Emerging Field Of Quantum Biology – Interaction Between Quantum Mechanics and Nature (Biology)


According to quantum biology, the European robin has a ‘sixth sense’ in the form of a protein in its eye sensitive to the orientation of the Earth’s magnetic field, allowing it to ‘see’ which way to migrate. Photograph: Helmut Heintges/ Helmut Heintges/Corbis http://www.theguardian.com/science/2014/oct/26/youre-powered-by-quantum-mechanics-biology#img-1

Learning from nature is an idea as old as mythology — but until now, no one has imagined that the natural world has anything to teach us about the quantum world.

Before the twentieth century, biology and physics rarely crossed paths. Biological systems were often seen as too complex to be penetrable with mathematical methods. After all, how could a set of differential equations or physical principles shed light on something as complex as a living being?

In the early twentieth century, with the advent of more powerful microscopes and techniques, researchers began to delve more deeply into possible physical and mathematical descriptions of microscopic biological systems. Some famous examples (among many) include Turing patterns and morphogenesis, and Schrödinger’s lecture series and book     ‘What is Life?’, [Schrödinger, E. What is Life? (Cambridge Univ. Press, 1992)] in which he predicted several of the functional features of DNA. [ Davies, P. C. W. Quantum Aspects of Life (Imperial College Press, 2008).] The pace of progress in this field is now rapid, and many branches of physics and mathematics have found applications in biology; from the statistical methods used in bioinformatics, to the mechanical and factory-like properties observed at the microscale within cells.[Longuet-Higgins, H. C. Quantum mechanics and biology. Biophys. J. 2, 207215 (1962).]

This progress leads naturally to the question:

Can quantum mechanics play a role in biology?

In many ways it is clear that it already does. Every chemical process relies on quantum mechanics. However, in many ways quantum mechanics is still a concept alien to biology, especially on a scale that can have a physiological impact.[ Wolynes, P. G. Some quantum weirdness in physiology. Proc. Natl Acad. Sci. USA 106,1724717248 (2009)].

Recent technological progress in physics in harnessing quantum mechanics for information processing and encryption puts the question in a different light:

Are there any biological systems that use quantum mechanics to perform a task that either cannot be done classically, or can do that task more efficiently than even the best classical equivalent?

In other words, do some organisms take advantage of quantum mechanics to gain an advantage over their competitors?

Many attempts to find examples of such phenomenon have been met with fierce criticism by both physicists and biologists. [Tegmark, M. Importance of quantum decoherence in brain processes. Phys. Rev. E 61, 4194–4206 (2000)][McKemmish, L. K., Reimers, J. R., McKenzie, R. H., Mark, A. E. & Hush, N. S. Penrose–Hameroff orchestrated objective-reduction proposal for human consciousness is not biologically feasible. Phys. Rev. E 80, 021912 (2009)].

However, over the past decade a range of experiments have suggested that there may be some cases in which quantum mechanics is harnessed for a biological advantage.

Artificial photosynthesis Plants have had millions of years to improve upon photosynthesis, and most green plants are fairly efficient at it, locking down up to 6 percent of the solar energy that strikes a leaf’s surface. Modern solar PV systems can achieve three times higher efficiency. Nonetheless, artificial systems that mimic natural photosynthesis typically don’t provide direct electrical output, as does solar PV. Instead, they use readily available water sources to create a stream of hydrogen that can be stored and burned as fuel. Exploring natural photosynthesis helps tease out the secrets plants have as model systems for larger fuel production. According to Thomas J. Meyer, Arey Distinguished Professor of Chemistry at the University of North Carolina, Chapel Hill, “The goal of artificial photosynthesis is to mimic the green plants and other photosynthetic organisms in using sunlight to make high-energy chemicals but with far higher efficiencies and simplicity of design for scale-up and large-scale production.” Photosynthesis begins when the pigments within a plant cell act as antennas that capture photons. These antennas then generate electrons that pass the energy along to other molecules in the multistep process of energy capture, redirection and storage. One or two types of pigments are necessary for a completely functional system: Photosystem I refers to the absorption of light via the main type of chlorophyll by itself. Photosystem II requires a second pigment. Light-harvesting polymers must be able to absorb sunlight over a significant span of the spectrum as well, in order to not waste photons. To compete with solar PV and other green energy systems, artificial photosynthesis research is leaning toward maximizing the efficiency of photon absorption. Generally, the way to do this is to find or develop materials that are easy and inexpensive to produce. Decades ago, Japan’s Akira Fujishima published research on the ability of titanium dioxide (TiO2) to split water molecules into their constituent oxygen and hydrogen atoms when exposed to light. Since Fujishima’s report, interest in TiO2 has languished because it is a relatively poor absorber of visible light. Still, researchers from the Pennsylvania State University in University Park, Arizona State University in Tempe, and the University of North Texas in Denton, U.S.A., have collaborated to improve TiO2-based systems. http://www.osa-opn.org/home/articles/volume_24/february_2013/features/artificial_photosynthesis_saving_solar_energy_for/#.VkA49UshhnU

In what form do these quantum effects usually appear?

In quantum information, arguably the most important quantum effect is that quantum bits can exist in superpositions whereas classical bits cannot. In quantum biology, the role of quantum effects can be subtle. However, we may consider a biological system that exploits coherent superpositions of states for some practical purpose to be the clearest example of functional quantum biology. [Neill Lambert, Yueh-Nan Chen, Yuan-Chung Cheng, Che-Ming Li, Guang-Yin Chen & Franco Nori; Quantum biology: Nature Physics 9,10–18(2013) doi:10.1038/nphys2474]

Are we ready for quantum biology?

Stomata: does entanglement play a part in plant biology? (Image: Power And Syred/Science Photo Library)

Are we ready for quantum biology?

Are we ready for quantum biology?

In Life on the Edge, Jim Al-Khalili and Johnjoe McFadden argue quantum effects are decisive in biology – but this challenging idea needs more proof.

FOR 15 years, theoretical physicist Jim Al-Khalili and molecular geneticist Johnjoe McFadden have been discussing how quantum physics, the science of the incredibly small, might affect biology.

Quantum physics and biology have long been regarded as unrelated disciplines, describing nature at the inanimate microlevel on the one hand and living species on the other hand. Over the past decades the life sciences have succeeded in providing ever more and refined explanations of macroscopic phenomena that were based on an improved understanding of molecular structures and mechanisms. Simultaneously, quantum physics, originally rooted in a world-view of quantum coherences, entanglement, and other nonclassical effects, has been heading toward systems of increasing complexity.

While in the days of Darwin and Mendel the life sciences were mainly focusing on botany or zoology, modern biology, pharmacology, and medicine are deeply rooted in a growing understanding of molecular interactions and organic information processing.

Quantum physics, on the other hand, was initially centered on microscopic phenomena with photons, electrons, and atoms. But objects of increasing complexity have attracted a growing scientific interest, and since the size scales of both physics and the life sciences have approached each other, it is now very natural to ask: what is the role of quantum physics in and for biology?

Erithacus rubecula, Arabidopsis thaliana

The magnetic compass of the European robin (Erithacus rubecula) has been extensively studied by Wiltschko et al. and others. Magnetic field effects in plants (Arabidopsis thaliana) have also been observed. A radical pair mechanism within the protein cryptochrome may underlie both phenomena. http://www.ks.uiuc.edu/Research/cryptochrome/

Erwin Schrödinger, most famous for his wave equation for nonrelativistic quantum mechanics, already ventured across the disciplines in his lecture series “What is life?” (Schrödinger, 1944). He anticipated a molecular basis for human heredity, which was later confirmed to be the DNA molecule (Watson and Crick, 1953). Since the early days of quantum physics, its influence on biology has always been present in a reductionist sense: quantum physics and electrodynamics shape all molecules and thus determine molecular recognition, the workings of proteins, and DNA. Also van der Waals forces, discrete molecular orbitals, and the stability of matter: all this is quantum physics and a natural basis for life and everything we see.

But even 100 years after its development, quantum physics is still a conceptually challenging model of nature: it is often acclaimed to be the most precisely verified theory of nature and yet its common interpretation stands in discrepancy to our classical, i.e., prequantum, world-view, and our natural ideas about reality or space-time. Is there a transition between quantum physics and our everyday world? And how will the life sciences then fit into the picture—with objects covering anything from molecules up to elephants, mammoth trees, or the human brain?

Still half a century ago, the topic had some rather skeptical reviews (Longuet-Higgins, 1962). But experimental advances have raised a new awareness and several recent reviews (e.g., Abbot et al., 2008) sketch a more optimistic picture that may be overoptimistic in some aspects.

[Quantum physics meets biology: Markus Arndt, Thomas Juffmann, and Vlatko Vedral. HFSP J. 2009 Dec; 3(6): 386–400. Published online 2009 Nov 9. doi: 10.2976/1.3244985 PMCID: PMC2839811]

What is Quantum Mechanics ? The weird world of quantum mechanics.

Quantum mechanics is the science of the very small: the body of scientific principles that explains the behaviour of matter and its interactions with energy on the scale of atoms and subatomic particles.

Quantum mechanics starts with the simple idea that energy does not come in just any amount; it comes in discrete chunks, called quanta. But deeper into the theory, some truly surprising – and useful – effects crop up

Superposition: A particle exists in a number of possible states or locations simultaneously – strictly, an electron might be in the tip of your finger and in the furthest corner of the Universe at the same time. It is only when we observe the particle that it ‘chooses’ one particular state.
Entanglement: Two particles can become entangled so that their properties depend on each other – no matter how far apart they get. Under quantum rules, no matter how far apart an “entangled” pair of particles gets, each seems to “know” what the other is up to – they can even seem to pass information to one another faster than the speed of light. A measurement of one seems to affect the measurement of the other instantaneously – an idea even Einstein called “spooky”.
Tunnelling: A particle can break through an energy barrier, seeming to disappear on one side of it and reappear on the other. Lots of modern electronics and imaging depends on this effect.

Experiments suggest this is going on within single molecules in birds’ eyes, and John Morton of University College London explained that the way birds sense it could be stranger still.

“You could think about that as… a kind of ‘heads-up display’ like what pilots have: an image of the magnetic field… imprinted on top of the image that they see around them,” he said.

The idea continues to be somewhat controversial – as is the one that your nose might be doing a bit of quantum biology.

Most smell researchers think the way that we smell has to do only with the shapes of odour molecules matching those of receptors in our noses.

But Dr Turin ( Luca Turin of the Fleming Institute in Greece) believes that the way smell molecules wiggle and vibrate is responsible – thanks to the quantum effect called tunnelling. The idea holds that electrons in the receptors in our noses disappear on one side of a smell molecule and reappear on the other, leaving a little bit of energy behind in the process.

A paper published in Plos One this shows that people can tell the difference between two molecules of identical shape but with different vibrations, suggesting that shape is not the only thing at work. Simon Gane, a researcher at the Royal National Throat, Nose and Ear Hospital and lead author of the Plos One paper, said that the tiny receptors in our noses are what are called G-protein coupled receptors. “They’re a sub-family of the receptors we have on all cells in our body – they’re the targets of most drug development,” he explained. “What if – and this is a very big if – there’s a major form of receptor-drug interaction that we’re just not noticing because we’re not looking for a quantum effect? That would have profound implications for drug development, design and discovery.”

What intrigues all these researchers is how much more quantum trickery may be out there in nature.

“Are these three fields the tip of the iceberg, or is there actually no iceberg underneath?” asked Dr Turin. “We just don’t know. And we won’t know until we go and look.”

Jim Al-Khalili of the University of Surrey is investigating whether tunnelling occurs during mutations to our DNA – a question that may be relevant to the evolution of life itself, or cancer research.

He told the BBC: “If quantum tunnelling is an important mechanism in mutations, is quantum mechanics going to somehow answer some of the questions about how a cell becomes cancerous?”

“And suddenly you think, ‘Wow!’ Quantum mechanics is not just a crazy side issue or a fringe field where some people are looking at some cranky ideas. If it really might help answer some of the very big questions in science, then it’s hugely important.”

Source: http://www.bbc.com/news/science-environment-21150047

Classical physics explains matter and energy on a scale familiar to human experience, including the behaviour of astronomical bodies. It remains the key to measurement for much of modern science and technology. However, towards the end of the 19th century, scientists discovered phenomena in both the large (macro) and the small (micro) worlds that classical physics could not explain. As Thomas Kuhn explains in his analysis of the philosophy of science, The Structure of Scientific Revolutions, coming to terms with these limitations led to two major revolutions in physics which created a shift in the original scientific paradigm: the theory of relativity and the development of quantum mechanics.

In this sense, the word ‘quantum’ means the minimum amount of any physical entity involved in an interaction. Certain characteristics of matter can take only discrete values.

Light behaves in some respects like particles and in other respects like waves.

Matter—particles such as electrons and atoms—exhibits wavelike behaviour too. Some light sources, including neon lights, give off only certain discrete frequencies of light. Quantum mechanics shows that light, along with all other forms of electromagnetic radiation, comes in discrete units, called photons, and predicts its energies, colours, and spectral intensities.

Some aspects of quantum mechanics can seem counterintuitive or even paradoxical, because they describe behaviour quite different from that seen at larger length scales. In the words of Richard Feynman, quantum mechanics deals with “nature as She is – absurd”. For example, the uncertainty principle of quantum mechanics means that the more closely one pins down one measurement (such as the position of a particle), the less precise another measurement pertaining to the same particle (such as its momentum) must become.

  • At Massachusetts Institute of Technology, Mass., U.S.A., Daniel Nocera and his colleagues have produced an

    The structure of an artificial leaf produced by researcher Daniel Nocera’s team features a silicon junction that captures photons. The cobalt-based oxygen evolving complex (Co-OEC) and a nickel, molybdenum and zinc alloy (NiMoZn) perform the water-splitting function and transport the captured energy into storage. http://www.osa-opn.org/home/articles/volume_24/february_2013/features/artificial_photosynthesis_saving_solar_energy_for/#.VkA49UshhnU

    artificial leaf made mostly of silicon, nickel and cobalt. The leaf is the size of a playing card, and it is about ten times more efficient than a natural leaf and can operate continuously for about 45 hours.When the layered leaf is exposed to light and water simultaneously, a silicon junction captures incoming photons and energizes the cobalt-based oxygen evolving complex at one end and a nickel, molybdenum and zinc alloy at the other. Together, they split the water touching the device and produce hydrogen that can be put into storage. Oxygen is released from the cobalt side of the leaf, and hydrogen gas from the nickel-molybdenum-zinc side. Separating the two sides while the gases are produced would produce ample hydrogen for fuel cells.Previously, platinum was the catalyst of choice for creating the electrolytic effect, but the nickel-molybdenum-zinc alloy performs more than adequately while being much less expensive.

Consequences of the light being quantised

Why Ultraviolet Light can cause sunburn but visible or infrared light cannot ?

The relationship between the frequency of electromagnetic radiation and the energy of each individual photon is why ultraviolet light can cause sunburn, but visible or infrared light cannot. A photon of ultraviolet light will deliver a high amount of energy – enough to contribute to cellular damage such as occurs in a sunburn. A photon of infrared light will deliver a lower amount of energy – only enough to warm one’s skin. So, an infrared lamp can warm a large surface, perhaps large enough to keep people comfortable in a cold room, but it cannot give anyone a sunburn.
All photons of the same frequency have identical energy, and all photons of different frequencies have proportionally different energies. However, although the energy imparted by photons is invariant at any given frequency, the initial energy state of the electrons in a photoelectric device prior to absorption of light is not necessarily uniform. Anomalous results may occur in the case of individual electrons. For instance, an electron that was already excited above the equilibrium level of the photoelectric device might be ejected when it absorbed uncharacteristically low frequency illumination. Statistically, however, the characteristic behaviour of a photoelectric device will reflect the behaviour of the vast majority of its electrons, which will be at their equilibrium level. This point is helpful in comprehending the distinction between the study of individual particles in quantum dynamics and the study of massed particles in classical physics.

Source: https://en.wikipedia.org/wiki/Introduction_to_quantum_mechanics

For years biologists have been wary of applying the strange world of quantum mechanics, where particles can be in two places at once or connected over huge distances, to their own field. But it can help to explain some amazing natural phenomena we take for granted.

Every year, around about this time, thousands of European robins, Erithacus rubecula, escape the oncoming harsh Scandinavian winter and head south to the warmer Mediterranean coasts. How they find their way unerringly on this 2,000-mile journey is one of the true wonders of the natural world. For unlike many other species of migratory birds, marine animals and even insects, they do not rely on landmarks, ocean currents, the position of the sun or a built-in star map. Instead, they are among a select group of animals that use a remarkable navigation sense – remarkable for two reasons.

The first is that they are able to detect tiny variations in the direction of the Earth’s magnetic field – astonishing in itself, given that this magnetic field is 100 times weaker than even that of a measly fridge magnet. The second is that robins seem to be able to “see” the Earth’s magnetic field via a process that even Albert Einstein referred to as “spooky”. The birds’ in-built compass appears to make use of one of the strangest features of quantum mechanics.

Over the past few years, the European robin, and its quantum “sixth sense”, has emerged as the pin-up for a new field of research, one that brings together the wonderfully complex and messy living world and the counter-intuitive, ethereal but strangely orderly world of atoms and elementary particles in a collision of disciplines that is as astonishing and unexpected as it is exciting.

Welcome to the new science of quantum biology.

Most people have probably heard of quantum mechanics, even if they don’t really know what it is about. Certainly, the idea that it is a baffling and difficult scientific theory understood by just a tiny minority of smart physicists and chemists has become part of popular culture. Quantum mechanics describes a reality on the tiniest scales that is, famously, very weird indeed; a world in which particles can exist in two or more places at once, spread themselves out like ghostly waves, tunnel through impenetrable barriers and even possess instantaneous connections that stretch across vast distances.

But despite this bizarre description of the basic building blocks of the universe, quantum mechanics has been part of all our lives for a century. Its mathematical formulation was completed in the mid-1920s and has given us a remarkably complete account of the world of atoms and their even smaller constituents, the fundamental particles that make up our physical reality. For example, the ability of quantum mechanics to describe the way that electrons arrange themselves within atoms underpins the whole of chemistry, material science and electronics; and is at the very heart of most of the technological advances of the past half-century. Without the success of the equations of quantum mechanics in describing how electrons move through materials such as semiconductors we would not have developed the silicon transistor and, later, the microchip and the modern computer.

However, if quantum mechanics can so beautifully and accurately describe the behaviour of atoms with all their accompanying weirdness, then why aren’t all the objects we see around us, including us – which are after all only made up of these atoms – also able to be in two place at once, pass through impenetrable barriers or communicate instantaneously across space?

One obvious difference is that the quantum rules apply to single particles or systems consisting of just a handful of atoms, whereas much larger objects consist of trillions of atoms bound together in mind-boggling variety and complexity. Somehow, in ways we are only now beginning to understand, most of the quantum weirdness washes away ever more quickly the bigger the system is, until we end up with the everyday objects that obey the familiar rules of what physicists call the “classical world”.

In fact, when we want to detect the delicate quantum effects in everyday-size objects we have to go to extraordinary lengths to do so – freezing them to within a whisker of absolute zero and performing experiments in near-perfect vacuums.

Quantum effects were certainly not expected to play any role inside the warm, wet and messy world of living cells, so most biologists have thus far ignored quantum mechanics completely, preferring their traditional ball-and-stick models of the molecular structures of life.

Meanwhile, physicists have been reluctant to venture into the messy and complex world of the living cell; why should they, when they can test their theories far more cleanly in the controlled environment of the lab where they at least feel they have a chance of understanding what is going on?

Yet, 70 years ago, the Austrian Nobel prize-winning physicist and quantum pioneer, Erwin Schrödinger, suggested in his famous book, What is Life?, that, deep down, some aspects of biology must be based on the rules and orderly world of quantum mechanics. His book inspired a generation of scientists, including the discoverers of the double-helix structure of DNA, Francis Crick and James Watson. Schrödinger proposed that there was something unique about life that distinguishes it from the rest of the non-living world. He suggested that, unlike inanimate matter, living organisms can somehow reach down to the quantum domain and utilise its strange properties in order to operate the extraordinary machinery within living cells.


Erwin Schrödinger, whose book What is Life? suggested that the macroscopic order of life was based on order at its quantum level. Photograph: Bettmann/CORBIS http://www.theguardian.com/science/2014/oct/26/youre-powered-by-quantum-mechanics-biology#img-2

  • Schrödinger’s argument was based on the paradoxical fact that the laws of classical physics, such as those of Newtonian mechanics and thermodynamics, are ultimately based on disorder. Consider a balloon. It is filled with trillions of molecules of air all moving entirely randomly, bumping into one another and the inside wall of the balloon. Each molecule is governed by orderly quantum laws, but when you add up the random motions of all the molecules and average them out, their individual quantum behaviour washes out and you are left with the gas laws that predict, for example, that the balloon will expand by a precise amount when heated. This is because heat energy makes the air molecules move a little bit faster, so that they bump into the walls of the balloon with a bit more force, pushing the walls outward a little bit further. Schrödinger called this kind of law “order from disorder” to reflect the fact that this apparent macroscopic regularity depends on random motion at the level of individual particles.

But what about life? Schrödinger pointed out that many of life’s properties, such as heredity, depend of molecules made of comparatively few particles – certainly too few to benefit from the order-from-disorder rules of thermodynamics. But life was clearly orderly.

Where did this orderliness come from?

Schrödinger suggested that life was based on a novel physical principle whereby its macroscopic order is a reflection of quantum-level order, rather than the molecular disorder that characterises the inanimate world. He called this new principle “order from order”.

But was he right?

Up until a decade or so ago, most biologists would have said no. But as 21st-century biology probes the dynamics of ever-smaller systems – even individual atoms and molecules inside living cells – the signs of quantum mechanical behaviour in the building blocks of life are becoming increasingly apparent. Recent research indicates that some of life’s most fundamental processes do indeed depend on weirdness welling up from the quantum undercurrent of reality.

Here are a few of the most exciting examples.

Enzymes are the workhorses of life. They speed up chemical reactions so that processes that would otherwise take thousands of years proceed in seconds inside living cells. Life would be impossible without them. But how they accelerate chemical reactions by such enormous factors, often more than a trillion-fold, has been an enigma. Experiments over the past few decades, however, have shown that enzymes make use of a remarkable trick called quantum tunnelling to accelerate biochemical reactions. Essentially, the enzyme encourages electrons and protons to vanish from one position in a biomolecule and instantly re-materialise in another, without passing through the gap in between – a kind of quantum teleportation.

[I believe,(although I do not have any proof or reference for it) it might be following the same physics principles, as is followed by an electrons that travels through a wire, when a potential is applied across it. The electron seems to be travelling at light speed although, what happens actually is that, as soon as an electron enters one end of wire, at the same time, at the other end of the wire, an electron which was initially part of wire itself ejects simultaneously.Now the time required for the electron to be ejected depends upon the electric potential applied across and the material of the wire itself.]

  • Quantum tunnelling (or tunneling) is the quantum-mechanical effect of transitioning through a classically-forbidden energy state. It can be generalized to other types of classically-forbidden transitions as well.

    Consider rolling a ball up a hill. If the ball is not given enough velocity, then it will not roll over the hill. This scenario makes sense from the standpoint of classical mechanics, but is an inapplicable restriction in quantum mechanics simply because quantum mechanical objects do not behave like classical objects such as balls. On a quantum scale, objects exhibit wavelike behaviour.               For a quantum particle moving against a potential energy “hill”, the wave function describing the particle can extend to the other side of the hill. This wave represents the probability of finding the particle in a certain location, meaning that the particle has the possibility of being detected on the other side of the hill. This behaviour is called tunneling; it is as if the particle has ‘dug’ through the potential hill.

    As this is a quantum and non-classical effect, it can generally only be seen in nanoscopic phenomena — where the wave behaviour of particles is more pronounced.

And before you throw your hands up in incredulity, it should be stressed that quantum tunnelling is a very familiar process in the subatomic world and is responsible for such processes as radioactive decay of atoms and even the reason the sun shines (by turning hydrogen into helium through the process of nuclear fusion). Enzymes have made every single biomolecule in your cells and every cell of every living creature on the planet, so they are essential ingredients of life. And they dip into the quantum world to help keep us alive.

Another vital process in biology is of course photosynthesis. Indeed, many would argue that it is the most important biochemical reaction on the planet, responsible for turning light, air, water and a few minerals into grass, trees, grain, apples, forests and, ultimately, the rest of us who eat either the plants or the plant-eaters.

The initiating event is the capture of light energy by a chlorophyll molecule and its conversion into chemical energy that is harnessed to fix carbon dioxide and turn it into plant matter. The process whereby this light energy is transported through the cell has long been a puzzle because it can be so efficient – close to 100% and higher than any artificial energy transport process.

Summary of Quantum Processes required for ATP synthesis The figure presents the scheme of the integral membrane proteins forming the photosynthetic unit. Light-absorption and excitation transfer within the light-harvesting proteins (LH-II and LH-I) are represented by wavy lines. Electron transfer within the photosynthetic reaction center (RC), cytochrome c2, and bc1 complex is represented by blue lines. Proton transfer in the bc1 complex and the ATPase is represented by red lines. The chemical reaction of ATP synthesis is represented by a black line. http://www.ks.uiuc.edu/Research/quantum_biology/

qubiot_schemeThe first step in photosynthesis is the capture of a tiny packet of energy from sunlight that then has to hop through a forest of chlorophyll molecules to makes its way to a structure called the reaction centre where its energy is stored. The problem is understanding how the packet of energy appears to so unerringly find the quickest route through the forest. An ingenious experiment, first carried out in 2007 in Berkley, California, probed what was going on by firing short bursts of laser light at photosynthetic complexes. The research revealed that the energy packet was not hopping haphazardly about, but performing a neat quantum trick. Instead of behaving like a localised particle travelling along a single route, it behaves quantum mechanically, like a spread-out wave, and samples all possible routes at once to find the quickest way.

Radical Pair

Schematic illustration of a bird’s eye and its important components. The retina (a) converts images from the eye’s optical system into electrical signals sent along the ganglion cells forming the optic nerve to the brain. (b) An enlarged retina segment is shown schematically. (c) The retina consists of several cell layers. The primary signals arising in the rod and cone outer segments are passed to the horizontal, the bipolar, the amacrine, and the ganglion cells. (d) The primary phototransduction signal is generated in the receptor protein rhodopsin shown schematically at a much reduced density. The rhodopsin containing membranes form disks with a thickness of ~20 nm, being ~15–20 nm apart from each other. The putatively magnetic-field-sensitive protein cryptochrome may be localized in a specifically oriented fashion between the disks of the outer segment of the photoreceptor cell, as schematically shown in panel d or the cryptochromes (e) may be attached to the oriented, quasicylindrical membrane of the inner segment of the photoreceptor cell (f). http://www.ks.uiuc.edu/Research/cryptochrome/

A third example of quantum trickery in biology – is the mechanism by which birds and other animals make use of the Earth’s magnetic field for navigation. Studies of the European robin suggest that it has an internal chemical compass that utilises an astonishing quantum concept called entanglement, which Einstein dismissed as “spooky action at a distance”. This phenomenon describes how two separated particles can remain instantaneously connected via a weird quantum link. The current best guess is that this takes place inside a protein in the bird’s eye, where quantum entanglement makes a pair of electrons highly sensitive to the angle of orientation of the Earth’s magnetic field, allowing the bird to “see” which way it needs to fly.

The avian magnetic sensor is known to be activated by light striking the bird’s retina. Researchers’ current best guess at a mechanism is that the energy deposited by each incoming photon creates a pair of free radicals. [Ritz, T., Thalau, P., Phillips, J. B., Wiltschko, R. & Wiltschko, W. Nature 429, 177–180 (2004).] — highly reactive molecules, each with an unpaired electron. Each of these unpaired electrons has an intrinsic angular momentum, or spin, that can be reoriented by a magnetic field. As the radicals separate, the unpaired electron on one is primarily influenced by the magnetism of a nearby atomic nucleus, whereas the unpaired electron on the other is further away from the nucleus, and feels only Earth’s magnetic field. The difference in the fields shifts the radical pair between two quantum states with differing chemical reactivity.

Radical Pair

Panoramic view at Frankfurt am Main, Germany. The image shows the landscape perspective recorded from a bird flight altitude of 200 m above the ground with the cardinal directions indicated. The visual field of a bird is modified through the magnetic filter function. For the sake of illustration we show the magnetic field-mediated pattern in grayscale alone (which would reflect the perceived pattern if the magnetic visual pathway is completely separated from the normal visual pathway) and added onto the normal visual image the bird would see, if magnetic and normal vision uses the same neuronal pathway in the retina. The patterns are shown for a bird looking at eight cardinal directions (N, NE, E, SE, S, SW, W, and NW). The geomagnetic field inclination angle is 66°, being a characteristic value for the region. http://www.ks.uiuc.edu/Research/cryptochrome/

“One version of the idea would be that some chemical is synthesized in the bird’s retinal cells when the system is in one state, but not when it’s in the other”, says Simon Benjamin, a physicist at the University of Oxford, UK. “Its concentration reflects Earth’s field orientation.” The feasibility of this idea was demonstrated in 2008 in an artificial photochemical reaction, in which magnetic fields affected the lifetime of a radical pair.[Maeda, K. et al. Nature 453, 387–390 (2008).]

The radical-pair mechanism for avian magnetoreception explains many of the behavioural studies performed on some species of migrating birds. Key properties of the proposed radical-pair model for avian magnetoreception are dependent on quantum mechanics; therefore, this may represent a functional piece of biological quantum hardware. a, A schematic of the radical-pair mechanism for magnetoreception that could potentially be employed by European robins and other species. It is thought to occur within cryptochromes, proteins residing in the retina. There are three main steps in this mechanism. First, light-induced electron transfer from one radical-pair-forming molecule (for example, in a cryptochrome in the retina of a bird) to an acceptor molecule creates a radical pair. b,c, Second, the singlet (S) and triplet (T) electron-spin states inter-convert owing to the external (Zeeman) and internal (hyperfine) magnetic couplings. d, Third, singlet and triplet radical pairs recombine into singlet and triplet products, respectively, which are biologically detectable. e, Singlet yield (a measure of the probability of the radical pair to decay into a singlet state) as a function of the external-field angle θ in the presence of an oscillatory field (taken from Gauger et al. 70). The blue top curve shows the yield for a static geomagnetic field (B0 = 47 μT), and the red curves show the singlet yield in the case where a 150 nT field oscillating at 1.316 MHz is superimposed perpendicular to the direction of the static field. The sensitivity of the compass can be understood as the difference in the yield between θ = 0 and θ = π/2. An appreciable effect on this sensitivity occurs once κ (the decay rate of the radical) is of order 104 s−1. f, Singlet yield as a function of the magnetic field angle θ for differing noise magnitudes (from Gauger et al. 70). The blue curve shows the optimal case with no noise (but with decay rate κ = 104 s−1). The red curves indicate that a general noise rate of Γ>0.1κ has a detrimental effect on the sensitivity. Both of these results indicate that the electron spin state must have a remarkably long coherence time. http://www.nature.com/nphys/journal/v9/n1/full/nphys2474.html

Benjamin and his co-workers have proposed that the two unpaired electrons, being created by the absorption of a single photon, exist in a state of quantum entanglement: a form of coherence in which the orientation of one spin remains correlated with that of the other, no matter how far apart the radicals move. Entanglement is usually quite delicate at ambient temperatures, but the researchers calculate that it is maintained in the avian compass for at least tens of microseconds — much longer than is currently possible in any artificial molecular system. [Gauger, E. M., Rieper, E., Morton, J. J. L., Benjamin, S. C. & Vedral, V. Phys. Rev. Lett. 106, 040503 (2011).]

Reference: The Dawn of Quantum Biology by Philip Ball , Nature, Vol. 474, 16 June 2011, pg 272-274.

This quantum-assisted magnetic sensing could be widespread. Not only birds, but also some insects and even plants show physiological responses to magnetic fields — for example, the growth-inhibiting influence of blue light on the flowering plant Arabidopsis thaliana is moderated by magnetic fields in a way that may also use the radical pair mechanism. [Ahmad, M., Galland, P., Ritz, T., Wiltschko, R. & Wiltschko, W. Planta 225, 615–624 (2007)] But for clinching proof that it works this way, says Benjamin, “we need to understand the basic molecules involved, and then study them in the lab”.

All these quantum effects have come as a big surprise to most scientists who believed that the quantum laws only applied in the microscopic world. All delicate quantum behaviour was thought to be washed away very quickly in bigger objects, such as living cells, containing the turbulent motion of trillions of randomly moving particles. So how does life manage its quantum trickery? Recent research suggests that rather than avoiding molecular storms, life embraces them, rather like the captain of a ship who harnesses turbulent gusts and squalls to maintain his ship upright and on course.

Just as Schrödinger predicted, life seems to be balanced on the boundary between the sensible everyday world of the large and the weird and wonderful quantum world, a discovery that is opening up an exciting new field of 21st-century science.

Reference: You’re powered by quantum mechanics. No, really… http://www.theguardian.com/science/2014/oct/26/youre-powered-by-quantum-mechanics-biology


Green Fluorescent Protein (GFP’s)- Inspirational And Motivational Story of Sheer Resilience.

Lessons from the jellyfish’s green light



Off the west coast of North America, floats the jellyfish Aequorea victoria. In its light-emitting organs resides the green fluorescent protein, GFP, which glows intensely under ultraviolet light. GFP now revolutionizes the life sciences, and the scientists responsible for its development have been awarded Nobel Prize in Chemistry for the year 2008. The green light enables scientists to track, amongst other things, how cancer tumours form new blood vessels, how Alzheimer’s disease kills brain neurons and how HIV infected cells produce new viruses.

An unexpected catch for O. Shimomura



Throughout the summers of the 1960s, Osamu Shimomura (rearmost in the picture above), his family and various assistants, caught tens of thousands of jellyfish in the Pacific Ocean. From the edge, which emits green light when the jellyfish is agitated, Shimomura isolated a protein. Surprisingly, that protein did not shine in green. It was blue. Shimomura assumed that additional proteins were involved, and indeed found one more. It was not luminescent but did glow bright green under the light of an ultraviolet lamp.



A green guiding star for biosciences

Today, scientists use GFP to understand the function of cells and proteins in living creatures. Proteins are the chemical tools of life – they control most of what happens within a living cell. Every human being functions thanks to the well-oiled machinery of thousands of proteins, like haemo­globin, antibodies and insulin. If something malfunctions, illness and disease often follows. Therefore it is fundamental for the biosciences to map out the role of various proteins. Using DNA-technology, scientists connect GFP to interesting, but otherwise invisible, proteins. GFP functions like a little lantern, which is activated by ultraviolet light. The green glow helps scientists  track these proteins in the body.



Tsien creates a palette with all the colours of the rainbow

During the 1990s Roger Tsien explored and changed GFP. His playful research resulted in proteins that glowed cyan, blue and yellow. However, he did not manage to produce any red colours. Red light penetrates the skin and other biological tissue more easily, and so is especially useful for research.



In 1999, Russian scientists isolated a red fluorescent protein, DsRED, from a coral. This protein was larger and more cumbersome than GFP. Tsien, however, managed to decrease the size of DsRED. From DsRED, Tsien also developed proteins with mouth-watering names like mPlum, mCherry, mStrawberry, mOrange and mCitrine.

A brilliant experiment by Chalfie



When Martin Chalfie first heard about GFP in 1988, he was delighted. He realised that GFP could possibly be used to colour cells and proteins. If that was the case, it would revolutionise the biosciences. The picture above shows Chalfie’s successful experiment. The touch receptor neurons of the millimetre-sized roundworm Caenorhabditis elegans fluoresces green. We can see the round bodies and the long slender projection of the nerve cells.


How cells become green
Chalfie positioned the GFP-gene behind a promoter (a gene switch), which is active in the touch receptor neurons of the round worm. He injected the gene construct into the gonads of a mature worm. The worm is a hermaphrodite and fertilizes itself. The GFP gene is passed onto the eggs that the worm lays. The eggs divide, forming new individuals. The GFP-gene is then present in all cells of the new generation of roundworms, but only the touch receptor neurons will produce GFP. When they fill up with GFP, they start to glow green under ultraviolet light.

The brainbow

The brainbow
Scientists have used three fluorescent proteins in cyan, yellow and red – colours similar to those used by a computer printer – to colour the brain of a mouse. Different neurons randomly produce different amounts of the proteins. We can distinguish single neurons interlaced within the dense network.

Tumour surrounded by nourishing blood vesselsTumour surrounded by nourishing blood vessels Scientists have coloured a breast cancer tumour with DsRED and the surrounding blood vessels with GFP. In this experiment, scientists discovered two proteins which help breast cancer cells spread. If scientists can neutralize these proteins, they might also be able to stop the cells from breaking away from the tumour area.

Osamu Shimomura                      Roger Y. Tsien              Martin Chalfie

This is an inspirational and motovational story of Osamu Shimomura.

Osamu Shimomura

Photo: Ulla Montan

Born: 27 August 1928, Kyoto, Japan.

Osamu Shimomura went on to share the Nobel Prize for Chemistry in the field of Biochemistry, year 2008, for the discovery and development of the green fluorescent protein, GFP.

Affiliation at the time of the award: Marine Biological Laboratory (MBL), Woods Hole, MA, USA, Boston University Medical School, Massachusetts, MA, USA

He shared his prize with Martin Chalfie (Columbia University, New York, NY, USA) and Roger Y. Tsien (University of California, San Diego, CA, USA, Howard Hughes Medical Institute). (Source: http://www.nobelprize.org)

Following are the excerpts from Nobel Lecture, December 8, 2008 by Osamu Shimomura.

Source: http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2008/shimomura_lecture.pdf

I discovered the green fluorescent protein GFP from jellyfish Aequorea aequorea in 1961 as a byproduct of the Ca-sensitive photoprotein aequorin [Shimomura, O., Johnson, F. H., and Saiga, Y. (1962), “Extraction, purification and properties of aequorin, a bioluminescent protein from the luminous hydromedusan, Aequorea,” J. Cell. Comp. Physiol. 59: 223–239.], and identified it’s chromophore (an atom or group whose presence is responsible for the colour of a compound) in 1979 [Shimomura, O. (1979), “Structure of the chromophore of Aequorea green fluorescent protein,” FEBS Lett. 104, 220–222.]

GFP was a beautiful protein but it remained useless for the next 30 years after the discovery. Now GFP and it’s homologues are indispensable in biomedical research, due to the fact that these proteins self contain a fluorescent chromophore in their peptide chains and they can be expressed in living bodies. The identification of the fluorescent chromophore, however, depended on the GFP that had been accumulated for many years in our study of aequorin. Without the study of aequorin, the chromophore of GFP would have remained unknown and the flourishing of fluorescent proteins would not have occurred.

In 1967, Ridgeway and Ashley microinjected aequorin into single muscle fibres of barnacles, and observed transient calcium ion-dependent signals during muscle contraction. They were the first to directly measure the free Calcium ions (Ca2+) in a muscle cell. They achieved this by injecting a large cell from barnacle muscle with aequorin, a Calcium ions (Ca2+) activated photoprotein. Three important points were made in these studies: 

  1. the Calcium ions (Ca2+) in the resting muscle cell is ∼0.1μM and rises transiently to no more than 10 μM when the cell is stimulated to contract.
  2. the rise in Calcium ions (Ca2+) follows the electrical stimulation but preceeds the onset of contraction.
  3. the Calcium ions (Ca2+) begins to fall before maximal tension is actually achieved.

Source: Ridgway EB, Ashley CC. Calcium transients in single muscle fibers. Biochem Biophys Res Commun. 1967 Oct 26;29(2):229-34.

An example of just how important the potential of GFP’s is found in the recent work of Jeff Litchman and Joshua Sanes, researchers at the Harvard Brain Center. They have created transgenic mice with fluoroscent multicoloured neurons. But it is not their colourful splendour that makes these genetically modified mice so amazing, it is their potential to revolutionise neurobiology that has scientists across the globe so excited. Using individual colour derived from GFP’s, researchers will now be able to map the neural circuit of brain. By creating a wire diagram, researchers hope to identify “defective” wiring found in the neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.

Brainbow is the process by which individual neurons in the brain can be distinguished from neighbouring neurons using fluorescent proteins. By randomly expressing different ratios of red, green, and blue derivatives of green fluorescent protein in individual neurons, it is possible to flag each neuron with a distinctive color. This process has been a major contribution to the field of connectomics, or the study of neural connections in the brain. The study of neural pathways is also known as hodology by earlier neuroanatomists.
The technique was originally developed in the spring of 2007 by a team led by Jeff W. Lichtman and Joshua R. Sanes, both professors of Molecular & Cellular Biology at Harvard University. Their demonstration of the technique in mice first appeared in the November 1, 2007 issue of the journal Nature.The original technique has recently been adapted for use with other model organisms including Drosophila melanogaster and Caenorhabditis elegans.

While older techniques were only able to stain cells with a constricted range of colors, often utilizing bi- and tri-color transgenic mice to unveil limited information in regards to neuronal structures, Brainbow is much more flexible in that it has the capacity to fluorescently label individual neurons with up to approximately 100 different hues so that scientists can identify and even differentiate between dendritic and axonal processes.

Source: https://en.wikipedia.org/wiki/Brainbow

File:Brainbow (Lichtman 2008).jpg

a) A motor nerve innervating ear muscle. b) An axon tract in the brainstem. c) The hippocampal dentate gyrus. In the Brainbow mice from which these images were taken, up to ~160 colours were observed as a result of the co-integration of several tandem copies of the transgene into the mouse genome and the independent recombination of each by Cre recombinase. The images were obtained by the superposition of separate red, green and blue channels. From Lichtman and Sanes, 2008.  Jeff W. Lichtman and Joshua R. Sanes.

My story begins in 1945, the year the city of Nagasaki was destroyed by an atomic bomb and the World War II ended. At that time I was a 16 year old high school student, and I was working at a factory about 15 Km north-east of Nagasaki. I watched the B-29 that carried the atomic bomb heading towards Nagasaki, then soon I was exposed to a blinding bright flash and a strong pressure wave that were caused by gigantic explosion. I was lucky to survive the war. In the mess after the war, however, I could not find any school to attend. I idled for 2 years, and then I learned that the pharmacy school of Nagasaki Medical College, which had been completely destroyed by the atomic bomb, was going to open a temporary campus near my home. I applied to the pharmacy school and was accepted. Although I didn’t have any interest in pharmacy, it was the only way that I could have some education.

After graduating from the primary school, I worked as a teaching assistant at the same school, which was re-organised as a part of Nagasaki University. My boss Professor Shungo Yasunga was a gentle and very kind person. In 1955, when I had worked for four years on the job, he arranged for me a paid leave of absence for one year, and he sent me to Nagoya University, to study at the laboratory of Professor Yoshimasa Hirata.

Cypridina Luciferin

The research subject that Professor Hirata gave me was the bioluminescence of the crustacean ostracod Cypridina hilgendorfii. Cypridina emits blue light when it’s luciferin is oxidised in the presence of an enzyme luciferase and molecular oxygenFigure imgb0001Mg2+acts as an inhibitor.

The ostracod Cypridina hilgendorfi freshly caught, and placed on a dark surface.

Source: http://www.nobelprize.org

Source: https://www.tumblr.com/search/sea%20firefly

Vargula hilgendorfii, sometimes called the sea-firefly, one of three bioluminescent species known in Japan as umi-hotaru, is a species of ostracod crustacean. In 1962, the name of the species was changed from Cypridina hilgendorfii to Vargula hilgendorfii. The species was first described by Gustav Wilhelm Müller in 1890. He named the species after the zoologist Franz Martin Hilgendorf (1839–1904). Dried sea-firefly were sometimes used as a light source by the Japanese army during World War II to read maps in the dim lightV. hilgendorfii is a small animal, only 3 millimetres long. It is nocturnal and lives in the sand at the bottom of shallow water. At night, it feeds actively.

Source: https://en.wikipedia.org/wiki/Vargula_hilgendorfii

How Bioluminescence Works

Source: http://animals.howstuffworks.com/animal-facts/bioluminescence3.htm

The luciferin had been studied for many years at Newton Harvey’s laboratory at Princeton University [Harvey, E. N., (1952). Bioluminescene, Academic Press, New York.], but it had never been completely purified, due to it’s extreme instability. Prof. Hirata wanted to determine the structure of the luciferin of Cypridina, and he asked me to purify the luciferin and to crystallize it, because crystallisation was the only way to confirm the purity  of substances at the time.

Using 500 gm of dried Cypridina (about 2.5 kg before drying), I began the extraction and purification of luciferin in an atmosphere of purified hydrogen using a large specially made Soxhlet apparatus.

A Soxhlet extractor is lab equipment designed for processing certain kinds of solids. These devices allow for continuous treatment of a sample with a solvent over a period of hours or days to extract compounds of interest. Typically, a Soxhlet extraction is only required where the desired compound has a limited solubility in a solvent, and the  impurity is insoluble in that solvent.

   Crystals of Cypridina luciferin

Mg2+ acts as an inhibitor. Bioluminescence vs. Fluorescence. Bioluminescence (left) is emitted from the reaction of luciferase enzyme and its substrate, such as firefly luciferase and luciferin, respectively. Cofactor requirements (e.g., ATP, O2) vary depending on the luciferase used. Fluorescence (right) is the product of a fluorophore (e.g., FITC, DyLight dyes) absorbing the energy from a light source and emitting the light energy at a different wavelength.

After 5 days of day-and-night work, 500 gm of dried Cypridina yielded about 2 mg of luciferin after purification. I tried to crystallise the purified luciferin, but all my efforts ended up with amorphous precipitates, and any leftover luciferin became useless by oxidation by the next morning. So I had to repeat the extraction and purification, again and again. I worked very hard, and tried every method of crystallisation that I could think of, without success. Ten months later, however, I finally found that the luciferin could be crystallised in a highly unusual solvent. [Shimomura, O., Goto, T., and Hirata, Y. (1957), “Crystalline Cypridina luciferin,” Bull. Chem. Soc. Japan 30: 929–933.] The solvent I found was high concentration of hydrochloric acid. Using the crystallised luciferin, we were able to determine the chemical structures of the luciferin and it’s oxidation products [Kishi, Y., Goto, T., Hirata, Y., Shimomura, O., and Johnson, F. H. (1966), “Cypridina bioluminescence I: structure of Cypridina luciferin,” Tetrahedron Lett., 3427–3436.] Those data became essential later in the study of aequorin.


Early in the summer of 1961, we travelled from Princeton, NJ, to Friday Harbour, WA, driving 5,000 km. Friday Harbour was a quiet, peaceful small village at the time. The jellyfish were abundant in water. At the University of Washington laboratory there, we carefully scooped up the jellyfish one by one using a shallow dip net. The light organs of Aequorea aequorea are located along the edge of the umbrella, which we called a ring. The ring could be cut off with a pair of scissors, eliminating most of the unnecessary body part.

The jellyfish Aequorea aequorea in nature.

At the time, it was a common belief that the light of all bioluminescent organisms was produced by the reaction of luciferin and luciferase. Therefore, we tried to extract luciferin and luciferase from the rings of the jellyfish. We tried every method we could think of, but all our efforts failed. After only a few days  of work, we ran out of ideas.

I was convinced that the cause of our failure was the luciferin-luciferase hypothesis that dominated our mind. I suggested to Dr. Johnson that we forget the idea of extracting luciferin and luciferase and, instead, try to extract a luminescent substance whatever it might be. However, I was unable to convince him. Because of the disagreement  on experimental method, I started to work alone at one side of a table, while, on the other side, Dr. Johnson and his assistant continued their efforts to extract a luciferin. It was an awkward, uncomfortable situation.

Since the emission of light means the consumption (loss) of active bioluminescent substance, the extraction of bioluminescent substances from light organs must be performed under a condition that reversibly inhibits the luminescence reaction. Therefore, I tried to reversibly inhibit luminescence with various kinds of inhibitors of enzymes and proteins. I tried very hard, but nothing worked. I spent the next several days soul searching, trying to find out something missing in my experiments and in my thought. I thought day and night. I often took a rowboat out to the middle of the bay to avoid interference by people. One afternoon, an idea suddenly struck me on the boat. It was a very simple idea: “Luminescence reaction probably involves a protein. If so, luminescence might be reversibly inhibited at a certain pH.”

I immediately went back to the lab and tested the luminescence of light organs at various pHs. I clearly saw luminescence at pH 7, 6 and 5, but not at pH 4. I ground the light organs in a pH 4 buffer, and then filtered the mixture. The cell free filtrate was nearly dark. But it regained luminescence when it was neutralised by sodium bicarbonate. The experiment showed that I could extract the luminescence substance, at least in principle.

But a big surprise came the next moment. When I threw the extract into a sink, the inside of the sink lit up with a bright blue flash. The overflow of an aquarium was flowing into the sink, so I figured out that sea water had caused the luminescence. Because the composition of sea water is known, I easily found out that calcium ions (Ca2+activated the luminescence. The discovery of Calcium ions (Ca2+)  as the activator suggested that the luminescence material could be extracted utilizing the Ca-chelator EDTA, and we devised an extraction method of the luminescent substance.

The process was ⇒ Rings of jelly fish ( tissue of light organs) ⇒ shaken in saturated  (NH4)2SO4 ⇒ squeezed through gauze ⇒ filtered ⇒ Granular light organs observed ⇒ shaken in EDTA solution ⇒ Filtration ⇒ Crude aequorin solution ⇒             PURIFICATION ⇒ Aequorin and GFP.AequorinCa2+ sensitive luminescent protein – Aequorea aequorea- Inhibited by Mg2+ and also triggered by Eu2+, Sr2+ and Ba...Source

During the rest of the summer of 1961, we extracted the luminescent substance from about 10,000 jellyfish. After returning to Princeton, we purified the luminescent substance and obtained a few milligrams of purified protein. The protein emitted blue light in the presence of a trace of Calcium ions (Ca2+). We named the protein aequorin Shimomura, O., Johnson, F. H., and Saiga, Y. (1962), “Extraction, purification and properties of aequorin, a bioluminescent protein from the luminous hydromedusan, Aequorea,” J. Cell. Comp. Physiol. 59: 223–239].

Aequorin was the first example of photoproteins discovered [Shimomura, O. (1985), “Bioluminescence in the sea: photoprotein systems,” Symp. Soc. Exp. Biol. 39: 351–372]. During the purification of aequorin, we found another protein that exhibited a bright green fluorescence. It was only in a trace amount, but we purified this protein too, and called it “green protein”. The protein was renamed “green fluorescent protein” by Morin and Hastings (1971).[Morin, J. G., and Hastings, J. W. (1971), “Energy transfer in a bioluminescent system,” J. Cell. Physiol., 77: 313–318.]

We wanted to understand the mechanism of the aequorin bioluminescence reaction; because it became clear in 1967 that aequorin was highly useful and important as a calcium probe in biological studies (Ridgeway and Ashley, 1967).[Ridgway, E. B., and Ashley, C. C. (1967), “Calcium transients in single muscle fibers,” Biochem. Biophys. Res. Commun. 29: 229–234.]

First, we tried to isolate the light-emitting chromophore of aequorin. However, there was no way to extract the native chromophore [Shimomura, O., and Johnson, F. H. (1969), “Properties of the bioluminescent protein aequorin,” Biochemistry 8: 3991–3997.][Shimomura, O., Johnson, F. H., and Morise, H. (1974), “Mechanism of the luminescent intramolecular reaction of aequorin,” Biochemistry 13: 3278–3286.], because any attempt to extract the chromophore always resulted in an intramolecular reaction of aequorin that triggered the emission of light, destroying the original chromophore. Indeed, the secret of light emission of Aequora was well protected.

We nevertheless found that a fluorescent compound was formed when aequorin was denatured with urea in the presence of 2-mercaptoethanol [Shimomura, O., and Johnson, F. H. (1969), “Properties of the bioluminescent protein aequorin,” Biochemistry 8: 3991–3997]. We named this fluorescent compound AF-350, based on it’s absorption maximum at 350nm. We decided to determine the structure of AF-350. However, to obtain the 1 mg of AF-350 needed for a single experiment toward the structural study of this compound, about 150 mg of purified aequorin was needed, and that meant we had to collect and extract atleast 50,000 jellyfish. Considering that we probably would need several milligrams of AF-350, the structure determination was a huge undertaking for us. 

The jellyfish ring cutting machine constructed by Frank H. Johnson in 1969. A specimen is placed on the black Plexiglas platform and rotated to spread the edge of the umbrella. While rotating, the specimen is pushed toward the rotating blade (10-inch meat cutting blade) to cut off a 2–3 mm wide strip containing the light organs. The strip drops into a container below.

In processing a large number of jellyfish to obtain a sufficient amount of AF-350, we found that cutting rings with a pair of scissors was too slow. To speed up the process, Dr. Johnson constructed a jellyfish cutting machine, which enabled one person to cut more than 600 rings per hour, or 10 times more than by hand. We started to collect jellyfish at 6 a.m, and a part of our group began to cut off rings at 8 a.m. We spent all afternoon extracting aequorin from the rings. Then, we collected more jellyfish in the evening, 7 p.m to 9 p.m, for the next day. Our laboratory looked like a jellyfish factory and was filled with the jellyfish smell.

After five years of hard work, we determined the chemical structure of AF-350 in 1972 [Shimomura, O., and Johnson, F. H. (1972), “Structure of the light-emitting moiety of aequorin,” Biochemistry 11: 1602–1608]

The result was surprising. The structure of AF-350 contained the skeleton of 2-aminopyrazine that was previously found in the oxidation products of Cypridina luciferin, although the side chains are different. This finding suggested a close relationship between the luminescence systems of Aequorea and Cypridina. Based on that information, we were able to determine the structure of the chromophore of aequorin to be coelenterazine.


The luminescence and regeneration of aequorin.

The photoprotein aequorin binds with two calcium ions [Shimomura, O. (1995), “Luminescence of aequorin is triggered by the binding of two calcium ions,” Biochem. Biophys. Res. Commun. 211: 359–363.][Shimomura, O., and Inouye, S. (1996), “Titration of recombinant aequorin with calcium chloride,” Biochem. Biophys. Res. Commun. 221: 77–81.], and decomposes into coelenteramide, CO2 and apoaequorin accompanied by the emission of light (emission maximum at 465 nm). Apoaequorin accompanied by the emission of light (emission maximum at 465 nm). Apoequorin can be regenerated into the original aequorin by incubation with coelenterazine in the presence of oxygen.

The chemical structures of AF-350 (coelenteramine), coelenteramide (o product of luminescence reaction of aequorin) and coelenterazine, compared with those of Cypridina oxyluciferin and luciferin.

Lighting mechanisms of marine luciferases and fluorescent proteins. (A) Marine luciferases oxidize coelenterazine (CTZ) to emit bioluminescence; (B) Chromophore of GFP, 65SYG67, is matured by oxidation. The chemical structural backbone is similar to that of CTZ. Abbreviations: CTZ, coelenterazine; GFP, green fluorescent protein; RLuc, Renilla luciferase. This figure was obtained from a reference by Dr. Kim [Kim, S.B. Labor-effective manipulation of marine and beetle luciferases for bioassays. Protein Eng. Des. Sel 2012, 25, 261–269.]

Source: http://www.mdpi.com/1422-0067/13/12/16986/htm


In a live specimen of Aequora, the light organs contain GFP in addition to aequorin, and the energy of the blue light produced by the aequorin molecule is transferred to the GFP molecule, and GFP emits green light [Morise, H., Shimomura, O., Johnson, F. H., and Winant, J. (1974), “Intermolecular energy transfer in the bioluminescent system of Aequorea,” Biochemistry 13: 2656–2662.]

GFP (100mg) ⇒ Denature at 90°C ⇒ Digest with papain ⇒ Extraction with butanol at pH 1 ⇒ TLC purification ⇒ Isolated chromophore (0.1 mg)

Although GFP is highly visible and easily crystallisable, the yield of GFP from the jellyfish is extremely low, much lower than that of aequorin. Therefore, to study GFP, we had to accumulate GFP little by little for many years while we studied the chemistry of aequorin luminescence. The amount of GFP we accumulated reached a sufficient amount to study this protein in 1979. Thus, we tried find out the nature of the GFP chromophore by a series of experiments, using 100 mg of the protein in one experiment.

We first cut the molecule of GFP into small pieces of peptide by enzymic digestion. We isolated and purified the peptide that contained the chromophore, and then analysed the structure of the chromophore. I was surprised when I measured the absorption spectrum of the peptide. The spectrum was nearly identical to that of a compound that I had synthesized in my study of Cypridia luciferin 20 years earlier. Based on the spectral resemblance and some other properties, I could quickly identify the chromophore structure of GFP [Shimomura, O. (1979), “Structure of the chromophore of Aequorea green fluorescent protein,” FEBS Lett. 104, 220–222].

Fluorescent proteins are usually a complex of a protein and a fluorescent compound. However, GFP was a very special fluorescent protein that contained a fluorescent chromophore within the protein molecule.

GFP picture

[Cody, C. W., Prasher, D. C., Westler, W. M., Prendergast, F. G., and Ward, W. W. (1993), “Chemical structure of the hexapeptide chromophore of the Aequorea green-fluorescent protein,” Biochemistry 32: 1212–1218.]

The finding was extremely important because it showed that the chromophore is a part of the peptide chain, and thus it opened the possibility of cloning GFP. The chromophore structure was later confirmed by Cody et al. (1993)

When I found the chromophore of GFP in 1979, I  thought I had done all I could do with GFP, and decided to terminate my work on GFP in order to concentrate my efforts in the study of bioluminescence, my  lifework. Then a mysterious thing happened. The population of Aequora in the Friday Harbor area drastically decreased after 1990, thus making it practically impossible to prepare any new samples of natural aequorin or GFP. Fortunately, however, aequorin had been cloned by Inouye et al. [Inouye, S., Noguchi, M., Sakaki, Y., Takagi, Y., Miyata, T., Iwanaga, S., Miyata, T., and Tsuji, F. I. (1985), “Cloning and sequence analysis of cDNA for the luminescent protein aequorin,” Proc. Natl. Acad. Sci. USA 82: 3154–3158.][Inouye, S., Sakaki, Y., Goto, T., and Tsuji, F. I. (1986), “Expression of apoaequorin complementary DNA in Escherichia coli,” Biochemistry 25: 8425–8429] and Prasher et al.] [Prasher, D. C., Eckenrode, V. K., Ward, W. W., Prendergast, F. G., and Cormier, M. J. (1992), “Primary structure of the Aequorea victoria green fluorescent protein,” Gene 111: 229– 233], thus making  the natural proteins unessential. In 1994, GFP was successfully expressed in living organisms by Chalfie et al. and it was further developed into it’s present prosperous state by Roger Tsien.

What Evolutionary Forces Drove A Dramatic Increase In Brain Size? Bipedalism, Birth and Brain Evolution.

Hominid and hominin what’s the difference?

The terms ‘hominid’ and ‘hominin’ are frequently used in human evolution.

The most commonly used recent definitions are:

Hominid – the group consisting of all modern and extinct Great Apes (that is, modern humans, chimpanzees, gorillas and orang-utans plus all their immediate ancestors).

Hominin – the group consisting of modern humans, extinct human species and all our immediate ancestors (including members of the genera Homo, Australopithecus, Paranthropus and Ardipithecus).

Source: http://australianmuseum.net.au/hominid-and-hominin-whats-the-difference#sthash.494DMBty.dpuf

‘Ontogeny Recapitulates Phylogeny’

The theory of recapitulation, also called the biogenetic law or embryological parallelism— often expressed in Ernst Haeckel’s phrase “ontogeny recapitulates phylogeny”—is a largely discredited biological hypothesis that in developing from embryo to adult, animals go through stages resembling or representing successive stages in the evolution of their remote ancestors. Since embryos also evolve in different ways, within the field of developmental biology the theory of recapitulation is seen as a historical side-note rather than as dogma.
With different formulations, such ideas have been applied and extended to several fields and areas, including the origin of language, religion, biology, cognition and mental activities, anthropology, education theory and developmental psychology. Recapitulation theory is still considered plausible and is applied by some researchers in fields such as the study of the origin of language, cognitive development, and behavioural development in animal species.[Source: Wikipedia]

Though, I am a strong votary of the ‘Recapitulation Theory’

The human brain, though complicated, is also a well evolved organ of the body.

How the Brain Works How the Brain Works

One of the things that makes our species unique is our exceptionally large brain relative to body size. Brain size more than tripled during the course of human evolution, and this size increase was accompanied by a significant reorganization of the cerebral cortex, the prominent convoluted structure responsible for complex mental functions, which accounts for something like 85% of total brain volume.

What evolutionary forces drove this dramatic increase in brain size?

Many theories have been put forward over the years, a popular one being that our ancestors’ brains expanded to accommodate the faculty of language. A fossilized skull fragment belonging to a human ancestor that lived several million years ago provides yet more clues.

A new analysis of the skull suggests that human brain evolution may have been shaped by changes in the female reproductive system that occurred when our ancestors stood upright. What Drove the Evolution of the Human Brain?


Image Source  Image: Marcia Ponce de León and Christoph Zollikofer/University of Zürich guardian.co.uk

At some point in evolution, our ancestors switched from walking on all four limbs to just two, and this transition to bipedalism led to what is referred to as the obstetric dilemma. The switch involved a major reconfiguration of the birth canal, which became significantly narrower because of a change in the structure of the pelvis. At around the same time, however, the brain had begun to expand.

One adaptation that evolved to work around the problem was the emergence of openings in the skull called fontanelles. The anterior fontanelle enables the two frontal bones of the skull to slide past each other, much like the tectonic plates that make up the Earth’s crust. This compresses the head during birth, facilitating its passage through the birth canal.

In humans, the anterior fontanelle remains open for the first few years of life, allowing for the massive increase in brain size, which occurs largely during early life. The opening gets gradually smaller as new bone is laid down, and is completely closed by about two years of age, at which time the frontal bones have fused to form a structure called the metopic suture.

  • A fontanelle (or fontanel) (colloquially, soft spot) is an anatomical feature of the infant human skull comprising any of the soft membranous gaps (sutures) between the cranial bones that make up the calvaria of a fetus or an infant. Fontanelles allow for rapid stretching and deformation of the neurocranium as the brain expands faster than the surrounding bone can grow. Premature complete ossification of the sutures is called craniosynostosis. During infancy, the anterior fontanelle is known as the bregma.
  • Image Source: https://en.wikipedia.org/wiki/Fontanelle

In chimpanzees and bonobos, by contrast, brain growth occurs mostly in the womb, and the anterior fontanelle is closed at around the time of birth.

When this growth pattern appeared is one of the many unanswered questions about human brain evolution. The new study, led by Dean Falk of Florida State University, sought to address this. Working in collaboration with researchers from the Anthropological Institute and Museum at the University of Zürich, Falk compared the skulls of humans, chimps and bonobos of various ages to the fossilized skull of the so-called Taung Child.

Taung Child was found in 1924 in a limestone quarry near Taung, South Africa, and was the first Australopithecine specimen to be discovered. It belonged to an infant of three to four years of age, and is estimated to be approximately 2.5 million years old. The skull is incomplete, including the face, jaw and teeth, but it contains a complete cast of the brain case, which formed naturally from minerals that were deposited inside it and then solidified.

“Most of Taung child’s brain case is no longer present, but you see all kinds of interesting structures in the endocast, like the imprints of the cortical convolutions,” says study co-author Christoph Zollikofer. “We looked at the imprints of the sutures. These features are very well preserved, and have been known about for 50 years, but nobody paid attention to them.”

In 1990, researchers from Washington University Medical School published a three-dimensional CT scan of the Taung Child endocast, and Falk subsequently reconstructed it again using more advanced computer technology. Comparison of this more recent reconstruction with scans of other species now reveal that the skull of Taung Child has a small, triangle-shaped remnant of the anterior fontanelle.

This suggests that Taung Child had a partially fused metopic suture at the time of death and, therefore, that the pattern of brain development in this Australopithecine species was similar to that of anatomically modern humans. Delayed fusion of the metopic suture indicates that fast brain growth in the period following birth came before the emergence of Homo, the genus that evolved from Australopithecines and eventually gave rise to our own species, Homo sapiens.

“There’s a trade-off between walking bipedally in an optimal way, which narrows or constricts the birth canal, and evolving fat, big-brained babies which need a wide birth passage,” says Zollikofer. “Bipedalism and big brains are independent evolutionary processes. Hominins started walking bipedally long before the brain expanded, but these trends collided at birth, and we believe this happened much earlier than previously thought.”

Evolution is an opportunistic processspecies change over time, but only some of these changes prove to be advantageous to an organism’s survival. Some of them can prove advantageous in different and unrelated ways, and this seems to be the case for evolution of the human brain. Delayed fusion of the metopic suture apparently evolved to overcome the obstetric dilemma that arose when our ancestors stood upright, but had the added advantage of allowing for the pattern of modern human brain growth.

There are other ways in which bipedalism could have led to increased brain size. It would, for example, have freed up the forelimbs, and this would likely have led to the expansion and reorganization of the sensory and motor brain areas that process sensation and control movement. Similarly, standing upright would have led to big changes in what our ancestors saw, which may have led to an expansion of the visual areas at the back of the brain.

The new findings suggest that further brain expansion, as well as reorganization of the prefrontal cortex, could have occurred as an indirect result of the pelvic modifications that followed the transition to bipedalism.

All evolutionary changes are due to changes that occur at the genetic level, and the dramatic increase in brain size that occurred during human evolution is no exception. Numerous genes have been implicated in human brain evolution, but it is difficult to link any of them to specific changes in brain organization or structure.

Evan Eichler and colleagues reported that a gene known to be involved in development of the cerebral cortex was duplicated multiple times, and that this occurred exclusively in humans. They also estimate that these duplications took place between two and three million years ago, so it is tempting to speculate that they are somehow linked to the changes that may have occurred as a result of bipedalism.

Source: http://www.theguardian.com/science/neurophilosophy/2012/may/07/1

A Discussion on the above findings (for individuals with a knowledge of medical sciences)


Among non-human primates, the rhesus macaque is the animal of choice for cognitive studies.
While there may be similarities between the brains of humans and non-human primates, the monkey brain is not a scaled down version of the human brain. Rather, each primate brain is the unique result of evolutionary biology, molded over millions of years in response to environmental, social, and genetic influences (Figure). With the human brain, the effects of cultural evolution are also considered.

There are numerous differences in the anatomy and physiology of the CNS in monkeys and humans, including differences in locations of specialized areas in the brain. The primary visual 1 area (blue) accounts for 10% of the total cortex in the monkey but only 3% in humans, and anatomically corresponding visual areas in monkeys and humans can perform very different functions.
The human brain’s architecture and physiology is far more complex than that of the monkey brain.

  1. One indication of this is the length of time it takes for the brain to develop in its major phase: 136 days for monkeys and 470 days for humans.
  2. Other significant differences include the number of synapses a human neuron makes (between 7000 and 10,000) compared with the number a rhesus monkey neuron makes (between 2000 and 6000) and
  3. The expression of at least 91 genes involved in a variety of neural mechanisms that differ between monkeys and humans.
  4. According to Kreiman and associates:  Even though the hippocampus appears to be one of the most conserved areas of the brain (most similar among mammals), there are still considerable differences.
  5. Neurotransmitter receptor distribution varies widely between species. For example, there is an additional small layer of high-density kainate receptors in the deepest part of the hippocampal molecular layer in the monkey, but not in humans.
  6. The inhibitory GABAA receptors are located with high density in the human CA 1 hippocampal region, but not in the same region in monkeys. These results demonstrate considerable changes of the regional and laminar distribution of important signaling molecules in an otherwise evolutionary conservative brain region.

Are Animal Models Relevant in Modern Psychiatry?: Page 3 of 5#sthash.cJJZ8Tz5.dpuf

  • Glutamate Receptors – Several types of ionotropic glutamate receptors have been identified. Three of these are ligand-gated ion channels called NMDA receptors, AMPA receptors, and kainate receptors. These glutamate receptors are named after the agonists that activate them: NMDA (N-methyl-d-aspartate), AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate), and kainic acid. All of the ionotropic glutamate receptors are nonselective cation channels, allowing the passage of Na+ and K+, and in some cases small amounts of Ca2+.
  • In addition to these ionotropic glutamate receptors, there are three types of metabotropic glutamate receptor (mGluRs). These receptors, which modulate postsynaptic ion channels indirectly, differ in their coupling to intracellular messengers and in their sensitivity to pharmacological agents. Activation of many of these receptors leads to inhibition of postsynaptic Ca2+ and Na+ channels. Unlike the excitatory ionotropic glutamate receptors, mGluRs cause slower postsynaptic responses that can either increase or decrease the excitability of postsynaptic cells.

Source: http://www.ncbi.nlm.nih.gov/books/NBK10802/

As per a recent paper

Metopic suture of Taung (Australopithecus africanus) and its implications for hominin brain evolution presented in the

Metopic suture of Taung (Australopithecus africanus) and its implications for hominin brain evolution

File:Australopithecus africanus - Cast of taung child.jpg

Australopithecus africanus – Cast of taung child 

Cast in three parts: endocranium face and mandible, of a 2.1 million year old Australopithecus africanus specimen so-called Taung child, discovered in South Africa.
Collection of the University of the Witwatersrand (Evolutionary Studies Institute), Johannesburg, South Africa. Sterkfontein cave, hominid fossil.  Source 

The infant’s skull consists of the metopic suture, coronal sutures, sagittal suture, and lambdoid sutures. The metopic suture is supposed to close between three to nine months of age. The lambdoid, sagittal and coronal sutures are supposed to close between 22 to 39 months of age. [ https://en.wikipedia.org/wiki/Craniosynostosis ]

The type specimen for Australopithecus africanus (Taung) includes a natural endocast (https://en.wikipedia.org/wiki/Endocast) that reproduces most of the external morphology of the right cerebral hemisphere and a fragment of fossilized face that articulates with the endocast. Despite the fact that Taung died between 3 and 4 yr of age, the endocast reproduces a small triangular-shaped remnant of the anterior fontanelle, from which a clear metopic suture (MS) courses rostrally along the midline [Hrdlička A (1925) Am J Phys Anthropol 8:379–392]. In this paper they describe and interpret this feature of Taung in light of comparative fossil and actualistic data on the timing of MS closure. In great apes, the MS normally fuses shortly after birth, such that unfused MS similar to Taung’s are rare. In humans, however, MS fuses well after birth, and partially or unfused MS are frequent. In gracile fossil adult hominins that lived between ∼3.0 and 1.5 million yr ago, MS are also relatively frequent, indicating that the modern human-like pattern of late MS fusion may have become adaptive during early hominin evolution.

Selective pressures favouring delayed fusion might have resulted from three aspects of perinatal ontogeny ( https://en.wikipedia.org/wiki/Ontogeny ):

(i) the difficulty of giving birth to large-headed neonates through birth canals that were reconfigured for bipedalism (the “obstetric dilemma”),

(ii) high early postnatal brain growth rates, and

(iii) reorganization and expansion of the frontal neocortex. Overall, their data indicates that hominin brain evolution occurred within a complex network of fetopelvic constraints, which required modification of frontal neurocranial ossification patterns.

Overall, their data indicate that hominin brain evolution occurred within a complex network of fetopelvic constraints, which required modification of frontal neurocranial ossification patterns.

The large body of modern genetic evidence indicates that a network of at least 10 key genes mediates neurocranial suture fusion, and that these genes act differently on different sutures. It is intriguing that the recent sequencing of the Neanderthal genome provides evidence for positive selection in the modern human variant of one of these key genes, RUNX2 ( RUNX2 is a key transcription factor associated with osteoblast differentiation https://en.wikipedia.org/wiki/RUNX2 ), which is known to affect MS fusion. RUNX2-related disorders, such as cleidocranial dysplasia

(Mutations in Cbfa1/Runx2 are associated with the disease Cleidocranial dysostosis https://en.wikipedia.org/wiki/RUNX2 ), result in delayed MS fusion and pathologies, such as extreme bulging of the forehead and hypertelorism. Premature closure of the metopic suture (metopic synostosis), on the other hand, typically results in trigonocephaly: that is, a narrow forehead with an external metopic ridge (keel) extending from glabella to the midforehead, relatively close-set orbits and no lateral browridge.

Coussens AK, et al. (2007) Unravelling the molecular control of calvarial suture fusion in children with craniosynostosis. BMC Genomics 8:458.


  • Craniosynostosis, the premature fusion of calvarial sutures, is a common craniofacial abnormality. Causative mutations in more than 10 genes have been identified, involving fibroblast growth factor, transforming growth factor beta, and Eph/ephrin signalling pathways. Mutations affect each human calvarial suture (coronal, sagittal, metopic, and lambdoid) differently, suggesting different gene expression patterns exist in each human suture. They have identified genes with increased expression in unfused sutures compared to fusing/fused sutures that may be pivotal to the maintenance of suture patency or in controlling early osteoblast differentiation (i.e. RBP4, GPC3, C1QTNF3, IL11RA, PTN, POSTN). In addition, they have identified genes with increased expression in fusing/fused suture tissue that they suggest could have a role in premature suture fusion (i.e. WIF1, ANXA3, CYFIP2). Proteins of two of these genes, glypican 3 and retinol binding protein 4, were investigated by immunohistochemistry and localised to the suture mesenchyme and osteogenic fronts of developing human calvaria, respectively, suggesting novel roles for these proteins in the maintenance of suture patency or in controlling early osteoblast differentiation. They showed that there is limited difference in whole genome expression between sutures isolated from patients with syndromic and non-syndromic craniosynostosis and confirmed this by quantitative RT-PCR. Furthermore, distinct expression profiles for each unfused suture type were noted, with the metopic suture being most disparate. Finally, although calvarial bones are generally thought to grow without a cartilage precursor, they showed histologically and by identification of cartilage-specific gene expression that cartilage may be involved in the morphogenesis of lambdoid and posterior sagittal sutures.
  • Craniosynostosis is amongst the most common cranial defects, second only to cleft palate. It occurs in 1 in 2500 live births and can be associated with significant morbidity, including mental retardation, deafness, and blindness, in addition to the significant social stigma associated with craniofacial deformation. The condition may be caused by various genetic mutations, exposure to teratogens such as retinoic acid, mechanical stress, or result from certain metabolic or haematologic disorders. Non-syndromic craniosynostosis refers to sporadic suture fusion in the absence of other developmental abnormalities and most commonly affects the sagittal suture. Syndromic craniosynostosis occurs as a result of simple genetic mutations and is accompanied by additional developmental abnormalities particularly involving the limbs. Syndromic forms of craniosynostosis commonly affect the coronal suture but other sutures may be affected depending on the underlying genetic mutation. FGFR2 mutations are the most common and most severe affecting the coronal, metopic, sagittal, and lambdoid sutures. FGFR3 mutations affect the coronal and/or metopic sutures. FGFR1, TWIST1 and EFNB1 mutations generally affect only the coronal suture. FNB1 and TGFBR1 mutations have been associated with synostosis of the sagittal and/or lambdoid sutures, while gain-of-function MSX2 mutations result in synostosis of the coronal and sagittal sutures.
  • Calvarial bones form by the proliferation and differentiation of multipotent mesenchymal cells into osteoblasts. This process, known as intramembranous ossification, is distinct from the development of the majority of other bones in the body which form by the ossification of a pre-existing cartilaginous matrix (endochondral ossification). Calvaria first form from a condensation of mesenchyme termed the primary centre of ossification. Mesenchymal cell proliferation and subsequent differentiation into osteoblasts occurs at the margins and the bone grows in a radial fashion until the osteogenic fronts of two calvaria approximate each other and structures called sutures form between the bones.These intervening fibrous sutures act as flexible joints between the developing bones allowing the skull to change shape and grow during development. Maintenance of growth at the osteogenic fronts at the edges of the sutures requires a fine balance between proliferation and differentiation. Additionally, apoptosis has a role ensuring that the two osteogenic fronts remain separated. Disruption of any of these processes can result in the premature fusion of calvarial sutures, known as craniosynostosis.

As per the paper, the MS normally becomes obliterated later in humans than in chimpanzees. Furthermore, unfused or partially fused MS in adults of Neolithic to contemporary human populations are relatively frequent, with a global average around 3–4%. Early MS fusion likely represents a primitive feature of haplorhine primates, or even of euprimates, and is a feature uniting crown anthropoid primates. Late MS fusion in humans thus appears as a derived state, and early fusion, as observed in the great apes, appears as the primitive state.

This paper hypothesizes that selective pressures favouring late fusion might have resulted from three different, but mutually nonexclusive, aspects of perinatal ontogeny:

first, the obstetric dilemma;

second, high early postnatal brain growth rates;

and third, reorganization of the frontal neocortex.

Proposed Timeline of Hominin Evolution

  • It is important to note that there is significant, continuous scientific debate regarding the timeline for human evolution
  • Models are continually being proposed, rejected and refined as more fossil evidence comes to light

Image Source

Image Source

  • Bipedalism developed in late Miocene to early Pliocene hominins (~6 – 4 m.y.a), possibly in response to more open habitats

Image Source 

Image Source 

A. Obstetric Dilemma 

Illustration of the female pelvic bones and babies of

Image Source 

Image Source 

  • In the evolution of the human pelvis, repositioning of the sacrum has created a complete bony ring through which the birth canal passes. The need to pass the large human brain through this opening has resulted in the human newborn having a brain less than 30% of it’s adult size. The brain of all the other animals are almost completely developed at birth.
  •  The bony pelvis lacks inherent anatomical structural stability, but is stabilized by a system of tightly woven muscles and ligaments that provide its support. Strong ligaments arranged transversely, oblique, and horizontally resist forces that can externally rotate the pelvis, thereby opening it. Among these are the short posterior SI ligament, the anterior SI ligament, the ilio-lumbar ligament, sacro-spinous ligaments and others. Their function is to counter opposing forces such as AP compression. These ligaments fail when forces exceed their ability causing compression type injury. Vertical stability is provided primarily by the short and long posterior SI ligaments. Other inter-osseous ligaments within the sacroiliac joints also provide additional vertical stability. ( Imaging The Sacrum and Coccyx; Pelvic Stability :  https://www.ceessentials.net/article47.html )
  • These stabilizing ligaments help perform one of the main functions of the pelvis, to transmit weight from the trunk and lumbar vertebrae to the lower extremity. Weight bearing forces from the body are transmitted primarily along vectors to the posterior pelvis, then to the sacrum and sacroiliac joints. Weight-bearing forces are then transmitted to the acetabula for distribution to the femurs. During active weight bearing movements of the body, the anterior pelvic arch functions like a strut maintaining the shape of the pelvic ring. During passive weight bearing such as sitting weight force is transmitted down vectors to the ischial tuberosities. ( Imaging The Sacrum and Coccyx; Pelvic Stability :  https://www.ceessentials.net/article47.html )

As bipedalism was refined in conjunction with an evolutionary increase in neonate and adult brain sizes, the morphology of the birth canal constrained the size and shape of the neonate. Although exactly when during hominin evolution the obstetric dilemma arose has been a subject of debate, this dilemma is especially severe in humans because of their large-headed (and relatively large-brained) neonates and relatively constricted birth canals. The anterior fontanelle and patent metopic suture of human neonates facilitate parturition. During delivery, contractions of the birth canal cause the edges of the neonate’s frontal and parietal bones to overlap and glide together in the region of the anterior fontanelle, which compresses the head and facilitates expulsion of the neonate from the birth canal. In early hominins, increased mobility of the neurocranial bones through delayed MS fusion might have represented an adaptive advantage facilitating birth.

B. High Early Postnatal Brain Growth Rates.

Compared with chimpanzees, human brains continue to grow at high fetal-like rates throughout the first postnatal year of life, which “may reflect the ontogeny of the ‘infrastructure’ required for rapid cognitive development”. They hypothesize that late MS closure in modern humans reflects an evolutionary adaptation of the growing frontal neurocranium to keep up with high brain growth rates. When sustained early brain growth appeared during hominin evolution is still a matter of debate. The large endocranial volume of the Mojokerto child (https://en.wikipedia.org/wiki/Mojokerto_child) at an age of < 2 yr provides evidence for high early brain growth rates in H. erectus. Direct evidence for australopith early postnatal cranial ontogeny is currently not available, but evidence for delayed MS fusion in australopiths indicates that early brain growth may already have been fast before the emergence of the genus Homo. If so, rapid early postnatal brain growth preceded the increase in brain size in Homo, which could be because of the obstetric dilemma shifting prenatal brain growth rates postnatally in association with pelvic modifications for bipedalism, or because of an increase in relative brain size (i.e., increased encephalization) in australopiths compared with their (unknown) ancestors.

C. Reorganization of the Frontal Cortex.

The association of unfused MS with increased interorbital and frontal bone widths in extant humans is intriguing when one considers brain shape and possible neurological reorganization in early hominins in conjunction with the frequencies of unfused MS in different taxa. As noted, a sample of Australopithecus and early Homo specimens that lived between ∼3.0 and 1.5 million yr ago shows an unfused MS, but no Paranthropus specimen does. In keeping with the tendency for an unfused MS in humans, A. africanus is characterized by increased interorbital and frontal bone widths compared with Paranthropus. Also consistent with findings for extant humans with unfused MS, endocasts of A. africanus have increased frontal widths in the region of the rostral prefrontal cortex (in addition to an expanded orbital frontal cortex) compared with endocasts of Paranthropus. It is therefore reasonable to hypothesize that, in addition to reflecting an adaptation to high postnatal brain growth rates, an unfused MS in Taung and other early gracile hominins may have been associated with the evolution of certain morphological and cytoarchitectural features of the prefrontal cortex, parts of which are differentially enlarged in humans and known to be crucial for their advanced cognitive capabilities. [As an aside, it is worth noting that humans also have a unique phase of shape change in their braincases before their deciduous teeth begin to erupt that results in a more general neurocranial globularization compared with chimpanzees.] If so, the evolution of increased rates of postnatal brain growth and neurological reorganization were probably entwined in (at least some) species of gracile early hominins.
Immature fossil hominins are currently playing a greater role in shaping the ways comparative data from living primates are interpreted, and it is within this context that the suture morphology of Taung and other fossil hominins that lived more recently than 3 million yr ago is interesting. Although it is beyond the scope of the present article, we hope that future researchers will test and extend the present findings by systematically collecting data on MS, anterior fontanelles, and endocranial size and shape in a wider sample of hominins, including those that lived before ∼3 million y ago (e.g., Australopithecus afarensis) as well as hominins that lived more recently than the fossils we have sampled. Such data are expected to contribute to a more detailed understanding of when, and in which hominin species, rates of postnatal brain growth first began to increase. This understanding, in turn, may contribute to a better grasp of the relationship between the evolutionary refinement of bipedalism and the evolution of brain size and shape.