Monthly Archives: March 2016

20% off our book thanks to GSML

Thank you Gulf Specimen Marine Lab!

Big news at Gulf Specimen     
“Embryogenesis Explained”
Now available for pre-order!!
Announcing the newest book by co-authors Dick and Natalie Gordon, about embryology; that Gulf Specimen fully recommends to anyone interested in conception of life and the development of cells.
Here’s a video directly from the author herself, explaining the purpose behind their book, “Embryogenesis Explained”

For years, these Canadian scientists have been involved as volunteers and advisors on a wide variety of technical subjects.  Such as digitizing all of Jack & Anne Rudloe’s book to be available on Kindle, applying for government grants to improve the facility, helping  with the success of our online fundraising campaigns and studying the behavior of octopuses and their human interactions.

They also have decades of experience of raising aquatic life in captivity, including disease control and nutrition. Over the past few months, Dick and Natalie have spent their evenings finalizing their book, ” Embryogenesis Explained” right here in Panacea, FL.

Now is your chance to get in on the ground floor of this unique and easy to understand book.  Pre-order your copy today and use the code “WSGSML20” and receive an extra 20% off.
Click the link below to find out more:

http://www.worldscientific.com/worldscibooks/10.1142/8152

Our latest publication!

Gordon, N.K. & R. Gordon (2016). The organelle of differentiation in embryos: the cell state splitter [invited review]. Theoretical Biology and Medical Modelling 13(Special issue: Biophysical Models of Cell Behavior, Guest Editor: Jack A. Tuszynski), #11. (The publication is open source, no fee to read.)

Abstract

The cell state splitter is a membraneless organelle at the apical end of each epithelial cell in a developing embryo. It consists of a microfilament ring and an intermediate filament ring subtending a microtubule mat. The microtubules and microfilament ring are in mechanical opposition as in a tensegrity structure. The cell state splitter is bistable, perturbations causing it to contract or expand radially. The intermediate filament ring provides metastability against small perturbations. Once this snap-through organelle is triggered, it initiates signal transduction to the nucleus, which changes gene expression in one of two readied manners, causing its cell to undergo a step of determination and subsequent differentiation. The cell state splitter also triggers the cell state splitters of adjacent cells to respond, resulting in a differentiation wave. Embryogenesis may be represented then as a bifurcating differentiation tree, each edge representing one cell type. In combination with the differentiation waves they propagate, cell state splitters explain the spatiotemporal course of differentiation in the developing embryo. This review is excerpted from and elaborates on “Embryogenesis Explained” (World Scientific Publishing, Singapore, 2016).

The Problems with the Gradient of Morphogen Models of Embyrogenesis

gradient

A superb illustration of the morphogen gradient model.

Physiological gradients do exist in embryos. The best known example is the bicoid gradient in Drosophila. Given the discovery of physiological gradients in embryos, it then became common for embryologists and molecular biologists to speak of a “morphogen gradient” across developing tissue that begins at the site of induction, creating a gradient of gene products or “morphogens” across tssue. Morphogens are the basis for the concept of positional information which presumes that a cell can know its position by “reading” the concentration of the molecules of the gradients and then deciding what it is supposed to do, by “looking up” its coordinates in some sort of stored table in its DNA. With these epicycles the problem of embryogenesis was “solved” and, like the far more quantitative Ptolemaic version of the solar system, permeated textbooks and teaching for an extended period of the history of science. Morphogens are still widely taught, along with gene regulatory networks, as if they are a full explanation of embryogenesis.

There are numerous problems with the morphogen gradient model:

  1. In order to maintain a gradient at steady state, besides a steady, spatially defined source for the diffusing molecules, there has to be a sink. This means there must be a way in which diffusing molecules are destroyed or removed along the way and/or at some boundaries. Most people who invoke gradients don’t bother with analyzing and solving the partial differential equations for diffusion of molecules to show how the gradients work. Sinks are rarely, if ever, even considered when the gradient model is invoked.
  2. A common supposition is that the molecules diffuse outside cells instead of through them. This is a convenient assumption, because it permits one to ignore the cellularized structure of space inside an embryo, But even so diffusion must occur in a confined space, if a gradient is to be established. Otherwise the molecules will just diffuse away. If the diffusion is extracellular, then its course is critically dependent on the existence of such confining boundaries. Most of the early development of the axolotl occurs in the outside layer of cells, and is normal whether or not the jelly layers and vitelline membrane are present. So in this case no such confined space exists.
  3. The speed of development may not permit steady state to be reached. This is sometimes considered an advantage in cases where the steady state could not possibly lead to the correct morphology. So we have a steady state invoked except when we don’t want it. In any case, the rate of development varies substantially with temperature over a species’ temperature range for normal development. This would have to be matched to the temperature dependence of diffusion of the molecule which is itself dependent on the temperature variation of the viscosity of the medium.
  4. Ordinary diffusion gradients do not scale well. The consequence for embryos is that for embryos of different sizes there should be widely different proportions of parts but we know that is not the case. There is a limit on the “range” of a morphogen gradient. Such range limits also limit their potential role in growing tissues. Amphibian embryo eggs vary from 0.75 mm to 35 mm, and yet produce adults with substantially the same body plan. As we have a common ancestor with amphibians, our own eggs at 0.07 mm extend the linear size range down by another order of magnitude.
  5. Diffusion gradients follow the superposition principle. This means that a gradient of one substance in, say the x-direction, and a gradient of the same substance in the y-direction, result in a single one-dimensional gradient in the diagonal direction, not a two dimensional gradient. Yet biologists frequently invoke a two dimensional gradient to get the gradient model to fit their data. If you want a two dimensional gradient system you have to have two morphogen gradients with two different sources and sinks placed approximately perpendicular to one another, and three to invoke the third spatial dimension. That’s 6 unidentified sources and sinks.
  6. The fundamental principal of gradients is that cells in high concentrations will respond in one way, while those at low concentrations respond in a different way while those in the middle respond in yet another way. Fluctuations in gradients always occur, especially if the number of diffusing molecules is low. Fluctuations of purported morphogen concentrations make response to particular concentration thresholds problematic.
  7. Each cell has to be able to “read” the morphogen concentration accurately, lest boundaries between tissues become ragged. Gradients are frequently invoked without any explanation how a cell measures a concentration. Yet in embryos boundaries between tissues are generally sharp, at the cellular level.

    Many doubts about the functioning or existence of these so-called “morphogen” gradients have been raised, with alternatives and elaborations, and transport mechanisms other than diffusion being proposed. Like epicycles, multiple, overlapping gradients in the same direction are sometimes required. We won’t review the numerous molecules that have been proposed to be morphogens, but as new biologically active molecules are discovered, they tend to be added to the list and then later sometimes removed. While gradients such as bicoid in Drosophila one-cell embryos are indeed found, the existence of polyembryonic wasps reasonably similar to Drosophila in adult appearance, whose fertilized eggs split into up to 2000 embryos, raises doubts as to the importance of even these intracellular maternal gradients for embryogenesis.

This post contains excerpts from our book Embryogenesis Explained and also from our  article “The organelle of differentiation in embryos: the cell state splitter”, Theoretical Biology and Medical Modelling  (invited review) (Biophysical Models of Cell Behaviour) 2016 in press. We did ask permission to use the gradient model image but they haven’t replied so we hope simply giving them full credit and linking to their website location will do.

Let a hundred flowers bloom: Mao & Bill Gates

IMG_2799

A small bit of tall grass prairie in “Silver Bog” in bloom. Photo by Dick Gordon

I am presently reading the magnum opus of philosopher of science Michael Ruse, Monad to Man: The Concept of Progress in Evolutionary Biology (http://www.amazon.com/Monad-Man-Concept-Progress-Evolutionary/dp/0674032489). He told me when we met recently at Gulf Specimen Marine Laboratory & Aquarium (http://www.gulfspecimen.org/) that he is working on another book on Progress (or perhaps P/progress, human/biological, as he puts it) and I sent him our chapter from Embryogenesis Explained on Why evolution is progressive. The concept of progress has been a conundrum, ever since the ancient Greek atomists conceived the world as a collection of particles rattling around, bumping into one another and occasionally sticking. The idea was decried as leading to atheism. It is at the root of the much maligned reductionism, which itself may be at the root of much of successful science modelled on mathematics. We start with a set of assumptions and deduce the rest.

Atomism led to the problem of “How can there be anything new in the world?”. In other words, what are the sources of innovation? In social terms, how can we make a better world? Concepts of P/progress are indeed intimately entwined, as Ruse observes.

Yesterday (February 28, 2016) I read Bill Gates’ 2016 annual letter: More energy after hearing him talk about it on CNN. He and a number of lesser billionaires have decided that:

“…we need an energy miracle…. We need a massive amount of research into thousands of new ideas—even ones that might sound a little crazy—if we want to get to zero emissions by the end of this century. New ways to make solar and wind power available to everyone around the clock could be one solution. Some of the crazier inventions I’m excited about are a possible way to use solar energy to produce fuel, much like plants use sunlight to make food for themselves, and batteries the size of swimming pools with huge storage capacity.”

So I tested the waters:

***************
Bill Gates
Breakthrough Energy Coalition
http://www.breakthroughenergycoalition.com/en/index.html
info@breakthroughenergycoalition.com
Dear Bill,
​Heard you on CNN this morning. In 2009 I published:
Ramachandra, T.V., D.M. Mahapatra, Karthick B. & R. Gordon (2009). Milking diatoms for sustainable energy: biochemical engineering versus gasoline-secreting diatom solar panels. Industrial & Engineering Chemistry Research 48(19, Complex Materials II special issue, October), 8769-8788.(http://pubs.acs.org/doi/abs/10.1021/ie900044j)

and have since gathered an international group of scientists (USA, France, India, Egypt) ​working on various aspects of the project. If we ever get the efficiency of artificial photosynthesis to an acceptable level compared to diatoms, we could then go the next step. For now diatom biofuel solar panels would use live diatoms.

Our primary goal is nothing less than replacing fossil fuels by diatom biofuel. Advantages of diatom biofuel solar panels ​are:

  1. Local, rooftop production of gasoline.
  2. Storable energy for transportation, heating, cooling, cooking, etc., riding through the day/night cycle and wind/no wind that plague electric solar and wind energy. No batteries needed. Gasoline has 44x the energy density of the best batteries.
  3. Estimated 10-200x oil production per unit area compared to seed oil crops.
  4. Retention of the matured gasoline engine technology, including well known methods for safe storage.
  5. No competition with food production (the bane of much ethanol production).
  6. Zero carbon footprint.
  7. Diatom biofuel solar panels may prove to be of low maintenance.
  8. Total energy independence for everyone, disrupting the current geopolitics of oil.

​Interested?

Yours, -Dick Gordon <DickGordonCan@gmail.com>​

***************

Now Natalie and I had previously run a workshop explicitly suggesting to Bill Gates how to spend the billions he wanted to use to stop HIV/AIDS, which resulted in a special issue:

Smith?, R.J. & R. Gordon (2009). The OptAIDS project: towards global halting of HIV/AIDS [Preface]. BMC Public Health 9(Suppl. 1: OptAIDS Special Issue), S1 (5 pages). Web:  http://www.biomedcentral.com/1471-2458/9/S1/S1; http://www.biomedcentral.com/bmcpublichealth/supplements/9/S1

We didn’t ask him for any money, just that he send someone to hear us out. I broached the idea with and wrote to his representatives at the 2006 AIDS Conference in Toronto. No one came. I have no idea if he ever heard our request that he send a participant, nor if he read our articles. I had to conclude that he surrounds himself with gatekeepers, who filter out potentially innovative ideas. Sure enough, here is the reply to my present missive:

***************

Breakthrough Energy Coalition<info@breakthroughenergycoalition.com>

Automatic reply: Diatom biofuel solar panels

Thank you for contacting the Breakthrough Energy Coalition.  This is an automatic response acknowledging receipt of your email.

Due to the high volume of interest, we are not able to respond to each inquiry individually.  If you have contacted us regarding opportunities for funding, collaboration, or employment, we will keep your information on file.

***************

So much for the support of innovative ideas. Then I read the fine print: “I recently helped launch an effort by more than two dozen private citizens that will complement government research being done by several countries. It’s all aimed at delivering energy miracles.” In the name of innovation, ideas screened by big governments will be passed on to the billionaires, or at least their gatekeepers, who will thereby receive the sifted wisdom of layers and layers of sifting out of (good) ideas. Yes, in my experience it is rare that good ideas, let alone the best ideas, survive such massive bureaucracy. Bill Gates has merely added another layer, a globalized layer, to the suppression of innovation. This is what I meant when I wrote:

Gordon, R. (1993). Grant agencies versus the search for truth. Accountability in Research: Policies and Quality Assurance 2(4), 297-301.http://www.tandfonline.com/doi/abs/10.1080/08989629308573824?journalCode=gacr20

I woke up early this morning realizing I had heard Bill Gates’ words 60 years ago: “Let a hundred flowers bloom; let a hundred schools of thought contend”, espoused by Chairman Mao. The resulting cacophony in China was swiftly followed by a “crackdown… against those who were critical of the regime and its ideology. Those targeted were publicly criticized and condemned to prison labor camps” (https://en.wikipedia.org/wiki/Hundred_Flowers_Campaign). The innovators, the intellectuals, were humiliated, as they were in the subsequent Red Guard movement in China (https://en.wikipedia.org/wiki/Red_Guards_(China)). We live in a milder time now, at least in places where beheadings and labor camps are no longer in style, new ideas being dismissed with “Automatic reply”.