Magdalena Zernicka-Goetz: The Dance of Life: Symmetry, Cells and How We Become Human. Book review.

The Dance of Life

Magdalena Zernicka-Goetz, Roger Highfield (2020) The Dance of Life. Symmetry, Cells and How We Become Human.

Magdalena Zernicka-Goetz is a Polish-British developmental biologist and experimental embryologist. "I am one of the relatively small number of scientists who have cultured human embryos, allowing them to grow and thrive, although most of my work has been with mouse embryos (...) But I have to admit that I was also driven by the oldest scientific motive of all: I wanted to gain fundamental understanding of a critical chapter in the story of a human life, as this is when the embryo starts to grow and the overall body plan starts to be decided."

Roger Ronald Highfield is an author, science journalist, broadcaster and Science Director at the Science Museum Group.

Magdalena Zernicka-Goetz

This is an interesting and important book about ground-breaking discoveries of the development of the human embryo and also because of how her scientific research unexpectedly has been intertwined with her personal life:

"Magdalena Zernicka-Goetz was pregnant at 42 when a routine genetic test came back with that dreaded word: abnormal. A quarter of sampled cells contained abnormalities and she was warned her baby had an increased risk of being miscarried or born with birth defects. Six months later she gave birth to a healthy baby boy and her research on mice embryos went on to prove that – as she had suspected – the embryo has an amazing and previously unknown ability to correct abnormal cells at an early stage of its development." (from the publisher)

It appeared that her prenatal test of her pregnancy showed a trisomy 2: three copies of chromosome 2 (one extra copy) in a quarter of the tested cells. This is a very rare but serious chromosome abnormality [1]. 

normal human chromosomes (♂) wikipedia

The most frequent trisomies are 13, 18 and 21, and they are the only ones compatible with life birth. This is because these three chromosomes are small and have few protein-coding genes: chromosome 13 has 327, chromosome 18 has 270,and chromosome 21 has 234 protein-coding genes. Of those three, trisomy-21 is most frequent, this chromosome happens to have the smallest number of protein-coding genes. However, chromosome 2 is the second-largest human chromosome with 1309 protein-coding genes. A trisomy-2 in all cells is not compatible with life. The fact that later she had a healthy baby is surprising at first sight. However, the test was a CVS (Chorionic Villus Sampling)  performed between 10 and 13 weeks gestation. CVS is a sample of tissue from the placenta. It appeared that there was a mosaicism. Later in her pregnancy she had a second test, an amniocentesis (usually between 16 - 20 weeks) which had a normal result. So, she did not really take a huge risk by continuing the pregnancy [1]. Obviously, this was a very emotional and stressful period in her life. These personal details add greatly to the value of the book. So, it is not 'just' a book about her scientific discoveries. These personal details matter, because after getting the CVS result, she switched her lab research activities immediately to the question whether an embryo was able to get rid of abnormal cells ('self-repair').

Although I am familiar with chromosomes, prenatal and postnatal chromosome analysis, I was unfamiliar with the in vitro culture of human and mouse embryos and learned a lot of new interesting facts. She consequently refers to 'self-repair' of the embryo with abnormal chromosomes. I am inclined to interpret the disappearance of abnormal cells in an embryo as a case of the dying of chromosomal abnormal cells. Anyway the hypothetical 'self-repair' fails in the case of trisomy-13, 18 and 21 and all other chromosomal abnormalities (too many to list them here!). Trisomy occurs in a relatively high frequency of 1 in every 700 babies born. So, in these cases 'self-repair' fails. Furthermore, "Around 30 percent of early pregnancies fail before the embryo implants in the body of the mother, with another 30 percent around that time". And then there are hundreds of other birth 'defects' such as Conjoined twins, Cleft Lip, etc. A problem for both 'self-repair/dying of cells' interpretations is to explain the fact that trisomy-2 placental cells were able to grow to a rather large percentage of 25% despite this serious abnormality.

'Self-organizing' human embryos

"To illustrate just how remarkable your origins are, and the extra-ordinary process of embryo self-organization, let's imagine building a house in the same way as your body built itself. First of all, there would be no plans, as such, to construct your body. Nor would there be a blueprint or an architectural drawing or design. There are instructions, but if they work in the same way as the twenty thousand genes used to build your body, there would be no simple relationship between these instructions and how the final house appears, just as there is no simple relationship between a recipe and the appearance of a cake. There is no project manager ... Because this house self-organizes ..." (from the Introduction) [3].

Ethics

Should human embryos be used in research?

 

Chapter 7 is the first chapter in which Magdalena Zernicka-Goetz discusses ethics of experimenting with human embryos. "Although an early embryo is not a person, I believe that it deserves protection." She extends this respect to mouse embryos:

"In my lab, everyone is taught to show the early mouse embryo respect. I have a rule that ad hoc meetings, seminars, coffee breaks, and other distractions have to wait until an experiment using a mouse embryo is finished and the embryo has been safely returned to the incubator to continue its development, as it would in the body of the mother. Woe betide anyone in my laboratory who does not treat life with respect." (Chapter 7 Should human embryos be used in research?)

This is the first and only instance she discusses the ethics of mouse embryos [2]. Chapter 7 is exclusively about the ethics of culturing human embryos (page 588/1273 of my eBook). Magdalena Zernicka-Goetz has worked for three decades with mouse embryos and created hundreds of mouse embryos just for one project. So, the total number must be in the thousands. I could not find how mouse embryos are created. The obvious source is mouse mothers. She mentions 'foster mothers' and 'foster mouse mothers'. Despite the claimed respect for mouse embryos, respect for the adult mouse, the mothers of the embryos, seems to be totally absent:

"Because, of course, we could not test my hypothesis on human embryos, we tested it on mouse embryos." (chapter 8)

Adult mice are exempt from moral considerations. You just use them in unlimited quantities. In contrast to an embryo of a few weeks, adult mice feel pain and stress.

Conclusion

I highly recommend this book. If you are not interested in welfare of lab animals the book is very enjoyable and brings you up to date in the field of developmental biology and artificial embryos. However, if you care about the welfare of lab animals, her complete lack of interest in animal welfare is disturbing. Unfortunately, Magdalena Zernicka-Goetz is no exception. The majority of experimental biologists do animal experiments.

 

Appendix

Scientific and ethical arguments against animal experiments illustrated with quotes from her book:

• "we needed to study not only mouse but also human embryos because they do not develop in quite the same way from the time of implantation." (Chapter 6)
  
•  "Surprisingly, human and mouse embryo architectures diverge widely at this point" (Chapter 6)
• ""although human and mouse blastocysts appear similar at first, their architectures look dramatically different after a few days." (Chapter 6)
• "while we can get valuable insights by carrying out research on other mammals, only by studying human embryos will we be able to understand human development." (chapter 6)
• "Different species of mammal have adopted different strategies to implant in the uterus ..." (Chapter 6)
  
• "Given the important differences in development between the mouse and the human..." (Chapter 7)
• "we start to understand why the development of mice and humans is so different, even though they share virtually the same set of genes." (Chapter 9)
• "The atlas indicates that some organs in humans develop much earlier than in chick or mouse embryos and some later, yet another warning that it is not straightforward to extrapolate from the findings of animal research, say, the effect of toxins on development." (Chapter 10) 
• "We now know that this can happen in the mouse embryo, but we still don't know for sure whether this might occur in a human embryo." (Chapter 10, 76/138)
• 'this emphasizes the value of the mouse embryo as a model system and, at the same time, the need for studies of human development." (Chapter 10).

Further Reading

• Zernicka-Goetz lab home page features the most important and ground-breaking publications ('synthetic' embryos). A synthetic embryo is an embryo which is generated from different stem cells, not generated by the fusion of egg and sperm (chapter 9) and can be made in large numbers. Interesting aspect is the factors that cause self-assembly of a synthetic embryo (see: Philip Ball How Life Works).
• Gretchen Vogel (2016) Pushing the limit. By culturing human embryos for longer than ever, Magdalena Zernicka-Goetz is revealing their “powerful beauty”—and sparking debate. Science, 28 Oct 2016 (recommended!).
• video: The Dance of Life: How Do We Become Ourselves? - Magdalena Zernicka-Goetz (youtube).
  
• EPA scraps plan to end mammal testing by 2035 Science 19 jan 2024.

"New technologies are useful as a supplement to animal experiments, Sass says, “but I’m not sure that they’ll ever be able to tell us whether a child exposed to lead as a fetus is going to have trouble sitting still in a classroom.”

 Nederlands:

• Prof. Kees Brunia over vivisectie: Onze weg naar de kennis van het centrale zenuwstelsel is bezaaid met dode kikkers. blog 17 maart 2015
  
• Duizenden muizen voor niets opgeofferd voor de medische wetenschap? blog 9 april 2013
• De meeste medische experimenten met chimpansees waren overbodig blog 5 nov 2012
   

Update 24 Apr 24

The Dutch government invests in animal-free innovations 

Kabinet investeert in proefdiervrije innovaties

"Het Nationaal Groeifonds investeert 124,5 miljoen euro in een nieuw Centrum voor Proefdiervrije Biomedische Translatie. Van deze investering wordt 55 miljoen euro direct en 69,5 miljoen euro onder voorwaarden toegekend. Het doel van het centrum is om veiligere, effectievere en betere medische behandelingen te stimuleren en tegelijkertijd dierenleed te verminderen. ... 

Tegelijk blijkt steeds vaker dat de resultaten verkregen uit dierproeven maar beperkt of zelfs helemaal niet vertaald kunnen worden naar de mens. In de meeste van deze biomedische ontwikkelingstrajecten blijkt pas tijdens de studie met patiënten dat dierproeven niet de therapeutische werking in de mens voorspellen."

Most remarkable:

it’s becoming increasingly clear that the results obtained from animal experiments can be limited and ineffective. In most biomedical development pathways, it is only during in-human studies that it becomes apparent that the animal experiments conducted were unable to predict therapeutic effects in humans. " !

Update 26 Apr 24

Mariana Lenharo (2024) Do insects have an inner life? Animal consciousness needs a rethink. Nature 19 April 2024.

A declaration signed by dozens of scientists says there is ‘a realistic possibility’ for elements of consciousness in reptiles, insects and molluscs.

Crows, chimps and elephants: these and many other birds and mammals behave in ways that suggest they might be conscious. 

Notes

1. Outcome of pregnancies with trisomy 2 cells in chorionic villi   Prenat Diagnosis, 2010. Conclusion: In at least 95% of cases with trisomy 2 in CVS cultures there is confined placental mosaicism (CPM). The prognosis is good, but in about 15% of cases there is fetal growth restriction. On the other hand: "most embryos from women ⩾40 years old are chromosomally abnormal and rarely develop further." from: Egbert R. te Velde , Peter L. Pearson (2002) The variability of female reproductive ageing.
   
2. Ignorance and indifference: "Despite the plethora of scientific evidence for climate change, for instance, many people still avoid engaging with facts about global warming. Nor do they always want to know about the harsh living conditions of farm animals. And consumers often ignore the ethical origins of the products they purchase." Scientific American article Why Some People Choose Not to Know, 11 Dec 2023. 
3. This idea that there is no blueprint of the body in DNA is forcefully argued by Philip Ball (2024) How Life Works. See my previous blogs. Magdalena Zernicka-Goetz uses the word 'self-organization'. This a very general and vague concept. Turing models make 'self-organization' quantitative and testable.