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Biotechnology and Society---Part II
-DNA is Destiny (?)
The Moving Finger writes; and having writ,
Moves on; nor all thy Piety nor Wit
Shall lure it back to cancel half a Line
Nor all thy Tears wash out a Word of it.
-The Rubaiyat of Umar Khayyam
(1048-1122 CE)
Note to readers:
I plead for forbearance with the readers for taking occasional detours from the main theme. My purpose in writing these articles here is not to teach a graduate level biotechnology course but to provide a platform which contains pertinent information and provides opportunity for down-to-earth instruction and discussion. When one is bound for a destination in an automobile the fastest way is to take the superhighway and zoom to your destination. However, by taking the scenic byways, the travel serves a dual purpose, viz.; get to your destination while enjoying the travel landscape. ----SS
DNA (the fundamental driver of all living systems)
is destiny – or is it? It is somewhat controversial to say so. In the Indian mindset, destiny is a constant fixture which explains and justifies everyday happenings to one and all. However, to the Western thinking it is a social taboo to think that our lives are dictated by fate. Even in India, especially in Tamil
Nadu, there are common adages like ‘muyaRchi
thiruvinaiyAkkum’ (efforts will lead you to good
action), and ‘vithiyaiyum mathiyAl vellalAm’
(you can conquer fate using your brain) which counter a fatalistic philosophy. Let us examine how both these points of view are applicable in human genetics.
The quoted quatrain verse by Umar Khayyam reflects an epicurean philosophy exhorting people to enjoy today with “a book of verse underneath the Bough, a jug of wine, a loaf of bread, and thou beside me singing in the wilderness” since everything is pre-ordained in this world. According to him, Fate determines one’s actions and the consequences despite religious virtuosity, and fervent appeals against perceived or real injustices go unheeded. This is a contentious statement at best although not without parallel in Hindu mythology.
In the Hindu religious folklore it is said that in BrahmA’s (the Lord of all creation) factory to produce human beings, there is an instrument known as
Brahma dhandam (the scribe of
BrahmA) at the end of the assembly line which determines the fate of every newborn by writing on a random basis an unedited script on the forehead of every baby. After writing, the scribe reads what it wrote. If the verdict is good the scribe feels happy but if it is deleterious it shrugs itself and moves on to the next baby. It will not and cannot erase the bad script. Umar Khayyam’s verse reflects, pretty much, this concept.
DNA’s composition and function: Now let us turn our thoughts to real life at the microcosm level. Our body consists of various organs; each organ is composed of various tissues, which are in turn bundles of cells. Each cell is a tiny factory in itself and works in unison with other cells to perform their daily chores. All the cells have the same DNA (genetic material) but all the cells do not do the same work. The composition of DNA is pretty simple. The double helical structure of DNA is like a twisted ladder; the two poles are directional (running in opposite directions), with the rungs joining them at a specified constant width throughout the length of the ladder. The two poles (strands) represent linear linkages of a sugar known as deoxyribose with a mineral known as phosphate. The sugars also have a lateral linkage with what is known as a base which can be any one of the four bases known as adenine (A), thymine (T), guanine (G), and cytosine (C). That is it. The bases in each strand (pole) bond with their counterparts on the other strand in a perfect geometric pattern, with adenine always pairing with thymine on the opposite strand while guanine bonds with cytosine. The middle lines joining the two twisted ribbons shown at left are the bases joined together. It is a marvel that such a simple arrangement is capable of directing all activities from birth to death in organisms ranging from a tiny bacterium to a giant animal. There are 46
chromosomes (arranged in 23 pairs, all of them composed of DNA interspersed with some proteins) in each cell, each chromosome has several genes (stretches of DNA), and each gene has a specific function to either make a protein product or direct a specific function such as housekeeping or regulating cellular activities. Sometimes more than one gene is involved in making even a simple product like an antibiotic.
The average length of a chromosome is 5 cm. The total length of all the 46 chromosomes inside a cell would thus be about 3
metres. The average cell diameter is 10 micrometre (10 millionths of a metre). It is again another marvel that such an enormous length of DNA is compacted into such a small space and yet it is able to function precisely.
The blueprint for all cellular activities is mapped into
codons (triplets of DNA bases – ex. ATG, CGG, TCA, etc.) which represent coded instructions within a given gene to make specific amino acids. The codons are pretty universal, with some minor exceptions. The same gene can work in a virus or bacterium as well as a giraffe or human being. The coded instructions can be considered as “molecular software” running the “living systems hardware”. The two main functions of DNA are facilitating growth and maintenance. Either one requires precise coordination of several simultaneous activities.
DNA replication choreography: Let us take a telescopic look at how DNA conducts its ordained function. As we see in the schematic below, the compact structure of the double helix unwinds, makes an exact copy of each strand, a segment at a time, along the whole length of a chromosome in all the chromosomes with the help of several enzymes, and other chemicals. Once two “daughter” (it is not a “son”) molecules are made for all the chromosomes, then the cell divides into two pieces, each one identical to the other. This is growth. The reproduction of the two daughter molecules is done with extreme fidelity, any errors caused during the process being corrected by another set of agents which are in turn governed by the DNA itself.
On a mundane level the replication (copying or cloning) can be considered as equivalent to building a brick house, the DNA acting as the brick mason, directing all the labourers to carry the bricks, cement and water, assemble the bricks at the right places and build the floor, walls and the ceiling. The mason will supervise and make corrections as needed.
On a sublime level, we can think of the replication process as an exquisitely choreographed aquatic operatic ballet. It is all done in a confined space (the stage). There are so many participants (actors). DNA is the prima ballerina. The theme is the manufacture of an exact copy of the prima ballerina herself. The ambience is characterised by water, proper temperature and supporting cast in addition to the observers. Some general rules, as in an opera, such as formation of specific structural elements, the order in which certain species appear, etc., are applicable. While the ballerina has to perform an exquisite act, she is also vested with the responsibility to make sure she reproduces herself perfectly. A glorious divine act, wouldn’t you say?
Now comes the destiny part. In spite of the best efforts by the ballerina (DNA), mistakes do occur which go uncorrected and get perpetuated in subsequent replications too. These defects manifest in metabolic (bodily function) diseases, degenerative diseases and inherited diseases. In this respect the ballerina resembles our Brahma
dhandam, which despite its best intentions cannot rectify an error. The Brahma dhandam is at least sorry for the error which crept in. The ballerina (DNA) does not even have a feeling - or if she has, no one (not even a molecular biologist) can recognise it.
Let us finish this segment with a scene from a thamizh movie,
ThiruviLaiyAdal. In the court of a Pandya king, there comes a famous musician who performs exquisitely and throws a challenge to the king to present a match to him the next day. Everybody is awestruck and no one (even at the command of the king) is willing to take up the challenge. One of the temple devotees was “volunteered”, who goes into a tailspin upon knowing what befell his fate. Lord Shiva, in order to protect his devotee, takes the form of a country bumpkin, arrives at the outer precincts of the quarters, where the musician and his retinue are staying, in the middle of the night and starts singing. The musician comes out upon hearing such divine music and learns that the bumpkin is actually a third-rate disciple of the fellow who was assigned to challenge him the next day. That sends the arrogant musician packing in the middle of the night and out of town in a hurry.
There are two relevant passages in the song worth noting.
1. “ pAttum nAnE, bhAvamum nAnE, …….ethilum iyangum iyakkam nAnE, ennisai ninRAl adangum ulagE” (I am the music, I am the feeling…I am the force behind every motion, when my music stops, the world will
collapse). At this point, the visuals on the screen show everything from the trees, to the birds in the sky, to the waves in the ocean freeze.
2. “nAn asainthAl asaiyum akhilam ellAmE, ithai arivAi manithA..,” (when I move, the whole world moves; thou shalt know
this). The visuals now restore all the regular activities of living beings. It is very typical of DNA too. All activities of living beings depend on DNA. When DNA stops working life ends.
We will look a little deeper into how destiny can be accommodated and/or manipulated in our next article.
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