A cookbook, a photocopy of a recipe from the book and a tad bit of scribbling, highlighting and overwriting on this recipe. Ring a bell? All this could be akin to the workings of the holy grail of life aka DNA (DeoxyriboNucleic Acid).
The code for human evolution and physiology, DNA has been ‘encoded’ by eons of evolution, and has to be decoded by each cell in the body. When a chef gets an order, let’s say pasta, he refers to the cookbook (DNA). But, for ease of use, rather than carrying around the whole book around the kitchen all the time, the chef transcribes only the pasta recipe to a piece of paper (RNA - RiboNucleic Acid). But according to the customer’s demand, for someone with a liking to the spicy edge (the environment), the chef adds a little seasoning or some extra sauce to make it spicy. Voila! The spicy pasta (protein), to please the customer, is ready !
A biologist from Indiana University, James Watson, and a physicist, at the Cavendish Lab in Cambridge, Francis Crick were working on the structure of DNA with the aid of research findings of Rosalind Franklin and Maurice Wilkins. On Saturday, February 28, 1953 it is reported that Crick came into the Eagle, a Cambridge pub, and announced to everyone there that they had ‘found the secret of life’. In 1953 they proposed the double helix model of DNA . In April of 1953 the Watson and Crick paper appeared in the journal Nature. April 25th 2003 was declared as DNA Day to celebrate the completion of the human genome project and the 50th anniversary of the description of DNA.
People have always known that many illnesses (and traits such as physical appearance and even behaviour) ‘run in the family’, and psychiatric illnesses are no exception. Our DNA is like a long diary of human history, passed down from one generation to another, containing many fascinating stories of all our ancestors, with each new generation adding its bit. Scientists uncover these stories by making sense of small differences in our DNA. Studying human DNA and genetics help scientists better understand where humans came from as a species, and also understand the genetic basis of diseases, to list a few.
While many genetic disorders are not treatable, by the methods available at present, early diagnosis helps improve the quality of life, and even extend it. Genetic studies locating thousands of new genes related to different psychiatric illnesses such as schizophrenia, bipolar disorder, movement disorders etc. gives scientists new avenues to look for novel medications and other treatments.
Dadaji: So what are you doing in the lab, Genie beta?
Dr. Genevago: These days I am helping with a research article on genetic variants in mental illness.
Dadaji: Oho… can you tell me what that means in English?
Dr. Genevago: Haha, sorry Dadaji! So, it’s like this: all cells in our bodies have DNA. Any time that cells divide, all of the DNA needs to be copied, to be divided equally among newly created cells. As it happens, Nature is not a perfectionist when it comes to copying DNA, so changes get made. This is what I meant by ‘variants’. Most of these are harmless and we never even know they are there. But some of them can spell trouble! How exactly some of these variants relate to mental illnesses is what I am studying in the lab.
Dadaji: So what have you learnt so far?
Dr. Genevago: We are trying to piece together how these changes in the DNA link to one or the other kind of mental illnesses!
Dadaji: Sounds challenging!
Dr. Genevago: Very! It’s like a million-piece jigsaw! We started with genes where we found variants, the bad ones, in people with mental illness. We found 28 such genes. Of these 7 are entirely new, meaning no one ever knew that these are connected to mental illness!
Dadaji: That sounds exciting! So where does that lead you?
Dr. Genevago: Well, now we have new leads to follow. We first checked what the proteins (that these 28 genes code for) do and if there are any functions in common among them. Some of these proteins do seem to be working together, in what’s known as a ‘pathway’. Next is to do experiments to see how these variants in DNA might change the functions of the proteins and/or pathways.
Dadaji: And how do you go from that to a mental illness?
Dr. Genevago: That’s the million dollar question! We use a very popular technology called ‘disease in a dish’, where we take blood cells from patients with different kinds of mental illnesses and turn them into stem cells. These in turn are used in a lab to study how the brain develops and works. We can study many processes and pathways, or even compare them with cells of others who do not have illness! That could tell us about what’s different in brain cells of patients with psychiatric disease – something that we would never otherwise know.
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Dadaji: Let me just sanitise my hands beta, wait a minute.
Dr. Genevago: What? That’s literally the 100th time you are sanitising your hands today!
Dadaji: I was wondering if I have that illness called OCD. You watch that show right, The Big Bang Theory? I remember seeing a character named Sheldon behaving the same way. Even I like colour coding stuff and having a strict bathroom schedule, just like him! And we even know how strict many families are about maintaining cleanliness!
Dr. Genevago: You mean Obsessive Compulsive Disorder? Oh, don’t worry Dadaji, I’m pretty sure you don’t have it. Organising your stuff or meticulously planning anything doesn’t necessarily mean you have that OCD; it just means you are an organised person! People with OCD have thoughts that become impossible to control, and they are forced to do things over and over again, like a mechanical clockwork toy. They have no control over this, and that makes them very anxious! But you seem to be quite relaxed about your organising skills!
Dadaji: So, is this just stubborn behaviour or ..?
Dr. Genevago: No, no! Research actually suggests that OCD sufferers’ brains are wired to behave in a particular fashion. In fact, in our lab we recently found out that cells from patients with OCD show reduced capacity to divide and form new cells! This may be because of some sort of damage to the DNA, or some sort of visible changes in the brain cells affecting their function. Maybe one day this could answer the question of how OCD is caused!
Of course, it also opens the door to another mystery. If every cell in the body bears a trace of the mental illness that a person has, how subtle and gossamer-like this would be, so that even a slight change traps the person in a web of illness.
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Dadaji: You seem to be working a lot these days, beta. Don’t you get stressed?
Dr. Genevago: I like the work I do, and I know when I need to take a break so that I can relax! But that reminds me, the impact of stress in children is another topic of research in our lab.
Dadaji: Oh, but how can you possibly pinpoint what effect something intangible, like stress, can have on the DNA?
Dr. Genevago: DNA doesn’t always work on its own to bring about changes within our body. It is like the notes of music; these two are fixed but every musician plays them a bit differently. And a single false note by anyone in the orchestra spoils the whole symphony!
Similarly, each person’s DNA ‘expresses’ itself differently, and as harmoniously as it can, depending on the environment (physical, social and psychological). The environment thus plays a very important role in controlling the DNA, and helping or harming the workings of our body. Children from different parts of our country face different kinds of stress, and these could have consequences far into the future. This is known as epigenetics and this is what we try to understand in our lab!
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Devdas singing off key after returning with a new refill:
Dost: Bhai, take it easy! You have been drinking too much!
Devdas: Just let me be. Haven’t you seen what every thwarted hero does? Start the music, we need to dance! That’s all I can do right now..
Dost: Ok, if you insist! Try dancing to this -
Music plays…..Devdas tries to stand up but staggers and falls in a heap
Devdas: What just happened? My feet are not listening to me anymore!
Dost: Right now it’s just your brain; if you go on like this your liver is gone too!
Devdas: Yeah, but I will stop one day. It will all go away and pass like a bad dream….
Dost: No my friend, it doesn’t work that way. Not if you keep up the levels of drinking you are at. My friends who have been researching this very thing tell me that their work has shown that drinking too much, for too long, leaves a lasting bad mark on the DNA, the stuff of life! The blueprint that tells our cells what to do. This same DNA is there in your brain cells and your liver cells. Believe me , things may never be the same again!.
These marks are not stains that can be washed away. They are here to stay. For a while. So listen up!
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We hope you have learnt something new and interesting this ‘World DNA Day’ about the workings of the human brain. If you found our work interesting, we welcome you to explore our website or visit our lab to learn more!