Developmental Biology: the cauldron of the biological sciences

Disclaimer: I am not a historian of Science and these views are, simply, sketches from the fringes of my interest in the subject as a practitioner of Developmental Biology.

Sometimes it is possible to draw some sort of a straight line in the history of Science. For example, one can build a sensible narrative across an axis Galileo-Copernicus-Kepler-Newton….or, sort of, as most of the time a scientific discipline is a pidgin of varying questions, thought traditions, data and, importantly, visions of different scientists and surprising experimental results. Any attempts to trace a scientific discipline to a specific root will be difficult. Visions and technical advances will always collide in unpredictable manners to answer old questions and find new ones. It would be easy to say that the combination of hindu-arabic numbers and modern Calculus is at the root (the stem cell?) of Physics and yet, the babilonians and the greeks did very well without either. The history of Science is, first and foremost, a history of progress through change, a blend of experiments, ideas and reasoning. Furthermore, it is usually when different languages and visions come together that something interesting happens. One can trace paths but there are no unique roots.

I am saying this while reflecting on an article published in PLoS Biology by Scott Gilbert, claiming that Developmental Biology is the ‘stem cell of biological disciplines’ (http://journals.plos.org/plosbiology/article/authors?id=10.1371/journal.pbio.2003691 ). The reason for this musing is the feeling that Developmental Biology, specifically Developmental Biology, is under threat as a discipline (a widespread thought in the field these days) and that this kind of revelation should lead us to place the discipline in its rightful place and make funders and other scientist give it a credit which many people think is overdue. I do not see any of this to be the case. Developmental Biology is no more under threat than other branches/areas of Biology (talk to prokaryotic biologists or virologists!). What is under threat (more change than threat) is a certain way of doing Science –but I shall leave this to another time, as here I want to focus on some specific aspects of the piece by Gilbert. All I will say for now about this is that we need to do is to adapt and to change. The point I would like to make here is that, even if the drama underpinning Gilbert’s statement were true, one does not help the cause by rewriting history and shoehorning facts. The author states at the beginning that it is good to create myths to defend a realm and while this could well be true, mythologies are not history and one should be careful with the consequences that go with creating myths which can mislead current generations of students, and pay lip service to the cause it pretends to help.

Let me go to the two specific claims I take issue with: that developmental biology is the birth place of Genetics and Neurobiology (I would add here immunology and cell biology but then this would be too long). Let me start with Genetics, something I have worled with, and make things clear from the beginning: the questions that led to the emergence of Genetics had nothing to do with Embryology (Developmental Biology did not exist at the beginning of the XX century), absolutely nothing. The fact that embryos of different species might have been used to answer some questions posed by the gene based theory of inheritance does not mean that Embryology was at the roots of Genetics. The questions that concerned Mendel, and later de Vries, Tschermak and Correns, had to do with hybrids, plant hybrids to be more specific, and the laws that regulate the inheritance of some of their phenotypic characteristics. If one goes back in history, one will find that the forerunners of Mendel, plant breeders in Germany like Kolreuter, were not interested in questions of Embryology. This bit is easy to demonstrate and I suggest that anybody with some interest in the matter reads the little book by Robert Olby ‘Origins of medelism’ (Schoken books New York 1966) .

The intervention of TH Morgan in the story lends itself to misconstruction as he was, first and foremost, an embryologist. However, at the time, it was not rare –as it is the case today- that people were interested in Evolution and, in particular, in matters of the inheritance of characters (not the genetic basis of development). Morgan had an interest in these matters which were of paramount interest to biologists at the time, with a particular focus in the nature of mutation. It is this that led him to start working with Drosophila and, in an inadverted manner, to lay down the foundations of Genetics in Columbia University with a small group of superb students led by Sturtevant, Bridges and Muller. All this without a single thought for embryology. It is true that Morgan did refer, particularly in his Nobel lecture, to the connections between Genetics and Embryology, but he did not see how to do it and, actually, in his latter years in Caltech he returned to embryology without even attempting to bridge the gap (see the excellent biography of Morgan by G. Allen, Princeton Univ. Press 1978).

With his work, Morgan starts what Sydney Brenner has called the ‘great deviation”, a proces in which Genetics and Cell Biology need to get on good footing before Embryology can answer the questions it had at the start of the XX century. In many ways and with the exception of the work of Spemann and his collaborators, Embryology enters into suspended animation until the emergence of developmental biology when the consolidation of a number of disciplines –in particular Genetics and Biochemistry- allows a new vista of old questions. Thus Morgan pioneers the Genetics branch of this path and does so in a somewhat unconscious manner. In this regard, Boveri’s work is interesting and important but is a thin (though important) strand in the cell biology stream which also develops –for the most part- answering specifc questions (the residence of the particles of inheritance). Let me repeat, the work of Sturtevant, Muller and Bridges under Morgan –and on their own- has nothing to do with and owes nothing to Embryology. Like classical physics lies in the axis mentioned above (Galileo-Copernicus-Kepler-Newton) one can draw an axis for Genetics: Kolreuter-Mendel-Bateson-Morgan-Avery-Watson and Crick-Nirenberg; will led the reader to decipher (of degoogleized) some of those names. There is not a whiff of Embryology here which at the time was concerned with other questions, many of which were difficult to tackle.

Once Developmental Biology emerges as a discipline, an offshoot of the Entwincklungsmechanick and Embryology, it has something to do with Genetics, particularly in the latter part of the XX century, but Embryology –as such- has very little to do with Genetics. An interesting observation about this lack of a relationship between Genetics and Embryology in most of the first half of the XX century can be seen in what came to me called “the modern synthesis which tried to reconcile Genetics and Evilution. There are two disciplines that are left out of this endeavour: Embryology/Developmental Biology and Paleontology. The reasons are different but in the case of what is the object of this discussion, the reason was that at the time the connection between Genetics and Developmental Biology is, for the most part, non existent. Later on, in the 80s there is much of a relationship, but it is not the one expressed by Gilbert, it generates Evo-Devo.

The application of Genetics to questions associated with the development of plants and animals, changes the way we practice the discipline and, most significantly, provides insights that we are still digesting. Thus, while Genetics does not owe much, if anything, to Developmental Biology -and much less to Embryology, Developmental Biology owes a huge amount to Genetics. The reasons for this are many and are made very clear every day but the most important one is that IF there is one discipline that is stem of biological sciences, this is Genetics. However, Genetics is not the stem cell of Biology (I think this is the wrong way of looking at history of Science) but the unifying language, the unifying discipline and the one that ever since its emergence provides a clarity of thought and argument to old biological questions and this includes those related to development.

I shall be brief on the second issue: that of the ‘historical lineage’ relationship between Developmental Biology and Neurobiology. The claim is not very difficult to challenge as Neurobiology is not just the study of the development of the nervous system but, more significantly, its function. The origin of Neurobiology lies in the discovery of electricity. Volta and Galvani, Hodgkin and Huxley had no interest in Embryology nor developmental biology but it is them and their work that creates the roots and the basis of Neuobiology. There is little one can add to this well established fact. Ross Harrison, referred to in the Gilbert article,  is a pioneer of Developmental Neurobiology and, in particular, of tissue culture and ex vivo approaches to biological questions. He should be celebrated (as he has) for that. To place him at some root of such an advanced, complex and insightful branch of Biology as Neurobiology, is to reduce Neurobiology to Developmental Neurobiology, a somewhat narrow view of he field. Even on the example given by Gilbert, it is true that certain aspects of Neurobiology have their roots in embryos –but NOT EMBRYOLOGY- for it was the vision of Ramon y Cajal to use embryos to look at the structure of the nervous system, where he thought that a simpler system would yield answers to the disputes with Golgi raging at the time about the individuality of neurons. Thus, I think this is a better example to relate Developmental Biology to Neurobiology but, again, Ramon y Cajal was not interested in developmental questions but in very specific issues of cell biology associated with the nervous system.

In Biology, as in Science, one needs to use specific systems to find about the world through experiments but this does not mean that certain disciplines associated with those systems are at the root of further developments. Furthermore, I don’t believe that there are stems to whole branches of Science. Particular branches: quantum mechanics, astronomy, organic chemistry, Cell Biology and, of course, Genetics are pidgins of many ideas and languages and in the blends that they represent lies their greatness and their value.

I appreciate the enthusiasm of the piece in PLoS Biology but we should be careful not to distort history for the younger researchers. In the context of the theme of the essay we should not create weak phylogenies but rather thrive in the diversity that gives so much to Science and encourage interactions between disciplines as it is here that discoveries lie.  Developmental Biology is, today. a pidgin of  many disciplines: Genetics, Biochemistry, Cell Biology, Evolution, where the  recent application of Physics and computations methods is stimulating the development of these fields and providing, as it should, new vistas of old problems in Developmental Biology. Rather than a stem cell, I encourage you to see Developmental Biology as an alchemic cauldron where the blend of disciplines produces exciting and interesting findings which, slowly, will find their way into practical applications. Cell Biology and genomics are good examples where the application of these disciplines to developmental systems has revealed issues that cannot be addressed, because they don’t exist, in different contexts e.g transcriptional states during cell fate transitions or the emergence of tissue level behaviours from individual cells. More recently, the application of Physics and Maths is changing our view of developmental systems, providing intriguing new insights and also transforming the fields (Physics and Maths) in surprising and interesting ways

As for the real problem that the article identified and tried to address, it is not the lack of recognition of Developmental Biology . Furthermore, it is not specific to Developmental Biology. The issue is deeper and it has more to do with the way we do Science today as opposed to a few years ago, the fabric and form of Science. I have mentioned some of the issues before. By creating a mythology of the past we do not solve this. What we should be doing is identifying the exact challenges that we face and rising to them by looking at the future in search of creative solutions.

 

Notes

  1. I shall not discuss the uses of the words ‘evolution’ and ‘development’ in the late XIX century which are raised in the article. This would require more time, space and study that I am able to provide now. The issue is typical of nomenclature and the use of words in Science which acquires large dimensions in Biology where definitions are loose. It is very similar to what is happening with ‘epigenesis’ nowadays.
  2. There are many excellent texts about the history of Genetics but I like, specially EA Carlson “Mendel’s legacy’ Cold Spring Harbor 2004 . There are less single books on the history of Developmental Biology –though there are many collections. I suggest two: J. Oppenheimer “Essays on the history of embryology and biology’ MIT press 1967 and “A history of embryology’ edited by T. Horder, J. Witknowski and C. Wiley Cambridge University Press 1985.

 

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