply grow into a bigger and bigger, symmetrical, ball of cells. Except, it doesn't: symmetry is broken and form emerges as embryonic cells divide to produce progeny cells that differ from one another.

In frog embryos, this developmental 'polarisation' begins at the outset in the fertilised egg. Mammals, however, were deemed to be special; orthodoxy dictated that each cell of a two-cell mammalian embryo had the same potential to lead to different developmental pathways, such as towards the development of the placenta or future body, as each other. And so, this apparently niche claim had real world implications, and was stoutly defended. Questioning it would polarise Magdalena's own direction in life.

Inspired by Alan Turing's 1951 paper on the emergence of form from formlessness in theoretical embryos, Magdalena sought to understand the origin of bias - the source of form - in real ones. By gluing microbeads onto fertilised eggs to create a frame of reference, she confirmed that polarity arose at the earliest stage of development. Feathers ruffled. An eminent scientist at the Max Planck Institutes publicly attacked her science. An anonymous referee blocked funding for further research, declaring that there was 'no evidence' for what she had demonstrated.

Eventually, on the day her son Simon was born, her paper on the molecular mechanism for symmetry breach was published, destroying the cherished dogma. Years later, she would elucidate the mechanism of transcription factors involved in determining polarity.

Magdalena's inquiry into symmetry-breaking led to a milestone in developmental biology: the creation of simulated mouse 'embryos' using individual stem cells from all three embryonic types, constructed by the cells themselves. Proceeding meticulously, step by step, first with cells en route to becoming a body, then adding those on course to becoming placenta, then those developing in the yolk sac direction, she watched cells organise themselves 'as if they knew what they were doing and had a goal'.

Cells polarised, types parted in a 'pas de deux', a cavity appeared resembling the rosette cavity she had discovered in implantation-stage embryos, and finally a gene associated with establishing the body's head/tail axis was expressed. Reading about the development of these simulated 'embryos' leaves one gasping: sequence, architecture and gene activity all matched those of naturally developing embryos. A gift to future researchers studying this aspect of development, and understanding why human and mouse development diverge, the achievement has overwhelming emotional impact.

The Times headlined its preview of The Dance of Life: Symmetry, Cells and How We Become Human, 'I knew my prenatal test was wrong'. She didn't: she was as shocked as any mother. Her science suggested that her baby might possibly be healthy, but it was hardly conclusive.

Securing funds to investigate whether embryos could correct themselves, using normal/abnormal eight-cell chimeric embryos, she found that abnormal cells destroyed themselves at twice the rate of normal ones: some embryos even self-corrected when 75 percent of their cells were abnormal.

Following a marathon series of experiments to confirm the result by other means, Nature Communications published her team's results: solid evidence of progressive depletion of aneuploidic cells in mammalian embryos. Simon, born healthy and bright, by now was nine.

Magdalena's descriptions of her feelings for her tiny, inconvenient embryo, willing him into healthy life, are deeply moving, her respect for early life, palpable and profound. She doesn't just demand respect for the few human embryos she works on: meetings and coffee breaks must wait until mouse embryos are returned to the incubator, as if to their mothers.

Her work has led some to propose extending the 14-day research limit on human embryos, but she advocates allowing time for insights gained from longer culture periods, ethical reflection and informed public support. She would also prohibit the implantation of synthetic human 'embryos', created for experiments, requiring researchers to follow equivalent guidelines, and legislators to focus upon intention, not embryonic equivalence.

Magdalena adores collaborative science, crediting her peers, colleagues and students no less than herself. The book abounds with joy. Science has to be fun; success celebrated with champagne. Scientific progress, she remarks, 'depends on being creative, being open and fearless in questioning well-established wisdom' while being thoughtful and modest. Speaking of the seminal twin papers published in May 2016 on self-organisation of late stage embryos, she airily remarks that, 'as it turned out' the US lab that told her it was working on non-human primates had actually been using her culture technique on human embryos while her own work was delayed by a laboratory move, but 'science was the winner'.

Remarkable as her achievements are, it's also a book about failure. 'I have had to deal with more failure than success' in science and personal life, Magdalena reflects. If scepticism underpins the advance of science (most experiments fail), prejudice impedes it (so do 'most grant applications proposing bold ideas'). Speaking passionately against the unjust treatment of women scientists, she calls for real equality. In a moving coda, Magdalena reflects on time lost seeing her beloved children growing up, and on the present. Facing reduced grant funding, Brexit uncertainty and the rise of the far right, she has moved to Caltech. Her tone is elegiac, but hopeful.

Easily the best written popular book on human embryology, a unique record of a scientific golden age, and a moving insight into the life of a great scientist seeking to balance her life, 'The Dance of Life: Symmetry, Cells and How We Become Human' has the capacity to become a classic beyond the realms of popular science. It will inspire for many years to come.

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