It was 15 or so years ago, that as a PhD student I attended my first Indian Society of Developmental Biology Meeting. It was held somewhere in Pune, I don’t know where. The late Veronica Rodrigues ran the show, I remember her as this scary organizer who could scare even the bosses. I don’t remember much from then except the decision that I wanted to do developmental biology (and I promptly paid the lifetime membership fee for InSDB!) and the realization that if I wanted to study development I had to do it in drosophila. What little developmental biology I knew came from Dr L S Shashidhara’s classes as part of our coursework, where he introduced the beautiful processes of embryonic development ruled by funny-sounding genes names. The names all ran into each other, but the processes were amazing. I was a product of the recently started MSc Biotechnology, where we were introduced to the modern science of Molecular Biology but knew little of the old world of embryology.
This time, I went to the developmental biology meeting to hear about new research but even more to meet friends in the developmental biology community. We have a thriving one, a community, today. Perhaps many are from labs that attended that InSDB meeting 15 years ago. And an increasing number works on organisms other than drosophila, the reigning king even today. I already had an inkling of this from the two InSDB meetings I have attended in the span of last three years. So, this time I decided to look at the data quantitatively. A plot of the number of abstracts vs. model organisms shows that many new model organisms have arrived at the scene in Indian developmental biology labs. But even more importantly a number of models that had been studied for years by isolated researchers around the country are growing into mini-communities themselves. So, what is the big deal about communities?
Communities catalyze research. As a student, when I went to the InSDB meeting, I had a poster, and some tantalizing data from mouse cell culture. But typical of a frustrated PhD student, when this bouncy lady came to my poster, all I could talk about was my experiments that were not working. The lady was Dr Shubha Tole, and she promptly invited me to her lab to learn the technique, RNA in situ hybridization. I did my life’s and her lab’s first RNA in situ hybridizations on mouse embryos and also in the process found a mentor for life. In last week’s meeting, I saw many such new relationships kindle and many seeds of collaboration between PIs, and also between students get sowed.
Then communities also make science not just interesting, but fun! You look forward to meetings because you can steal away and relish a Hyderabadi biryani in the evenings or hike up to the Golconda fort to admire the city from the ramparts!
It was a pleasant November afternoon. I just walked into my lab following a customary post-lunch siesta. In came my ex-supervisor and looked at me sharply. A bit of chill went down the spine, a prospect of losing the position and prestige in my own lab also played at the back end of my mind. She said, – ‘how would you like to be a life member of the Indian Society of Developmental Biologists? Here is the form, fill in, and give me 500 rupees’. It took me a little while to recover from the unexpected request, and to savor the relief of avoiding an awkward question in front of a newly acquired student. I tried a meager attempt at resistance – ‘but Veronica,.. I no longer work on development related issues..’ She said – ‘oh! Doesn’t matter, you will do it eventually. I am now the president of the society and I will recommend your name for a life membership.’ So, that’s how the fledgling Society acquired its newest life member. That was a decade and half ago. By no stretch of imagination I could have been counted as a developmental biologist at that time. I am also unsure if I can be counted amongst one even now! Well it’s a different debate and we may revisit it at some other occasion in future.
Many years later, and after several presidents having graced the society, I found myself in a very similar situation on an early December afternoon at TIFR. It was the occasion of the Annual Meeting of the Society, being organized at TIFR after a long gap. I went to greet some old friends at the Homi Bhabha auditorium when the serving president called me out for an ‘informal meeting’ outside, over a cup of tea. Some of the serving members of the executive committee and a past president also joined in. After some usual discussion about the future plans and current activities, the issue of nominating the president came up. A name was proposed and all of us seconded it, but the person declined. And then, without any warning, some of the people present turned towards me and asked if I would be willing to do the job. The rest joined in and encouraged me to say yes. Once again, a chill went down my spine. Once again I made a feeble attempt to wriggle out. Alas! It was not to be. And, that’s how the Society got its latest president.
In the intervening period, the society went through significant morphogenesis. It has a large number of new members. Many of them are young faculty. Nearly 300 people attended the Mumbai meeting. Therefore, the challenge was to continue with the momentum and introduce new ideas to invigorate the members. The new president must identify a new team – most importantly, a new Secretary-Treasurer, because the serving one had enough of it already – and learn the rules and bylaws of the society to steer it. A tough job for someone who does not really understand what Developmental Biology is after all.
Therfore, it brings me to the moot question: what is Developmental Biology? Moreover, what should a Society of Developmental Biologists do?
Well, as a start, the society URL went through a metamorphosis form InSDB.org to DevBioIndia.org, and it got a new website. If these can be considered development, then of course, we are developing. However, it does not quite feel right. My fellow members, I put these questions to you and request you to clear my ignorance with some vigorous responses. Let’s Blog!
Krishanu Ray, Tata Institute of Fundamental Research (TIFR), Mumbai
Today, I got news that a close friend is in the early days of what might be a difficult pregnancy. The opening remarks of the book “Unweaving the Rainbow: Science, Delusion and the Appetite for Wonder” by Richard Dawkins came to mind. Dawkins marvels at how statistic-numbingly lucky each one of us is to have survived the odds of a sperm and an ovum fusing and giving rise to a living cell. How we are a nanoscopically small number of the total combinations that are possible for the human genome. But as a developmental biologist, for me, this is just the starting point of the great obstacle course. The hurdles that the embryo will clear in the mother’s womb to make it to the light and sunshine, the warmth and fragrance, the colours and music of this, our second home.
We see numerous reminders of each step that falters, in the birth defects that abound our world (according to statistics, 3-6% of infants born). A less than perfect infant brings anguish for the mother and potential disability for the baby. For civilizations, societies, religions, and the superstitious a baby with a birth defect can have many connotations; a symbol of the wrath of God, an indication of uncertain morality in parents, an evil incarnate, a sign of bad times ahead. And the prescriptions to prevent these also come in many flavours; don’t look at the eclipse, don’t face ugly people, don’t eat mango, don’t think ill thoughts, etc., etc. Even in mythology we meet with mothers who were not careful enough and paid the price for it; Ambika, who closed her eyes, and Ambalika, who turned pale upon seeing Vyasa in their bedchamber, the results were Dhritarashtra, born blind and Pandu, born pale.
In colonial Europe, many such mutant foetuses became curios in museum jars or if they survived, became celebrities. It was a world that had suddenly discovered and was entranced by the sheer variety in the human species; to the extend that even the ‘normal’ ‘native’ from the colony was an object of marvel to a people used to standard ‘white’. Armand Marie Leroi, in his book “Mutants, On Genetic Variety and the Human Body”, beautifully traces back the history of some of these famous human ‘monsters’ of the western world and tries to weave our understanding of development and genetics into the past, to identify the syndromes that might have affected these individuals.
Our current understanding of embryonic development has come a long way from the myths and imaginations of our ancestors. As with all other matters of the natural world, Aristotle had a theory on this matter. He observed the different stages of the chicken egg through time and concluded that the animal comes into being in a succession of steps from unformed material and that the force guiding this development is the soul, that enters the egg immediately after conception. But even before naturalists could follow this trail, there came on the scene, the preformationists. They postulated that the egg or sperm come packaged with a small animal or human (homunculus) inside it and that each homunculus has hundreds of homunculus in its own sperm, ad infinitum. Thus, if you extrapolate far back enough the whole of humanity was packed in the groins of Adam.
Most embryonic studies, as can be imagined, relied heavily on model organisms and the opinions and conclusions of scientists could be quite diametrically opposite depending on whether they were looking at insects or amphibians or birds or mammals. Embryos (perhaps fully formed) could be encased in multiple layers of sheaths that are apparently shed in succession as in an insect larva, pupa and adult. New organisms could grow out of parts of the old, as in an amphibian or planaria. Embryos may look like membranous structures with well-populated blood vessels if you open a chicken embryo few days into development.
Model organisms remained the mainstay, but the microscopes improved and Europe went through a rush of scientific enlightenment. Inspired by the question of how much each cell in the embryo knows about becoming an animal, Hans Spemann performed an experiment; a similar one has been described in the ever-imaginative Mahabharata where Gandhari cut up her unformed embryo into 101 pieces to unleash an army of Kauravas on the Indian subcontinent. What Spemann, the master of microsurgery did was a much more refined and precise experiment; he separated the cells of a 2-cell stage newt egg with a sophisticated surgical instrument, a baby hair. He found, to his surprise, two completely formed embryos. This said that each cell had the complete information to make an embryo. What was this information, was it the soul? Could soul be split into two? Shortly afterwards, in 1924 Spemann and his Ph.D. student Hilde Mangold (who was lost to a kitchen explosion even before her paper came out), published a paper. It showed that a small portion of the embryo, which we now call the Spemann-Mangold organizer, can organize the rest of the cells to form an embryo, head and tail, heart and lung, eyes and anus, the full complement. In 1929, Walter Vogt dyed a few cells in a developing Xenopus embryo and traced their fate. This kind of fate mapping of cells, finally showed us conclusively that cells, as they divide, take on different roles in the embryo. That the cells in the embryo are not dumb spectators of a tennis match, but rather a well-choreographed dance troupe that moves in unison to a subsonic music of mysterious nature.
The quest for the soul of the embryos was intensifying. The time was ripe. Molecular biology was at the threshold. The molecular and genetics revolution ushered into embryology by Thomas Hunt Morgan, Conrad Waddington, Salome Gluecksohn-Schoenheimer and others created what we now call developmental genetics. Developmental biology became all about genes, genes that are necessary, genes that are sufficient, genes that are modifiers, genes that are master regulators and so on. In the midst of all this, it is heartening to hear that there are genes I can live without; very recent efforts at whole genome sequencing of more than 2000 individuals in Iceland have discovered a number of genes that are ‘non-essential’ for development.
Today we can watch the dance of cells and hear the music of molecules live in an embryo; even a human embryo can share a smile with its father through the ultrasound screen. But with this also comes our increasing awareness of ‘non-genic’ factors that can influence the foetus and its wellbeing. Let alone the alcohol and drugs that the mother consumes even the nutrition that the father consumed or the lack of nutrition its grandfather experienced may all have an effect on the organism’s development and physiology. As we become better at identifying the obstacles in the journey of an embryo from the single cell to a free-living organism, perhaps we are also becoming ever more uncertain of the control we have over these obstacles.
A friend once told me, that after all the grand dreams and high hopes that you have for your baby, when it is finally born all you care about is that it does have the right number of appendages and sensory organs. Perhaps this is where the biologist and the parent in me meet. To steal Feynman’s thoughts: for me, the scientific knowledge of how an embryo develops and in how many ways it could all go wrong, makes the birth of a baby even more of a miracle than the layman. A baby that has skipped and scaled and sidestepped all the obstacles thrown in its course to make it here, to blink unseeingly at me and to grab my extended finger, is meaning enough for what I do.
by Chetana Sachidanandan, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), New Delhi