Tag Archives: developmental biology

“You Did Not Use the Standard Nomenclature and Terminology of Embryology!”

When I was an undergraduate there were two things I hated more than anything else. First I hated being forced to memorize and regurgitate. The best example of this was Intermediate Biochemistry 101 in my second year as a biochemistry major. I was essentially handed a huge book as thick as telephone book and told to memorize it. It was one of the most boring courses I ever had to take. Lectures consisted of writing out all the steps of the Kreb’s cycle, glycolysis, glycogenesis and other pathways. I don’t ever recall being taught what these pathways were for. Our professor wrote out all the steps of the pathways and talked about carbon backbones and proton transfer. Our exams required we precisely regurgitated the complex diagrams and pathways. Marks were deducted for every letter and sign we did not put on the paper. No matter how hard I tried I could not regurgitate those diagrams without mixing things up. I literally cried over the pages I practiced on as I wrote it out again and again and again. I always failed.

If I had not gotten lucky about something else I probably would have given up biochemistry. I had to juggle day care needs of my children with my class schedule so I asked for permission to take a third year biochemistry course as a co-requisite that same year. This course was taught in totally different fashion. It was called Nitrogen Fixation. I loved this course! It was so fascinating! The professor gave us the diagram about nitrogen fixation and we learned about the role of fixation in the life cycle of plants. We studied where and how nitrogen fixation takes place. We learned wonderful things such as how farmers cultivate floating plants that can fix nitrogen in rice paddies to increase yield. We also studied how the system worked as whole including what the effect of specific mutations of genes for enzymes. My final exam had a two sentence questions.

“The enzyme GlnA in a specific legume is mutated so the efficiency drops to 15% of normal. What happens to the plant?”

Even more amazing, we actually had a diagram of the cycle to consult!

nitrogen-cycle

I ended with the term two things that were stunning and depressing. I got an A in Nitrogen Fixation and I got a C in Intermediate Biochemistry. My kindly nitrogen fixation professor saw me struggling to regurgitate those diagrams for Intermediate Biochemistry and he told me that he thought I had a learning disability similar to his daughter’s. She had dyslexia. He referred me to student services. After testing, it turned out I did indeed have a genuine, measurable, real, learning disability so that I flipped groups of atoms at random on the carbon backbones of those diagrams. it wasn’t my fault. I was not stupid, sloppy or lazy!

For the rest of my undergraduate career I would have to go to the department head at registration time and ask for an exemption. All the subsequent biochemistry courses I took required a C+ in Intermediate Biochemistry and I only had a C. I would pull out my official diagnosis of a learning disability with my proof of a need to be accommodated.  Each and every time the department head would look at me and shake his head in wonder and ask me “How could you get a C in Intermediate Biochemistry and an A in Nitrogen Fixation? Everyone knows that the Nitrogen Fixation is a much harder course and hardly anyone ever gets an A.” Then he would sign the waiver for me.

How indeed. It was many years until I figured it out. It was partly my learning disability. The Intermediate Biochemistry course was based entirely on the ability to memorize and regurgitate a set of diagrams and I just couldn’t do it. No understanding was required to pass that course. No ability to think was needed. You just needed an ability to reproduce diagrams which I did not have. You don’t even have to be able to speak English. You just needed to be able to draw the pathway precisely as laid out in the textbook. After you have completed that “essential” learning step, then and only then can you, as a student, move on to learning real stuff.

Nitrogen fixation was taught in a manner that required I really understand how the whole thing worked. The professor who taught it complained (and warned us) that many of the student who took the course would write out the diagrams for him in the exam but they would fail. He was not interested in having us write out the diagrams. He was interested in knowing we understood the content he was teaching in the context it operated in. No wonder it was such a fascinating course!

My Introduction to Embryology course was much the same though not as bad (for me) as Intermediate Biochemistry. I was required to memorize and regurgitate all the proper labels of diagrams on stages of embryogenesis. This included correct spelling of terms like coelom, archenteron, and blastocoel. If you had a single letter wrong you got a zero score. This did nothing to increase my understanding of embryology. There was a really great lab with three dimensional models and time lapse movies. We also got to study carefully prepared serial section slides of stages of development over time. I learned the anatomy of the embryo from those labs, not the lectures. I got almost nothing out of the lectures. For the exams I got lucky because I have always been fascinated by Latin and Greek elements in words. I even took an optional course in it simply because I liked the topic. That made it much easier for me to reproduce that arcane language correctly because I knew the roots all the horrid words came from. My fellow students without such a background struggled terribly and most left the course with a C for poor spelling and hating embryology as a topic.

So why do we make students go through the pain and suffering of memorizing and regurgitating in the first courses they take in a topic? It can’t be because it helps students learn. It does the opposite. It bores them and drives them away. It can’t be because it helps understanding. There is no understanding required. It can’t be to give them “a solid grounding in the basics” because I have never encountered a need to have the entire Kreb’s cycle memorized or the correct spelling of “gastroceol” in any work I ever did. Active researchers use databases and computer programs of such things and always check their memory against real data. Memory is unreliable and not something to be trusted. The greatest metabolic geneticist I ever knew, Dr. Cheryl Rockman-Greenberg, had the pathways she encountered most often in the clinic memorized but I still saw her consulting a text book more than once. We would be working on something and she would get telephone calls from clinicians from all over the world. We would pause while she took the calls and I would sit and listen. She would often pull out a textbook and consult it in her conversations. it was fascinating to watch her really using biochemistry but she did not count on her memory. I kept asking my question about why we do this to students but no one had a good answer. When I got a little more senior in my studies, when I was closer to being ‘one of us’ as a PhD student, I still kept asking. Why do we make students memorise and regurgitate diagrams?

Finally one professor literally snarled at me and said “I had to do when I was an undergraduate and they are all damn well are going to suffer through it too!”

That’s when I finally understood. This is a form of hazing. We make students do this horrible useless exercise in order to make them prove they really want to be “one of us”. We force students to learn and then adopt the special language we use. This special language keeps “us” as an exclusive group that outsiders can’t join easily because they can’t understand our private conversations. You want to be an embryologist? You have to first prove you deserve to become one of us by proving you will let us make you spell every arcane, old fashioned word there is in our special secret language. You want to be a biochemist? You have to memorize a textbook of stupid diagrams to show you really want to belong to our special club no matter what we do to you. This hazing creates a nice camaraderie within the profession. It also drives away some of the best and brightest at their first exposure. Worse, it stifles those who think independently and who might therefore challenge the current consensus of whatever is considered the great truth scientific of the day. it helps explain why scientific breakthroughs resulting from paradigm shifts take so long to occur and meet so much resistance before they are accepted.

When I taught engineers and mathematicians embryology, I did not use diagrams with all those arcane names and labels. I used models with clay, and pictures and movies and live embryos. I explained how the embryo changed over developmental time giving them only a few key terms. I never mistreated them for a misspelling. I did not make them memorize anything. I allowed as many questions as they wanted to ask. I noticed these students learned much more quickly and understood much more thoroughly than the poor biology student who is forced to memorize and regurgitate diagrams. And my students never got bored with either biochemistry or embryology. And I don’t see why an engineer should be prevented from applying his skills to development because he hasn’t been forced to prove he can correctly spell “syncytiotrophoblast” or “integumentary”.

This is also why I am not bothered by the criticism that I did not use the standard nomenclature and terminology of embryology in our book. We wanted a book that was accessible to as broad an audience as possible, and one that reveals the miraculous beauty of embryogenesis without the stultifying jargon. We don’t want embryology to be a closed society with a secret language. We want everyone to love embryology as much as we do.

Another Review!

“Embryologenesis Explained is a pleasure to read, presenting difficult concepts clearly and effectively. It carries deep biological thought, and whether one agrees with the differentiation waves theory or not, it is inspiring and stimulating.”

Biol Theory
DOI 10.1007/s13752-017-0260-z

BOOK REVIEW

Mechanistic Development

Natalie K. Gordon and Richard Gordon: Embryogenesis Explained; World Scienti c, Singapore, 2016, 784 pp., £164 hbk, ISBN 978-981-4350-48-8

Jean-Jacques Kupiec1

© Konrad Lorenz Institute for Evolution and Cognition Research 2017

 

Excerpts:

“Overall, Embryogenesis Explained is a very interesting book. Although it is primarily intended to be theoreti- cal, it provides a large overview of the data collected on various subjects of developmental biology and could thus also be used as a complementary textbook. Of course, it raises a number of questions. The main question concerns the di erentiation waves theory itself. I am typically one of those biologists referred to by the authors who usually does not put the cytoskeleton and mechanical forces at the forefront for understanding development. So, was I con- vinced that the cell state splitter is the driver of develop- ment? The theory is certainly coherent. It is based on data and it suggests testable hypotheses. In this regard it should be accepted, and its research program should be developed. Natalie and Richard Gordon undoubtedly point to some- thing very important, and molecular biologists focused on gene expression will bene t from reading this book.”

“Am I entirely convinced, however? When reading this book, a question will inevitably arise in the mind of any reader: could it be that simple? In the preface, the authors argue that a theory of embryogenesis has to be simple. But, I am perplexed. Although I agree that the physics of biology has not been su ciently taken into account, and this is why Embryogenesis Explained is valuable, I have some reservations about the purely mechanical theory proposed here and the broader holistic philosophy in which it is inserted. First, the di erentiation waves theory is totally deterministic, whereas the stochastic aspects of cellular physiology, notably in gene expression, are amply docu- mented now. Integrating the randomness of cells into the picture will produce a radical change. Because of this inherent stochasticity in cellular behavior, cell fate cannot be determined exclusively by the cell state splitter as described here in a purely deterministic way. I would rather see the physics of biology as imposing constraints that give a direction to cells but not as acting as their rst causal mover. Second, I am not at ease either with the holistic philosophy the authors wrap their theory in. I even nd it to be paradoxical. Mechanism is philosophically associated with reductionism. There is no doubt that if Descartes were alive today he would enthusiastically approve and applaud the authors’ mechanistic theory. But, I think there is a widespread confusion among a number of biologists today. Because they reject genetic reduction- ism they tend to reject reductionism in general and adopt a holistic perspective. However, there are different forms of reductionism. Natalie and Richard Gordon’s theory is physicalist, and physicalism is an even more radical form of reductionism than genetic reductionism. In my mind this is not an infamy. Historically reductionism has been (and still is) the prima philosophy and methodology of science. It is beyond the scope of this review to analyze these issues in depth. I mention them only to show possible further discussions. It does not diminish the merit of Natalie and Richard Gordon. Clearly, they are successful writers, and I enthusiastically recommend their book. Embryology Explained is a pleasure to read, presenting difficult concepts clearly and effectively. It carries deep biological thought, and whether one agrees with the differentiation waves theory or not, it is inspiring and stimulating.”

Stadium Waves and Embryogenesis.

brownie

I (Natalie) was at a southern barbecue eating good food and enjoying good company when our book came up in conversation. With it came a request to explain the waves in simple terms. Being surrounded by a bunch of really keen American football fans I invoked the stadium wave.

The stadium wave (also called the Mexican wave) is great fun phenomena where someone starts a “wave” that is made by people in the stands leaping up and putting their arms in air. The wave will travel around the stadium. The differentiation waves are much the same. A sheet of cells is ready to participate in the wave but each cell doesn’t actually stand up and wave its arms until the cell next to it does it first. If you look at the stadium way, the people can watch what other people are doing. A cell has no eyes and no brain. So instead of watching for the wave and watching it as it passes, the cell has its bistable organelle on top to sense if a wave is coming its way. When the cell next to it “waves” it gets its signal to do its thing.

When I was a little girl in Brownies we attended a huge event in honour of Canada’s 100th birthday in 1967. The Montreal Arena was absolutely packed full of little Brownies all in uniform and we each had a cushion. My cushion was yellow on one side and brown on the other. All those in my pack had the same cushion. All the packs sitting in my section had the same colour. Other packs in other sections had other cushions, with different pairs of colours but always light and dark. I recall being absolutely fascinated by how the person directing from the floor was able to make incredible patterns across the stadium by the simple act of saying things like “Everyone on the south side hold up their cushion with the dark side out.” The arena became a brown sea. “Now everyone turn your cushion over!” and suddenly the area erupted in gigantic patches of bright colours.

Imagine a bunch of little girls in their cute little Brownie uniforms but instead of one cushion each Brownie has five cushions. The cushions are numbered 1 through 5. The Brownies are all in their seat and they follow instructions to take out cushion number one and be ready. Cushion number 1 is red on one side and white on the other. Now the leader gives instructions. Everyone on this row, turn your cushions to white. In the row beside them everyone turn their cushions to red. Now “go”.  In embryonic terms, the cell is ready with a “cushion” that is the bistable organelle, the cell state splitter. The cell state splitter can either expand or contract in response to an outside mechanical signal or to what the cell next to it can do. Red cushion is analogous to contraction, white to expansion.

The result would be a moving wave of white in one direction and red in the other other that would move around the stadium until the red and white meet on the opposite side and then the wave would stop. We would now have the stadium neatly divided into half red and half white. This is exactly what happens during the embryonic stage in mammals known as compaction. A ball of cells is neatly divided into two parts, the inner cells mass and the outer trophoblast. Instead of red and white we have contraction of the inner cell mass and expansion of the outer trophoblast. The contraction action actually moves the contracted cells into the inside. The expansion results in an outer sphere of cells. The balls of cells of the recently fertilized egg undergoes it first differentiation. The inner cell mass will become the future mammal. The outer sphere will come the placenta, and amniotic sack and other supportive tissue which is later discarded at birth.

What part do “genes” play? Go back to our little Brownies. Now once the first wave has gone by the leader says to the Brownies “Check your cushion for instructions!” The white side of the cushion has printed on it “Put the red and white cushion away and put cushion number 2 (brown and orange) away with it and take out cushion number 3 (green and yellow). The red side of the cushion has the instructions “Put the red and white cushion away and take out cushion number 2 (brown and orange) and put cushion number 3 (green and yellow) aside with the red and white cushion. Now repeat the entire event but this time the two start rows are not at one end of the stadium but instead are started in the middle. Two rows in the middle of the white section are instructed to have one row wave green and the other row wave yellow. Meantime in red section the two rows are to use their brown or orange side respectively. The result of triggering the waves again is the division of the stadium into four sections, brown, orange, green and yellow.

The only “outside” information required to do this division of Brownies in a stadium is to watch the girl next to you and do what she does except for the ones in the start row. This is how the differentiation waves work. The only information a cell has is what the cell next to it does. The response is inherent in the colour of the cushions the child is carrying and the directions on those cushions which is analogous to the genetic code each cell carries. The code includes instructions of which part of the code (cushion) each girl is to use next. The code also contains instructions for which genes (cushions) to put away and not use.

This response to the wave, reading the cushion instructions, is the embryonic process of “determination”. If we wanted to carry the analogy even further, imagine that each little girl has brought a suitcase of clothing along, separated in five numbered bags that match the cushion colors. After she participates in the red wave, the instruction on the cushion include the directive to take out and change into the clothing in one of the bags. Eventually all the girls are wearing a new outfit corresponding to which waves she participated in. This changing of clothing would be analogous to “differentiation” where cells stop producing one set of proteins and change to another set of proteins and in doing so become a new type of cell. The genetic code carries not just the instruction on the cushion (which are signal transduction to the nucleus i.e. determination) but the instructions for how to make the clothing in the suitcases (differentiation). Each different cell uses some of the code but not everything in the code (some cushions nut not others) depending on where the cell is and what sequence of waves it has participated in.

In our cell sheets, the start of the wave is signalled by some mechanical force in the cell sheet instead an announcer/leader. If we take the ectoderm contraction wave as an example, the underlying invagination of mesoderm touching the underside of the sheet of cells is the signal. This mechanical signal is passed from cell to cell the pushing and tugging of neighbours.

The ectoderm contraction wave actually goes through more than one tissue. It starts in tissue that will eventually become notochord then passes through tissue that will become tailbud mesoderm and then finally through to the ectoderm. In early embryogenesis, many of the waves go through more than one tissue. However, if the cell in that tissue has been previously subdivided by earlier waves, the result is simply that the wave passing through more than one tissue type will create a pattern duet each cell having a different set of instructions (or a different cushion). If you look at the “Best Wave” sequence, the audience has previously been divided by being given different cushions. The wave in the stadium simply exposes a preexisting difference in a spectacular fashion. Note how once the wave has created the beer glass pattern, there is another wave inside just the beer glass that empties it visually. A second wave (or third or fourth or fifth) on one section of an embryo but not another allows refinements of the pattern of embryogenesis.  In our model, the people who make the beer glass drain would be a tissue type that once triggered is primed to be trigger again even though the people around it stay quiet. Repeat waves are also very common in embryogenesis in development of the early brain, for example.

One other little bit of embryological jargon. A cell can only participate in a wave if it is “competent” as in ready to go. In the case of the beer commercial below, it is like the people waiting, cushions ready, like the people at the beginning to the video.

 

 

It is hard to explain the waves of embryogenesis in few sentences in a break between barbecued steak and key lime pie to a group of people whose sole common interest, aside from being related, is that we have all watch football. But the stadium wave, and my experience as a Brown back in 1967, served as an excellent analogy where everyone seemed to “get it”. Yes, “the genes” do it but waves explain why genes only “do it” in the right place at the right time.

iu

Our First Review Now Available Online!

Igamberdiev, A.U. (2016). Book Review: Morphomechanics of Development. Lev V. Beloussov, Andrei Lipchinsky. Springer International Publ. BioSystems, In press. Web:  http://www.sciencedirect.com/science/article/pii/S0303264716302532

The article is now available on line (though behind a paywall if you don’t have a university or similar library access. Here are our two favourite excerpts!

The title of the book is based on the belief of the authors that the fundamental phenomenon first described by them forms the basis for a profound explanation of the phenomenon of embryogenesis and represents a “right theory” of individual development of biological organisms. Thus the book provides an expanded explanation of this new theory of how embryos build themselves using the phenomenon of generation of differentiation waves. The background given for the theory combines simple physical principles with the most recent breakthroughs in genet- ics, biochemistry, and biophysics. Despite a huge amount of detail and experimental data, the book is accessible to a broad audience includ- ing not only embryologists but also biologists of different profiles, researchers working in many fields of science, teachers and students.

This book by Natalie and Richard Gordon represents an important development in the field of developmental biology and in the foundations of theoretical biology. Its clear presentation and style makes it a perfect complementary textbook for teaching embryogenesis and re- lated courses. It is strongly recommended to everybody who is interested in the problems of embryogenesis and, in general, in foundations of biological organization. In the end, after reading this book, we are convinced that the concept of differentiation waves explains the mystery of embryogenesis. Further elaboration and strengthening of the experimental basis of research related to the phenomenon of differentiation waves may provide new further evidence in support of this great concept.

Embryogenesis Explained Feedback 1

220px-quinzy

We sent out a message to everyone of of the 1900+ scientists we referenced in our book. Some of the answers we have gotten back have been fun to read.

Dear Richard,

I can’t imagine why you might have cited my work in ecology in Embryogenesis Explained.  You’ve certainly piqued my curiosity, though. Can you give me a hint?  :o)
Congratulations on your achievement.  I look forward to hearing back from you.
All the best,
Peter

Dear Peter,

Well, I’ve lived in Canada long enough to know how to build a quinzhee. Here’s the paragraph in Chapter 12 ending with a reference to:

Marchand, P.J. (2014). Life in the Cold: An Introduction to Winter Ecology. Hanover,  University Press of New England, 4th.

In biology, the atom is generally the level at which we start our studies.

The energies involved in splitting atoms or fusing atomic nuclei releases

ionizing radiation which damages living organisms. So we think of

organisms as made up of stable atoms, and usually do not have to trouble

our thoughts with what is going on at lower, subatomic levels. Exceptions

are when we have to think about the key role of natural background

radiation in generating mutations, and thus in evolution23. This energy

also keeps the ground warm in winter (ref 24), permitting life to go on under

the snow (ref 25).

This is part of the background setting up reductionism vs holism in solving embryogenesis. The rub is that quantum mechanics is holistic, as I show. Had this checked by a friend who writes books on quantum mechanics.

While it’s not my forte, I have taught Pollution Biology, and learned some ecology in the process. There seems to be a nice overlapping field of ecoembryology waiting to be developed. I coined the word while writing a grant application:

Rudloe, J., N.K. Björklund-Gordon, R. Gordon, A. Hodges, M. Hodges, K. Lu, E.W. Cake & C. Rudloe (2013). A Vision for Sustainable Farming of Oysters Along Florida’s Forgotten Coast: A Restore Act Proposal. Panacea, Florida,  Gulf Specimen Marine Laboratory.

which didn’t get funded. I suspect that oyster embryos differ in salinity tolerance depending on the salinity in which their mothers existed, and that seeding with spat would be more successful if this were understood.
So that’s the tale, and you might enjoy our book. Thanks.
Yours, -Dick Gordon