A talk by Nobel Laureate Dr. Brian Kobilka

When I came across a flyer for the above, கொஞ்சம் ஆர்வக் கோளாறுலேயும் கொஞ்சம் அசட்டு தைரியத்துலேயும், registered immediately. 

- ஆர்வக் கோளாறு - when else will i get a chance to attend a Nobel Laureate lecture in person?

- அசட்டு தைரியம் - the speaker is bound to know the average knowledge base of the audience. After all it's a public forum.

Came the day, I was happy to be accompanied by Gopu! (who I was sure would understand more than me & may not be averse to a few explanations.)

Let me confess - I left Chemistry and all other Science subjects behind in High School, all of 40+ years back. Am not very updated on current happenings in the Practical Scientific world, leave alone Research! In fact I was happy, Dr. Kobilka is an American and I could at least pronounce his name properly and would understand his accent. (The few times in my life, when my Hollywood addiction is put to good use.)

IIT and Vallabha

This lecture was arranged by IIT Madras under their 'Eminent Speaker Lecture Series' at Music Academy, Chennai. The topic for the talk was 'From Fields to Frontiers: The Journey of a Physician - Scientist'.

The Talk....

At the outset, it was amusing to hear Dr. Kobilka say, 'This was his largest audience and he was nervous!' If most of the audience was like me - he had no idea, how nervous we were.

But surprisingly he started on a non scientific note. Highlighting his background, his academic journey, the various institutes he had associated with etc. This put the audience, at least me - at ease. I was all ears & comprehending. Slowly Science crept in, but I was still in sync - Thanx to the simple Graphic slides!

Dr. Kobilka's Early life....

(Growing Up In Little Falls, Minnesota)

Born into a baker's family in Little Falls, Dr. Kobilka said the town was hardly 8sq miles in area (No more than 3 miles in any direction) with a max population of 7500. The 3D map showed the relative locations of various buildings in the town and his first job was slicing bread in his father's bakery. It was a family owned business run by his grandfather.

He attended St. Mary’s elementary school through the eighth grade then moved onto Little Falls High School. His interest in science started with wanting to become a physician. Alas! there was no usual noble thoughts behind this, but the mere impression that local physicians were given a lot of respect.

His favorite classes in high school were math, physics, chemistry and biology. (Fortunately I had Maths in common with him!)

Undergraduate Years....

After school, he entered the University of Minnesota, Duluth to prepare for medical school, in 1973.

In his very first term, he was lucky enough to meet both his future wife (Dr. Tong Sun Thian) and his mentor Professor Conrad Firling. He met Dr. Tong the very first week, in the Biology Lab, and they seem to have been together since.

Professor Conrad Firling, was a  biology professor, who was willing to take undergraduates into his lab to work on projects in developmental biology. Under him Dr. Kobilka learnt

- first to wash glassware, in a lab, properly.

- later to develop an organ culture medium for studying the salivary glands of some insects and their chromosomes.

(Science was beginning to creep in & I've no idea what those insects were!)

He also worked on a summer project with Professor Robert Carlsen, an organic chemist and this sowed the seed for a growing interest in basic research.

Majoring in Biology and Chemistry, he applied to ten medical schools, but was selected only in 2. Fortunately for him, one of them was Yale and he moved there from Duluth. 

Yale University Medical School....

At Yale, as part of their curriculum, all medical students were required to write a thesis based on original research. 

Dr. Kobilka's very first research project involved dengue fever, on which he worked, through a summer in a lab in Malaysia, involving both field and bench research.

For his thesis project, he worked with Professor Denis Knudsen, a virologist, studying the genetic diversity of rotavirus, a common cause of gastroenteritis in children.

According to him, both these projects were not successful, because they were short termed and gave no fresh scientific insights, into their respective domains. Their only benefit was reinforcing the passion for pure research in him.

After his first year of Med School, he married Tong Sun, who was not a Doctor yet.

Clinical Training At Barnes Hospital...

Owing to financial constraints, a career in research was not an immediate option and Dr. Kobilka decided on a residency in internal medicine at Barnes Hospital, affiliated with Washington University School of Medicine in St. Louis, Missouri, for 3 years.

Dr. Kobilka explained that The Human nervous system can be divided into two functional parts: the somatic nervous system and the autonomic nervous system. The autonomic nervous system regulates many of the internal organs through a balance of two aspects, or divisions. The two divisions of the autonomic nervous system are the sympathetic division and the parasympathetic division. The sympathetic system is associated with the fight-or-flight response, and parasympathetic activity is referred to by the epithet of rest and digest. Homeostasis is the balance between the two systems. At each target effector, dual innervation determines activity. For example, the heart receives connections from both the sympathetic and parasympathetic divisions. One causes heart rate to increase, whereas the other causes heart rate to decrease.

During his training at Barnes, his interest in intensive care medicine, led him to continuously take rotations at the 3 intensive care units - medical, pulmonary and cardiac. Here he found that, patients were typically unstable and required urgent medication

-  to regulate their heart rate and blood pressure

-  to control pain.

He went onto mention that these medications acted on GPCRs (G protein coupled receptors), which are of several types.

Those regulating BP and pulse are called adrenergic and muscarinic receptors, while those controlling pain are opioid receptors.

By now, I was at sea and slowly drowning. The talk was going above my head. I, ofcourse, went back and googled and somewhat surfaced from deep water. Sharing some of that here....

What are GPCRs?

GPCRs are proteins located in the cell membrane that binds extracellular substances and transmits signals from these substances to an intracellular molecule called a G protein (guanine nucleotide-binding protein). 

GPCRs are found in the cell membranes of a wide range of organisms, including mammals, plants, microorganisms, and invertebrates. There are numerous different types of GPCRs—some 1,000 types are encoded by the human genome alone—and as a group they respond to a diverse range of substances, including light, hormones, amines, neurotransmitters, and lipids.

Nearly every function of the human body, from sight and smell to heart rate and neuronal communication, depends on G-protein-coupled receptors (GPCRs). Lodged in the fatty membranes that surround cells, they detect hormones, odours, chemical neurotransmitters and other signals outside the cell, and then convey their messages to the interior by activating one of several types of G protein. The G protein, in turn, triggers a plethora of other events. The receptors make up one of the largest families of human proteins and are the targets of one-third to one-half of drugs. Working out their atomic structure will help researchers to understand how this central cellular-communication system works, and could help drug-makers to design more effective treatments. 

The Net

A GPCR is made up of a long protein that has three basic regions: an extracellular portion (the N-terminus), an intracellular portion (the C-terminus), and a middle segment containing seven transmembrane domains. 

Beginning at the N-terminus, this long protein winds up and down through the cell membrane, with the long middle segment traversing the membrane seven times in a serpentine pattern. The last of the seven domains is connected to the C-terminus. 

When a GPCR binds a ligand (a molecule that possesses an affinity for the receptor), the ligand triggers a conformational change in the seven-transmembrane region of the receptor. This activates the C-terminus, which then recruits a substance that in turn activates the G protein associated with the GPCR. Activation of the G protein initiates a series of intracellular reactions that end ultimately in the generation of some effect, such as increased heart rate in response to epinephrine or changes in vision in response to dim light.

The existence of GPCRs was demonstrated in the 1970s by American physician and molecular biologist Robert J. Lefkowitz. Lefkowitz shared the 2012 Nobel Prize for Chemistry with his colleague Brian K. Kobilka, who helped to elucidate GPCR structure and function.  

In 1984, after his residency, Kobilka applied for cardiology fellowships, and he was particularly interested in the program with Robert Lefkowitz at Duke University in Durham, North Carolina. It was the premier lab studying receptors for adrenaline, which had become a model system for all hormone receptors. This gave him the opportunity to explore basic research in an area relevant to cardiovascular and intensive care medicine. 

It is interesting to note that Dr. Kobilka, never became a cardiologist.

With his young family started in St. Louis.

Fellowship Training At Duke University...

Joining the Lefkowitz lab, Dr. Kobilika found that, almost everybody there, seemed to know more than him and he was yet to familiarise himself with the research work being done there and the techniques they were using.

When Kobilka joined, the lab was just starting to think about how to clone the gene for the β2 adrenergic receptor (β2AR)  and determine its genetic sequence. But the receptor was produced in such small amounts that the team was only able to collect enough protein to work out a few scraps of its likely genetic sequence. 

From now on, we were in the midst of Scientific talk about Scientific research, and there was a lot, that I did not understand or misunderstood. I tried correcting a lot of my misunderstandings with further reading, but there may still be errors here - a direct result of my limited understanding.

Kobilka, joining the programme, decided to construct a library of mammalian genomic sequences and screen it with the scraps of sequences they had. This would pull out longer clones that could be pieced together to reveal the full sequence. However, when the team stitched together the receptor sequence, it had a real Eureka moment: several strings of amino acids that are typically found in cell membranes showed that the receptor snaked through the membrane seven times, just like rhodopsin, the light-detecting receptor in the retina that was also known to activate a G protein. 

It was a surprise that, these receptors looked alike,  one turned on by light, and the other by a hormone.

At the time, about 30 proteins were known to turn on G proteins, and they concluded that it was a whole family of look alike receptors. This family became known as seven-transmembrane receptors, or GPCRs, and is now known to have nearly 800 members in humans. 

Dr. Kobilika, then, wanted to understand receptor structure and how the receptor worked in molecular detail. Thus the project extended to obtaining a crystal structure. Several years earlier Deisenhofer and Huber had obtained the first crystal structure of a membrane protein, proving that membrane proteins could be crystallized and demonstrating the value of protein structure in understanding mechanisms. However, the photosynthetic reaction center was a naturally abundant protein that could be obtained from bacteria. In contrast, even in lung tissue, where the β2AR was most abundant, it represented a very small fraction of membrane proteins.

Stanford University...

Around this time (1989), at Stanford, Professor Richard (Dick) Tsien, had just moved from Yale, and was building a new Department of Molecular and Cellular Physiology in the Beckman Center. Dr. Kobilka was offered a junior faculty position, which he accepted and moved to Stanford. To make ends meet, he moonlighted as a doctor in the emergency department at weekends. 

In the lab they focused on two objectives: 

- understanding the structure and mechanism of activation of the β2AR and 

- determining the physiologic role of specific adrenergic receptor subtypes. 

Cloning and pharmacological studies had identified 9 adrenergic receptor subtypes coded by 9 different genes: three βARs, three α1ARs, and three α2ARs. The drugs available at that time were not sufficiently selective to allow assignment of specific functions to each receptor subtype. 

Dr. Kobilka wanted to see what the receptor looked like in three dimensions using X-ray crystallography, in which a beam of X-rays is fired at a protein crystal and the resultant diffraction pattern is used to reveal the arrangement of its atoms. However to produce an intelligible X-ray diffraction pattern, one first needed to crystallize the receptor- a formidable process of packing millions of identical copies of protein so tightly that they form a solid that looks like a microscopic shard of glass. 

Working out the conditions that will allow a protein to crystallize can take years, and membrane proteins such as GPCRs are the hardest of all: they must be coaxed out of the membrane intact, but it is the membrane that holds them in shape. GPCRs are also constantly shifting into various states, and most are expressed in very low quantities. To collect enough β2AR protein, one had to express about 100-1,000 times the levels at which it is normally produced in a cell. Later, they also used fluorescence spectroscopy, one of the most sensitive biophysical techniques, to investigate receptor structure.

Gopu & Rajagopal V

As the years rolled by, Kobilka's lab was carrying out various biochemistry and biophysics experiments aimed at getting to know the β2AR more intimately, and he was inching forwards in expressing and purifying the protein. But there were a lot of setbacks. They found that the GPCRs have big, floppy loops inside and outside and the receptor writhes and squirms, adopting a variety of levels of activation, which only made crystallization more and more difficult.

 

Finally, in late 2004, the group managed to grow tiny crystals, too small to be analysed at Stanford's synchrotron facility. Based on the suggestions of Gebhard Schertler, a crystallographer, Kobilka took his samples to the European Synchrotron Radiation Facility (ESRF) in Grenoble, France, which had the tightly focused beamline needed to analyse such small crystals. 

But the crystals diffracted to a resolution of only around 20 angstroms - so low that there was no discernible image. A resolution of about 4 A is needed to see the organization of individual atoms.

Further frustration followed, when the team couldn't get the crystals to grow any bigger or diffract any better. The receptor's changeable activation states and floppy segments, made it very difficult to trap all the proteins in an identical conformation. The team realized that they'd have to do something radical: chop off the loose ends, and either anchor the loop in place with an antibody or replace it altogether with a protein known to crystallize well.

The two approaches....

In 2005 Dan Rosenbaum and Søren Rasmussen, two very talented and intrepid postdoctoral fellows, joined the lab with the goal of crystallizing the β2AR. Søren and Dan took two different approaches to generate better quality crystals of the β2AR. 

Søren identified antibodies that bound to a particularly flexible region of the receptor and Dan used protein engineering to replace the same region of the β2AR with T4 lysozyme (T4L), a highly crystallizable soluble protein. During 2006 crystals were obtained using both approaches combined with a newly developed lipid-based media known as bicelles consisting of a mixture of lipid and detergent. Initial crystals of the β2AR-Fab (3.4A) and the β2AR-T4L (2.8A) fusion protein complex, both diffracted to below 4A. 

A trio of papers marked a milestone in structural biology, and intensified aggressive research into GPCR structures.

But these GPCR structures had been snapshots of receptors in an inactive state. To really understand the receptor's workings, researchers needed to see it as it was being activated by a ligand and turning on the G protein. This project was even more technically daunting than the last. The protein complex was too big to hold in the fatty scaffold; the G protein kept falling off; and this time, the extracellular part of the receptor wouldn't sit still for crystallization. 

Dr. Kobilka reached out to all manner of experts for help and the various groups developed a detergent for stabilizing the receptor with its G protein; a lipid scaffold that could support the complex; and an antibody that could hold it together. And then they tested thousands upon thousands of crystallization conditions and ways to engineer the protein.

Finally, after another 5 years, they solved it and got a resolution of 3.2A revealing a tangled molecular threesome: β2AR with a ligand clasped at one end and the G protein nested up on the other. 

The β2AR-Gs crystal structure was published in 2011 together with two companion studies using single particle electron microscopy and deuterium exchange mass spectrometry to characterize the dynamic aspects of this complex. These combined studies provided unprecedented insights into GPCR signaling at a molecular level.

It was for this pioneering work, that, The Nobel Prize in Chemistry 2012 was awarded jointly to Robert J. Lefkowitz and Brian K. Kobilka "for studies of G-protein-coupled receptors."

Brian. K. Kobilika receiving his Nobel Prize from H M King Carl XVI Gustaf of Sweden
at the Stockholm Concert Hall on 10th Dec 2012.

After this climax, there were 2 more sections of Epilogue...

Why 20 long years?

Gopu R

According to Dr. Kobilka, this entire research took almost 20 years mainly because

-  It was a new field and they almost started from scratch

-  They had to learn how the receptors are built, how they transmit signals over the membrane and how they are regulated

-   Purifying the Protein, Crystallizing it to a high level of resolution in both their active and inactive stages, ensuring their stability, even when drawn out of their shells - all took their own time.

-   The mechanisms for diffraction were also not so developed and Computer Docking was in its developmental stage.

The entire team managed to sustain their interests, hopes and irrational optimism through these years because

-  They constantly achieved incremental advances & successes that kept their hopes alive.

-  They were simultaneously learning so many new things about the Human nervous system, especially with respect to the GPCR.

-  The nurturing scientific & academic environment of which they were a part.

-  Their family and friends and the entire scientific fraternity and last but not the least, his wife, who worked with him every step of the way, supporting him both professionally and personally.

-  His own temperament, love for his work and the sheer joy he derived in research.

His post Nobel Work....

I had very poor understanding of this section and the Graphs shown.

This part of the lecture is paraphrased in my own words.

Along with a team Professor Brian Kobilka, discovered the drug called PZM21 after evaluating some three million different compounds. His research is mainly aimed at finding an alternate to Morphin as a painkiller.

Morphine, derived from the opium poppy, works by acting on a receptor in the brain that reduces pains, but it also affects a different receptor that can lead to fatal breathing problems in the event of an overdose. But PZM21, which so far has only been tested on mice, appears to act on the first receptor to about the same level as morphine without significantly changing the second one.

It also caused less constipation than opiate drugs, a factor that limits how much of the drug can be given. The new drug dulls the feeling of pain in the brain because it has a “potent, selective and efficacious” effect on the brain receptor involved in the sensation of pain, without dangerous side effects.  

Studied against Morphine, on mice, PZM21 did not appear to affect their breathing and the painkilling effect of PZM21 lasted for up to three hours, “substantially longer” than the maximum dose of morphine. The “constipating effect” was also “substantially less than morphine” and the mice did not show signs of addiction.

Morphine addiction is a result of the activation of the brain’s dopamine reward circuits. When this happens in mice, they tend to run about a lot. But PZM21 had “no apparent effect on locomotion”.

Vallabha Srinivasan

What is PZM21?

PZM21 is an experimental opioid analgesic drug that is being researched for the treatment of pain. It is claimed to be a functionally selective μ-opioid receptor agonist which produces μ-opioid receptor mediated G protein signaling, with potency and efficacy similar to morphine, but with less β-arrestin 2 recruitment.

In tests on mice, PZM21 was slightly less potent than morphine or TRV130 as an analgesic, but also had significantly reduced adverse effects, with less constipation than morphine, and very little respiratory depression, even at high doses.  

Dr. Kobilka concluded his lecture, by thanking his team & family and introducing them via pics.

Rajagopal V

My own take aways from the lecture

- As a speaker Dr. Kobilka was not flashy, aggressive or imposing. Rather soft spoken, his talk was delivered like a classroom lecture in a low sonorous voice.

- Yet he was very impressive. Kept the audience fairly hooked.

- The 2 main aids to this were - His presentation slides, that were simple, clear and precise and 

- His own unbridled passion for his work that came through even when he was describing complex and inanimate Protein structures.

Lastly, I must read up, atleast about Basics, before attending such lectures, if I want to optimise the experience.

Acknowledging Vallabha, Vidya, RV, Jayakamala & their kids - 

என் சக ஆர்வலப் பயணிகள்!

A big Thank you to Gopu, who made this an enjoyable experience and matched my every step in weathering sudden winds, rains, pot hole filled roads and Chennai peak hour Traffic to attend this lecture. The upturned umbrella and his valiant attempt to turn it back remains etched in my mind!

It seemed like a metaphor.

Standing exposed in ur ignorance, as science rains all around u.

Thankfully, he straightened the umbrella soon!

Buddhist Tales across Visual Media #1 Taming of Nalagiri

I first came across, visual Depiction of Buddhist Tales, in the Amaravati Gallery at Chennai Museum.

Buddhist art normally depicts

- Episodes and scenes from Life of Buddha

- Jataka Tales

across paintings and sculptures.

Because

-  I had read most of the Buddhist and Jataka tales (at least the important ones)  

-  Gopu was extremely lucid & patient in his explanations
I was mesmerized, to say the least of it. 

True to my nature, I went back a couple of times to the Gallery on my own, admiring and understanding, apart from other things, the grammar involved in depicting a story, visually, in such a small area.

Jataka Tales... (To the uninitiated...) 

The Jātaka Tales are a voluminous body of literature native to the Indian subcontinent which are mainly concerned with the previous births of Gautama Buddha in both human and animal form. A Jataka tale relates an episode in a past life of the Buddha. 

There is always a character in the story who is identified as the Buddha-to-be. He is often (but not always) the hero, usually referred to as Bodhisattva, because he is yet to attain his enlightenment.

Many stories illustrate general Buddhist moral ideals, including honesty, wisdom, kindness, generosity and detachment. Usually it is the Buddha who narrates the story of his past life, in order to explain something about a situation or character that he or his followers have encountered.

 

Bodhisattvas come in many forms of life. Swans, Deer, Nagas or Snakes, Monkeys, Elephants, and of course Human beings of a lesser order of enlightenment.

Jataka stories were depicted on the railings and torans of the stupas . The circular Medallions in the Chennai Museum are remains from the Stupa at Amaravati.

Medallions from the Amaravati Stupa - Chennai Museum

Amaravati Art...

The Amaravati school of art and sculpture is supposed to have flourished in the second century BC especially in the second half.

Satavahanas were the first patrons of this school.

The Major Features of this school include 

- The 'narrative art' - The medallions are carved in such a way that they depict an event in a sequential manner.

-  In human, animal, and floral forms, there is a sense of movement and vitality, as well as profound and serene naturalism.

- Amravati, Nagarjunikonda, Goli, Ghantasala, and Vengi are notable locales where this style flourished.

I don't know if it was the fact that an ELEPHANT was the central character, portrayed in all its grace, Majesty and grandeur; or the story itself, which was the allure; 

But I quickly zeroed in on these 2 

- Nalagiri - The Taming of an elephant (Story from Life of Buddha)

- Shaddantajataka (A jataka Tale)

as my favourite panels.

Ajanta... 

In early March, when we visited Ajanta, I was eagerly waiting to see these 2 depictions there - in 2D - as paintings.

To my surprise there was an additional tale there(Matriposhaka Jataka), with an elephant as its central character.

Although all the 3 paintings are quite damaged, with the help of earlier photographs and line drawings - we can appreciate both the similarity and subtle differences in the depiction of 'the Elephant and its kin and kith' between these 3 paintings.

Apart from the above, Elephants are also portrayed frequently in many other panels - leading a royal procession, part of a marching retinue going for a war, part of a jungle scene or as a stand alone emblem/motif in the Ceilings/ Pillars.

Depictions of Elephant(s) in Ajanta  

After coming back, I revisited the Museum, and was struck both by the

- Similarity in the depictions

- Variations obviously due to the difference in media and scale.

Subjugation of Nalagiri 

In this tale, Devadutta, a cousin of Buddha wants to seize power of the monastic order and conspires with King Ajatashatru, to kill Buddha. They decide to release a wild elephant named Dhanapala / Nalagiri. 

Accordingly when Buddha comes begging for alms, in the main street of Rajagriha, Nalagiri is let out of his stable. The elephant charges into the street, destroying and stamping over all in its path. However when he sees Buddha, he is tamed by Buddha's power of benevolence and bows down on his knees before him.

In Ajanta, this highly damaged panel, is located in the Verandah of Cave 17, on the right side, largely above the Lintel. It can be divided into 5 scenes. 

1. Devadutta conspiring with Ajathashatru in his palace.

2. People waiting for Buddha to arrive.

3. Nalagiri released from the stable.

4. Charging down the street.

5. Nalagiri subjugated.

Nalagiri - Cave 17 Verandah - Schlingloff

Scenes 4 and 5 from the Panel

Nalagiri is portrayed essentially only in Scenes 3,4 and 5. Out of these Scene 3 is largely destroyed.

In the scenes 4 and 5 we can see the Majestic elephant in all its grace and strength - dynamically portrayed, 

- First as it charges in the street - personification of power and destruction and

- Later as it bows in front of Buddha, it is portrayed in all its benevolence and submission - seeking Buddhas grace and acceptance.

The beautiful market scene at the back, helps to capture these 2 moods.

- In the first scene people are scared and horrified with shop keepers hurriedly closing their shutters.

- In the 2nd scene, people are awed by Buddhas power and grace, and ladies are cheering and throwing their ornaments as offering.

Scene 4 - Charging of the Rogue Elephant

Scene 5 - Nalagiri's submission and surrender to Buddha   

The scale of Buddha, towering over the entire frame and Nalagiri, and his posture of benevolence, kindness and blessing, complementing the majestic elephant bowing on its all 4s is the beauty of this composition. 

The frenzy of activity in the background also contrasts with the minimalistic foreground, highlighting the focus.

Typical of Ajanta art, Architectural elements have been used, effectively, to delineate the individual scenes and connect them into a coherent composition. Some of these are

-  The 2 storeyed building in Scene 1 depicting 2 scenes of simultaneous action

-  Pavilion in Scene 2 to create focus

-  Gates on either side of Scene 3 - acting as transition and depicting the movement of Nalagiri as he is charging

-  The series of buildings at the back, in Scenes 4 and 5, creating the space and milieu of the street and helping to create the moods of the people from shock, horror to amazement and happiness at last.

Amaravathi - Nalagiri Panel

This panel is hardly 75cms in diameter and carved in Limestone with a polished finish. 

The story is concise and the 2 important scenes depicted are

- Nalagiri charging and destroying

- Nalagiri subjugated.

The similarities with the depiction in Ajanta (inspite of the variations in scale, size, medium and time period) is amazing.

-  Emphasizing on the focal scenes with a dynamic central Nalagiri.

-  The 2 contrasting poses of Nalagiri (portrayed even better here).

-  Scale of Buddha dominating over Nalagiri and the people.

-  Contrasting moods of completely detailed people portrayed on the street and balconies of buildings.

-  Use of Architectural elements to depict a space, a scene, movement and transition and the moods of people.

The differences or contrasts, as already mentioned, arise out of the limitations of size and medium.

-  Concise and abridged depiction with no preliminaries.

-  Fewer people and buildings.

Yet the fluidity of motion and passage and the completeness of the story is retained, making this an absolute masterpiece!

The 2 poses of Nalagiri and the scale vs Buddha

Architectural Elements used to identify space, transition and create moods.

While googling I came across, several more depictions of Nalagiri, alas, none of which have I seen in person.

A Panel from Goli in Chennai Museum (not on display)

Amaravati Panel from British Museum

Gandhara Art - Location Unknown

2nd century, Khyber Pakhtunkhwa, Pakistan, Central Archaeological Museum in Lahore
3rd century, Pakistan (Gandhara Culture), Kushan Period, Indian Museum, Kolkata.

2nd-3rd century, Gandhara, Private collection, Indian and Southeast Asian, Christie’s.
3rd-4th century, Gandhara, private collection
4th century, Northwest Frontier, Peshawar, Pakistan, Government Museum.

Undated, Gandhara, Indian Museum in Kolkata (India).
5th century, Khyber Pakhtunkhwa, Pakistan, Central Archaeological Museum, Lahore (Pakistan). 

Preah Palilay, Angkor, Cambodia (on the Northern Gopuram)

From all these depictions, we can clearly see the variations and variety in Buddhist Art through the Centuries and through the styles of Ajanta, Gandhara and Amaravathi.

Yet we can also observe and appreciate the similarities in these depictions

- In their Narrative Format

- Focus on the Primary Scene (Climax of the Story)

- Sense of Scale - Buddha is uniformly larger than Nalagiri

- The quality of Movement, Fluidity and Dynamism within the Panel even though Buddha himself is static (He is not performing like the Hindu sculptures where the God is fighting, dancing, slaying etc).

- People who form part of the scene are completely detailed out including their varied phyiscal actions and expressions.

- Architectural Elements, acting as Integral components, highlighting the sense of identity, space, scale and as backdrops to the focal scene. 

This is a true revelation to me and appears unique only to Buddhist Art.

No other form of Indian Art or Western Art seems to have borrowed any of these key elements.

Modern Depictions of Taming of Nalagiri

Yet our Modern depictions, either through ignorance or willful thwarting of style, seem to have completely lost both the sense of scale and the true narrative idiom of the Ancient Buddhist Art and come across only as cheap imitations at best, completely lacking the fluidity and richness of style present in the old Art.

They show no context or identity in the detailing of their people, and architectural elements are non existent. Infact Buddha seems to be taming Nalagiri in some scenic tourist spot, rather than a crowded Market place.

I wonder, if this is how our Art becomes more and more mediocre & root less

- in cutting off its ties with Ancient traditions

- yet not able to establish a relevant modern context or identity leaving it in a limbo of vacuum, showing no evolution or continuum, with our past.

My Favourite Nataraja - Chennai Museum

It was almost 10 years ago, I was visiting the Bronze Gallery of the Chennai Museum with my friend.

Like 99.99% visitors, I too was traipsing along from one exhibit to the other without paying too much attention, when suddenly my feet felt rooted. I was in front of the most mesmerizing Nataraja, I had ever seen. My eyes could not behold him enough & I was transfixed. 

I whispered - Sudha! Just look at him! He is easily the most beautiful that I have ever seen. She was like 'Hmm! Many of the others are equally beautiful!' 
I woke up and looked around. Of course, he was surrounded by a bevy of Natarajas - some bigger and some smaller, some more shiny & better lit and some still framed within an aureole of flame. Was he special? Was he more beautiful? Definitely seemed so to me. Reluctantly I said Goodbye! (No.....Make it till we meet again!), just noting the fact that the plaque below said, He is from Tiruvalangadu.

Thus began my secret tryst with Him. Every time, I was in the vicinity, I'd quickly hop across to look at him. Initially I tried to play 20 differences. What is it, that's different about him? Failed. Each piece there is unique in its own way and I couldn't frame his special features in bullet points. In fact the unique Nataraja there was the Pandya one from Madurai, because He had his right leg up.

After a few visits, I zeroed in on his expression. That's what's special - I said to myself. He has the most restrained, subtle smile. He is so content and happy where he is! When I asked him to confirm, he gave me his usual குறு நகை, புன்னகை or whatever.

Through those days - 

- It somehow never struck me to either google him or find his antecedents.

- To click a pic of him, even from my basic non smart phone.

He was simply etched in my mind's eye & fortunately, right here in Chennai, to visit whenever I wanted.

Then, between the 2 phases of Corona, my son & I visited the Museum, mask and all in place & maintaining social distance from one & all, but not each other. I quickly dragged him to the 1F and Wow! What do I see? They are cleaning and sprucing the place up. My Nataraja was out of his glass case and dim light & sitting right there on a table. 

How I wish, my blind friend was with me. He could have felt Him & may be found out what's so special about Him?

I did the next best thing. Coaxed the Museum staff to let my son take some photographs of him. Corona, or maybe Suriya's usual charm - worked. The staff not only co-operated by moving the Nataraja as per Suriya's specifications. They offered to hold my black Dupatta as a backdrop - for him to click. Tirelessly they stood on stools and held it up stiffly, while he freaked out clicking. 

My day, month, year, entire life was made.

It was, at last, time to google and find out who my Nataraja is and where did he come from? 

Before that I HAD to understand the iconography of a Nataraja and what he represents.

The Thiruvalangadu Nataraja - Chennai Museum - Suriya

Shiva as a God, is worshipped in many forms across India. One among these is the NRTTA or TANDAVA MURTHY form. The two most common forms of Shiva's dance are the LASYA (the gentle form of dance), associated with the creation of the world, and the TANDAVA(the dance of frenzy) associated with destruction of the world.

As Nataraja, he is supposed to be the King of Dancers, a unified and dynamic composition expressing the rhythm and harmony of life. He performs the cosmic dance 'ANANDA TANDAVA' (the Dance of Bliss/Delight), which represents the cosmic cycles of creation, preservation and destruction, as well as the daily rhythm of birth and death.

The Legend...

In the Thillai resided a group of sages who believed in the supremacy of magic and the thought that God can be controlled by rituals and mantras or magical words. In order to defy the sages, Shiva came into the forest assuming the form of Bhikshatana, a simple mendicant seeking alms. On seeing the handsome form of Shiva, the wives of the sages were enchanted. 

- This enraged the rishis and they invoked scores of serpents by performing magical rituals. Shiva lifted the serpents and donned them as ornaments on his matted locks, neck and waist. 

- Further enraged, the sages summoned a fierce tiger, whose skins were used by Shiva as a wrap around his waist.

- The rishis gathered all their spiritual strength and invoked a powerful demon Muyalakan or Apasmārapuruṣa - a symbol of complete arrogance and ignorance. 

Shiva wore a gentle smile, stepped on the demon's back, immobilized him and performed the Ananda Tandava disclosing his true form. The sages surrendered, realizing that Shiva is the truth and he is beyond magic and rituals.

History...

Though Nataraja has existed in this form for more than a thousand years, its ascent to ubiquity and fame is a relatively recent phenomenon, brought to the forefront by the Chola Bronzes.

The classical form of Nataraja first appeared in a pillar in the rock cut temple at Seeyamangalam – Avanibhajana Pallaveshwaram Temple constructed by a Pallava King Mahendravarman I in 6th century CE, which is known by Archeological Survey of India and Archeological Survey of Tamil Nadu as the oldest known Nataraja sculpture in India. 

The stone reliefs at the Ellora Caves and the Badami Caves, around the 6th century, are also among the oldest Nataraja sculptures in India. Ancient Tamil songs during the Bhakti movement written by the four Shaivite saints of Sambandar, Appar, Manikkavacakar, and Sundarar, extol Nataraja and describe the Nataraja Temple, Chidambaram, thus dating Nataraja worship way before the 7th century CE.

Around the 8th to 10th century, statues emerged in Tamil Nadu in its mature and best-known expression in Chola bronzes, as UTSAVA MOORTHYS. These are some of the best expressions of Indian art and acclaimed and accepted internationally. Nataraja reliefs have also been found in many parts of South East Asia such as Angkor Wat Cambodia, Bali etc.

Stone Natarajas - Seeyamangalam, Ellora and Badami - Me and Wikepedia.

The Iconography and the Symbolism...

Broadly the various aspects represented in the Nataraja include

• He dances within a circular or cyclically closed arch of flames (prabha mandala), which symbolically represents the cosmic fire that in Hindu cosmology creates everything and consumes everything, in cyclic existence or cycle of life. The fire also represents the evils, dangers, heat, warmth, light and joys of daily life. The arch of fire emerges from two makara (mythical water beasts) on each end.
• He looks calm, even through the continuous chain of creation and destruction that maintains the universe, that shows the supreme tranquility of the Atma.
• His legs are bent, which suggests an energetic dance. His long, matted tresses, are shown to be loose and flying out in thin strands during the dance, spread into a fan behind his head, because of the wildness and ecstasy of the dance.
• On his right side, meshed in with one of the flying strands of his hair near his forehead, is typically the river Ganges personified as a goddess, from the Hindu mythology where the danger of a mighty river is creatively tied to a calm river for the regeneration of life.

On a Chola Bronze...

Chola Bronzes from the Chennai Museum - Me.

• His headdress features a human skull (symbol of mortality), a crescent moon and a flower identified as that of the entheogenic plant Datura metel.
• Four-armed figures are most typical, with a few exceptions of 8-10 arms.
• The upper right hand holds a small drum shaped like an hourglass that is called a ḍamaru in Sanskrit. A specific hand gesture (mudra) called ḍamaru-hasta is used to hold the drum, which symbolizes rhythm of creation and time.
• The upper left hand contains Agni or fire, which signifies destruction.
• A cobra uncoils from his lower right forearm, while his hand is in the abhaya mudra gesture as a sign to not fear
• The lower left hand is bent downwards at the wrist with the palm facing inward, we also note that this arm crosses Naṭarāja’s chest, concealing his heart from view. It represents tirodhāna, which means “occlusion, concealment.”
• The face shows two eyes plus a slightly open third on the forehead, which symbolize the triune in Shaivism. The eyes represent the sun, the moon and the third has been interpreted as the inner eye, or symbol of knowledge (jnana), urging the viewer to seek the inner wisdom, self-realization. The three eyes alternatively symbolize an equilibrium of the three Guṇas: Sattva, Rajas and Tamas.
• He wears mismatching Earrings - the Makara Kundala in his right ear and the Patra Kundala in his left ear, thus representing the Unification of the male and female aspects of the divine. This also symbolizes the fact that he holds Shakthi within him.
• The idol rests on a Lotus pedestal, symbolising the creatives forces of the universe.
• The dwarf underneath his foot is the demon Apasmara purusha or Muyalaka, who symbolizes ignorance which Nataraja destroys.
• The slightly smiling face of Shiva represents his calmness despite being immersed in the contrasting forces of universe and his energetic dance.

The Details of the Eyes, Ears, Hair, Hand Mudras

The Tiruvalangadu Nataraja...

How the Tiruvalangadu Nataraja came to the Chennai Museum is an interesting story.

In July 1905, K.V. Subramania Ayyar, a Tamil Assistant in Madras with the Archaeological Survey, visited Tiruvalangadu, further west, to recover two ancient copper plates from a temple. His abilities of persuasion got him not two, but 31 copper plates. He also managed to get a number of metal images, which the temple officials had found in an underground chamber. Not realising their importance, the Archaeological Survey, in its annual report to the government, recommended a routine acquisition of the images. Thus, in 1907, the Tiruvalangadu Nataraja and the other metal images reached the Madras Museum.

It is only much later, that Art Historian Havel realised the importance of this statue and it acquired its position of importance.

With all this knowledge, under my belt, I visited my friend again. Beamed at him and told him, I know a lot more about you now.

I also know that you are somewhat damaged, have lost your aureole and maybe some exotic flying out manes, but you are still the most beautiful - to me.

He, as usual gave me his all knowing smile.

Then, last year, on Museum day, I visited the museum, with a docent. Dr. Deepika, a Professor of History & Archaeology from MCC. For the first time, we lingered in front of each exhibit, observed the details, inched along & finally stood before my idol.

Bronze Gallery at Chennai Museum

Imagine my surprise, when she said, the Tiruvalangadu Bronze is one of the most beautiful Bronzes ever made, acknowledged so - not just by Indian Artists & Art Historians, but even internationally. In fact, when ever lists are made & updated on the world's finest objects of art, he always makes it to the top 10 list. I couldn't stop beaming. 

I was like a proud mother whose son wins the race. Or a woman whose boyfriend was declared Mr. Madras (Actually Mr. Universe - no less!)

Also fast acquiring this smug expression - which said 'See! I'm no less a connoisseur. What the Art historians across the world decided upon, after perhaps detailed research & study, I've spotted with my untrained eye!' 

On this note - I asked Dr. Deepika, 'What is it that makes him so special?'

She gave the standard answer. 'Google it!'

Thus I went back to my key(drawing) board and found this.

Indian Art and its International Acceptance...

In the early part of the 20th century, influential orientalists hardly reckoned Indian sculpture to be art. In the words of Vincent Smith, “the figures both of men and animals (in Indian sculptures) become stiff and formal, and the idea of power is clumsily expressed by the multiplication of members.” Even the official handbook to the Indian section of the Victoria and Albert Museum derided them. In fact, the West clearly branded Indian (mostly Buddhist) sculptures as poor versions of Greek and Roman art.

Binfield Havell, an art historian (who was a columnist for The Hindu) who worked in the Madras and Calcutta colleges of art for many years, was one the earliest to argue for the artistic merits of Indian art by presenting exalted examples to an International audience.

In 1908, he wrote an important book 'Indian Sculpture and Painting', where he substantiated his arguments with examples. The bronze sculpture of Nataraja, acquired by the Madras Museum in 1872 from Velankanni, found a prominent place in it.

However, Havell recalibrated his assessment when photos of the Tiruvalangadu bronze reached him. Though both the Nataraja icons were identical, he was clear about which one was preferred. “There is a great difference in the feeling which animates the two,” he wrote in favour of the Tiruvalangadu Nataraja. He declared that the ‘gaiety' of this ‘delightful bronze' was ‘the perfect art' and that it was superior to the ‘trivial' sculptures prevalent in Indian Art till then. Havell published the photographs of the Tiruvalangadu bronze for the first time in 1911 in his book, 'The Ideals of Indian Art.'

The Chola Bronzes from Velankanni & Tiruvalangadu

Around that time, Ananda Coomaraswamy, the art theorist, also took on critics who dubbed Indian sculptures with many arms and heads as ‘hideous'. In an important essay published in 1913, he demonstrated that multiple limbs helped stage a ‘sculpture drama', and exhibited ‘the wonderful creative energy of the Indian genius'. He made this point first by using the ‘profoundly expressive' figure of Durga, and followed it up with the ‘perfectly balanced' Tiruvalangadu bronze. When Coomaraswamy reworked this essay in 1918, the Tiruvalangadu Nataraja moved up the list of examples.

Coomaraswamy's seminal work, titled The Dance of Siva, played an important role in popularising Nataraja. This much-cited essay ‘decoded' the art and made the meaning accessible to many. However, it did not receive much notice when first published in 1912, in a Saiva Siddantha journal without any illustration. But its reprint in 1918, as part of a book under the same name by a New York publisher, reached audiences across the world. Coomaraswamy used the photograph of the Tiruvalangadu bronze as the front piece.

Havell and others pointed to the merits of Indian art, but their reputation as ‘friends of Indian art' came in the way of some critics accepting their assessment. However, finally, doubts about the significance of Indian sculptures came to rest in 1921.

Auguste Rodin, considered the ‘father of modern sculpture', was widely respected for his works such as ‘Thinker' (1904). When the photographs of the Tiruvalangadu and Velankanni bronzes reached him, probably given by Rothenstein or Victor Goloubew, a French art enthusiast and photographer who had lived in Pondicherry for a short time, the plastic quality of the sculptures captivated Rodin. In the elegance of these bronzes, he found ‘grace' and ‘above the grace' he admired their ‘ modeling'. Nataraja sculptures were the ‘perfect expression of rhythmic movement in the world', he waxed eloquent. These comments, coming as they did from a revered sculptor, created a stir and led to the instant popularity of the Nataraja form.

Rodin wrote his essay on the dancing Siva (in French) a couple of years before he died in 1917, but it was posthumously published in 1921. The same year, the English translation of the article appeared in the Indian art journal Rupam . Though images of the Velankanni and Tiruvalangadu bronzes accompanied Rodin's essay, there was little doubt about which among the two had created an impact.

Opinions on Indian art changed in the later part of 1920s. Images of the Tiruvalangadu Nataraja began to appear regularly in essays and books. Stella Kramrisch, an authority on Indian art, in 1922 used the sculpture as an illustration with her article on space in Indian sculpture. Havell, too, in 1928, when he rewrote his book, Indian Sculpture and Painting, chose to print the Tiruvalangadu bronze instead of the Velankanni one. 

The enduring spell of the Tiruvalangadu Nataraja was cast worldwide. Museums across the world could not help but compare their own bronzes with the “famous example in the Madras Museum”. Cleveland museum, for instance, in 1930, took pride that its own Nataraja “fails by only three and a half centimetres” when compared with the Madras icon. Newspapers, as The Hindu did in 1941, featured the Tiruvalangadu bronze as one of the world's most delightful bronzes. The Indian postal department was not far behind. When it decided to publish a definitive series of 16 stamps focusing on Indian heritage in 1949, the Tiruvalangadu icon was a natural choice.

In many ways, the exhaustive account given in 1974 of Nataraja in art and literature by C.Sivaramamurti, the reputed art historian, firmed up the significance of this sculptural form and summed up its renown. In Sivaramamurti's list, too, the Tiruvalangadu bronze found a special place. After analysing hundreds of sculptures, he concluded that it was “the best known image of its kind in any public museum”. The journey came a full circle in 1992 when the Madras museum published a brief catalogue of its select bronzes. The Velankanni bronze was left out, but Tiruvalangadu Nataraja adorned the cover, and was prominently included in the catalogue.

Well!  With this my story should end - on a glorious note!

But there's a twist...

The true significance of my Nataraja...

My moment of epiphany came just last month - when I attended a series of lectures on Chola Bronzes by Vijayakumar (of the Idol Thief fame).

Vijayakumar said that all Bronzes are called  திருமேனிகள் for a specific reason. They were commissioned, conceived and executed as Representations of God, meant to be housed in Temples and nurtured with all the rituals as prescribed in the Agamas, which is what endowed them with their aura, presence and vibration.

They were to be approached as GODS, with an inherent feeling of spirituality.

To view them as mere objects of art amounted to a sacrilege and showed great disrespect to both the creativity of the sculptor and the intent of the creation.

With this in mind, I visited my Nataraja again. Having read Gopu, I also had a new term for his smile 'சிறுமுறுவல் வந்தெனது சிந்தை வௌவ' - seemed to clearly describe the impact of his smile on me. (This phrase is from Appar's Thevaram on the Shiva from the Valampuram temple, which was referenced by Dr. Nagaswamy in his book Oviyapavai and which in turn inspired Gopu!)

Standing before him, I finally understood, what it was, that he had been trying to tell me for over 10 years. He was damaged (the Framework that defined him and gave him stability had gone). He was displaced. His identity reduced to a 2 line plaque at his feet. 99.99% people who visited him, passed him along with nary a 2nd thought.

Yet HE WAS. And CHOSE TO BE. Complete, beautiful, at peace and full of equanimous joy. Accepting Himself and His audience for what they were.

Is this not how we should be? Accepting ourselves with all our seeming flaws and incompletion, finding our own Home & identity, no matter where we are placed and above all finding Equanimous joy, every moment of our lives! I truly felt blessed & what began almost 10 years ago as a clueless quest found its culmination at last!

A small error rectified - as pointed out by my friend Vallabha.

The oldest Nataraja Sculpture (present as of today) is at Asanapet Odisha (and not Seeyamangalam).

Belonging to a date around 4th century CE,

The Asanapat Nataraja has a 13 line inscription below, in Sanskrit Language with Post Brahmi or early Kalinga script.

It describes the achievements of  King Satrubhanja  as a conqueror and spiritual man.