Scientists Simplifying Science

Category archive

SciWorld

Blogs about the hottest research papers

The Gentleman’s Hesitation….& The Invention of Stethoscope

in Medness/SciWorld by

René Laennec (1781 – 1826) was a thorough gentleman. In retrospect, he’d turn out to be a knight in shining white apron.

In 1816, the young French doctor was worried that he could be getting ”inappropriately close’ to a young patient who had been suffering from chest infection. He would recall later, ”…. I was consulted by a young woman laboring under general symptoms of diseased heart, and in whose case percussion and the application of the hand were of little avail on account of the great degree of fatness.The… method of direct auscultation [was] being rendered inadmissible by the age and sex of the patient…”

Laennec resolved the problem of medical diagnostics and social decency in one shot. He ”rolled a quire of paper into a kind of cylinder and applied one end of it to the region of the heart and the other to my ear ”
Within a few months, he had invented that universal symbol of medical science – the STETHOSCOPE

Reference:

  1. https://www.medisave.co.uk/blog/the-invention-of-the-stethoscope/
  2. https://thechirurgeonsapprentice.com/2015/04/21/laennecs-baton-a-short-history-of-the-stethoscope/
  3. https://commons.wikimedia.org/wiki/File%3ARene-Theophile-Hyacinthe_Laennec_(1781-1826)_with_stethoscope.jpg

 

Author Profile:

for sciwri

Anirban Mitra, Ph.D.

Anirban Mitra did his PhD from the Department of Microbiology and Cell Biology, Indian Institute of Science (IISc), Bengaluru and is now a teacher of biology, based in Kolkata. His interests range from biological evolution to history of science and facets of India’s past.

Blog Design and infographics: Abhinav Dey

Featured Image: Ipsa Jain

Creative Commons License
This work by ClubSciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Time perception in the brain

in SciWorld by
Featured Video Play Icon

In our previous two entries, we discussed how painters and writers reflected on the passage of time, and we also learned what philosophers and physicists had to say about this issue. Now it’s the time of neurobiology! How does our brain perceive time? What are the neural bases and possible mechanisms underlying time perception? Is there any internal clock or pacemaker? Is timekeeping distributed among different brain areas?

via GIPHY

Temporal processing is a daunting task. A rich gamut of behaviors depends on our capacity to calibrate and align incoming signals timely. We sample these inputs at various channels, in distant brain areas, and with different processing speeds. However, our brain does an excellent job in generating a coherent picture of the world around us, updating this report to match the fluctuation of external signals.

From prestissimo to largo

We have the ability to compute timing differences that span 10 orders of magnitude, from microseconds to a day (Fig. 1). Separate channels deal with this wealth of information. It seems that we have distinct neural systems that process different timescales. On the high-end of this spectrum, we encounter the neurons of the cochlear nuclei that are responsible for sound localization. They achieve an astonishing feat: they can detect time differences of microseconds in the arrival of sound to both ears. Entrained by the light/dark cycle and other signals, the suprachiasmatic nucleus of the hypothalamus is the mammalian master clock that regulates aspects of metabolism and the daily sleep/wakefulness cycle. In between these two extremes of performance, a network of regions associated with the thalamus, cortex, and striatum operate in the range of seconds to minutes, working as coincident detectors (Buhusi & Meck, 2005). Recent research has also implicated the hippocampus in keeping track of how much time elapsed and in discriminating between similar intervals in the scale of minutes (Jacobs et al., 2013).

Figure 1. Time-scale of temporal processing (taken from Buonomano & Karmarkar, 2002).

Given the scope of this subject, in this article we will concentrate on events taking place in tens or hundreds of milliseconds: speech perception, motion processing in the visual and somatosensory systems and some cues in music perception occur in this time scale.

Time matters for neural circuits

In “The organization of behavior” (1949), Donald Hebb recognized the importance of time in sculpting network properties when he introduced the groundbreaking concept of concurring excitation as a way of strengthening synaptic connections. The Hebbian synapse model suggested that if a neuron is repeatedly involved in the excitation of another neuron, the connection between them will be more efficient as a result of changes taking place in one or both cells. Basically, if two neurons fire together, they wire together. Another plasticity rule appeared later: spike-timing dependent plasticity (STDP). STDP goes one step further, proposing that the strength of a synapse depends on the relative timing of presynaptic and postsynaptic action potentials (Fig. 2). The spike order can make a dramatic difference, potentiating or depressing the synapse.

Figure 2. Scheme of spike-timing dependent plasticity (STDP). In the canonical form of STDP shown here, a presynaptic action potential closely precedes a spike in the postsynapse (red and black bars on top), leading to long-term potentiation (LTP, positive change in synaptic strength). On the contrary, the reversal of this sequence results in long-term depression (LTD, negative change in synaptic strength). In some systems, the temporal requirements for LTP and LTD are exactly the opposite, compared with the canonical STDP. The time window (about 50 ms) can also change depending on the brain region (for details, see Sjöström et al., 2008).

In silico, neural network models incorporating time-dependent realistic features were able to extract temporal information (see Buonomano & Merzenich, 1995). One of these implementations was paired-pulse facilitation (PPF); a known plasticity mechanism in which an impulse evokes a larger postsynaptic potential if it was closely preceded by another impulse. A dynamic neural profile essentially means that a train of action potentials will change the state of the network, inducing activity-dependent transformations in the circuits. When new inputs arrive later, even if they have the same duration and amplitude, they may still evoke a different pattern of activity simply due to the altered state of the circuit. We will come back later to state-dependent networks and their relevance for time-keeping mechanisms.

Central clocks or distributed mechanisms?

In the literature, there are two models that account for the locus of temporal processing in the millisecond time scale. Some authors maintain that an internal clock in our brain sets the pace, pretty much like a computer’s clock. Others think that various regions of the brain share the job of encoding timedifferences (Eagleman et al., 2005; Buonomano & Karmarkar, 2002). In the latter model, the dynamic state of the networks could per se, encode durations, as seen above (Buonomano & Merzenich, 1995). One of the building blocks of this temporal code might be short-term synaptic plasticity, which could instruct circuits with their recent history of activity, keeping track of what happened on the network a few hundred milliseconds ago.

The centralized and diffuse models can, in turn, be subdivided into two classes: in one of them, the same group of neurons encodes time irrespective of the sensory modality. In the second class, the group of neurons that sets the pace, change depending on the type of sensory input (visual cues, tones, touch stimuli, etc.).

Psychophysics can help us discriminate between these scenarios. This discipline quantitatively addresses the complex relations between incoming physical stimuli and our responses to them. In time perception experiments, the participant is confronted with two stimuli (a tone for instance) separated by a variable interval of time. Paired-stimuli are randomized, and the subject has to indicate whether the longer segment was the first one or the second one (Fig. 3).

Figure 3.  An experimental paradigm in psychophysics. Two tones flank time intervals of varying duration; the participant is asked to tell which stimulus presentation was longer. Taken from Buonomano & Karmarkar, 2002.

If there is a centralized time-sensing area in the brain, individuals that are good at discriminating visual cues might be equally good at discriminating sound stimuli. The psychophysical data so far show that for some tasks there seems to be a central time-sensing mechanism. This clock is tuned to particular time intervals and can be generalized to different modalities, as long as the tested duration remains the same (Buonomano & Karmarkar, 2002). According to some authors, there could be labeled lines, where groups of neurons would be tuned to specific intervals. If this is true, then it would be possible to selectively abolish timing for an interval of time while leaving others untouched, but this idea awaits experimental backup. It is also not clear how these experiments can dissect between a pacemaker and a timekeeper for millisecond durations. For stimuli lasting seconds to minutes, pharmacological manipulations could discriminate between the clock stage and memory storage, based on their sensitivity to dopamine and acetylcholine, respectively (see Buhusi & Meck, 2005).

Neural basis of time perception

The cerebellum works as an internal clock operating in the millisecond range, particularly in motor processing tasks like the eyeblink conditioning. In this protocol, the training of an animal includes paired presentations of a tone and an air-puff delivered to the eye. Trained animals learn to blink their eyes in response to the sound cue alone. Interestingly, they do so after a particular interval of time that matches the gap between tone and puff presentation during training sessions. Lesions in the cerebellum abolish the timing of the response (Buonomano & Karmarkar, 2002).

Time distortion by causality

Our internal register of time can be expanded or compressed depending on factors such as causality and sensory feedback. Haggard and collaborators showed how voluntary actions contract the perceived duration of time between two stimuli, as a mechanism of conscious binding of actions and their effects. Involuntary actions, on the contrary, perceptually expanded the time interval between stimuli, indicating a prominent role of agency in the internal representation of temporal information (Haggard et al., 2002).

As a baseline assessment, subjects had to watch the clock and judge the onset of four different stimuli, which were initially presented all alone. In the voluntary condition, they had to press a key at a time of their choice. In the involuntary condition, trans-cranial magnetic stimulation (TMS) was used to induce a muscle twitch by stimulation of the motor cortex. There was a sham TMS condition, in which they had to indicate the timing of a click produced by TMS, with no muscle twitch following afterward. Finally, in the auditory condition, they had to signal the occurrence of a tone (Fig. 4).

Figure 4. The pattern of perceptual shifts is the evidence of a binding effect mediated by voluntary movement, as opposed to involuntary actions. Negative perceptual shifts (in ms) indicate that an event is perceived earlier in an operant environment compared to its presentation alone in the baseline condition. Binding of the first event toward the subsequent tone is shown as an anticipatory perception of the tone and delayed perception of the key press. Taken from Haggard et al., 2002.

In the operant condition, voluntary action, sham TMS, and the TMS click were followed 250 ms later by the sound. Interestingly, perceptual shifts between single event presentations (baseline test) and their operant context, indicated a strong attraction for voluntary actions and the tone. The involuntary action (muscle twitch triggered by TMS stimulation, without the intention of the subject) and its subsequent sound showed the opposite behavior. In other words, conscious, intentional aspects of motor control perceptually anticipated the perceived occurrence of the tone and delayed the key press action.

 

Did you know this?

Source: YouTube

 

References

Buhusi C V & Meck W H. What makes us tick? Functional and neuronal mechanisms of interval timing. Nature Reviews in Neuroscience, vol. 6, pp. 755-765 (2005). doi:10.1038/nrn1764

Haggard P, Clark S & Kalogeras J. Voluntary action and conscious awareness. Nature Neuroscience, vol. 5, nr. 4, pp. 382-385 (2002). doi: 10.1038/nn827

Sjöström J, Rancz E, Roth A & Häusser M. Dendritic excitability and synaptic plasticity. Physiological Reviews, vol. 88, pp. 769-840 (2008). doi:10.1152/physrev.00016.2007.

Buonomano D V & Karmarkar U R. How do we tell time? Neuroscientist, vol. 8, nr. 1, pp. 42-51 (2002).

Jacobs N S, Allen T A, Nguyen N & Fortin N J. Critical role of the hippocampus in memory for elapsed time. The Journal of Neuroscience, vol. 33, nr. 34, pp. 13888-13893 (2013). doi:10.1523/JNEUROSCI.1733-13.2013

Eagleman D M, Tse P U, Buonomano D, Janssen P, Nobre A C & Holcombe A O. Time and the brain: How subjective time relates to neural time. The Journal of Neuroscience, vol. 25, nr. 45, pp. 10369-10371 (2005). doi:10.1523/JNEUROSCI.3487-05.2005

Buonomano D V & Merzenich M M. Temporal information transformed into a spatial code by a neural network with realistic properties. Science, vol. 267, pp. 1028-1030 (1995). doi: 10.1126/science.7863330

 

Featured Video source: Youtube

About the Author: My name is Gaston Sendin, and I am a neurobiologist who is passionate about science communication and the history of art. The sensory systems are particularly attractive to me, because they can be exquisitely tuned to specific features of our world. I have so far used electrophysiological and optical methods to study sensory processing in the zebrafish and in mice, focusing on vision and hearing.

After finishing my studies in Biology at the University of Buenos Aires (Argentina), I went on to pursue a Ph.D. in Neuroscience at the International Max-Planck Research School & the University of Göttingen (Germany). Doing research in sensory neurobiology, I was a post-doctoral fellow at the MRC-Laboratory of Molecular Biology in Cambridge (UK), the Department of Artificial Intelligence at the University of Groningen (Netherlands) and the Inserm-Institute for Neuroscience of Montpellier (France).

Curiously Robert

in Face à Face/SciWorld/Theory of Creativity by

“A great storyteller dances up the ladder of understanding, from information to knowledge to wisdom. Through symbol, metaphor, and association, the storyteller helps us interpret information, integrate it with our existing knowledge, and transmute that into wisdom”, said Maria Papova. Going by that, it is only fair to say that Robert Krulwich is a good storyteller -one curious soul who learns and talks and writes about the wonders of science.

Starting his career as a journalist to cover politics and economics, he had his first brush with science while covering the story of identifying Huntington’s Chorea disease. It was then he met Milton Wexler, a psychoanalyst popular among Hollywood stars, who wanted to understand if his daughter and wife suffer from the same disease. It was in his pursuit that he invited young science stalwarts for parties in Los Angeles, among his usual Hollywood clients. Amidst those fun-filled activities in the unusual teaming of scientists and movie actors in LA, they went on to find the first ever genetic marker for Huntington’s Chorea back in 1983 when there was no PCR or fancy sequencing machines. Covering this story had Robert thinking that, unlike finance analysts and politicians (who he had reported about regularly until then), scientists were having the time of their lives being ‘curiously alive and busy.’  The excitement of learning the unknown was so contagious that Robert decided to be the ‘reporter of very little things’ for ABC News, so he could cover bacteria, genes, atoms and other little things which cannot be seen with the naked eyes. While his boss was not too keen on the whole idea, he did manage to do it. The desire to explore and learn about this completely different world had got into him. While he did not train in science (he studied law), he has learned science as a part of his job.

With his new found passion, he did a television show on string theory – something that he admits might have been the most difficult thing to show on television. His show went on after an hour long show that had cocktail waitresses and extra terrestrials (E.T.) having sex. And to his joy, he could keep the audience (3.5 million people) glued to the television screen, listening to him talking about a ‘squiggly wave’ that some scientists believed to be the fundamental particle of the universe. His boss was surprised that the audience that enjoyed the show about cocktail waitresses and E.T. would watch a show about Physics.  He believes that people can have seemingly contradictory ideas in a span of two hours. And that people will listen, if you have a good story to tell.

He makes stories that are ‘beautiful’.  While beauty is a subjective meditation, a musician knows she got it right when she listens to the notes. Likewise, he ‘just knows’ when he achieves the right balance and knows when a story will hook you and stay in your mind long after it has been told. He calls it ‘renting the brain space’.  This is what Robert and Jad Abumrad do at Radiolab. He and Jad use a system to arrive at a delicate balance of ‘beauty’ which is a combination of fun, learning, and the simplicity of storytelling. The method involves what Robert calls, ‘smarty and dummy edits.’ After working on a piece, researching it, writing, and recording; he turns to replaying it. During this exercise, one part of him knows the story and one does not. While one questions the choice of words, the other thinks about whether concept is understandable as a whole. After that, the story goes to someone who is an expert on the subject to make sure that the content is scientifically correct. Then the story is conveyed to a lay person who does not know about the subject, to specifically identify the parts that are not clear. Speaking of a lack of formal science training, he conceded that not understanding science could be a disadvantage, “because of all the things that you don’t know, you don’t know.”  The advantage, he thinks, is that he is closer to the audience, who is as naïve as him. It is through this process of multiple edits and re-edits, filtering the script multiple times by both the informed and uninformed that a right balance (the beauty?) is arrived. This process of learning brings surprises, wonder and joy for him and those elements are then successfully conveyed to the audience. From his experience at Radiolab, he knows if you describe something joyously, ‘it is hard to resist’.

Jad and Robert, hosts of Radiolab. (Photo Courtesy: WNYC)

He mentioned that it is easy to appeal to basic curiosity. He shared the experience of talking to the slightly disagreeable bunch of politicians in Virginia who believed that science is a conspiracy against their God. He questioned them how the cloud stays in the air, or why is the sky blue. How the big white puffy cloud that is so huge- so moist- and hence so heavy, staying up in the air with nothing holding it beneath. And then he prompted them to use their God-given mind to answer the puzzle. He observed, if you ask a question, people always want to know the answer.

Sun and clouds. Drawing by Robert Krulwich.

He pointed out that much of the hostility to science comes from the fact that science language is inaccessible to the masses. People assume that they are not going to be able to understand it; they feel left out of the conversation and, hence, threatened by science. He revealed his tricks for sharing science with people who are suspicious of science. He mentioned that simple visualizations of science are particularly useful in these kinds of scenarios since not everyone can read scientific data. Like to an anti-vaxxer, you would present the data may be like this:

A representational graph that depicts the drop in disease prevalence after introduction of vaccine at Year 3

And then, adopt the other person’s view, conspire with them. Ask them why they think the government or the doctors would want to make so many people sick. And often such people are not able to come up with good arguments and then you can gently show the data again while generating doubts about their arguments. This, in his experience, opens up people’s minds to the idea of science, and educates them about the rational underpinnings of how nature works.

I wondered if religion could be the reason of hostility towards science, as religion and science are often perceived as exclusive of each other. Carl Sagan wrote in ‘The demon-haunted world, “the very act of understanding is a celebration of joining, merging even if on a very modest scale, with the magnificence of the cosmos…. Science is not only compatible with spirituality; it is a profound source of spirituality.” I asked Robert’s opinion about these two seemingly contrasting ideas. He made a poignant observation, pointing out that faith is about seeking a closer relationship with the universe and seeking ‘enlightenment’. While faith and religion give you the feeling that you know certain things about the universe, science gives you a sense of being stupid. A scientist is often excited while standing next to a mystery, trying to understand it, devising tests of the universe, discovering some of the answers, which in turn opens up more questions. Hence, the practice of science, while trying to understand the universe, always keeps one feeling stupid and sometimes even wrong in light of the newly revealed data. Scientists are, he noted, like excited people watching the climax of a cricket match when it’s still not clear who will win. Religion is more about seeking peace and comfort and staying away from trouble. While they are different, he says, it is possible to practice the two together.

Creature in the woods. Drawing by Robert Krulwich.

He opines that by provoking fundamental curiosity of the human mind, one can get people interested in science, irrespective of religious affiliations. He asserted that his job is not to convince anyone of anything. This is reminiscent of what Isaac Asimov said once, “Now, they may say that I believe evolution is true and I want everyone to believe that evolution is true. But I don’t want everyone to believe that evolution is true; I want them to study what we say about evolution and to decide for themselves.” This is exactly what Radiolab does!

During the discussion on hostility towards science, he also mentioned that science fiction, poetry, and literature prepare humans for newer ways of appreciating science. It is kind of interesting, he pointed out, that time travel is not mentioned in any ancient text in eastern or western culture, but H.G. Wells and his peers thought of it way back in 1850’s all of a sudden. They not only took us to the future but also got us back from the future.  Fast forward 150 years and now a seven-year-old dreams of traveling back in time and meeting dinosaurs. Time travel, now a part of human imagination, was not the case a few centuries ago! It (Science fiction) often operates within the confines of known boundaries of science, and trespasses from there to explore new ideas. The contribution of science fiction to the progress of science is celebrated well.  It is known that space travel, the internet, online learning, wasting time on the web (yes, I know you are reading this online) were predicted much before they happened by the likes of H.G. Wells, Jules Verne, Arthur C Clarke and Issac Asimov. Isaac Asimov said, “Science fiction is important because it fights the natural notion that there’s something permanent about things the way they are right now.”  Such literary artwork allows science to remain in public imagination. And Robert has clearly done his part by bringing science to everyone via his art of storytelling.

A portrait of Robert by the author

During my discussion with Robert, I could observe in action what Maria Papova said about storytelling. Through his experiences of storytelling, his observations have transcended knowledge and into wisdom. Stephen Hawking wondered, “Why does the universe go to all the bother of existing?” As thinkers, let us take an infinitely small step closer to the answer, perhaps the ultimate wisdom.

Cover image: Curiosity. Drawing by Robert Krulwich.

About the Author

Ipsa Jain is a Ph.D. student at IISc. She wants to gather and spread interestingness. She prefers painting and drawing over writing. She posts on Facebook and Instagram as Ipsawonders.

Dr. Ananda Ghosh, Dr. Somdatta Karak and Anand Varma edited the article.

Coomassie Blues- A Colonial Legacy(?) in Molecular Biology

in SciWorld by

Editor’s note: Ask any biochemist and they will tell you about the joy of seeing a single blue band after painstaking hours/days of protein purification. After all, the one sermon from Kornberg that every biochemist will take to their graves is to “Never waste pure thoughts on an impure protein”. Yes we have been through those blues of seeing more blue bands in a gel than expected. But, did you know the stain that we use to paint our gels and lab coats was named before it was synthesized? Either ways, take a trip down the memory lane and know more about Coomassie sans the Blues in #ClubSciWri’s latest post from Anirban Mitra. –Abhinav Dey

 

By the late 19th century, the British Empire was the largest political entity in human history. Queen Victoria’s government ruled over 1/4th of the planet’s land mass and 1/4th of its population. However, one region that was still unconquered was Western and Southern Africa.

The wars that the British launched to subdue the Zulu tribes of South Africa are well-known (thanks to several dramatic movies from Hollywood). But the African monarchy that arguably gave the British their toughest competition was the ASHANTI.

At its height, the Ashanti Kingdom covered a significant part of Western Africa, in the region that is today’s Ghana and neighboring lands. Their expanse had been built largely by a successful military which had come up, independent of ‘civilized’ Europe, along with several modern innovations including improved tactics for jungle warfare and even a medical corps. It is, thus, no surprise that 4 wars had to be fought before the British subdued them totally. Finally in 1896, the 4th Anglo-Ashanti war ended Ashanti dominance. Newspapers across the world reported that the British army had finally captured the Ashanti capital of Coomassie .

Few months later, Levinstein Ltd, a British dye-manufacturing company, introduced a new acid wool dye to the markets of Europe. And, as a marketing strategy, they used the name of a recently-conquered city for their new product. It was kind-of natural. Thanks to the colonial victory, Coomassie had become a well-known name.

Thus, was born the name ‘Coomassie Brilliant Blue’.

Decades later, as the modern discipline of ‘molecular biology’ kicked off in the far-away universities of Europe and the USA, 2 Australian scientists found the same dye could be very reliably used to tag a variety of protein molecules. They published their findings in the well-known journal Biochemica Biophysica Acta.

Today Coomassie staining of proteins after electrophoresis is one of the routine techniques for any biochemical laboratory. It’d not be an exaggeration to say that almost everyone uses it everyday. Of course, the dye’s oblique connection with the subjugation of Africa is all but forgotten. And, the city is now known by its non-anglicized name – Kumasi.
Something like ‘Calcutta’ and ‘Kolkata’ 😉

 

Infographic by: Abhinav Dey

 

Meanwhile, at a bench near you

Comic Source

About the Featured Image from Ipsa jain: The image shows the daily life of person from Kumasi on one side. The right side depicts how a dye for wool yarn is used to stain proteins (secondary structures come from wool ball, then unwound for electrophoresis of proteins). The right hand corner shows the shapes of three places where this story took place, Kumasi (Now in Ghana), Britain and Australia. The two seemingly disconnected stories on left and right are connected by the story of origin of the name for Coomassie blue dye.

 

 

Author Profile:

for sciwri

Anirban Mitra, Ph.D.

Anirban Mitra did his PhD from the Department of Microbiology and Cell Biology, Indian Institute of Science (IISc), Bengaluru and is now a teacher of biology, based in Kolkata. His interests range from biological evolution to history of science and facets of India’s past.

Blog Design: Abhinav Dey

Creative Commons License
This work by ClubSciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 

The time of philosophers

in SciWorld by

Editor’s Note: With our cameras, we ‘try’ to capture time, well preserved in our sequential snapshots on a daily basis. But have you ever wondered how our consciousness perceives the sense of time and the temporal sequences? Is it a mere birth of our illusionist memories enabling us to differentiate the past, present and thereafter the future? Or maybe time is real and not a product of our mind- well quantified and qualified in the metric sense.

If these questions ever flooded your mind while wrapping up your To Do List, you are at the right place. Do not miss the Sunday Blog at ClubSciWri where Gaston revisits the controversies on the physical nature of time and sheds light on what neuroscientists/philosophers have to say on the enigma of time. – Rituparna Chakrabarti


In the novel A l’ombre des jeunes filles en fleurs (Within a budding grove), written by Marcel Proust in 1919, Madame Swann says: ¨The soldier is convinced that a certain interval of time, capable of being indefinitely prolonged, will be allowed him before the bullet finds him, the thief before he is taken, men in general before they have to die.¨ Such a high hope also pervades Jorge Luis Borges’ tale El Milagro secreto (The secret miracle), included in the collection Ficciones (Fictions).

Jorge Luis Borges

In this narration, we learn that a writer is going to be executed at 9 am. As he stands in front of the firing squad, thanks to an unexpected intercession, his death is momentarily suspended. First surprised, then grateful, he realizes that the world around him came to a timely pause. The bullets froze halfway during their trip, and the curls of smoke from his last cigar have not yet dissipated. In his mind, however, that fraction of an instant will take a full year. Enough time to revise his entire literary output. Immobile, fixed like a pinned butterfly, he goes through Virgil’s poems. He takes the opportunity to mentally finish a sluggish play that had been waiting for a proper end, but just when he found it, he was fatally shot. It was 9.02 am. Two precious minutes were magnanimously granted, not a second more.

Borges argued that time could not have possibly stopped because the writer’s thoughts were still flowing: in short, it is our mind that dictates the tempo. Inasmuch as we are consciously aware of ourselves and what surrounds us, time persists. But what time was he talking about? The internal time of the unfinished play, the writer’s life, the external time of the firing squad and the story itself all converge on a multiple epilogue, leaving us to the idea that Death correctly realigns all timelines, closing all books in synchrony. This tale points to a singularity: an apparent divorce might exist between the metric sense of time and its tensed counterpart.

Proust’s novel inaugurated a new direction in storytelling, featuring a low-pace parade of subjective states, where we often find vignettes, psychological studies of characters and reminiscences. These two examples help to illustrate an intriguing idea: do we use our consciousness to sense time? We appear to perceive events unfurling over that canvas which is our conscious experience. Interestingly, we also grasp their temporal sequence. In this essay and its follow-up, we will succinctly revisit two significant controversies on the nature of time and learn what neuroscientists and philosophers have to say on this elusive subject.

La plage de Cabourg (The beach at Cabourg), painted by René Xavier François Prinet (1910).
Most of Within a budding grove takes place on a seaside resort called Balbec, probably inspired by
Cabourg. © RMN (Musée d’Orsay)/ Hervé Lewandowski.

Time recaptured

One of the first attributes that come to mind when we talk about time is the duration of events. In the Vth century, Saint Augustine reasoned that whatever is measured and computed as duration cannot be in the past, because whatever happened, ceased to be and therefore cannot be perceived any longer, nor it can be in the present since the present lacks any duration. To solve this insurmountable problem he invoked memory as the necessary bridge between the two.

In The experience and perception of time (Le Poidevin, 2015) we learn that E.R. Clay and William James coined the term “specious moment”. This interval of time goes from a few seconds to about a minute, and represents a duration of time that is perceived both as present and as temporally extended. However, the concept of presentness is more complicated than it may appear: we can perceive something that is happening right now, but we can also momentarily hold something in our short-term memory and still recognize it as belonging to the past. But then what is pastness, if such a word exists? Pastness could also be encoded in our memory because it is our memory that forms past-tensed beliefs. According to this view, by merely having a memory of something, we could know that that something already happened, lying further away from our “specious moment.” This approach to characterize past events is troublesome because we can also have false memories: we can recall events that never occurred.

Der Entdecker (The discoverer), painted by Siegfried Zademack (2012).

The “specious moment” could, therefore, define a sliding window over which we integrate what goes on in our conscious experience. The contents of this time interval could be safely labeled as our present experience at any given moment and then moved for storage to vacate space for new incoming experiences. Failure in updating this register could probably compromise our common functioning mode. Many authors believed in the “strength of the memory trace” as a way of explaining how the past is engraved: the older the event, the stronger its persistence. But again, here we encounter a problem because recent events can fade more quickly than older ones.

How do we establish a time order of events? In his article, Le Poidevin discusses two alternative explanations. According to D.H. Mellor, the time at which we formed experiences specifies the temporal order of events, following a protocol that would be insensitive to the contents of those memories. Daniel Dennett’s view is exactly the opposite: the brain might establish the right causal order of events, taking account of the content of the experiences and inferring the correct temporal order.

Newton, Leibniz, and Kant

In the early XVIIIth century Isaac Newton and Gottfried Leibniz held a controversy over the fatherhood of infinitesimal calculus. But this was not the only point of divergence: the nature of time would prove to be another intellectual battlefield. In his article Kant’s views on space and time (Janiak, 2016), Andrew Janiak digests Kant’s contributions under the light of the XVIIth century metaphysics and the Newton-Leibniz debate. In this context, if time was real and not a product of our mind, then it had to be a substance in its right or a property of a substance.

Newton believed that time was an actual entity that could be objectively measured, a substance that could persist on its own. Leibniz, on the contrary, thought that time was inherent to objects and emanated from their relations.According to Leibniz, time does not exist independently of objects and is merely a property of them. What was Kant’s take on these two conflicting views? He rejected the absolutist transcendental realism supported by Newton, arguing that time is not a substance because it is causally inert and inaccessible (it cannot be affected by interactions with things) and also imperceptible. He also attacked Leibniz’s version of transcendental realism, claiming that time does not depend on substances for its existence.

Top view: Leibniz’s manuscript sketching the first calculating machine. Bottom: Leibniz’s calculating machine from 1694.

To escape from this gridlock, Kant introduced a groundbreaking concept: time is an a priori intuition. In Kant’s terminology, intuition is an objective, singular and immediate conscious representation that becomes apprehensible right away. For instance, I have a direct conscious intuition of “my laptop” right in front of me, e.g. I can represent it without invoking any accessory bit of information. A concept, however, is something different. Concepts are also objective but general and mediate. To clarify the representation of “my laptop” as a concept, I would need to refer to other concepts like “computing portable device”, “battery operated”, “operator of symbols”, etc. Now for Kant, time is not something objective and real, neither a substance nor the property of a substance; instead it is something ideal, a product of our mind.But is it a concept? He argues that it cannot be a concept because we cannot grasp it by making reference to other concepts that define it; in short, we cannot place it within other classes. Time pertains to a class of its own.

After discussing concepts and intuitions as different types of objective conscious representations, Kant went one step further and reflected on how we get to those representations. He distinguished between an a priori way of representing things, which does not require previous experience, and an empirical way. He concluded that time is an a priori intuition because it is an innate product of our mind and we can represent it without any prior experience of it. This idea was the stepping stone to the development of his philosophical system, known as transcendental idealism.

Einstein and Bergson: Relative time vs. absolute time

In her book The physicist and the philosopher (Canales, 2015), Jimena Canales offers a gripping account of the famous debate on the nature of time held in 1922 between Henri Bergson and Albert Einstein at the Societé Française de Philosophie in Paris. This clash and its ramifications sent ripples through the international community of physicists and philosophers and ultimately led to their alignment on either side of an intellectual rift that would oppose two fundamentally different views on this subject. Canales makes the point that this controversy, that ended with the setback of Bergson’s influence, ushered in a period of expansion of science as a dominant framework to understand our world.

For Bergson, time included aspects that we cannot entirely capture by a materialistic approach such as the one preconized by science. He wanted to overcome Descartes’ mechanical view of the universe and claimed that our subjective experience of time is a necessary part of its study. The mystery of time, which was the fabric of the universe and our lives, transcended any attempt to quantify it; arid science, with its emphasis on clocks and measuring devices, could only grasp it partially. He believed that time was absolute, making itself evident through the constant change of the universe, like an unstoppable vital impulse (élan vital) that traversed all processes. Bergson was not so much interested in clocks: he wanted to know, first of all, why we are obsessed with time and why we created watches in the first instance.

Albert Einstein on a picnic day. Albert Einstein Archives / Princeton University Press

Einstein was awarded the Nobel Prize in Physics in 1921, but he would only receive the prize one year later and not for relativity. An internal memorandum of the Nobel Institute later revealed that Bergson’s critique had been central to this decision. Although in 1919 Sir Arthur Eddington had provided experimental evidence supporting Einstein’s predictions that light bends in gravitational fields, relativity was far from being widely accepted. Even the people whose work had been seminal for the development of this theory were skeptical about its implications.

Henri Poincaré, for instance, did not believe that it was revolutionary and indeed took sides with Bergson against materialism and mechanistic philosophies. He was a supporter of conventionalism, a current of thought that maintained that scientists choose one theory in particular just because it is convenient.Einstein’s view was exactly the opposite; he believed that theories were meant to be a model of the Universe and not just a suitable formulation. Likewise, Hendrik Lorentz, who developed the relativity equations together with Einstein, believed that there was a difference between time and space and continued to look for an absolute concept of time.

An important consequence of relativity implied that the time-space frame of a moving object slows down and contracts when measured in the observer’s frame. If we would place a clock in a space rocket and another one on Earth, which clock would give the correct time? Einstein would reply both because time depends on the system of reference and is not absolute, as Bergson maintained. Einstein accepted that we could have a psychological understanding of time, (for instance when we are too anxious or bored), but this was not objective, and therefore irrelevant to its study. Einstein accused Bergson of objectifying psychological aspects of time that are purely mental constructs. Bergson, in turn, stated that by considering a time-space continuum and denying an absolute time, Einstein “was grafting a dangerous metaphysics into his science.”

Other efforts tried to reconcile these two opposing views. Heidegger sketched a possible third way that could overcome this duality. He argued that human life does not happen in time, but rather is time itself. Heidegger incorporated the dimension of “everydayness”, where the time measured by clocks, the time of the Universe would be interwoven with the psychological time, the time of our lives.

Perhaps it would be fitting to end this article in the same way that we started it.Bergson’s vitalism and its emphasis on the psychological intuition of time were a significant influence in Marcel Proust’s writing. Indeed both men shared more than philosophical interests: Bergson married Proust’s cousin.

“The time which we have at our disposal every day is elastic; the passions that we feel expand it, those that we inspire contract it; and habit fills up what remains.” (Madame Swann in Within a budding grove).

References

  1. Marcel Proust, A l’ombre des jeunes filles en fleurs, Editions Gallimard, 1954.
  2. Jorge Luis Borges, El milagro secreto (en Ficciones), Emecé, 2004.
  3. Le Poidevin, Robin, “The Experience and Perception of Time”, The Stanford Encyclopedia of Philosophy (Summer 2015 Edition), Edward N. Zalta (ed.), URL = <https://plato.stanford.edu/archives/sum2015/entries/time-experience/>.
  4. Janiak, Andrew, “Kant’s Views on Space and Time”, The Stanford Encyclopedia of Philosophy(Winter 2016 Edition), Edward N. Zalta (ed.), URL = <https://plato.stanford.edu/archives/win2016/entries/kant-spacetime/>.
  5. Jimena Canales. “The Physicist and the Philosopher: Einstein, Bergson and the debate that changed our understanding of time”. Princeton University Press, 2015.

 

Feature image: Pixabay

About the Author: My name is Gaston Sendin, and I am a neurobiologist who is passionate about science communication and the history of art. The sensory systems are particularly attractive to me, because they can be exquisitely tuned to specific features of our world. I have so far used electrophysiological and optical methods to study sensory processing in the zebrafish and in mice, focusing on vision and hearing.

After finishing my studies in Biology at the University of Buenos Aires (Argentina), I went on to pursue a Ph.D. in Neuroscience at the International Max-Planck Research School & the University of Göttingen (Germany). Doing research in sensory neurobiology, I was a post-doctoral fellow at the MRC-Laboratory of Molecular Biology in Cambridge (UK), the Department of Artificial Intelligence at the University of Groningen (Netherlands) and the Inserm-Institute for Neuroscience of Montpellier (France).

Seeing the movement: our visual brain at work

in SciWorld by

Editor’s note: When on Facebook, whether you choose to ignore your frenemy’s vacation pics or hit ‘like’, your brain is consistently driving under influence of visual stimuli. Life never lets your brain take a moment of pause from decision making. If you ever wondered how your brain is wired to decide, you cannot miss the Sunday Blog from #ClubSciWri. Gaston traces the history of neurological research in perception and decision-making.  We might soon be headed towards an AI-based world, but it is undeniable that in the race to replace, human intelligence will always be the yardstick and the checkered flag.- Abhinav Dey

 

Having discussed the ways in which painters tackled the problem of representing motion in art, we can, therefore, ask ourselves the following question: how is this type of information processed in our brain? On a different occasion, we will describe the stream of visual information from the retina via the lateral geniculate nucleus (LGN) to the posterior pole of the occipital lobe, which contains the primary visual cortex (V1).

From V1, information flows along two channels: a ventral pathway extending towards the temporal lobe and a more dorsal pathway, that projects towards the parietal lobe (see figure below). The ventral stream of information is mainly concerned with establishing identities and building categories of visual objects. Running in an anterior direction from the occipital lobe, neurons lying along this pathway are selectively activated by increasingly more complex visual stimuli. Disruption of this network leads to a deficit in object recognition, called agnosia.


Neurons with complex response profiles in the inferotemporal lobe are capable of responding not only to different pictures of a person (celebrities like Scarlett Johansson and unfortunately, your mother in law as well) but also to that person’s written or spoken name. This feature suggests an ability to encode concepts beyond the boundaries of sensory modalities. But this will be the subject of another entry in the blog.

Motion perception in blindness?

Here we will focus on the dorsal pathway which contains the middle temporal region (MT) also called V5. The discovery of this area is an attractive story in itself. One century ago, WW1 was ravaging Europe, and severely injured military personnel flooded hospitals like the Empire Hospital for Officers, where the first character of our story was working as a promising neurologist. In 1917 George Riddoch performed a series of visual tests on soldiers that suffered from shell shock wounds affecting the occipital pole. Below I show the visual fields of Lieut. Col. T.

His right occipital pole was damaged, resulting in left hemianopsia (blindness of a half-field of view). Interestingly, he would perceive moving objects lying on his left-field but not stationary ones. He would typically miss pieces of meat on the left side of his plate, but he could detect moving objects on that side, although he reported blurry shapes and grayish colors. Riddoch quickly realized that there was a complete dissociation of both visual attributes: objects presented in the blind hemifield were invisible when kept stationary but were soon detectable when they moved. These results suggested the existence of separate pathways dealing with static and kinetic visual information.

V5 & The rise of the modular visual brain

Another piece of the puzzle was added in 1969 when Semir Zeki identified a prominent tract of thick fibers connecting V1 with a clear zone in the temporal lobe, a region he called V5. Were the neurons in this area responsible for detecting motion?

In 1974, Zeki recorded in monkeys the electrical activity of these neurons in response to presentations of visual stimuli on a screen. Below I show a representative experiment.

The visual stimulus is on the left, which in this case was a bar that moved in two directions, as indicated by the arrows. The dashed line square shows the borders of the receptive field for that particular neuron. The receptive field of a visual neuron is the area of the visual field in which a presentation of a visual stimulus evokes an electrical response from that neuron. The right panel shows the action potentials (stereotyped all or none electrical signals) fired by the neuron as a readout of its electrical activity during the processing of visual information. All cells within V5 were motion sensitive, and interestingly, a subset of them was directionally selective.

This discovery served as the basis for a modular theory of how the visual brain works in primates, arguing that functionally specialized regions handle specific attributes of a visual scene. Several lines of evidence indicate that color, shape, and motion are processed in parallel by separate areas of our brain, populated by neurons that are selectively excited by those features and following a ¨division of the labour¨ scheme. However, since we normally have a unique and integrated perceptual impression of the world that surrounds us, how does the brain succeed in merging back the scattered information bits to yield a coherent view? We do not have a definitive answer to that yet, but we will sketch it in a different article on this blog.

Neuronal correlates of decision-making

Another interesting question is the following: what is the relation between perceptual judgment and the electrical activity of neurons? When sitting a behavioral test in which we are asked to discriminate between two visual stimuli by their features, is the activity of one or a few neurons driving the perceptual decision? Is this decision based on any complex function of the firing rate of one or a few neurons? Or is it rather a pooled signal coming from a larger circuit, what counts here?

In 1989, Bill Newsome addressed this question by doing an elegant experiment. Monkeys were trained to report the direction of motion of a random dot display (basically a cloud of points moving stochastically in all directions of the screen), in which some dots moved coherently while the rest did it in a haphazard fashion. They changed the strength of the signal by varying the percentage of coherent dots: the higher the percentage of coherence, the more obvious was the general direction of the movement emerging from the pattern of dots. At the same time they recorded the activity of single neurons in area MT (V5). For any given neuron, they placed the dots cloud in the receptive field and adjusted the motion direction to match the neuron’s preference.

They alternated tests in which they presented the optimal stimulus and a ¨null¨ one (an 180°-rotated version of the best stimulus, which evokes no response from that neuron). At the end of each trial, the monkey had to indicate his judgment and report whether the stimulus corresponded to the ¨null¨ or preferred direction. The authors computed a psychometric function from the animal’s behavioral responses and a neurometric function that characterized the neuron’s sensitivity to the motion’s signal. The results are shown below for the neuron’s electrical activity (full black circles) and the psychophysical values (white circles), recorded simultaneously for each trial.

First, we observe that already at 12% of coherence (meaning that 12% of points move in one direction, 88% are stochastic) both curves saturate: the monkey gets it right 100% of the time. On the Y-axis, the curves start at a correctness value of 0.5 because the performance would be 50% correct by chance.

The result is surprising: both curves are similar, but the neuronal data lies to the left of the behavioral data, meaning that the neurons were somewhat more sensitive than the monkey. In other words, had the monkey strictly used his MT neurons as predictors to guide his choice, he would have probably outperformed himself. These results show that we can construct quite an accurate description of the monkey’s performance from the signals of a small number of neurons whose selectivities match the demands of the perceptual task.

A new route?

And now, to finish this article we go back to Riddoch because we still need to complete the puzzle! As I said before, his patients reported the perception of movement in the blind field of view. Loss of V1 due to gunshot wounds affecting the occipital pole has a devastating effect on eyesight, because it cuts off retinal inputs (sent to V1 via the lateral geniculate nucleus), to cortical visual areas that process particular features of a stimulus, like V5 (MT).

But then, if they were blind, how could they possibly detect movement? In 2004, Sincich and coworkers provided a possible explanation. Using retrograde tracers, they revealed the existence of a direct anatomical connection between the lateral geniculate nucleus (LGN), which receives input from the retina, and motion-sensitive area MT. The funny part is that this tract bypasses V1, and therefore Riddoch’s patients might have still preserved some residual perception-notably for moving stimuli- despite having suffered substantial damages to V1.

This example illustrates the modular organization of the visual brain, with functionally specialized areas that treat specific attributes of a visual scene. When one of them does not do the job, our brain puts together the pieces…but the puzzle remains incomplete.

References

  1. From Neuron to Brain. Nicholls, JG; Martin AR; Fuchs PA; Brown DA; Diamond ME & Weisblat DA. , pp. 476-496, 5th Edition, Sinauer Press (2012).
  2. Functional organization of a visual area in the posterior bank of the superior temporal sulcus of the rhesus monkey. Zeki S. The Journal of Physiology, 236, pp. 549-573 (1974).
  3. Dissociation of visual perceptions due to occipital injuries, with especial reference to the appreciation of movement. Riddoch G. Brain 40, 15–57 (1917).
  4. Neuronal correlates of a perceptual decision. Newsome WT; Britten KH & Movshon JA. Nature 341, 52–54. (1989).
  5. Bypassing V1: a direct geniculate input to area MT. Sincich LC; Park KF; Wohlgemuth MJ & Horton JC. Nature Neuroscience 7, pp. 1123-1128 (2004).

 

This blog was originally published here by Gaston Sendin.

Featured image source: Pixabay

About the Author: My name is Gaston Sendin, and I am a neurobiologist who is passionate about science communication and the history of art. The sensory systems are particularly attractive to me, because they can be exquisitely tuned to specific features of our world. I have so far used electrophysiological and optical methods to study sensory processing in the zebrafish and in mice, focusing on vision and hearing.

After finishing my studies in Biology at the University of Buenos Aires (Argentina), I went on to pursue a Ph.D. in Neuroscience at the International Max-Planck Research School & the University of Göttingen (Germany). Doing research in sensory neurobiology, I was a post-doctoral fellow at the MRC-Laboratory of Molecular Biology in Cambridge (UK), the Department of Artificial Intelligence at the University of Groningen (Netherlands) and the Inserm-Institute for Neuroscience of Montpellier (France).

Motion seen through a painter’s palette

in SciWorld by

Editor’s note: The science of motion continues to fascinate us. For Kepler it was the planetary, for Ansel Adams it was the optical, and for Heisenberg it remained uncertain. But have you ever wondered how captivating it was for the pioneers of art and sculpture to capture the different forms of motion? In the Sunday Blog from #ClubSciWri, Gaston Sendin walks us through this intriguing journey from static to kinetic art of representing motion.Abhinav Dey

This blog was originally posted by Gaston Sendin (February 17, 2017) on neurokunst.com

The illusion of movement

Motion has always fascinated humanity. In pre-Socratic Greece, Zeno of Elea distrusted its credentials, arguing that “it is impossible to move because what moves must reach the half-way point earlier than the end.” Since the number of half-points between two end-points of a journey is infinite, he concluded that it is impossible to traverse an infinite number of states in a limited time. He was inadvertently sowing the seeds of calculus, which would remain dormant for a while.

At the beginning of XXth century, poets and painters were adamant in proclaiming the virtues of motion and speed. In his Manifesto del Futurismo (1909), Marinetti wrote: Up to now, literature has glorified contemplation, ecstasy and reverie. We want to exalt the aggressive movement, feverish insomnia, the racing step, the deadly jump, the slap and the punch. We declare that the world’s magnificence has been enriched by a new beauty: the beauty of speed1. They defied the current artistic canon and sought a new creative vigor in burgeoning cities with their tingling mixture of urban life traits: multitudes rushing through the streets on their way to the theaters, cars moving in a frenzy and virulent outdoor political meetings. They woke up to a new sensitivity and celebrated the polyphony of modern industrial societies.

The Italian Futurism

In this context, Giacomo Balla painted ¨The hand of the violinist¨. Both hands and musical instrument are far from being portrayed as stationary objects; in fact, quite the opposite is true. Balla’s use of force lines to accentuate the feeling of motion visually disintegrates matter into a finely powdered cloud of vibrating lines, describing an arc that extends from the lower right corner to the upper left one. Reminiscent of the discovery of atoms and sub-atomic particles, which was occurring almost simultaneously, it enthroned a new pulsating life. Suddenly, Zeno’s infinite halfway-points reappear, and this time we can almost grasp them. The original V-shaped framing, unfurling like a fan, further stresses the kinetic energy trapped in this scene.

Giacomo Balla- The hand of the violinist, 1912

The Russian avant-garde

Almost at the same time, in Soviet Russia, Vladimir Tatlin, was infusing the geometric abstraction of Suprematism, with a new vigorous architectural scope. Suprematists regarded the geometric forms in primary colors as intermediate snapshots (Zeno’s halfway points) taken during their evolution against a white background (representing the infinite space in El-Lissitzky’s cosmovision). Tatlin went one step further, reaching a new level of complexity.

He intended to more explicitly represent all those fractional states of movement, at the same time. He aimed at organically embodying time-space (El-Lissitzky’s fourth dimension) in a new entity that defied the painting’s two dimensions. This approach necessarily required new forms of expression that hybridize architecture and sculpture. His vision gained considerable momentum when he was commissioned with the construction of a kinetic tower to commemorate the 3rd International Socialist.

The Monument was supposed to be a third higher than the Eiffel Tower. Tatlin conceived this colossal structure as a shrine for governmental institutions. The iron and glass structure would contain three building blocks which would house the executive, administrative and propaganda offices of the Comintern. They would rotate at different speeds (the first one, a cube, once a year; the second one, a pyramid, once a month; the third one, a cylinder, once a day). This kinetic project, which was born out of an obsession for the transforming power of machines (and therefore, a hopeful and celebratory role for the industry), propelled by the speed of historical changes, was never completed but it opened the eyes of other artists. His interest in movement and machines would eventually lead him to study bird-flight and design gliders.

In a convoluted way, his spiraling lines paid tribute to another artist who was also concerned with faithfully conveying the illusion of motion. In his Assunzione della Vergine (1515-1518, Santa Maria Gloriosa Dei Frari, Venezia), Tiziano confronts us with a scene of dramatic power which would immediately put him at the forefront of the Venetian school. The view represents the heavenly ascension of the Virgin. At the bottom, the disciples extend their arms upwards, directing their gaze to follow the supernatural event and this vertical upheaval is further echoed by the angels that surround the Virgin, who in turn reinforces the general direction of the movement. Bottom-up zigzagging lines organize this turmoil, acting like a whirlwind and drawing the agitated masses of characters to it. The viewer too is compelled to follow them. The kinetic force of this painting is evident from its helical construction and deviates from the serene and dignified template set before by Giovanni Bellini.

Orphic painters and kinetic art

After the Italian futurists and the Russian constructivists like Tatlin, other artists would take over the illusory representation of movement. Already in the 1910s, the Orphic painters (Sonia and Robert Delaunay) would create circular patterns where the illusion of rotation, like blades of a spinning windmill, was based on the interaction of light and color. Delaunay would write: ¨Vision is our highest sense, the one that most intimately communicates with our brain, with consciousness. Our understanding is in correlation with our perception¨ 2

Robert Delaunay, Formes circulaires. Soleil n°2, 1912-1913. Centre Pompidou, Mnam.

However, so far all these different attempts to represent motion in painting were static; they subtly hinted at the movement, but they did not explicitly address it. The breakthrough would come with the work of artists like Alexander Calder, Julio Le Parc, Jesús Soto and Jean Tinguely, among others. As preconized by the Bauhaus school, they would integrate technology and the use of industrial production methods into their work (not surprisingly, one of their mentors was Laszlo Moholy-Nagy, who also combined light and movement into luminokinetic works). Within the so-called kinetic art movement, different approaches lived together. In many of Soto’s works, for instance, the illusion of movement is recreated when the spectator walks around an otherwise static geometric pattern. Tinguely added a good pinch of irony: his purposeless automata, built around unlikely combinations of discarded industrial elements, seem to incarnate the old idea of perpetuum mobile while satirizing the teleology behind modern means of production, questioning their role in modern societies.

Jean Tinguely, Gismo, 1960, coll. Stedelijk Museum Amsterdam. Foto Gert Jan van Rooij.

QUOTES

1 La letteratura esaltò fino ad oggi l’immobilità pensosa, l’estasi ed il sonno. Noi vogliamo esaltare il movimento aggressivo, l’insonnia febbrile, il passo di corsa, il salto mortale, lo schiaffo ed il pugno. Noi affermiamo che la magnificenza del mondo si è arricchita di una bellezza nuova; la bellezza della velocità. From Le Figaro, February 20th, 1909.

Translation: “The exalted literature up to now thoughtful immobility, ecstasy and sleep. We intend to exalt aggressive action, a feverish insomnia, the running pace, the mortal leap, the punch and the slap. We affirm that the world’s magnificence has been enriched by a new beauty; the beauty of speed.”

 2 L’œil est notre sens le plus élevé, celui qui communique le plus étroitement avec notre cerveau, la conscience. […] Notre compréhension est corrélative de notre perception. Robert Delaunay. De l’impressionnisme à l’abstraction, 1906-1914, éditions du Centre Pompidou, 1999, p.167.

Translation: “The eye is our highest meaning, the one that communicates most closely with our brain, consciousness. […] Our understanding is correlative of our perception. Robert Delaunay. From Impressionism to Abstraction, 1906-1914, editions of the Center Pompidou, 1999, p.167.”

References

https://plato.stanford.edu/entries/paradox-zeno/

https://monoskop.org/Monoskop

Peter Humfrey, ¨La Peinture de la Renaissance à Venise¨, Societé nouvelle Adam Biro, Paris, 1996.

Semir Zeki, ¨Visión interior¨, Antonio Machado Libros, Madrid, 2005.

About the Author: My name is Gaston Sendin, and I am a neurobiologist who is passionate about science communication and the history of art. The sensory systems are particularly attractive to me, because they can be exquisitely tuned to specific features of our world. I have so far used electrophysiological and optical methods to study sensory processing in the zebrafish and in mice, focusing on vision and hearing.

After finishing my studies in Biology at the University of Buenos Aires (Argentina), I went on to pursue a Ph.D. in Neuroscience at the International Max-Planck Research School & the University of Göttingen (Germany). Doing research in sensory neurobiology, I was a post-doctoral fellow at the MRC-Laboratory of Molecular Biology in Cambridge (UK), the Department of Artificial Intelligence at the University of Groningen (Netherlands) and the Inserm-Institute for Neuroscience of Montpellier (France).

Featured Image source: Pixabay

Light Music for the Masses: A Story of LEDs

in SciWorld by

This blog was originally posted by Gaston Sendin (January 28, 2017) on neurokunst.com

Optics: fast and furious imaging

With optics coming of age and its widespread use in biomedical sciences, scientists invest substantial efforts in new imaging technologies. The aim is to reconcile versatility, performance and cost issues. Developments take place in the design of new molecules with expanded capabilities (e.g., increased resistance to photodamage, exquisite sensitivity to excitation frequency, chemical stability). But they also pursue the engineering of more flexible sensors and stimulators with improved performance (e.g. higher quantum efficiency detectors, higher signal-to-noise ratios and the choice of selectable wavelengths of excitation with narrower bandwidths).

Being able to quickly switch across different stimulation wavelengths while keeping them as narrow as possible is of great value for the experimenter. The optical properties of most materials largely depend on the wavelength that is used to study them. Working with “pure” light, as monochromatic as possible, is, therefore, a highly coveted aspiration that guides current efforts in optics.

The most popular type of optical setup in cellular neurobiology consists of a light source (usually a xenon lamp) coupled to a monochromator, a device that allows selecting a particular wavelength from the many available at the input. The output of the monochromator is coupled to the microscope and can, therefore, excite the biological sample lying under its objective. Although this design has been widely successful, to achieve a multi-band output and faster changes, some optical elements need to be brought on board, having an impact on the overall price. In a recent paper published in Nature Scientific Reports, Belušič and co-workers (1) found an elegant and inexpensive solution to circumvent this drawback and obtain multi-band stimulation at an extremely attractive price tag of 700€!

The LED synthesizer & how it works

The light source of this multi-spectral synthesizer, as they call it, is comprised of 20 LEDs of different colors, which are aligned in a row and forming an intrinsic multi-band light stimulator. The light coming from these LEDs is focused on a planar reflective diffraction grating. A grating is a flat optical component containing ridges at very precise intervals along its surface.According to the principle of diffraction established by Fresnel and Huygens, light hitting such a periodic structure is decomposed into several beams traveling in different directions. The wavelength of each light source and the spacing of the ridges on the grating set these trajectories. Diffraction of longer wavelengths (red) will be larger than shorter ones (violet). Therefore, using the grating, one can combine beams of different wavelengths.

LED synthesizer
                             The LED synthesizer in action!

The resulting composite beam then travels through a light guide equipped with a single aspheric lens. This lens minifies the diffracted “rainbow-type” pattern of colors produced by the grating and brings it into focus at its center. The combination of grating and light-guide fiber also had an unexpectedly beneficial consequence. The emerging light had significantly narrower spectral bands; the planar refractive grating not only combines several wavelengths into a single output beam but also cleans their spectra, narrowing their bandwidth.

What can we do with LEDs?

How about testing this gadget in a biological preparation? The authors used sharp electrodes to measure changes in the membrane voltage evoked by short pulses of monochromatic light, in photoreceptor cells from the blowfly’s eye. Stimuli were given with the LED synthesizer or with a classic photo stimulator. To map the photoreceptor’s response to light of different colors, they swept across a series of wavelengths, from 355 nm (ultraviolet) to 625 nm (red light) and were able to obtain a full spectral sensitivity curve in less than 2 seconds. These curves, constructed from the electrical responses to each wavelength presentation, were the same for both stimulation strategies.

As a proof of concept of its potential in biomedical imaging, they moved on to determine the absorption spectrum of oxyhemoglobin and deoxyhemoglobin species in a blood lysate. They presented a series of monochromatic light pulses spanning from 393 nm to 625 nm using either the LED synthesizer or a conventional spectrophotometer. A comparison of experimental results with tabulated data from the literature revealed that for measurements above 440 nm, both absorbance curves were nicely matching, indicating a similar performance for both optical devices.

Their next goal was to find out whether the LED synthesizer could as well discern between oxygenated and deoxygenated hemoglobin in a living tissue and therefore imaged blood vessels of the frog’s abdominal skin. Here the advantage is that oxyhemoglobin is enriched in the veins whereas arteries contain its deoxygenated counterpart. The results were very promising: they could identify spectral components containing enough optical information to discriminate between arteries and veins in the visual field, purely based on their absorption values.

Applications of the LED synthesizer

The LED synthesizer, therefore, represents a robust imaging device offering fast switchable control of the wavelength’s output and equalling to a large extent the performance of a monochromator-based setup, but at a considerably lower price. It can be assembled using inexpensive off-the-shelf equipment, namely cheaply available LEDs, a light guide, an aspheric lens and a planar reflective grating. The amount of undesired light (stray light) in the optical system is significantly reduced. LEDs also have a long operational life, a stable output and one can easily manipulate them and replace them if necessary, unlike the more cumbersome xenon lamps. When coupled to an ophthalmoscope, this imaging device is useful in clinical vision physiology (fundus examination, for instance) and more sophisticated applications in biomedical science (optogenetics, fluorescence microscopy).

Photodamage: Fluorescent molecules do not last forever. Upon repeated excitation, they undergo irreversible chemical changes after which they are no longer fluorescent. Photobleaching, as this process is also known, depends on the illumination level. Photobleaching is used in an optical imaging strategy called FRAP (fluorescence recovery after photobleaching), which is used to track the mobility of fluorescently labeled cellular proteins of interest. With this technique, we can selectively wipe out the fluorescence within a cell region and subsequently monitor its recovery as non-bleached fluorescently labeled proteins in the vicinity gradually start to repopulate the bleached area.

Quantum efficiency of a detector: the percent of incident photons that generate a signal. Not to be mixed with the quantum yield of a fluorescent molecule, which is a measure of its fluorescence efficiency, given by the fraction of all excited molecules that relax by fluorescence emission.

Signal-to-noise ratio: Electronic detectors are often compared by their signal-to-noise ratio, which is a measure of the variation of a signal that indicates the confidence in the measurement of its magnitude.

LED: Light emitting diodes. Resistors, capacitors, and inductors are linear circuit elements, meaning that a doubling of an applied signal (for instance, voltage) will lead to a doubling of the response (current). Diodes, on the contrary, are non-linear and let current flow in one direction, behaving as rectifiers. LEDs contain a semiconductor crystal coated with impurities that generate two regions: a negative n-region (charged with electrons), and a p-region (with positive charge carriers). If sufficient voltage is applied, electrons flow across the junction between both regions, releasing energy in the form of photons.

References

1) A fast multi-spectral light synthesizer based on LEDs and a diffraction grating.
Belušič G, Ilič M, Meglič A & Pirih P
Scientific Reports 6, Article number: 32012 (2016).
doi:10.1038/srep32012

2) Methods in Cellular Imaging, edited by Ammasi Periasamy, Oxford University Press, UK, 2001.

3) Imaging: A Laboratory Manual, edited by Rafael Yuste, Cold Spring Harbor Laboratory Press, US, 2011.

About the Author: My name is Gaston Sendin, and I am a neurobiologist who is passionate about science communication and the history of art. The sensory systems are particularly attractive to me, because they can be exquisitely tuned to specific features of our world. I have so far used electrophysiological and optical methods to study sensory processing in the zebrafish and in mice, focusing on vision and hearing.

After finishing my studies in Biology at the University of Buenos Aires (Argentina), I went on to pursue a Ph.D. in Neuroscience at the International Max-Planck Research School & the University of Göttingen (Germany). Doing research in sensory neurobiology, I was a post-doctoral fellow at the MRC-Laboratory of Molecular Biology in Cambridge (UK), the Department of Artificial Intelligence at the University of Groningen (Netherlands) and the Inserm-Institute for Neuroscience of Montpellier (France).

Featured image source: Pixabay

From Bangalore to Boston-IISc Igem 2016

in SciWorld by

Many articles have already been written about research and the intricacies of a life in it. Most of them, though, are from the perspective of graduate students; written by graduate students themselves, or people reminiscent of their time in graduate school. This is probably because that is when a person generally evolves from a student into a researcher, and it is during this transition that the properties of life in research become more stark. The entire point of the IISc undergraduates participating in the iGEM competition was to shift this frame slightly to the left in the timeline. All of us were under the impression that the researcher in us, though far from being developed, has already started developing. iGEM, to us, was a path to verify this rather ambitious speculation of ours.

The IISC IGEM TEAM 2016 in BOSTON lead by Arunavo

iGEM stands for International Genetically Engineered Machines (I never really understood why the ‘i’ is in lowercase, but in defense of the ‘i’, ‘I’ never really ventured to determine the reason). As the name suggests, it is an international synthetic biology competition, mostly for undergraduates, though some high-school and over-graduate teams also participate in their respective categories. It started out as an effort from MIT to standardize plasmid backbones. Most people who do wet-lab work regularly in biology, would have faced this problem — “I have my gene of interest in plasmid A, and I want to put it downstream of some other gene in plasmid B. I need restriction enzymes m, n, o, and p for this relatively simple exercise, but there is no enzyme ‘q’ in the lab! Now all I have to do is get a quotation for it from the vendors, wait for about 6729 years for it to arrive while I finish a few more seasons of my favorite TV series, and lament after 20867 years how excruciatingly long a PhD in Experimental Biology takes to complete.” The next time a similar experiment needs to be performed, suddenly enzyme z is out of stock and the same sequence of events repeats. Instead, if most plasmids come with cut sites of a specified (and very small) set of restriction enzymes, having those in stock will be sufficient to do most research work. iGEM started an attempt to make a library of plasmids with specific cut sites (which, certainly, should not be present in your gene insert), and develop/validate this library either by using or improving the pre-existing plasmids (known as BioBricks), or making a new plasmid that fits the library criteria. Possibly the reason for the target participants being undergraduates, was because a failure for them is much less costly (with no PhD thesis at stake!), and because of this, they often tend to explore improbable regions, with hidden answers.

ABHIJEET KRISHNA in one of his moods

Like most student initiatives, the idea of forming an iGEM team came to us one day, over junk food, late at night, in our first semester at IISc. Arunavo, being a YouTube-phile, had come across a video of the formation of the iGEM team of King’s College, London, and suddenly, we thought, “Why can’t we have an iGEM Team?”. The next day, we went and talked to our instructors, who were pretty interested at the prospect, and took an active interest in discovering what the competition was and why it is worth participating in. But, like most sudden peaks of academic excitement and interest that originate in one’s hostel room, it died away soon. Thankfully, our instructor (Dr. Narmada Khare) had not forgotten about the conversation we had, and one day, while conversing with a PhD student at NCBS (National Centre for Biological Sciences, Bangalore), she came to know that this PhD student, known to her colleagues as Chaitra Prabhakara, was a member of the IIT-Madras iGEM team in her undergraduate days. Both Narmada and Chaitra considered the formation of an IISc iGEM Team a possibility, and Chaitra came and gave us a talk about her experience with the competition. That was the activation energy we needed, and a team suddenly formed out of thin air, comprising of 21 students (of course the number is not exact; all I can say is that it is of the same order of magnitude as the original number!). Anyone with any interest in biology was willing to help.

Aiswarya-You can tell she is the no nonsense person in the group

As many would have noticed in their personal life, or in the dynamics of academia around them, in the initial days after formation, the number of members in an undergraduate team follows a roughly exponential decay, until it hits a threshold number. Interestingly this threshold is often a number which is practically the minimum requirement of calling a collective a team. It finally settled down to the four of us — Abhijeet, Arunavo, Shreyas and I (Prabaha). Actually, at a point of time, the team was practically two people — Arunavo and Abhijeet, because Shreyas and I were busy discovering our startling incompetence at even starting to solve an assignment anytime before ‘the-night-before-the-deadline’. Now, since both of us were taking a lot of courses, once we solved an assignment at the last minute, the next day was always the last minute for some other assignment/test. Eventually, this oscillation in the number of members settled down, and the four of us consented in each other’s calling ourselves part of the IISc iGEM Team, which was still to be recognized by the authority – the Undergraduate Department.

Sreyas making the most of the Halloween

The next step was the rate determining step — convincing the authority of the existence and legitimacy of the first team from our college. No one had any problem with undergraduates trying out original research; after all, the entire objective of the UG program was to promote exactly this! But, the problem is, there exist factors like intellectual property rights, and many more words, whose exact definitions still elude me, which noobs like us had not exactly accounted for (to be truthful, we had, but iGEM was open source — a philosophy we wanted to be a part of, but the authority was still getting used to). Also, $!

The team and the mentorDr. Srinath T

After multiple discussions, Prof. Umesh Varshney, the UG Dean at that time told us one of the most encouraging things we had heard, “You people take care of the science, and we adults will handle the bureaucracy”. What more does an undergraduate need? We had spent almost one and a half years, discussing among ourselves, and getting our ideas validated (generally rejected) by Chaitra, Sachit (another PhD student from NCBS) and our biology instructors in finally coming up with an original idea that was interesting, and could be verified in the time window (roughly the summer time). But research needs funds, and though the UG department had funds, it was allocated for specific purposes. We discovered a competition called iBEC that was being organized by DBT (Department of Biotechnology) for the very first time that year, for Indian iGEM teams. The teams had to submit a grant proposal, and a select few teams would receive financial aid up to an amount of Rs. 10,00,000. We got the complete Rs. 10,00,000 that we had asked for. The UG department loaned us the registration fee (~Rs. 4,00,000), because the iBEC results were to be announced after the deadline to register for iGEM, and thus the IISc iGEM Team was officially established, lead by Prof. Deepak Saini from the MRDG department (Molecular Reproduction, Development, and Genetics) and Prof. Umesh Varshney, the contemporary UG Dean. We even took in 3 of our juniors — Aiswarya, Aneesh, and Ayan, so that next year’s team got a head start.

 

Then began a stream of failed experiments, with one or two successful ones in between, and the not-very-uncommon waiting periods for enzymes to get delivered (I know that the entire point of iGEM was to avoid this very thing, but one or two of the iGEM prescribed restriction enzymes were not the most commonly used ones in our labs). But that is all known to anyone who has done science; most people reading this article can teach advanced courses on failed experiments, and I am just a beginner. The challenging hurdles we faced, other than the scientific ones, were the non-scientific ones. I won’t be surprised if someone now shouts, “10 points from Ravenclaw for stating the obvious”, but what one needs to understand is that we had no idea about how to solve the non-scientific ones. The registration fee ensures the recognition of the existence of the team, and the shipment of a collection of pre-existing BioBricks; it does not cover for anything else! When the team goes to present at the Giant Jamboree (the event at which the teams present their work) another registration fee for each team member had to be paid, and that, again, covered nothing else. We had to arrange for our own lodging, food, and travel. We needed to raise more money for that, the amount promised by DBT was not even close to sufficient!

Thus, in addition to spending sleepless nights in the UG bio labs doing experiments, we started thinking about how to get more money. Our professors promised to manage the money, and even help us get it, but we had to come up with the sources. We jotted down the list of funding agencies that help startups, successful startups that might be interested in our work, people who might help us point towards a source of money, and started emailing any and everyone. One day I was talking to Kuldeep from MBU (Molecular Biophysics Unit), a PhD student I worked with in my first summer, lamenting about the soup we were in, and he told me about the existence of a Facebook group called Career Support Group (CSG), comprising largely of IISc students and alumni. I thought that this group might help stranded IISc students going abroad get a place to stay. It took me some time to discover that the pre-stated description of CSG was as complete as calling a university a place with classrooms.

Imagination has no bounds

The first post I made on the Facebook page was requesting the members to allow the team members to stay at their apartment(s) for the duration of their stay. The response was overwhelming! Many people offered us a place at their apartment, but it was not limited to that. Dr. Selvaraj Nataraja from the group proposed that we try crowd funding, so that we could book an apartment for the entire team, and gave us a seeding amount of $300. Dr. Ananda Ghosh, the founder of the group contacted us and advised us to campaign in the group — regularly post about who we are, what we are trying to do, about the program we are a part of, about the Jamboree and the associated opportunities and exposure, etc. In addition to learning to do science, we started learning people skills, and the methods of pitching and funding one’s research endeavors. Finally, after campaigning, we asked the CSG members to help us in organizing the fundraising, and Dr. Kushagra Bansal (an IISc alumnus, and currently a Postdoc at Harvard) took up the responsibility of collecting the money for us. Once again CSG surprised us with its response and within a week, we had raised enough money to book an apartment for the duration of our stay.

In the meantime, we were trying other avenues to get funding for our travel and sustenance, and we managed to convince the IT, BT and S & T department of the Karnataka Government that our project was worth funding and got a grant worth Rs. 6,00,000 (toward consumables) from them. Also, we had applied for the Indian Alliance (Wellcome-DBT) travel grant, which is generally meant for PhD students, but surprisingly, we got that grant too! IISc-AANA (Alumni Association of North America) also agreed to make payments for the rest of the predicted amount of money required. Finally, we had all the money we needed. All that was left was the science.

If one tries to track the evolution of the answer to the question “What exactly are we trying to show?” in a project, often, the trajectory takes massive downward leaps along the axis of ambition. Our case was not much different. Our idea made sense, the genetic circuits made sense, the two modules we made also made sense, and so did the expected crosstalk between them. The only thing that did not make sense was the amount of time all the experiments we designed were taking to perform, and the astounding number of parameters that cause failures and delay work by days — reasons like “The liquid nitrogen we brought this morning has evaporated” or “The glycerol in the polymerase caused the entire PCR mix to precipitate (it took us a good part of a month to discover that that was what was going wrong with our PCRs; also, some wells in the PCR machine were not working!)”. Finally, when the week before our date of travel arrived, we had got both the modules to work independently, but did not have time to show the effects of combining both of them in a cell. We decided to present what we had done, and that in itself involved new scientific work, but were dissatisfied at the fact that we did not quite live up to our soaring ambition.

The Award

Finally, Abhijeet, Arunavo, Aiswarya, Srinath (instructor), Shreyas and I headed towards USA to present the work of IISc-UGs to the world. All of us were so relieved at the last minute completion of experimental work and documentation, it did not occur to us that we should be feeling excited about where we were going and what we represented.

None of us had ever visited Boston, but we did not feel any degree of alienation when we reached, on account of Dr. Kushagra Bansal and Dr. Gajendra Dwivedi (another CSG member in Boston) picking us up from the airport. That night, all of us enjoyed the placid, dreamless sleep brought on by exhaustion from the journey. The next day, all of team but I explored Jamaica Plain while I went to meet a professor I had mailed about the coming summer. The meeting was fruitful, the trip not only enabled us to present our work but also got me a funded project for the next summer at Harvard. On that same day, Dr. Selvaraja took us all to dinner; at this point, Boston was almost a home away from home. It was after the dinner that we realized that we had a significant portion of our presentation to complete, thanks to some experimental success right before our departure. In addition to the content, the design of the presentation was crucial; a brief look up of past years’ winning presentation revealed style was almost as important as content and delivery. And thus began a highly awkward yet effective process of outsourcing the design to India; a couple of our peers — Prokash and Sai had volunteered to draw the figures and design the layout of the presentation respectively. Another realization struck us on the night of the dinner – the poster needed significant revision; it has too much text and too few illustrations. We sat through most of that night annotating the pdf version of the poster with the changes and mailed it to Sai to implement. We needed the poster on the very next day!

We made the poster deadline (thanks to a nearby Kinko’s and the design team’s efficiency) and rehearsed the presentation in a room set up very similar to the way the presentation hall would be. We realized some visibility problems (some of the text was too small) and headed back home. Further changes were mailed to the exhausted design duo and we continued with a flurry of rehearsals during the next day and a half that finally culminated in our actual presentation. It went well, except for some unrehearsed time allotments to the different presenters. A wave of relief washed over all of us. Only 2 more days of poster presentations and we would know the result of our year and a half of blood, sweat and tears. We ended up winning a Bronze medal in the competition (not to be mistaken as the third prize; many gold, silver and bronze medals are given out, somewhat like the Olympiads). We had also contributed to something called the ‘InterLab Studies’ where volunteering iGEM teams across the world perform a particular prescribed experimental protocol, and produce robust statistically significant data. The theme for 2016 was standardizing fluorescence quantification. When we attended the InterLab committee’s presentation, we heard some ‘IISc iGEM Team’ had suggested a correction to the experimental protocol, that had reduced the error margins by 100x. “Must be a team of astoundingly brilliant students”, we thought.

We also spent a significant amount of our time watching other teams present. A trend we observed about the teams whose work was extremely elaborate (a large fraction of these teams eventually went on to win lots of awards) was the significant role of graduate students and Postdocs – some of these teams had up to 20 such researchers acting as mentors in addition to the PIs. And suddenly it hit us — a group of more experienced grad students, along with us charged-up UGs, could have hastened the lengthy process of troubleshooting our protocols, saving us precious time. Research requires both innovation and experience and the latter we lacked.

Overall, the experience was extremely valuable, not only in enabling IISc to put out better iGEM teams in the years to come but also in providing us undergrads a taste of all aspects of research, not limited to the science of it.

 

 

 

 

 

 

Prabaha Gangopadhyay is an undergraduate from Indian Institute of Science (IISc), Bangalore, India. Year: 3rd, Major: Biology This is what he has to say “I like learning about mechanisms underlying the existence of life. I find myself comfortable in the overlap of theoretical and experimental biology, because of the extreme interdisciplinary nature of the area, and being at IISc has allowed me to explore it. I am interested in doing my final year project, and eventually my PhD, in Neuroscience. Other than science, I love literature, classical music, and, like any other undergrad, food!”

Battle of Wisdom: CRISPR-CAS9

in Sci-IP/SciBiz/SciWorld by
Editor’s Note: Gene editing for a better (or worse) is coming to a store near you. Some of you may have followed the ongoing patent war on the ownership of CRISPR-Cas9 technology between University of California (Berkeley) and Broad Institute (MIT-Harvard). But there could be many who are wondering what is the fuss all about? At the Career Support Group (CSG) for STEM PhDs we might still continue the debate about CSG’s usefulness to biologists vs non-biologists, but as inventors we are always in unison about perfecting the art of claiming ownership. #ClubSciWri is always attempting to listen and respond to your expectations and we are pleased to present the “Battle of Wisdom:CRISPR-Cas9” from Dileep Vengasseri. Dileep has nicely deciphered the meshwork underlying this matrix of claims to the CRISPR invention. We hope this story helps make sure that the next big thing from your gray matter secures your rightful ownership to the intellectual property.- Abhinav Dey

My dear friend, this 60 minutes of my time and 1597 words are for you! As you rightly said, maybe we should discuss our opinion(s) in public at least for educating others on what we have learned during the due course of our time.

Disclaimer: All what is written/expressed here are my personal opinions, and are not to be construed in any manner as a reflection/opinion of the firm that I am associated with. My words are solely my words! I will try to be as generic as possible to ensure there is absolutely no conflicts of any interest. This is purely a personal blog, written within the constitutional freedom that my Country has offered me when I was born here.

Many great battles are won not in the battle fileds, but in the minds of the battle leaders. What we read, saw, and talked about were the after-effects of those battles won or lost inside those great minds. In the great epic Mahabharata, Arjuna was about to lose Kurukshetra battle even before it was fought. But, there was a Krishna to save him from that humiliation. Many may not be as lucky as Arjuna was.

Before I begin, with all due respect, let me remind all of us one trivia very clear. US is not the “World” … it is just one of the many countries [a privileged one, indeed] of this world.  A larger population residing outside that privileged country, do not play a “World Cup” between their states or clubs. They don’t re-spell a word to make it look like they have invented it. For them, the metal “Al” is still aluminium and not aluminum.

We, living at the periphery of the world of modern(?) science, have got enough fuel from CRISPR-Cas, the game-changing method of gene editing, to satisfy our ego of being a part of a ‘privileged community’ who understands (?) the words like ‘gene editing’ and ‘CRISPR-Cas’.  For all such ‘privileged souls’, the “IP Battle of CRISPR-Cas” is more than just another battle. Let me call it a “Battle of Wisdom”.

But, was this battle worth fighting?

Let me begin with disecting this IP battle to four main sections: (1) Technology (2) The Battle Field (3) The Win and (4) The Strategy. May be, in future, I can complete this article with “Lessons Learnt”.

  1. Technology: At least from what is publically available, we know that Doudna/Charpentier’s team made that beautiful gene editng system work in-vitro in prokaryotic cells, in a neater, simpler manner than what it was in the nature itself. Instead of using a 3-component system including tracrRNA, crRNA and Cas9, her team beautifully designed a 2-component system, including a key synthetic, single guided RNA (sgRNA), that effectively performed site specific genome editing along with Cas9 (It is interesting to note that in-vitro 3-component system is also IP protected!). What was the big deal? The big deal was its simplicity, efficiency, and marketability. It was not that gene editing methodologies never existed before… however, now the World has access to an elegant gene editing system that is much more easy to perform (no more protein engineering!) & predictable. We also know that Feng Zhang (don’t forget George Church’s back-to-back publication in Science along with Feng Zhang) made it work in the eukaryotic system.
  2. The Battle Field: No one (at least the majority of money makers) wants a gene editing system that works only in prokaryotic systems. So, the “Battle of Wisdom” eventually boiled down to the IP on gene editing in eukaryotic system with CRISPR-Cas. Duodna filed a US patent application (remember, US is not the World, more so when it comes to IP protection) first and Feng Zhang got the first granted patent in US (note that the USPTO could have  provoked an interference at that time itself, but they didn’t!). Feng Zhang’s patent ‘claims’ to ‘cover’ eukaryotic CRISPR/Cas gene editing system (no comments on its “claims” and/or its “coverage” as the battle is still on…at least let the battle be fought under the belief that the land that is going to be conquered is still fertile!).  Duodna had anyway made it easier for Feng Zhang to get his patent granted by ‘boasting about’ her team’s achievement in multiple forums and explaning ‘how difficult it is/was to make it work in a eukaryotic system’.   Alas! enough of such wisdom on eukaryotic system was passed on to that Patent Attorney who filed her provisional applications, at least before the one on 19th October 2012 that is prior to the Feng Zhang’s priority date of 12th December 2012. Now, the battle of wisdom (what we call as “Interference Proceedings”) is to establish who invented (i.e., conceived and/or reduced-to-practice) the “eukaryotic CRISPR-Cas” first. Duodna will be fighting to make a point that porting CRISPR to  eukaryotic system is just a non-inventive aspect. Feng Zhang is going to fight back at least on the ground that if it is that obvious why did it then take Doudna a good 6-9 months to achieve the same.   I refrain from making any comments on how long or short is 6-9 months in a field like Molecular Biology. I know that my dear friend, who forced me (as usual) to write this long article, has wandered in the wilderness of IISc campus behind an elusive protein for a good 6 years :-)). And, I must admit that I have made the entire story of this Battle of Wisdom to a deeply  abridged version as the facts of this case are much more than what this layman article can handle. But, I believe that this much background is good enough to make my “teaching moments” convincing.
  3. The Win: Does it matter who wins this battle? Of course, YES! All battles are known after the leader who has won it (Aravind Kejriwal and Hilary Clinton are no where near their counterparts, as of today). Generally, the winner get the privilege to write the history that we all can read and study. But, is this Battle of Wisdom the same as any other great battles fought, lost and won? No. What is required to win this battle? It is required to show that who has invented the “eukaryotic CRISPR-Cas” first; it is required to show what is inventive/not inventive in this field; and it is required to show what constitutes an adequate written description/enablement in this field so that the “public disclosure function” (spirit and letter of any patenting system in the world) of the patenting sytsem is intact.  But, as with any other battle, only one person can be the winner. But, what will they both win or lose? The loser will any way have a deep wound in ego that may take years to heal. But, will he/she lose everything? Need not be. It depends on what other IP portfolio or picket-fencing that he/she has done around this gene editing tool. For example, a good claim on the synthetic guide RNA, a good IP portoflio on a better Cas9 proteins,  a better method for transfecting the cell, or an alternative to Cas9 itself… all these can make or break a commercial deal.  Is the winner going to get everything? Need not be.  During this entire process, it might open a pandora box and a myriad of avenues to potentially invalidate the patent claims that the winner can take home, to limit its claim scope, to limit its application coverage etc.
  4. Strategy: Isn’t it important for everyone in the field of IP to realize that most often a “hand shake” may do more good than “a fight”.  Before taking the army to a battle, it is important to know if raisng a white flag will be more beneficial than a gruelling battle. It is important to understand for what one is fighting a battle.   Does anyone fight for satisfying an ego or to make a point?  It is imporant to  understand that in a patent battle field, a wiser does not fight from their heart, but from their mind!. It is  important for each of the fighting members to know “What will happen if we do not fight, but rather collaborate?”.  Both Doudna/Charpentier and Feng Zhang could have been still partners in Editas, and they could have ruled the field.  When you fight in public, you expose yourself…you expose more than what you wanted to. And, what you have exposed can kill you even if you win YOUR fight.

Three more points to ponder:

  1. IP protection of PCR technology made Roche the king of DNA amplificaiton for quite sometime. Why? It is true that PCR was a technology that literally transformed the world of Biotechnology. But, was the IP protection on PCR probes for important pathogens less important? Were Taqman probes for real time PCR less important? Were the chips that made thermal cycling easier less important? No. All of them “together” made PCR a “cult” technology. That’s what a strategy means.
  2. IP protection in the field of ESC took Thompson and Wisconsin Alumni Research Foundation (WARF) to the center of the scientific world. Many IP/Tech Transfer cells in the Universities across the world wanted to be like WARF. As far I know, WARF gave its rights for free to any academic instituties, but made any industry pay for the same. Great! What were the other things that were needed to sustain and progress that technology ? An environment that morally support ESC research, a completely synthetic media to grow ESC, a culture that is devoid of mouse fibroblasts … all these were essential for taking ESC to reach its maximum potential. In modern day science, it is unlikely that we will see a winner of a single battle emerging as the “real winner”. A real winner is going to be the one who knows the game and strategize accordingly.
  3. US is not the “World”, and IP rights are jurisdictional. So, make yourself open to strategize for the real world!

Another Disclaimer: While starting my blog in WordPress, I had promised that I will not proof-read what I have written. In the past, many times, I had become a victim of my perfectionism and my writings had never seen the light. So, please pardon any typographical, grammatical, or otherwise errors. I hope factual errors are not there. Please let me know if you find any errors so that I can correct the same.

Authored by

 

Dr Dileep Vangasseri, PhD (Indian Institute of Science, IISc); Post-Doctoral research, University of Pittsburgh; Senior IP Professional, John F. Welch Technology Center, GE India Technology Center Pvt. Ltd., GE Global Research, Bangalore, India). Dileep has over ten years of in-house IP experience in Life Sciences, Healthcare and Medical Diagnostics industry after eight years of academic research experience in Bio-Organic Chemistry, Gene Therapy and Cancer Immunotherapy. He is well versed in all facets of patent analytics, techno-competitive intelligence, technology forecasting and business development.

This blog was originally posted here on December 7 (2016).

Featured image source: Pixabay

Creative Commons License
This work by ClubSciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

1 2 3
Go to Top
%d bloggers like this: