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The power of dreams

“Jo sovat hai so paavat hai”

Those were the days when the brain would imagine a lot. All we had for input was the voices of the likes of Sushil Doshi and Narottam Puri to help us visualise how the events during a cricket match were unfolding at Wankhede Stadium or Feroz Shah Kotla. The gap in input and reality was not just due to limited engagement of sensory devices. We would also have to imagine what was happening during the time we were inside classrooms. Recesses were the only times when we would rush to the houses near our school to catch up on running commentary. To watch a match live was a luxury we could not even afford to imagine. And here I was watching a cricket match between India and West Indies sitting on a stand at a “khachakhach bhara” stadium. B.S. Chandrasekhar had just hit Andy Roberts for a boundary. A text book straight drive. Yes, Chandrasekhar! As I raised my hands to applaud, I felt the seat has become unstable and I was about to fall. Coming to my senses, I saw that I was sitting on the sewing machine cover in the middle of night. How I sleepwalked from bed to that point, I had no idea.

Such incidents of acting out dreams, while in the middle of REM sleep, arise because of partial failure of the brain to paralyse the body. But why do we dream in the first place?

Although the realms of sleep and dreams are active research areas, we know that during sleep time, the brain flushes off toxic substances. It also consolidates our learnings that happen via processing of sensory inputs during the day. More importantly, it clears the synaptic connections to make room for the next day’s learning.

Dreams are much harder to account for. There are a few initial hypotheses of which one appeals to me. The one by Erik Hoel.

A common thing about dreams is that they are weird. Some are more weird, even horrifying, than the cricket match dream I had. Hoel finds value in this weirdness. Let me see if I can explain in simple terms.

Stereotyping sucks. We hate it when people overemphasise our one trait/behaviour ignoring many others. Technology in the form of social media takes it to another level. The algorithmic intelligence as it stands now presents you with more of what you are consuming. It takes you down the specialisation route and, if you don’t control it, could potentially turn you into an extremist. There is a hidden assumption there that you want to only consume things similar to what you are consuming now. Imagine if nature behaved in a similar way. Let’s suppose that you encountered a dead bird on your morning walk and stood there for a while trying to figure out what might have happened. The next day you see three dead birds. Ten the following day. And so on. Do you see the problem? The world of Artificial Intelligence has this problem of overfitting to a specific dataset which hinders new learnings. We won’t be learning anything new if our brain worked the same way as the current state of AI. This does not happen thanks to the weird dreams that we see, according to Hoel.

The dreams purposefully provide random weird inputs to the brain to prevent it from overgeneralising based on the immediate past inputs it has been fed with. And by doing so it allows us to keep learning from each new experience in life. True or not, I find this hypothesis intriguing.

Hoel, E. (2021). The overfitted brain: Dreams evolved to assist generalization. Patterns, 2(5), 100244.

Cancer curiosities

Cancer has baffled mankind for a variety of reasons. It is a malady that arises from within – from inside our very own cells – and not from outside of the body, although onset of some cancer types, such as cervical cancer, is linked to viral infections. Unlike other diseases, which tend to stress cells and cause them to not function properly or even die, cancer causes cells to proliferate. Therapeutic strategies therefore target killing cells rather than saving them or repairing their functions. In the strictest sense, cancer has no cure. No one can guarantee that a cancer, once remitted via treatment, will not come back or will not have side effects. In spite of unprecedented money spent on cancer research, medical community is yet to come close to finding a cure. Continuing reliance on the age-old approach of “slash-poison-burn” for cancer treatment has frustrated the likes of Azra Raza who seek a shift in cancer research focus to detection of the first signs of cancer rather than finding a cure1. Finding the root cause is the key to solving a problem. As far as cancer is concerned, we are definitely not there yet. But are we on the right track in the first place?

Veteran scientist Paul Davies and his team tried to look at the problem from a different perspective – as having an evolutionary root at “the dawn of multicellularity”. Stated simply, they posit a model wherein cancer is caused by reactivation of ancient ‘vestigial’ genes that promoted proliferation of cells more than 600 million years ago when early multicellular organisms existed as tumour-like colonies of cells2. Multicellularity of the present kind where cell groups (tissues) are differentiated to perform specialized tasks had not evolved then. Their outside-the-box atavistic model points to an extremely deep trait of living beings of rising from the dead. I have witnessed such risings in the sprouts of eucalypts growing on trees decimated by the 2020 bushfires here in Australia. The strategy for cancer treatment, therefore, should target the conditions that trigger reactivation of these ancient genes, suggest Davies and colleagues3.

Eucalyptus sprouts on burnt tree

One such strategy is to expose the affected area with elevated oxygen levels. The idea stems from the fact that prior to extensive cell specialization, conditions on the earth were that of less oxygen. The cells used a different energy generation strategy then that relies on a mechanism called fermentation. The dominant energy generation mechanism in our cells uses oxygen to make more energy units via cellular respiration. Mind you, our cells also possess the provision of fermentation process. Cancer cells are known to downregulate cellular respiration in preference to this primitive mechanism of fermentation, a condition known to cancer specialists as Warburg effect. The idea of treatment with elevated oxygen levels is therefore an effort to eliminate the condition of less oxygen (hypoxia) in the vicinity of cancer cells which could have triggered reactivation of ancient gene and hence fermentation in these cells. The low oxygen environment of tumours is caused by high rate of proliferation of cancer cells which cannot have access to enough oxygen because of low rate of formation of new blood vessels for supply4.

Some researches ascribe the switch from cellular respiration to fermentation in cancer cells to malfunction in mitochondria, the organelle where respiration is carried out. The problem with such a conclusion is that Warburg effect is also detected in cancer cells with healthy mitochondria5. Mitochondrial functions, including energy generation, are now considered necessary for tumour formation and proliferation4. Not only that, some tumorigenic cells are found to depend on cellular respiration and, surprisingly, have defective fermentation line of energy generation6. Such cancer stem cells differ from other cancer cells in that they are also multidrug resistant.

Drug resistance is a major obstacle in cancer treatment and a cause of many cancer deaths. The most common cancer treatment of chemotherapy actually uses an inbuilt capacity of cells to self-destruct. The cell has a preprogrammed mechanism of demolishing itself without causing damage to adjacent cells. Programmed cell death occurs when mitochondria indicate to the cell that they are under environmental stress. Chemotherapy aims at signalling mitochondria to activate the death processes in cancer cells7. Such signalling works because cancer cells do not have their death machinery disabled. Cancer only causes cells to regulate some of their proteins that help with not initiating the death machinery and hence cancer cells continue to proliferate. In many cases, cancer cells gradually become resistant to chemotherapeutic agents during the course of treatment. Such resistance is allegedly caused by subdued response of mitochondria to the effects of agents8. What causes mitochondria to change their response is an intriguing unknown.

The pathways of fermentation and cellular respiration are connected in normal cells via an intermediate compound called pyruvate. Pyruvate forms outside of mitochondria from glucose and is carried inside mitochondria for further energy generation via respiration. Pyruvate is escorted into the mitochondria by a carrier complex. Intriguingly, in colorectal cancers, these carriers are found to be less in number. Thus the link between glucose metabolism outside of and inside mitochondria is broken in cancer. It has been further found that in such cases, fatty acid uptake from outside into mitochondria increases. Note that mitochondria can carry its functions via fatty acid metabolism in addition to pyruvate metabolism. With pyruvate pathway blocked because of loss of carriers, it relies for its functions on fatty acid pathway in cancers. This feature of break in pyruvate import into mitochondria is considered necessary and sufficient condition for cancer initiation9.

Normal (blue) and cancer (red) cell energy generation

Another feature of cancer that arouses curiosity is its uncanny resemblance to certain aspects of sex. One such aspect is that cancer cells frequently express genes that are normally exclusively expressed in testis10. Expression of such genes that are related to the sexual cell division (meiosis) and to germ cells in general has led to a notion that cancer development might represent transition from somatic to germline behaviour11, 12.

During normal cell division (mitosis), there is an important stage called G1/S checkpoint where the key decision whether to proceed with cell division or not is made. The decision is made after taking stock of availability of nutrients and enzymes required for the process. This important checkpoint is inactivated in some special cases, such as in primordial germ cells in mice before sex determination13 and in induced pluripotent stem cell (iPSC)14. The checkpoint is also found to be inactive in a majority of cancer cases15. At this juncture, I remind myself of the role mitochondria play during G1/S checkpoint. A study has found that mitochondria form an unusually hyperpolarized giant tubular network at the G1-S transition16. This hints at mitochondria controlling G1/S checkpoint which has been found to be the case in the fly Drosophila17. What happens to mitochondria during this stage in cancer cells, I ask myself.

As with most cellular processes, mitochondria appear to be deeply involved in cancer too. Is the mitochondrial DNA (mtDNA) in cancer cells any different from normal cells? I searched and found that tumour cells usually have fewer mtDNA copies than normal cells18. Further, mtDNA fragments are found to be inserted into the nucleus in cancer cells during the lifetime of patients and this could have had causative influence in cancer development19. A rather interesting side note here is that in yeast such mitochondrial insertions have been found to promote replication of nuclear DNA20. Also important in cancer development are mutations of mtDNA that exist in many cancers21, most notably in the control region of mtDNA but also of genes responsible for enzymes required for biosynthesis.

Meanwhile, support for the atavistic model of cancer is increasing by the day. Analysis of data from the Cancer Genome Atlas has shown that, in several cancer types, genes identified typically with unicellular organisms were upregulated and those belonging to multicellular organisms were inactivated22 indicating that cancer is driven by reactivation of ancient gene regulatory networks. Also supporting the atavistic model is a proposition that tumour growth represents an in-between mechanism of reproduction that utilises certain features of meiosis to reinstate tumour germline which manifests itself as altered chromosomes which is a hallmark of cancer23.

What to make of all this? I cannot overlook the pointers which tell me that we need to continue to have a closer look at mitochondria and its DNA, more than that of the cell itself. Cancer defies cell’s preprogrammed limit of 40-60 replications (Hayflick limit) by manipulating the limit enforcing structure (telomere). The focus naturally is therefore on the cell’s DNA. One study24 has even held random “bad luck” mutations of DNA mainly responsible for cancer over other factors such as environment and heredity. Such mutations, the study concludes, are caused by DNA replications and are responsible for variance of cancer risk among various organs. The root cause however must be a level deeper I believe. I think of my review article25 which takes a holistic view of mutations of mtDNA at various levels of containment. Mitochondria maintains its health and keeps mtDNA mutations in check by a fusion-fission dynamism where it destroys mitochondrial fragments carrying more mutation via a process known as mitophagy. Does mitophagy have any bearing on cancer? There indeed is a connection. More on that later.

References:

  1. Raza, A. (2019). The First Cell: And the Human Costs of Pursuing Cancer to the Last. Basic Books.
  2. Davies PC, Lineweaver CH. Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors. Phys Biol. 2011 Feb;8(1):015001. doi: 10.1088/1478-3975/8/1/015001.
  3. Lineweaver, C. H., Davies, P. C., & Vincent, M. D. (2014). Targeting cancer’s weaknesses (not its strengths): Therapeutic strategies suggested by the atavistic model.BioEssays, 36(9), 827-835.
  4. DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Sci Adv. 2016;2(5):e1600200.
  5. Liberti MV, Locasale JW. The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem Sci. 2016 Mar;41(3):211-218.
  6. Viale, Corti and Draetta (2015) Tumors and mitochondrial respiration: a neglected connection. Cancer Research 75(18).
  7. Sarosiek KA, Ni Chonghaile T, Letai A (2013) Mitochondria: gatekeepers of response to chemotherapy. Trends Cell Biol23:612-619
  8. Coku, J., Booth, D. M., Skoda, J., Pedrotty, M. C., Vogel, J., Liu, K., … & Hogarty, M. D. (2022). Reduced ER-mitochondria connectivity promotes neuroblastoma multidrug resistance.The EMBO Journal, 41(8), e108272.
  9. Bensard, C. L., Wisidagama, D. R., Olson, K. A., Berg, J. A., Krah, N. M., Schell, J. C., … & Rutter, J. (2020). Regulation of tumor initiation by the mitochondrial pyruvate carrier. Cell metabolism, 31(2), 284-300.
  10. Bruggeman, J. W., Koster, J., Lodder, P., Repping, S., & Hamer, G. (2018). Massive expression of germ cell-specific genes is a hallmark of cancer and a potential target for novel treatment development. Oncogene, 37(42), 5694-5700.
  11. Feichtinger, J., Larcombe, L., McFarlane, R.J. (2014) Meta-analysis of expression of l(3)mbt tumor-associated germline genes supports the model that a soma-to-germline transition is a hallmark of human cancers. International journal of cancer. 134(10):2359-65.
  12. McFarlane, R. J., & Wakeman, J. A. (2017). Meiosis-like Functions in Oncogenesis: A New View of Cancer. Cancer research, 77(21), 5712-5716.
  13. Bloom JC, Schimenti JC. Sexually dimorphic DNA damage responses and mutation avoidance in the mouse germline. Genes Dev. 2020 Dec 1;34(23-24):1637-1649. doi: 10.1101/gad.341602.120.
  14. Araki, R., Hoki, Y., Suga, T. et al. Genetic aberrations in iPSCs are introduced by a transient G1/S cell cycle checkpoint deficiency. Nat Commun 11, 197 (2020).
  15. Molinari M. Cell cycle checkpoints and their inactivation in human cancer. Cell Prolif. 2000 Oct;33(5):261-74.
  16. Mitra K, Wunder C, Roysam B, Lin G, Lippincott-Schwartz J (2009) A hyperfused mitochondrial state achieved at G1-S regulates cyclin E buildup and entry into S phase. Proc Natl Acad Sci USA 106:11960-11965.
  17. Mandal S, Guptan P, Owusu-Ansah E, Banerjee U (2005) Mitochondrial regulation of cell cycle progression during development as revealed by the tenured mutation in Drosophila. Dev Cell 9:843-854.
  18. Reznik E, Miller ML, ?enbabao?lu Y, Riaz N, Sarungbam J, Tickoo SK, Al-Ahmadie HA, Lee W, Seshan VE, Hakimi AA, Sander C. Mitochondrial DNA copy number variation across human cancers. Elife. 2016 Feb 22;5:e10769.
  19. Puertas, M. J., & Gonzalez-Sanchez, M. (2020). Insertions of mitochondrial DNA into the nucleus: effects and role in cell evolution. Genome, 63(8), 365-374.
  20. Chatre, L., & Ricchetti, M. (2011). Nuclear mitochondrial DNA activates replication in Saccharomyces cerevisiae. PLoS One, 6(3), e17235.
  21. Wallace, D. C. (2012). Mitochondria and cancer. Nature Reviews Cancer, 12(10), 685-698.
  22. Trigos AS, Pearson RB, Papenfuss AT, Goode DL (2017) Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors. Proc Natl Acad Sci USA 114:6406-6411.
  23. Salmina, K., Huna, A., Kalejs, M., Pjanova, D., Scherthan, H., Cragg, M. S., & Erenpreisa, J. (2019). The cancer aneuploidy paradox: In the light of evolution. Genes, 10(2), 83.
  24. Tomasetti, C., & Vogelstein, B. (2015). Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science, 347(6217), 78-81.
  25. Deonath, A. (2021). Evolution of eukaryotes as a story of survival and growth of mitochondrial DNA over two billion years. Biosystems, 206, 104426.

Believing is seeing

Our sense of sight mimics the mechanism of camera or maybe actually it’s the other way around. But that’s only half the story. Lights reflected by the dog’s face enter via lens and excite sensors at retina – the photographic film of the eye. That’s where the analogy ends I am afraid. The camera doesn’t interpret the image for us. We fall back on the eyes – rather the brain behind the eyes – for that, which is what you are doing right now if you are looking at the picture.

What is happening inside the brain is nothing short of miracle. Let alone the mechanisms we are yet to fathom, what we understand now is extremely complex processing. The retina map in the form of electrical signals are processed in many layers. The first layer deciphers the edges of the dog’s face and passes on that outcome to the next layer for a bit more detailed processing. And it goes on until we know it’s a dog’s face. But it needs to compare the outcome with something it knows. That aspect is taken care of thanks to our past experiences. We have seen many dogs before. This sums up how we experience seeing, most books say. The image analysis part of artificial intelligence is based on this processing. The ‘comparison with past experiences’ part is mimicked in deep learning. Recent success of AI then means that the above mechanism of ‘outside in’ processing really reflects how the conscious brain works. Right? Wrong – according to Anil Seth.

Seth in his book Being You says it all starts with our predictions based on our experiences. Sensory signals merely assist with error correction. In the end what we see is our best guess after all corrections. So it is ‘inside out’ processing and not ‘outside in’ that gives us our consciousness. The world our conscious mind sees is hallucination indeed, albeit a controlled one. That also explains why sometimes we only see what we want to see (the dog’s face in this picture for instance). The extra focus added by the camera kind of mimics the ‘precision weighting’ aspect of the brain’s mechanism.

Just another plant

It was just a weed. For this to lead to a serious ethical dilemma was the last thing I expected. But it did. Our thought process indeed knows no bounds.
It was a sunny Sunday after a rainy Saturday. I was pulling out weeds from my garden. The moist soil made the job easier. While pulling one tiny plant thinly spread over the pebbles I paused and thought of the effort and energy the plant had spent growing that far. And here I was nullifying all that expense in a snap by uprooting it. It’s a “weed” for me. For nature, it’s just another plant. It started its life like any other living creature. Its cells must have multiplied everyday and worked hard on the environment gathering nutrients and fixing carbon. So why did I single out that plant? Because it’s ruining the appearance of my garden. I wouldn’t be bothered about thinking beyond that. Until that time.
“We should have goats. I would rather this weed become part of food chain than throw it away.” I told my daughter who was weeding another section of the garden.
“Goats are good,” she said. “They feed on pretty much anything and grow. A self-sustaining organic mower.”
“And then they give milk which you could drink.”
“Umm… I don’t like goat milk. It tastes weird.”
“It’s an acquired taste. Nutrient-wise the milk is very good.”
“But it has to give birth to be able to produce milk. Have you thought about that? Which means you need to also keep male goats.”
“Not necessarily,” it was my wife who until then was quietly listening to us while sowing seeds in a fresh veggie patch. “You could take it to a goat farm.”
I added, “Also, there must be facilities these days for artificial insemination I am sure. But of course we need to think from end to end before taking any step.”
I noticed that my daughter was unusually quiet. I asked, “What happened?”
“I don’t like this idea of producing babies that will be ultimately killed for the sake of us having milk.”
“But we do drink milk…”
“Yeah I know…”
“Then isn’t it like turning a blind eye to a problem and pretending it doesn’t exist? It’s like the milk comes from fridge or at best from supermarket and I don’t want to know anything beyond that. Or even if I know I don’t care.”
“Yes I know. Perhaps it’s best to be as sustainable as we could.”
“And what about this weed?” I was hell bent on dragging the discussion back to weeds. “Just because this poor creature does not have a central nervous system to feel the pain, we can do anything with it?”
“Well we can put this in compost. That way there is reuse of resources.”
The argument ended there. But not the one brewing inside my mind. It’s not just the patch of land I own. We have changed the entire land habitat of the world in a big way.
We control lives of not only domesticated plants and animals but also wildlife. We decide which species should thrive alongside us. Artificial selection by us is rivalling natural selection at least in the ecosystems close to where we live. We have also made wholesale changes to ecosystems, for instance, by altering course and storage of surface water flow.
Our horizons are expanding by leaps and bounds. We are seriously looking beyond the planet we inhabit. We like to believe that we are the only creatures to have a pan-global outlook. With this self-confidence however comes greater responsibility. We cannot afford to be selfish anymore. Not even in the name of doing things beneficial to humankind. We must look beyond our species. Pandemic period has opened our perspective to alternative ways of leading our lives. As a living animal, we have to consume for survival. Yet what we consume and how we do it can be better managed. We must question what we have been doing as a matter of habit. Even a small act like weeding. We humans have been bestowed with exceptionally large neocortex for a reason.

Competition is overrated

The world actually runs on cooperation. The scientific and technological advancement we humans have achieved is impossible without cooperation. We shared knowledge. We worked together on projects. Our organ cells work in sync with each other to achieve outcomes. An organ going selfish invites cancer. Why do we then celebrate competition which motivates selfish behaviour? I ask and explore in this article: The devil is in the headline

Building Myself from Scratch

I was watching a sixties movie last week. Halfway through the black-and-white classic I remembered having heard from my father’s mouth that this was an outstanding movie. I was surprised that I had that insignificant and meaningless (to me then) one sentence film review in my memory because I must have been under 10 then. The movie really was very well made. It wasn’t a popular movie then and isn’t remembered much now either. It suited my taste and style though. I asked myself if I had acquired that taste from my father. This could be my wishful thinking. Yet it always amazes me to think how that half set of genes of each of my parents eventually shaped me to this day. How this 60+ kilos of my body with all its fully functioning organs emerged from that single tiny cell formed about 38 weeks before my birth? Read on …

Post-COVID-19 World: Is De-urbanisation on the Cards?

Cities emerged most likely as a consequence of the mankind’s shift to agriculture as the dominant occupation. Unprecedented urbanisation happened as an aftermath of the industrial revolution. So it’s basically the economic need that drove us here. Social needs hardly require us to live amidst hundreds of thousands of other people around. Now with internet connecting us without the need to be physically connected, it’s time we questioned the old, and still very much in vogue, model of city based services. Do we continue to allow the megacity dinosaur grow or let the small town/village birds fly? Here in this article I compare evolution of civilisation with evolution of life. Read on…

Lovelock Writes at 100

We are the “highest” species on the Earth, at least in our anthropocentric view. Would we continue to dominate in future? No, says the visionary James Lovelock. Who then is going to take over? When? Are we going to continue or become extinct? Read on… only 3 minutes long…

Game, set, match Mother, by design

Almost like a ritual before preparing to serve, a tennis player picks up three balls, looks at them once and rejects one. How efficiently could one reject a bad ball out of three with just a casual glance? Yet statistically this process makes sense. If not for one’s inability to grab more than three, the player has a better chance of ending up with the best two balls if there are more balls to reject. Anyway, this act passes off as a trivial routine – too mundane to register in our minds focussed on what is going to happen when the ball is in play. But this is exactly the process that mitochondria follow at a crucial stage in our lives and this has a huge impact on who we are.

A mitochondrion is technically an organelle – a tiny organ inside a cell. One of the curious features of mitochondrion is that, like a cell, it has its own DNA. This sure sets it apart from other functional organelles inside the cell and raises its status as something that might have its own life. Indeed it is now widely recognized that mitochondria were once free living bacteria that an ancient cell had engulfed. It has been living inside and producing offspring ever since. Mitochondria multiply and so do mitochondrial DNA. Cells too multiply and divide the mitochondrial population among themselves.

So far so good. But then something happens to certain cells as a result of organisms performing sex which disturbs this usual peaceful settlement process. These ‘sex-related’ cells are called germ cells. When an organism performs the act of sex, a germ cell from outside (sperm) fuses with the resident germ cell (egg) along with its genetic content. The two DNAs recombine and become DNA of the fused cell. Now think of the mitochondria inside each of the fusing cells. There are two sets of populations – one from Mars (sperm) and the other from Venus (egg). Too many individuals to accommodate in a restricted space. Some primitive form of sex had the two parties settle the score among themselves by trying to kill each other. Things are much streamlined in higher organisms like us humans. Not sure if this was a peaceful solution but one set of mitochondria completely vanishes from the scene and the individuals belonging to the other set occupy the newly formed cell. No prize for guessing which group sacrifices itself. The intruders – the mitochondria that previously belonged to the sperm cell – of course.

The offspring of mitochondria that belong to the mother organism’s germ cell occupy the newborn fused cell which eventually develops into a new individual organism. And life goes on. In all animals and most plants and other eukaryotes, only mother’s mitochondria are passed on to the next generation. The male’s only contribution is in providing sperm for sex. Everything else is a dead end for male. So much for the patriarchal society we are proud of!

Besides nurturing the egg and, in mammals, the pre-birth baby, the female body carries out some amazing processes inside the egg cell before and after sexual fusion that are beneficial to the offspring and to the living world in general. To be precise, to the mitochondria. One such process of great significance is called mitochondrial bottleneck. Let me explain.

The single biggest threat to life is damage to its DNA. Back in the times of early Earth, ultraviolet radiation from the Sun would do most of DNA damage. These days, a slow process of damage happens in the form of mutation during the process of creating copies. A few random mutations here and there are non-life-threatening. However, in bacteria such mutations tend to accumulate in the cells and over a period of time could potentially cause extinction of the species. The phenomenon has a popular scientific name – Muller’s ratchet. Mitochondrial bottleneck during the process of fertilization is a mechanism to mitigate the risk posed by accumulating mutations. Just like that tennis player, the egg cell sorts its mitochondrial DNA in clusters and then selects only a few to be passed along while rejecting the rest. Statistically, this process leads to reduced mutations in the mitochondrial DNA that is eventually passed on to the offspring thus ensuring a safer mitochondrial genome for the next generation.

You may be thinking, but that ‘purifies’ the mitochondrial DNA and not the DNA of the cell that in reality is the blueprint of an individual. How important are mitochondria to the overall functioning of the cell and eventually to the organism is a topic in itself – too big to cover here. From the obvious respiration which provides energy, to control of almost every aspect of the cell including sex, ageing and death, mitochondria have a critical role in our well-being. And in a yet another clever design by nature, a mother will pass on more mutational load to her male offspring (that cannot pass on the deleterious mutations further) than to her female progeny. This phenomenon – often referred to as mother’s curse – has been studied in the fly Drosophila – the most common guinea pig for genetics studies (Innocenti et al., 2011) and is likely to be present in all animals. If you are a male reading this, bad luck, but it’s just nature’s design to ensure the protection of what matters most – mitochondrial DNA!

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Innocenti et al. (2011) Experimental Evidence Supports a Sex-Specific Selective Sieve in Mitochondrial Genome Evolution. Science, 332, 6031.

Needless grapes

It took nature more than a billion years since the Earth was born to devise a mechanism for trapping Sun’s energy. This made life in the ocean self-sufficient. Then around half a billion years ago, it delegated the responsibility to plants and animals to carry life forward. To uncharted territories. Plants marched towards the land. Animals came along.

Passing the baton from generation to generation, life kept on conquering territories. There was a big deterrent on land though. In water based plants, male sperms swim to meet the female egg for fertilization. The fertilized egg then needs water to germinate. Water wasn’t as readily available on land as in the ocean. The very core of life’s survival – reproduction – was under threat.

After struggling for another 100 million years, nature invented pollens that carried the male sperms to the female egg using the wind. A neat strategy to overcome dependence on water. Sperms in the pollen and egg fertilize to produce seed which then germinates into a new plant on wet ground.

Now what if there’s not enough wind to carry pollens? Nature looked around and saw insects. They were feeding on pollen-bearing organs with no apparent benefit to the plant. Why not use these freeloaders to carry pollens? But they needed to be tricked into doing so. Thus came about one of the most effective innovations of nature – a rare combination of beauty and utility – flowers. Their colours and fragrance attracted the insects. They found nectar in there which they fed on unaware that the plants quietly loaded pollens onto them while they were busy feeding. This was a huge relief. Plants no longer needed to depend on natural agents – water or wind – to transport sperms to eggs. Reproduction was back on in full swing.

With plants going to far away places via this newfound reproductive strategy, a new challenge surfaced. The seeds that were produced as a result of fertilization still needed water to germinate. How do you carry the seed to wet grounds?

The plants went for the tried-and-tested strategy. They added an enticing structure called fruit around the seed. Again, it was not just a marketing ploy full of colours and fragrance. It did have value proposition too in the form of food. Many birds and mammals fell for it and inadvertently participated in dispersal of seeds.

And then came to this world a bipedal animal with specially modified thumb to easily pick fruits. This gave him advantage over other creatures. He did not however stop at helping the cause of plants by dispersing the seeds. He used the advantageous grip to pick and throw stones and other tools at fellow animals. He then began consuming the seeds on a large scale. Worse, he even invented seedless grapes!

Two sigmas ruin the bell curve

Campus of a premier national institute in India in the nineties. It was dark. Sounds of some people stomping next to the hostel building followed by glass shattering broke the eerie silence. There was a sudden surge of activity in the ground floor wing and everyone came out of their rooms. It was first year Science post-graduate students’ wing. Soon their seniors emerged from the upper floors. An extraordinary general meeting followed. It was a war-like situation. An Engineering graduate student had attacked the room of a Science post-graduate student.

It was not a personal feud. A full-blown inter-caste war it was. The echoes of which were felt decades later when the Engineering almuni left out the Science post-graduates from the celebration of 25 years of graduation. Such deep rooted was the strife.

Chevron fold at Ulverstone, Tasmania in December 2016

Superficial cause: Engineering students who held the majority decreed that a second year Engineering student was equivalent in ‘campus social status’ to a first year Science student. The right of ragging (hazing) a Science post-graduate fresher came with it.

Deep cause: An Engineering candidate was superior to a Science graduate because, ha, no brilliant student in his right senses would do a Science graduation ahead of Engineering and Medicine. So yeah, notwithstanding an altogether different discipline, Science graduates represented an inferior ‘caste’ and needed to be treated as such.

A classic case of conflict due to combined effects of majority-minority dichotomy and social stratification it was. One hopes the current generation is more sensible and that things are much better now.

Call it race, caste, tribe, religion, institutional loyalty, nationalistic pride, geographic superiority or “phylumbaazi” (a colloquial term frequently in use in the region) – excessive invocation by these groups of collective entitlement of their members render them nothing more than refuges of mediocrity. For people who do that are not contributors to the value of the group, but are exploiters of the current value. This applies as much to the “superior” group as to the “inferior” group. Fundamentally they are doing the same. One wants to continue to get the benefits by victimising others for the current perceived superiority of its group, and the other wants to continue to get the benefits of being the victim. None is bothered about the declining perceived value of their respective groups because of their frequent stake at entitlements.

True value-adders of either group do not need benefits of perception. On the other extreme, the bottom-dwellers of either group are content with what they have. It’s the mediocre people in the group who stake a claim to the cake without actually contributing to its making. Unfortunately, the statistical bell curve ensures that such mediocre people will be in the majority. So in the end whether this majority follow the value-adders or dictate their terms onto them determines the merits of the group. It’s not hard to see then why true value-adders sometime leave a group they naturally belong to.

We see people seeking entitlements for various reasons, often at the expense of true merit. One common scenario is: we stuffed it up and are now entitled to prevent others from stuffing it up further. Yet another: we once studied head-down-bum-up to acquire this highly coveted qualification or get into this universally revered institution and now will reap benefits for the rest of our lives. Or: we were treated unfairly when we were new and now that we have reached this position of dictating terms, why should the freshers have it easy? Or simply, we are the sons of the soil and therefore entitled to chew up all the resources here without being accountable to anyone. Whatever the cause, such claims of entitlements have one thing in common – the rhetoric usually comes from the mediocre in the business. And when they seek to extend such entitlements for their offspring, the caste comes in handy.

How to create in zero easy steps

Ever thought of writing a story or composing a piece of music? And wondered what training courses might help? Training helps. Not in creativity though. It might help you master the tools and techniques. But that’s it. It won’t help at all with the creative process.

The very fundamental requirement of training is existence. Of processes. Of tools. Of things. That’s what one will train on. And the very fundamental requirement of creation is non-existence. That’s what one will bring about. Did you see the contradiction?

Music is an arrangement of sounds into patterns. Sounds need to be produced using tools and knowing techniques on how to use the tools. The tools are, to name a few, a flute where wind has to be blown into, a guitar where the string needs to be plucked, or a drum that needs to be struck. Voice is also generated using our own biological tools. One can train on efficiently using any of these tools by mastering the techniques. Does that mean however one can produce music? No.

Learning to ‘use’ a tool to produce sound is similar to being literate. Mere learning to use a language can never make a creative writer. One may just know how to convey a message using a language. Some other may be expert in using the language with correct usage of syntax every time. Still, he or she is just ‘using’ the tool and not creating anything. As long as, of course, he or she is not ‘composing’ a new tangible using a new idea. Unfortunately there is no training for that. There cannot be.

Idea-to-tangible realisation does require the help of people trained in skills, but that’s further down the line. The first step is ‘generating’ the idea which requires one’s intuition to work. The second step of ‘composing’ something from the idea also is intuition-heavy though it may be assisted by learned skills. It is when one wants to convert the composition into tangible outcome that skills become important. Because this is where we are talking of tangible things, people become aware of things from this stage on. Unfortunately, many wrongly presume this to be the first step in creation. Without the first two steps of ‘generating’ and ‘composing’ the idea, there really is nothing new. It can at best be a smart rehash or at worst outright plagiarism.