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Limits to Perfection: Searching For Order in Chaos

Kumaresh Krishnan: “Understanding when the details of a model are satisfactory for the research questions being asked is one of the most critical steps in my work.”

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Kumaresh Krishnan

[su_boxbox title=”About”]Kumaresh Krishnan is a Ph.D. student at Harvard University in the lab of Florian Engert. His scientific world revolves around the wonders of the brain, and outside of the lab, you are equally likely to see him in a sports field all day or performing music elsewhere! He is attempting to uncover how the two eyes integrate information, and on his journey, has gained valuable insights on modeling, research, and life which is the central theme of this story. The story below was edited by Katelyn Comeau.[/su_boxbox]

[su_boxnote note_color=”#c8c8c8″]Key Points:

  • ‘Knowing where to draw the line’ is a key element both in research and in life
  • “All models are wrong, but some are useful” – George E.P. Box
  • Random’ only implies sweeping irrelevant factors under the rug [/su_boxnote]

Kumaresh Krishnan

 [dropcap]T[/dropcap]he dark clouds gave way to a heavy downpour, dampening the spirit of the crowd. The captivating match had to be abandoned, but our low stakes school tournament needed a winner declared that very evening! No degree of number crunching could separate the two teams that gave their all for an hour. After an extended debate, it all boiled down to the trusted, unbiased resolution technique that always leaves the loser frustrated – a coin toss.

Confused between two equally attractive options? – bring in the coin toss. Need to decide who goes first? – coin toss it is! This strategy can be dubbed the quintessential conflict resolver, an elegant way to shift the brunt of decision making. The equal likelihood of success and failure in predicting the outcome, makes a coin toss quite attractive for breaking deadlocks. A person making a prediction after the coin lands on heads thrice, still has the same uncertainty as one hazarding a guess following a single heads. This property is often referred to as ‘independence of event’. In this context arises a burning question – ‘Is the outcome of a coin toss truly random or have we withered away sufficient details to suit our purpose’?

A human hand is flipping a barely cylindrical object that can land on either side. There is no end to sources for variability and we bundle this under the delightful word – ‘random’. Let’s try adding some information that can theoretically boost the accuracy of our answer to ‘heads or tails’. Assume we know the force of the flip, the weight of the coin and the width of the air column. It is possible to ballpark the maximum height reached by the coin and the number of flips it would complete before landing. Piece it together with the side of the coin initially facing up and you are already more certain about your guess compared to going in knowing nothing.

Now, unless we are whiz kids or using technological assistance, these calculations should take a while. Throw in few such factors and we have our ‘model’ for the coin toss – a chance at conquering randomness, some may say.

By no means is this a complete model. We can think of missing factors like temperature which can directly impact the outcome, or something seemingly irrelevant like a butterfly’s flight in the neighboring town! Take this a step further and you realize that no usable model can account for every single factor in the universe.

No wonder the words of the British statistician George E. P. Box became famous – ‘All models are wrong, but some are useful’.

At every opportunity to create a model, we include only factors deemed to be significant contributors to the outcome at hand. The decision of where to draw the line is entirely dependent on the goal. Our dear conflict shattering coin toss has stood the test of time simply because the situation demands an instant response that is unlikely to provide time for extensive calculations.

For this purpose, our ‘model’ of the coin toss includes no factors, thereby appearing random. Posed as a physics problem though, we can include many factors as outlined earlier, to provide increasingly accurate descriptions of the toss. Knowing where to clip the detail is all it takes for models to have value in any given context.

Research too is no stranger to the concept of drawing these lines, one of the first insights provided by my advisor. In my quest to understand and model how the two eyes combine visual information, I too attempted my own version of uncovering structure in apparent randomness. Biological processes possess inherent variability, and clearly, any model would only approximate the phenomenon to a certain extent. Understanding when the details of a model are satisfactory for the research questions being asked is one of the most critical steps in my work. Like most research endeavors, I needed to devise experiments, collect meaningful data, build a model, and compile the work into a written form. In each of these components, we can chase perfection and remain stuck endlessly.

The context of a research question requires defining a certain scope for the work. This can serve as a guiding light to gauge when to transition from one phase to the next. Choosing the right level of abstraction to describe a certain phenomenon is dependent on the question being asked, much like the case of the coin toss. For the person using it to pick a restaurant for lunch, it is unnecessary to use the information about air pressure. However, a person focused on understanding the flight of a coin can make a detailed and useful description of the same phenomenon. Clearly, the same experimental setup can provide data which can be processed in numerous ways. For my work in the domain of neuroscience, modeling is essentially searching for order in the seemingly chaotic activity of billions of neurons in our brain. Here too, a useful model is often built by recognizing pertinent information that helps decide when to press for detail and when to bundle certain factors as ‘random’ or ‘natural variation’.

I was fortunate to have my advisor shower the lovely advice of ‘knowing when to move on’ early in my research career. On a more philosophical note, this is analogous to a strategy for life! Contentment readily translates to knowing where to draw a line. As I write this piece, I too am grappling with the constant thought of conveying my ideas in the perfect way. Perhaps I should draw a line here and leave the reader with a short yet important message. We can definitely chase perfection, but we must be simultaneously aware that the line of satisfaction has to be drawn at some point. Eventually, happiness will be ours to take, both in research and in life!

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Spanish Edition: Science Communicator, Alessandro Strobbe, teaches scientific topics with humor

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Alessandro Strobbe is a Peruvian science communicator with experience in public engagement through storytelling and creative writing. He also conducts research in science communication, critical thinking, and citizen science. He is most known as Doctor Trónico on social media, with his science popularization project for teaching science and skepticism with humor, using memes in social media. It has a range of 1-3 million prints per month, +500 creative writing columns, and +1000 graphic arts. His talk show Ciencia Picante, also uses language accessible to all audiences and creates an informal environment focused on the popularization of scientific studies and science engagement.

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A Development enhancing tale with a microbial rich cocktail

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Minisha Pereira

Dr. Minisha Pereira, Ph.D., is a Research scholar from Indian Council of Medical Research -National institute of Malaria Research, Field unit Goa, India. Her main area of Research is Vector biology which includes aspects of microbiology and molecular biology. Her recent publication titled “Characterization of midgut microbiome of Anopheles stephensi Liston” was published on March 2021 in Journal of vector borne diseases. The narrative below explores the story behind the unseen facts from her published work. She wants to bring the concept of her research in way which will be appreciated and also bring awareness to sustain public health. You can follow Dr. Pereira on Twitter @HMinisha.

Key Point

Spreading awareness among each other doesn’t need a lot support. But it necessitates a kind heart, a strong mind, and a never-fading goal. Let us identify the ways to save ourselves from vector-borne diseases and pests to live in harmony with nature and preserve the majority of useful insects. In these times of pandemic as we are living in anxiety and fear, Let us unite ourselves as beings and stop the spread of COVID far and near.[/su_boxnote]

With thoughts of COVID gushing in my mind, I was sitting down the lane next to my research lab during one evening time. Just then, I heard the conversations that got me stunned and startled. A conversation between two mosquitoes, sharing their knowledge and their thoughts. Curiosity and excitement gushed within me, leading to an elevated enthusiasm enforcing me to listen to their entire conversation.

The story was between two mosquito friends Anopheles stephensi and Anopheles subpictus who shared their thoughts about their current life status. So, without any delay, let us start the conversation replay…

An. subpictus: Hello!! My dear friend do you know we are at the brink of losing our significance because of COVID-19 outbreak globally??

An. stephensi: Do you feel so? My friends in scourges are already spreading Malaria. Luckily, the whole world around is so busy with the pandemic that they lost their focus on us.An. subpictus: Ohh great! But can we be as deadly as the virus?

An. stephensi: Deadly?? Stop misjudging yourself. We can be very fatal to all mankind, even though that’s not our intention. Our mission in life is to feast on their blood but,  that cunning parasite (Plasmodium) that comes along during our bloody diet can cause sickly malaria. With chills and shakes, we can make an all-powerful man go crazy and also cold-hot-sweaty.

“A few decades ago, actually around 1987, our ancestors set their sight on the lovely state of Goa, just like tourists. We made such a Merry in Goa, dancing and feasting so much on the blood that hundreds of people were put down with malaria and some did not raise again. Yes! They were dead and gone. But then they took revenge on us and something horrible happened to us. These creatures, the humans, do not give up easily as they say.

An. subpictus: What did they do?

An. stephensi: They set up a big institute named ICMR-NIMR (Indian Council of Medical Research-National Institute of Malaria Research) to pack us off from Goa. The team NIMR chased us so much that we were so scared. Clever that they were, firstly they started learning everything about us, our lifestyles, our activities and behaviour. With their knowledge and expertise, they managed to attack our homes (breeding sites: artificial containers, wells, freshwater pools, stream margins, water storage containers, construction sites) affecting all our kids (immatures: larvae & pupae) thereby leaving us homeless using all different kinds of ways. If they had used DDT powder, nothing much would have happened to us as we can deal with it.

But they were destroying our homes, clearing the water, using bacterial powder where our kids thrive. And that was not enough, they started to release fish that would pick up our kids (larvae and pupae) and eat them in hundreds. (Mosquito cries).

An. subpictus: But then how did you manage to continue to survive?

An. stephensi: You see we may be small but we are powerful. Nature has created us much before man, who tends to relax and celebrate his successes. But we mosquitoes are serious about our living and keep doing our jobs even at night and produce batches of eggs every 48 hours and thus manage to survive being so potent and productive.

Hey! There is some big Office WHO in Switzerland where they discuss us. Can you imagine our power? They were saying our entire sister species put together; we globally kill more than 400 000 humans every year. We don’t spare pregnant ladies and young children. They are our first targets. But again, that clever man has an answer. They have started using insecticide-treated mosquito nets (ITNs) and preventive antimalarial medicines which are so effective that we are losing our sting power.

An. subpictus: Oh yea!! Then this Goa team trained their guns on me recently and started blaming me for spreading malaria parasites from sick to the healthy alongside you, stephensi. They have found this out using a special machine called PCR.

An. stephensi: Yes these ICMR guys have turned out to be a big threat to all of us the last few years. I even heard that a Ph.D. student Minisha (author) is also working on various kinds of bacteria in our tummy (midgut microbial diversity) which she is planning to use against malaria-causing parasite Plasmodium.

She has killed hundreds of us to study our bacteria. One of our friends who escaped her slaughter voiced out. This Minisha first gives them a special clean-up! She calls it surface sterilization of our babies and us and then cuts us open, reaches our stomach and crushes it, and puts it on some medium to multiply these bugs in our stomach and study them.

An. subpictus: Oh My God!! May their soul RIP!! What she must have done after that?

An. stephensi: I heard that she has recognized (identified) many of them and she is calling them by names. Using so many chemicals and complex methods she has identified bugs that are already dead in our stomach and fail to grow. I heard her calling this method as molecular technique Metagenomics. I have never heard of these difficult words. But, she says, her work can be very helpful for us too.

An. subpictus: How is that possible? On one side she is doing this to harm us and on the other, she is spreading this news? What is the basis? You don’t believe her blindly.

An. stephensi: She identified microbes from our friend’s midgut and matched them with those residing in the curing water habitat where our babies live and also matched them up with us who are jailed in her laboratory. I even heard her saying that some of these bugs (microbes) help us grow from babies (larvae and Pupae) to adults.

She claims that our friend’s breeding and their larvae feeding in the laboratory in tap water have different bacteria in their stomach than the one she identified from curing waters. Since field water is healthier and has more variety of these bacteria, I have started to lay my eggs in the field sites so that I have stronger offspring with greater immunity. Is not she crazy???

An. subpictus: Oh really? That’s cool!! I think even I should tell my friends to do the same.

An. stephensi: No doubt’s she is a crazy girl. She did not stop here. She even treated hundreds of our friends with an antibiotic (Tetracycline hydrochloride) and compared their life events with our friends from the field and Laboratory population. By doing this she studied the influence of the microbe on our life cycle. Our sisters who received this special treatment laid a fewer number eggs compared to others who did not. That means these tummy bacteria are important for us.

An. subpictus: But my friend, I am warning you because she may be doing something else to control us. It is possible that she may be doing this for the same purpose.

An. stephensi: whatever she does she will do to put us down. I heard she has got some bacteria common in water, our babies, and us.

She got different kinds of bacteria common in all the stages viz. water, larvae, pupae, male and female by a metagenomic approach. She also confirmed the presence of Pseudomonas along with few more microorganisms. She says she will try to manipulate them against us for vector control.

An. subpictus: oh no!! I think her research is going to be a big threat to all of us in Goa.

An. stephensi: yes indeed! This crazy budding Scientist is dangerous.

An. subpictus: what you think we should do now

An. stephensi: First let us go and show her our power. We both will go and bite her.

An. subpictus: No! We should avoid her. She may catch us and open our stomachs also.

An. subpictus: Then let us be smart and use her study in boosting our immunity just like humans, who are enhancing theirs against COVID-19 now days.

An. stephensi: How do we do that?

An. subpictus: Let us breed and drink water from curing water site, the water-rich in the microbiome. Her research showed an increase of Bacillus sp. in tap water while more diversity of microbiome in the curing water habitat. This will boost our immunity making us stronger and healthier.

An. stephensi: subpictus my friend, we had a very informative dialogue. I will surely inform all my friends and also see that they take the precautions.

An. subpictus: Yes indeed, in fact, I asked my friend to stay safe because I heard she is searching for some more mosquitoes for her further research. In short, humans are running away from the Coronavirus and we should from this mosquito girl. People do not understand that we don’t harm humans intentionally. Since we need blood for the sake of our eggs and the future. If that was not the need and requirement we wouldn’t have bitten them, unlike males who only feed on nectar for their survival.

An. stephensi: it’s the law of nature and no one can change that, ultimately, it’s the fight for survival and the fit shall survive.

An. subpictus: yes, so true I just hope now the pandemic subsides so that we regain our importance very soon.

An. stephensi: Don’t worry my friend, this autumn will be a new start for us and for all mankind let us hope for the same.

Ending the conversation, both the mosquitoes bid goodbye to each other and went away. As they dispersed, I was left pondering so many questions.

Read more on the Journal of Stories in Science

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Growing up in Science: Anne Urai

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Anne Urai 

[su_boxbox title=”About”]Dr. Anne Urai received her undergraduate degree in cognitive neuroscience and philosophy at University College Utrecht in 2010, followed by a masters in brain and mind sciences at University College London and Ecole Normale Superieure in Paris. She then pursued her doctoral research with Tobias Donner at the Universitätsklinikum Hamburg-Eppendorf and University of Amsterdam, investigating how our previous choices bias the way we interpret later information, and how this process is affected by the confidence in our decisions. Her PhD was awarded the NVP brain and cognition thesis prize, specifically for its combination of interdisciplinary methodology and open science approaches. As a postdoctoral fellow in Anne Churchland’s lab at Cold Spring Harbor in New York, she studied the neurophysiology of decision-making using high-density neural recordings in the mouse brain. During this time she was a core member of the International Brain Laboratory, working with a global team of systems and computational neuroscientists to assess the reproducibility of systems neuroscience. She joined Leiden University in The Netherlands as an Assistant Professor in 2020, and was awarded tenure in 2022. Dr. Anne Urai’s research focuses on the neural basis of decision-making across mammalian species, and the interaction between learning and perception. A current focus of her work, funded by an NWO Veni grant, is on changes in neural and behavioral noise across the lifespan. The story below is co-published with Growing up in Science. [/su_boxbox]

[dropcap]I[/dropcap]had a careless childhood. I was good at school, but could never quite decide on my passions. I dropped high-school physics and chemistry in a streak of rebelliousness, only to realize my mistake a year later and catch up over the summer break. In my first semester at university, I randomly signed up for several interesting-sounded courses and got into cognitive neuroscience and philosophy.

I loved both of them, deciding on the spot that I would solve all of psychology by studying the brain. I spent my exchange semester traveling and eating my way through China, and another year working soul-crushing sales jobs, herding sheep in France and ultimately following my boyfriend to backpack through Asia. In a hot Moroccan internet cafe, I read that someone would pay my to live and study in London and Paris for two years, which seemed too good to true!

During my masters, I pursued my fascination for consciousness research (usually reserved for retiring professors) which mostly involved staring at EEG wiggles in windowless rooms. As a friendly collaborator was fixing my atrocious Matlab code, he off-handedly mentioned that Tobias Donner had just started a lab in Amsterdam – conveniently close to the city where said boyfriend had just started a new job. With my heart racing I approached Tobias at a meeting, didn’t faint, applied for a fellowship, and started my PhD in his group.

Having made most of my MSc thesis figures in Excel, I suffered serious imposter syndrome, but discovered I actually quite liked the technical and programming parts of the job. I passed through a serious crisis halfway through the PhD: my initial proposal turned out to be severely underpowered, psychology’s replication crisis was in full swing, my advisor’s lab had moved to another country, and I hadn’t published a single paper.

My advisor’s gentle persistence, many yoga classes and an adopted cat helped me follow through, and I decided to give postdoc life a chance. After getting stuck in a snowstorm when interviewing at CSHL, I accepted the offer to join the Churchland lab, got married, and defended my PhD within a frantic 6-months!

Coming from a background in psychology and cognitive neuroscience, it was both frightening and exhilarating to work with ‘real’ neuroscientists. I had to learn soldering, surgery and bluffing my way through genetics. I loved being a part of the (then early-stage) International Brain Lab, but started feeling terribly homesick after 1.5 years on Long Island.

Just as I prepared to spend the summer doing data analysis in NYC, Covid-19 hit. Bored at home in lockdown, I opened a long-forgotten ‘Jobs’ email folder and saw a vacancy for a combined psychology teaching and research position in The Netherlands. Within short succession, I found out I was pregnant, got the job, and learned the Churchland lab would be moving to California! Choosing my rainy, flat home country over sunshine, I hurried to finish experiments and returned home just in time for maternity leave.

So far, I have survived my first year of sleep-deprived parenthood and my assistant professorship, which has turned into a tenured position by happenstance (i.e. union negotiations). While getting settled into faculty life, I regularly experience existential dread and wonders if writing scientific papers is what I should be doing for the next 35 years. Since my postdoc in the US, I am increasingly concerned about the climate crisis, and I spend my evenings thinking about decarbonizing academia and worrying about the future.

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