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……. Inspirations October 13, 2006

Posted by sumesh in Biology, Chemistry, Culture, Nobel Prize, Philosophy of Science, Physiology or Medicine, Uncategorized.
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Besides inspiring those who take science seriously and pursue it dangerously  icon_rolleyes.gif   this year’s Nobel Prizes, at a minimum,  inspire many a coffee-table discussion on the business of science, its growth, serious research and the very idea of giving a prize.  Coffee-table discussions in the sophisticated time of Web2.0 techies, we must not undermine, are moving to blogophere and becoming etable discussions.

To begin with, consider Nobel Prize 2006 for Chemistry.  Dr. Kornberg is a structural biologist by vocation but the prize he won is a prize for chemistry and a surprise for many in chemistry.  Of all things, his discoveries are concerned with the transcription processes in cell.  As we have seen in the last blog his work tells a story of the information transfer from the prince DNA to the princess mRNA and the final protein production in the fortress of cell.

Isn’t it a story in pure biology?  By the measures of school bio, college bio, and advanced bio, it is so grumble chemists.  The only chemical tool he utilised in telling it was crystallography, which he used with uncanny originality to take the actual crystal structure pictures of an enzyme called RNA polymerase II in action- a lallapaloosa kind of great result however. 

Does this award hints at the increasing interdisciplinary nature of higher studies or the periferal biology eating into the more basic science of chemistry or the radical changes taking place in chemistry, biology and other sciences blurring all the distinctive nature of each one of them? (see the News piece “Nobel Prize blurs boundaries” by Katharine Sanderson in Nature 443, 615(12 October 2006).  One can have any of these options and it it too.   

But if we take into account the fact that most of the Nobel Prizes awarded in the last decade were like this years Prize for chemistry, one can safely predict that this trend is here to stay.  Further, the encroaching on the more basic sciences (like physics and chemistry) by the less basic sciences will increase as more and more scholars concentrate on basic research, on the complex issues of fundamental mechanisms of world and life.  However, this will neither blur the boundaries of the disciplines altogether nor reduce one discipline into another.  The complex nature of the issues and findings may unify the disciplines.  One major business of science when it grows is unification of its different branches earlier classified as per the needs of Aristotle & Co. Unification, needless to say, is the sure symbol of matured sciences and ‘the secure path’ to the increasing queerness in sciences.

As for the growth of science, let me just say that it does not work the way as Popper thought it or as Kuhn conceived of it.  One counter example did never come to outplace a theory living and kicking.  (This is a large topic, a topic for many blogs.  So search me taking this up in some near-future blogs.  That means I must move on to the next sub topic of this blog).

The next subtopic is serious research.  ‘What is it?’ you may ask.  When does it start? See the following link for a start. Well, just for a start.


The above link tells a story of research. 

The pursuit of research, it seems, starts when one finds interest in some problem which often happens at undergraduate period (or earlier) when people are at their creative and innovative best.  Generally, the problem for research is formulated at this level as the student works under a master of the field and master the ways of doing research, uninstructed.  

Those who are genuinely interested in basic research will not find it difficult to see the gravity of the problem as they struggle to get a handle on it, or as they tirelessly try or dare to imagine every possible options to tackle the problem at hand.  Some of them get the result at a very young age as many of the great physicist had, on the other hand, some of them take a life’s time to address the issue to their satisfaction. 

 [Isn’t it the case that undergraduates outperform graduates and postgraduates in basic-research-level-tests?  This is no denying the fact that some graduates or postgraduates are great performers.  We are taking the case, here,  in general. 

The difference between undergraduates and others is very evident, especially evident in technological institutes.  The reason for this difference is hard to pinpoint. However, there are some sign posts. 

The competition in undergraduate level courses even in ordinary institutes (again, for technological courses it is very evident) is very high.  Where as competition, if any, in higher level courses is abysmally low.  Most of the applicants take up higher level course as an afterthought, after realising that as other cherished options are not available, continuing education is the best option.  Research, as one friend on mine puts it, ‘is the last resort of the vanquished’. 

It is indeed a great thing (great politically and democratically) that educational set up works as a resort, but greater emphasize on original and innovative work is needed  and newer strategies for getting the best minds must be adopted to yeild interesting findings from research work.  As this year’s Noble Prizes in sciences point basic research is important in its own right.

When and why do we give a prize to someone.  Of course, we give a prize to someone if only there is a prize to give to.  To mention, if there is no Nobel Prize for biology as the case is, one can’t give a prize for biology, unless one introduce it anew.  So if there is a discovery in biology (Nobel prize is not awarded for biology; it is awarded for achievements in physics, chemistry, physiology or medicine, literature, peace and 1968 onwards, for economics) that is more important than the discoveries in chemistry, then awarding Nobel Prize 2006 for Chemistry for a biologist is not fully unjustifiable.  The reason being the second-best-choice. 

Another point is that giving a prize is not just an act of giving something away, or an act that culminates in giving something once and for all.  More often than not, it is an attempt at harnessing the future not just that of the recipient but of the larger world also.  It is an act that takes something from the recipient in the immediate future……..[to be continued]

This year’s Nobel Prizes in sciences are  pointers in this direction. 

The Nobel Prize in Physiology or Medicine for 2006

Biologists Andrew Z. Fire and Craig C. Mello won this year’s Nobel Prize for their work on the silence of the genes as the citation has it- for their discovery of “RNA interference – gene silencing by double-stranded RNA.

RNA interference-RNAi for short- is a gene silencing mechanism animals and plants use for controlling genetic information.  It works both as a tool to regulate gene expression and as a natural defence mechanism of cell against viruses. 

(See the  previous blog for an account of the general structure of a cell)

The information in a gene, if it is to have any use, have to be copied into mRNA molecule which, unlike double-stranded DNA, is single-stranded.

In a fascinating set of experiments Dr. Fire and Dr. Mello found that a matching strand for an mRNA(for it’s single strand) can silence all expression of the related gene that prevent protein synthesis.  The new matching strand binds to the target RNA to create a double-stranded RNA, (like a double-stranded DNA).  That is the new strand interferes with the functioning of the complementary RNA,by locking it, by making it double-stranded.  The resultant double-stranded RNA is destroyed by a set of proteins present in the cell. They found that in this way the gene expression can be silenced and any gene can be inactivated.

This method enables scientists to identify the function of each gene and to explore its pathways.  Thanks to RNAi, it may be possible to silence mutated or damaged genes that result in adverse health conditions.

These findings, along with many other recent experiments on RNA functions, allow us to peer into the detailed workings of cellular machinery.  They show that RNA plays far more important role in the cellular functions.  For instance, mRNA can regulate a specific cellular function all by its own and other types of RNAs such as micro-RNAs can function as gene  regulators.  The increasing realisation of the importance of RNAs in life constructing and sustaining functions of cell takes away much glitz and glamour from the politics of genetic determination.


Yearly Packs of Inspiration October 6, 2006

Posted by sumesh in Chemistry, Culture, Nobel Prize, Philosophy of Science, Research, Science.
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It is that time of the year when researchers from varied fields of intellectual enquiry experience the uncommon feelings of overwhelming elation and atypical ecstasy, thanks to the success some of their colleagues or predecessors achieved in carving nature at its joints and revealing some of the mysteries of the world and life. 

It is that kind of great success that makes every researcher humble and as they say, simple.  It often tells you the story of the remarkable, bold and queer steps taken by young researchers; The journey often starts with undergraduates who question everything and dare every ‘unimaginable options’, and pursue them at the cost of everything else, knowing well that the fascinating journey is the only thing that is guaranteed and not the destination.  It is a research-for-research-sake, knowledge-for-knowledge-sake odyssey.  In that journey of self-actualisation the journeyer who strikes out new paths metamorphose him/herself into a light-bearer who has mastered the path.  Prizes or results, if any, in that pursuit are just some extra benefits of continuing this inspired peregrination.

This year’s Nobel Prizes in sciences show the importance of the ground work done by researchers as a team, many researchers significantly contributing to the unraveling of the enigma of life and the world.  It would have been a great gesture if the Nobel Committee at least mentioned all those who contributed in solving the problem, even while bestowing the prize to one, two or more persons.  For science is rarely an individual enterprise, more often than not it is a group work extra ordinary.

Dr. Roger D. Kornberg won this year’s Nobel Prize in Chemistry for visually showing how genes transmit messages to copy cellular functions.  He has not only described the way by which genetic information in DNA is ‘read’ and copied into messenger RNA, but created detailed crystallographic pictures of it also. 

In his meticulous account of ‘the molecular basis of eukaryotic transcription’ which is cited by the Nobel Committee as the kind of “most important chemical discovery” mentioned by Alfred Nobel in his will, Dr. Kornberg details the mechanisms of transcription that suggests possible regulation of the process.

Once we understand the importance of transcription process in constructing and sustaining life in all organisms, we can’t miss out the significance of the prizewinning discovery and its obvious applications. 

In order to tell this story let me take you back to the basics(you may overlook this part altogether, if you consider it too basic to look into)

[[The building blocks of human/animal body are cells (there are approximately 50-100 trillion cells in a human body).  Cells typically have an outer membrane and contain fluid called cytoplasm.  The most important of the parts(organelles) in the cytoplasm is the nucleus.  Within the nucleus there are structures called chromosomes which contain the genetic material of the organism.  This genetic information is stored in long strings of DNA called genes. DNA molecules, as everyone knows, are like spiral staircase.  Each stair in this ‘double helix’ is composed of the DNA bases A, C, T, G which in particular sequences constitute individual genes. In other words, each cell contains  ‘recipe’ for protein production stored in DNA segments which are called genes. 

Human genome, ie. the complete set of genes, though contains around 30, 000 genes, only  a few of them are expressed, ie, used in each cell.  The role these unexpressed genes play in cellular functions is not known.  The expressed genes determine and help synthesize new proteins which construct and sustain the organism.  To put it simply, genes determine the function of particular cells

(#An aside:  Please note that this is a very simplifiedaccount of ‘gene’.  Present understanding of ‘gene’ is extremely complex that one may say that there is nothing like a well-defined gene in a cell.  Further, recent studies give much importance to the workings of RNA as are given in the Nobel Prize winning discoveries in Chemistry and Medicine this year. I put this interesting point as a topic for another blog. For now see these references.  news@nature Published online: 24 May 2006
Nature 441, 398 – 401 (25 May 2006). ]] 

Gene expression is controlled by transcription process in which DNAs in the nuclei of cells are copied to messenger RNAs whose job is to pass the information to the protein synthesizing machinery in the cytoplasm.

Transcription, if you remember,  is the process of copying and transferring genetic information to different parts of cell.  In this process information stored in the genes inside the central nucleus of cells get chemically transcribed into recipes for the proteins that are building blocks of living organisms.  And different parts of the cell work in tandem, as writers, editors, chefs, supervisors and assistants, in executing this highly complex programme and in trouble-free running of the machinery. (If the machinery is not running smooth which means some health-threatening conditions such as cancer, it is possible now at least to find where the problem lies and it may be possible in the near future to correct it)

This kind of transcription process occurs in eukaryotes, i.e., organisms having well-defined nucleus in cell.  Other organisms, for instance bacteria, use different transcription process.

Though it was known this process copied genes using RNA molecules thanks to the equally remarkable research work done by many others, what Dr. Kornberg has shown now(2000 onwards) is the detailed description of the role and workings of RNA, as he provides with the exact development of RNA- strand,   X-ray images of crystallised RNA molecules (this became a standard biochemistry tool since then), and the role of different molecules and even atoms in the process.  He revealed, through his study that spans nearly thirty years, the early phases of the transcription process which involves around sixty different protein molecules in converting DNA into messenger RNA molecules.

The transcription machinery which looked like a dark room in 1990s now turned into a well-lit, complexly organised room suggesting many a conceptual revolutions. 

#Roger D. Kornberg ,59, is a structural biologist at Stanford University School of Medicine.

#His father Arthur Kornberg, 88, a biochemist at Stanford, received the Nobel Prize in Physiology or Medicine in 1959 for his work on DNA replication. The Kornbergs are the sixth father-son duo to win Nobel Prizes.

#His one important article is here. Science 2001, 292, 1863 and 1876.

#Dr. Kornberg has used the simple yeast as a model

#His main research work centered around an enzyme called RNA polymerase that makes RNA and regulates the process of selecting genes from the pool of thousands of them, to produce the only protein a cell needed at any particular time.

#One DNA learning site is here http://www.dnalc.org/home.html

Courtesy: The Royal Swedish Academy of Sciences

[To be continued….]