Memories Of Science And More

I never find it easy to write about people I know well, so this is going to be a brief blog, with a link.

The Indian Academy of Sciences has begun an oral history archive, and as part of this, they have interviewed Dr. S. Varadarajan.  Dr. Varadarajan has been a part of Indian science from pre-Independence times, and still retains vivid and detailed memories of his experiences with industry, academia and administration in the area of science and technology.

The interview was conducted last year (when he was 87).  It was an 8 hour interview that has finally been spliced and presented as a 30 minute video.  It shows glimpses of a changing India and the challenges of building research and industry, post independence.

The editing may not be perfect (there are gaps and jumps) and Dr. Varadarajan is visibly tired by the end of the interview, but I still find myself being moved each time I watch it.  Many things perhaps are left out, due to various constraints and I can only add a few things which may not be evident to a viewer - his strong attachment to the country and its people, his tremendous urge to help when he sees people in need, his distress during national or industrial disasters.  (The Bhopal gas tragedy is one such example.  What he doesn't mention in this interview is that every evening he spent hours sitting by the lake, just to regain his equilibrium in the face of so much suffering).  I'm happy that a small part of his vast repertoire of memories has been recorded and that we can get a glimpse of a country and its changing scientific and industrial environment through this recording.

Here is the link:

https://www.youtube.com/watch?v=UsFhNQlQu0A

Remembering GNR

This week has been filled with chatter - scientific, nostalgic and gossipy - it has been a week commemorating 50 years since the Ramachandran map was published.  Most modern biologists are familiar with this plot, which defines the allowed torsion angles in a polypeptide chain.  This probably sounds incomprehensible to many readers of this blog, but the work (deserving of a Nobel prize and now a standard plot in many biology textbooks) laid the foundation for determining the spatial arrangement of amino acid chains that eventually form proteins.

Proteins are the objects that scurry around (or insert themselves in specific locations) in a cell and perform most of the important functions in a cell.  The specific task of a protein depends on its structure, hence it is very important to understand what these proteins look like.  The sequence of amino acids in a protein is defined by the genetic sequence (which can be easily determined nowadays).  But the way in which this linear chain of amino acids will fold into a three dimensional, active and stable protein is hard to deduce.

GN Ramachandran (generally called GNR by his colleagues) and his students approached this problem from a theoretical viewpoint and their calculations (plotted on a map called the Ramachandran map) described the kinds of angles that the links in the main chain (formed by the amino acids) could adopt and the angles that were not allowed.  This map, a completely new concept at the time (in the 1960s) continues to be relevant and useful, not just to theoreticians but to everyone who experimentally tries to solve a protein structure.  The manner in which the plot was worked out, in the University of Madras, with a remarkable idea, a lot of initiative and hard work and nothing other than a simple calculator and log tables, is an inspiring story.  Professor C. Ramakrishnan (CR), who actually carried out the calculations was present at the meeting and shared old memories with the audience, in what can only be termed the "CR style".  Armed with his thesis, original models and quirky wit, he spoke to a fascinated audience about the "birth" of this map.  Time flew by; I hoped and wished he had been able to speak for longer.

The meeting, which was large and diverse, allowed people from many different areas of structural biology to come together, mingle for a few days, exchange notes and thoughts.  Perhaps not very different at the outset from many meetings (though gigantic in scale with over 700 participants), it grew warmer and more animated with time as science melded with bittersweet memories, nostalgia and humour.  There was a place for everyone and everything.  For potentially unending conversations with fluent and famous scientists, for broken but interesting conversations with scientists who spoke English haltingly, for wacky snippets exchanged over beer, for strains of Russian folk songs spontaneously and wonderfully sung by one of the speakers, for new and jazzy T-shirt designs, for the chink of crockery at a candle-lit poolside dinner on a warm Bangalore night.

The meeting draws to a close today and people will go their own ways.  For me, it was nice to be able to observe a part of the events, to hear a few people I wanted to, to meet old friends and to see the Ramachandran map through CR's eyes once more.  Several years ago I had interviewed CR about his involvement with the Ramachandran map (part of which was published in Resonance,  http://www.ias.ac.in/resonance/January2008/p89-98.pdf ).  As this article is not easily accessible to readers outside India, I give below an excerpt from the original interview.


CR- My experience was that many people knew of a scientist called Ramachandran.  They knew only one thing about him, namely that he was almost close to getting a Nobel Prize.  But what more did they know about him?  Everybody said “Oh, he has worked with collagen.”

But what is GNR’s contribution to proteins? 

Proteins are complicated molecules, but they need not be studied in a complicated way.  There is a simple way to understand the various arrangements that proteins can take.

Everybody had the impression that the Ramachandran Map is the one which can be used for the prediction of protein structures.  I want to dispel that idea from their minds.  Ramachandran Map is a tool which can be used for testing a structure- this is now being done extensively.  It is not one which can be used for predicting whether it is an α helix or β sheet.

SV- How did you decide to enter research?

CR- Going back to my college days, I did what we called B.Sc. Honours, in Physics.  I did not have any background in Biology except in the school days, which was more descriptive in nature, and which did not go into my head very much.  I did not have much exposure to Chemistry because that was also over by the Intermediate stage.

In Madras University Physics department they had a course called ‘one year M.Sc.’, which was a specialization in Crystallography and Biophysics.  There were just 5 or 6 seats available for that course.  That was the department of which GNR was the head.

When I wanted to join the M.Sc. course, the only condition GNR put for me was that I continue research.  So, he was clear that this course is not for anybody except people who want to do research.

Though honestly, sincerely, I was not having any idea of research either in University or laboratories, nor had I been exposed to research in my earlier days, I said ‘Yes”, with the idea of joining the course, because if I said “No”, he may not give me the seat.

In that one year, when I was in the department, I was exposed to a research atmosphere.  After that year, he said “Now that it’s over, are you ready to join research?  I’ll give you a scholarship.”  The scholarship was Rs. 200 per month, which was a large amount.  Being familiar with the research atmosphere in the department, I thought “I can also do research.”

After joining came the question “Which branch do you want to do research in?”  I found that there were many people working in Crystallography and not many working in Biophysics.  So I said I would like to work in Biophysics and definitely not in Crystallography.  Any person who has asked this question would be very curious to know why I said I didn’t want to work in Crystallography.  But GNR didn’t ask anything.  He said “I am glad.  Now you can begin.”  That is how my whole future was set.

My fascination has always been with Mathematics.  So when I joined the department the first thing which attracted my attention was an electrical desk calculator, which was called a Marchette calculator.  It could do wonderful things like addition, subtraction, multiplication and division.

SV- When you began work, with collagen, what was the approach?

When I joined the department, in June 1960, it was buzzing with activity on collagen because there was going to be a symposium at the Central Leather Research Institute (CLRI) in December. Many students were working on the structural aspects. The amino acid composition of collagen was known but not the sequence.  Crick had proposed a Gly-Pro-HyPro arrangement, with one hydrogen bond for three residues.  GNR had proposed Gly-X-HyPro (where X is any other amino acid), with two H-bonds for three residues (wherever Pro occurs, the H bond will break).  The X-ray diffraction patterns agreed with both structures though there were some small things that the two-bonded structure showed better.

My job was to do a Fourier transform of both structures and to find out what should be the intensities of a collagen X-ray pattern for each.  I had to find out where the X-ray intensities will be for the entire space, and how much.  ‘Where’ was easy, ‘How much’ was difficult.

But collagen gave birth to the Ramachandran Map.  Crick’s objection to GNR’s structure was that when you have close packing, some of the Van der Waal’s distances will be violated.  This question was not approached from the collagen point of view by GNR, but from a generalized point of view.  He said “This is not just an isolated problem with collagen, this is a problem which is going to be involved in any molecule which has peptides and amino acids.”

At that time we didn’t have a computer.  Everything was developed ab initio.  Prof. Sasisekharan (a student with GNR at that time) was doing a literature search of peptide structures to develop the criteria (for bond lengths).

Regarding my work, some easy geometrical methods existed which were used to calculate the helical parameters of a polypeptide chain.  Peptides being planar was known from Chen and Pauling’s work from crystal structures.  Pauling had also given all the peptide dimensions.  Pauling focussed more on the α helix.  But GNR focussed on one level below that.  The initial idea was, if you take a pair of peptide units, how do you mathematically develop a helix out of it?  Then came the question of defining the orientation.  It can be angles between the planes, it can be angles between the two bonds, it can be anything.  In this case you need the angles of rotation.  The alphabet for the conformational study was a simple system of 4 atoms linked to each other, where you can have a rotation about the middle bond.

When the angles had to be defined there was no starting point.  GNR said “We will take the fully extended chain as the starting point.”

Torsion angles were known in Chemistry but they were used to describe preferred arrangements; to go from one conformation to the other was also known.  But to take two planar units and go from one conformation to another was not known..

It was a rigid body rotation.  Each peptide is a rigid body but the totality of the picture is not a rigid body.  So actually it was very difficult at that time to imagine an angle of rotation without having a defined initial position.  What was needed was to apply the principles (of physics and mathematics) to the actual case of a peptide, and to transform it in a way that you can work with.

SV- How long did it take you?

CR- About one and a half years.  From January 1961, it took about 3-4 months to get the ideas crystallized.  Journals were not easily obtained.  There was no computer.  The Ramachandran map formulation was based on the formulation of the matrix.  There was no book which gave the matrix explicitly.  For about two months I had to search for books.  Finally someone told me “You refer to Classical Mechanics by so- and- so, for the matrix.  I rushed but that book was not available in the library.  Then I had to find out who has taken the book, find out where he is and then, finally get the book.  There the matrix was available.  It took time because the library was in another campus and buses were not easily available. After getting the matrix I knew I was at home because matrix is something connected with Mathematics.

We had only two calculators in the department, one was mostly occupied by the crystallographers.  There was only one person who could service the calculators, and if something went wrong, somehow we had to find him.  There were no phones in those days so we had to go to his house.  Once it so happened that we could not get him.  Fortunately there was one more calculator in CLRI, so I used to sit there for some time.

SV- The amount of information that has been represented in a simple, two-dimensional way is impressive.

CR- Any mathematics or physics person always thinks of plotting.  When you have two parameters variable, it becomes an X-Y plot.  It is easy to perceive and to communicate, but if you are going to work with it you must remember that the two ends are the same; the top and the bottom are the same.  It is almost like a latitude and longitude: Φ and ψ are the latitude and longitude, which go from 0º to 360º each way.  In essence, it is something like a globe.

SV- Were you under any pressure while doing fundamental research?

CR- From the pressure point of view, both GNR and myself were in resonance that we must do the work for work’s sake.  It was not a question of application, it was a question of doing the work.  I didn’t have that pressure but I had the pressure of time, because GNR will say “Go and do it” and I have to do it because I really don’t know, from the next day onwards, when he is going to call me and ask for the results.

SV- What was GNR like, as a Professor and as a person?

CR- I can say only a few things- his sincerity to the work in the department was extraordinary. Whatever he wanted to do he would put his whole body and soul into it.  But the negative point was that he was very impatient.  He would think that everything should be done very fast and correctly, in the right way.  Though he appeared very strict, he had a very good heart.  He would give credit to whatever one did at every place.

He had a knack of seeing things correctly, and was very imaginative.  Though there may be people like him, I have not come across any..

SV- When did you realize the impact of the Ramachandran Map?

CR- For me, it was a continuous process because right from the beginning I have been using it.  I could see that whenever I had a problem about structure or conformation I could immediately use it.  It was my day to day tool.  At the same time one cannot exactly say how much it can be used.  It all depends upon the person (using it).

Now we have come far away from the Ramachandran Map.  As a tool it is has served its purpose and to that extent it was an amazing learning experience.  The main lesson was “Don’t think whether it will be finally useful or not, whether it will be really earthshaking or not, whether you can publish it in this journal or that, but start work, plan it carefully, execute it correctly and present it such a way that other people can understand”.

The Marvellous Maillard Reaction

One of the perks of cooking is being able to smell all the delicious smells that emanate as the food cooks.  This is often more satisfying than actually eating the food; one gets saturated after a few hours of just sniffing and tasting.  I recently discovered that several of the aromas produced during baking or roasting are caused by chemical reactions between amino acids and sugars, broadly classified as the Maillard reaction.  This array of chemical reactions was discovered by the French scientist, Louis Camille Maillard as part of his PhD thesis (discovered in 1912 and published in 1913).  The reactions describe how amino acids (components of proteins) react with reducing sugars (generally found in carbohydrates).  The catalyst is often heat (provided when we begin cooking foods) and the specific reaction depends on the kind of reactants, the pH, the temperature, the water and fat content etc.

The result is a browning (which is different from caramelization) and the formation of many different molecules which have specific aromas and flavours.  These molecules can break down into other smaller molecules (each with different properties of smell and taste); thus a gamut of flavours and textures can be created.  The Maillard reaction is partly responsible for the range of brown colours (formed by compounds called melanoidins) and roasted flavours of many breads, cookies, cakes, beers and popcorn.

I did not realize how important these reactions would become in my life until I began using my cast iron pans regularly.  Of course, these reactions have always been going on in the kitchen, but I did not give them much thought and never dreamt that so many changes would belong to just one family of reactions.  I began to pay more attention to the appearance and smell of food when I bought a book on artisanal breads by Peter Reinhart and began to experiment with a different kind of baking.  These breads are made with very wet dough that is fermented slowly overnight and baked at high temperatures in a moist environment, to give rise to a distinctive outer brown crust and inner open crumb.  The moisture in the dough, the surface tension and aeration are all important as is the temperature at which it will be cooked.  I had to experiment with several different conditions to get a good loaf.

Subsequently Smokey Joe (a small turquoise blue charcoal grill) entered my life and for a while I did not know what to do with it.  In order to understand the process of grilling and barbecuing, I bought a book written by an Argentine chef, Francis Mallman.  This book is titled 'Seven Fires, Grilling The Argentine Way' and it describes seven different ways of applying heat in order to grill foods (and improvised versions for people who do not have access to traditional Argentine grills and large open spaces).  Much of the cooking is done using direct heat of different kinds or in very hot cast iron pans.  I recently began with the simplest possible dishes - crusty potatoes and charred tomatoes, both of which tasted wonderful.  This was largely because while I was throwing in the ingredients, standing back and waiting, the Maillard reaction was doing its stuff - producing crisp, brown, delicious crusts on the outside and leaving the inside tender.

For me, this is a new way of thinking about heat and ingredients - trying to get a perfect roasted or slightly charred surface without burning it, trying to gauge when food is ready by its smell and appearance, trying to retain the lightness and freshness of the food (that is so easily lost on overcooking even slightly).  Of realizing the wonders of high heat, when used in controlled ways.

I am indeed indebted to this wise French scientist and to many chefs and cooks who perfected this art over the years.  Of course, the process does not end here, one can create endless variations by tweaking these reactions.  Molecular Gastronomy is exploring these aspects in academic and commercial ways while home cooks like me are discovering a new way of enjoying the results of this chemistry.

I have no pictures of my attempts at grilling as yet.  I am attaching here some pictures of my experiments with different kinds of breads.  As I have mentioned in an earlier blog, it is unfortunate that I cannot attach the smells as well!

Higgs Boson Joke

Today I read a joke that I enjoyed very much.  After all the grim intellectualizing, it's nice to be reminded that there's always a smiley part to everything.  So here it is:

A Higgs Boson walks into a church.
The priest cries out to him, "We don't allow Higgs Bosons in this church."
Higgs Boson looks puzzled and says, "But how can you all have mass without me?"

The Personal Side Of Science

Recent reports on the discovery of the Higgs Boson (a new subatomic particle) at CERN, not surprisingly, are evoking a multitude of emotions all round the world.  One of Bangalore's newspapers recently published a reprint of an article (from the Guardian) by Amit Chaudhuri.  He writes about S N Bose (after whom the boson is named) and ends by saying:

"Bose didn't get the Nobel prize; nor did his contemporary and namesake, J C Bose, whose contribution to radio waves and the fashioning of the wireless predates Marconi's. The only Indian scientist to get a Nobel prize is the physicist C V Raman, for his work on light at Kolkata University, called the Raman effect. Other Indians have had to become Americans to get the award.

Conditions have always been inimical to science in India, from colonial times to the present day; and despite that, its contributions have occasionally been huge. Yet non-western science (an ugly label engendered by the exclusive nature of western popular imagination) is yet to find its Rosalind Franklin, its symbol of paradoxical success. Unlike Franklin, however, these scientists were never in a race that they lost; they simply came from another planet."

 http://www.guardian.co.uk/commentisfree/2012/jul/03/higgs-boson-western-science

It was evident from the comments on the website that not many people agreed with him, but reading it made me think about why modern Indian science is not making more of an impact globally.

It is true that several deserving Indian scientists did not get the Nobel prize, but this prize has never been quite independent of politics and pushiness - hard for anyone to indulge in all the way from India.  It is certainly not true that most Indians have had to become 'American' to get the prize.  It is very unlikely that those who got the prize for their work overseas would have managed to accomplish what they did if they were in India.  The strengths of American and British science establishments have always been a strong scientific community and support (funding and infrastructure) for technically challenging projects.  This is, of course, changing in the present recession-hit days but it certainly applied to the times when Hargobind Khorana deciphered the genetic code and continued till a few years ago when Venki (Ramakrishnan Venkatraman) showed the physical  way in which the genetic code is translated.  India just did not have the mechanism (or the funding) to allow people to work on  problems of this magnitude.

What is our position now?  This is a question oft asked, especially with the government wanting '20 Nobel laureates by 2020'!!! (perhaps I should put 20 exclamation marks here, but I am restricted by space and time).  Eminent scientists of the country seem to think the way ahead lies in popularizing science by starting many more undergraduate science courses and offering fellowships as incentives to school students who opt for Science (instead of the more popular Engineering or Medicine).  I feel though that this is the wrong end of the stick - the reason the best students opt for Computer Science is because it pays!  It is neither appropriate nor wise to build a 'Science bubble', describing Biotechnology and Interdisciplinary Science in glowing, rainbow colours.  Many students reach the end of the rainbow to realize that it is all just a combination of Physics, Chemistry, Math and Biology - and either you always liked it or you didn't particularly and that there aren't very many jobs for scientists anyway.

My thoughts about how to improve the situation are a little different and are based on my experiences in research institutions and the interaction I continue to have with students and scientists of different backgrounds and ages.  Ultimately, I think, it is all a question of people.  It is people who drive the science not vice versa.  Each Indian research institution has its own system in place - one determined by the funding agency, amounts of money, geographical location etc.  While there usually aren't colossal sums allocated for research, most reasonable research proposals do get funded.  This means that it is certainly possible for many people to do at least a bit of reasonable work.  Projects need to be thoughtfully planned as it may not be possible or worthwhile attempting experiments that require cutting edge technology.  But many kinds of problems don't require that level of sophistication.  Overseas funding and collaborations are also ways by which scientists can get access to better infrastructure.  The real issue is not of being able to do science but of doing meaningful or suitably challenging science - tackling problems that are really worth solving as opposed to churning out reams of data.

There are few brave and motivated enough to pursue this approach, partly because of the desire (driven by those at the helm) to show something for every year that one puts in.  The number of publications seems all important in periodic institutional assessments.  The long term impact of the work, the contribution of each author and the kind of review the article has been subjected to are not given much (or any) value.  This is an unfortunate and widespread phenomenon.  There are just a handful of top quality labs in India that have reasonable funding for research, but unfortunately none of them has given enough thought to the administrative systems in place.  Often the director almost singlehandedly decides the direction the institution will take; many times the best  known scientists do not make the best administrators.

There is no clear tenure track system in place as there is in the US - most jobs (with the exception of those in a couple of institutes) are permanent.  However, insufficient thought is given to the hiring process.  Several times, the people who take the final decisions about prospective faculty are not very well informed about the areas of work of the applicants and their ability to do high quality, independent research.  The places that do have a tenure track system also sometimes pay scant attention to initial hirings, the attitude almost seems to be, "Let the candidates prove themselves, we have nothing to lose by keeping them here for a few years."  This generates an atmosphere of electric tension in the younger labs, each person straining to 'have something to show' to the local review committee that meets periodically.

An academic research institution is intrinsically different from an industrial lab.  Certain personal qualities as well as the value that a scientist will add to an existing scientific community, should be given some merit.  In India, if several researchers with different skills decide to focus on a few challenging problems as a group (apart from doing their individual work), the scope of research that can be done would be much wider. For this, people need to be able to read and think beyond their immediate area of research and have a genuine desire to communicate and collaborate with others.  The worth of an academic scientist is accurately viewed, I think, by the new ideas he (or she) brings, the kind of environment he generates, what his students attempt to do some years after having trained from his lab and, of course, the actual research he carries out and presents.

In my view, Indian science establishments (at least those doing research in Biology and Chemistry) would do well to study the setup at MRC Labs of Molecular Biology (in Cambridge, UK).  These labs have an impressive record of having supported a phenomenal number of Nobel prize winners, several for work done at MRC, and also for the number of alumni who have gone on to win the Nobel prize.  What kind of environment makes this possible?  My guess is that Max Perutz (Nobel prize winner, founder and chairperson of the Laboratory of Molecular Biology at Cambridge) had an eye for good people though some of his policies were criticized (especially allowing the sharing of Rosalind Franklin' s data with Watson and Crick without proper permission).  But the labs had an unusual mix of talented scientists and a highly interactive environment, which apparently still remains.  This in itself is not sufficient to result in innovative, exciting research.  The MRC Labs are very selective in the hiring of faculty, but once hired, sustained funding is ensured to support important and long term research goals.  In other words, the faculty do not need to keep proving their worth and spending large amounts of time worrying about future grants to support projects that may take several years to accomplish.  This combination of good people who talk to each other and who have no reason to be insecure about the future of their research  seems to work well.  There is no apparent reason why this cannot be attempted in India.  The money is there (one just has to count the number of millions of millions that have gone into people's pockets in scams uncovered in the last year).  But we desperately need the critical few who have the rare quality of vision - one that allows them to identify true talent (or potentially winning combinations) and the conviction to support them freely and wholeheartedly, oblivious to the whims of each new government.  We have had such personalities in the past and I hope the scientific community allows some more to come up in the present (or at least in the future).

Remembering Fred Richards

Fred Richards, eminent protein biochemist, founder chair of the department of Molecular Biophysics and Biochemistry (and later Sterling Professor Emeritus) at Yale was always bustling about in his office or lab. - at least this is how I remember him from my days as a graduate student. I was fortunate to work for a short while in the lab. adjoining his (headed by one of his former students) and to meet and interact with members of his lab. during this period. From time to time, memories of Fred fill my mind for the way he did science and the person that he was.

When I think of Fred, I always feel motivated and delighted by his ideas. He had an incredible, far-seeing mind, a knack of observing people and summing up situations in his frank and pleasantly energetic way. Today I was happy to lay my hands on an article of his that I had been looking for. Titled 'Whatever Happened to the Fun? An Autobiographical Investigation', it is written (not surprisingly) in 'Fred style' and was published when he was about 75 and still hard at work (reference: Annu. Rev. Biophys. Biomol. Struct. 1997.26:1-25).

The article is of general interest even though it is filled with scientific recollection because it also addresses pertinent issues faced by many of us in our varied professions. It discusses changing situations, polices, options and ends as it began - with a question. Asking questions was second nature to Fred - and the search for answers led him and his lab. to many wonderful discoveries in the field of protein structure, folding and packing, and how to view or measure aspects of these. I quote below a few (less technical) excerpts that I particularly enjoyed:

".. The following is the log of a day in the life of a typical 35-year old faculty member at one of today's research universities:

0730-breakfast meeting of the Committee on Revision of the Graduate Preliminary Examination; 0900-give today's lecture in the beginning course for premeds; 0950-put off student questions after the lecture because...; 1000-meeting of the Building Committee to discuss the color for repainting the 4th floor hall; 1100-meet with today's departmental seminar speaker to tell her all the wonderful things that "you" are doing in your laboratory; 1130-explain to your starting graduate student that you would like to discuss his thesis proposal, but that today is the deadline for a letter of recommendation for one of your other students who is applying for a postdoctoral fellowship; 1200-emergency Departmental lunch meeting to decide how to respond to a claim by unannounced EPA inspectors that a waste bottle for organic solvents in your hood was not stoppered; 1330-missed an appointment with a potential postdoc previously arranged for 1300, use the unexpected 30 minutes to scan and reply to your E mail; 1400-meeting of the University Junior Appointments Committee in the Humanities (you are the token scientist); 1530-call from the Provost asking you to serve on an Ad Hoc Committee to examine the claims of fudged data by a whistle blower; 1545-start the rewrite of a grant request that had already received rave reviews but got a priority of 1.28, which was .02 below the payline for this round; 1630-attend Departmental seminar; 1745-call your spouse and explain that Bill W. had called in sick and you had been asked to stand in at dinner for the seminar speaker-yes you remember that it is "concert night" but can't someone else go in your place-after all you just have to tend out.

This may seem a little exaggerated, but not by much. Is this really what research is all about, what you were trained for and looked forward to doing with your life? Where is the fun and excitement of discovery? Or, God forbid, is this the new definition of "fun"?

... This decision (to become a chemist) started with a Christmas toy, a chemistry set, when I was 10. At that time chemistry sets were allowed to actually do something; smoke, smells, even the occasional explosion, and always the possibilty of getting sick if you ate out of the wrong bottle. In other words, fun; no "consumer protection."

.. High school years were spent at Phillips Exeter Academy. The excellent science department even permitted certain students the unsupervised run of the laboratories outside of class hours. This attitude played a strong role for my roommate John King (destined to be a physicist) and me in cementing our commitment to scientific careers. (I believe that no such access would be permitted today in any school owing to fear of legal actions.) We learned many useful trades at that time with Strong's text on Procedures in Experimental Physics as a major resource: glassblowing to the level of a two-stage mercury diffusion pump, a differential thermometer to clock the hours of sunlight, an attempt to measure the universal gravitational constant. For the latter we made a torsion pendulum with a 20-min period in a vacuum chamber, and we used 100-pound cannonballs borrowed from the village green as moveable weights. This particular project was unsuccessful but very educational!

..After receiving a PhD, I spent an additional year working directly with Edwin Cohn. I did some team teaching with Frank Gurd in the first year of the then-new, all encompassing Medical Science program for first-year medical students. To indicate other applications for his protein separation procedures Cohn arranged that I share a stage in the auditorium of the Boston Museum of Science with a farmer and a cow. The latter was attached to a milking machine, which was attached to a milk separator, which fed the whey into a precipitation chamber, which transferred the suspended precipitate to a centrifuge, which delivered the dissolved precipitate to the automatic machinery developed for protein fractionation of blood plasma. I was supposed to explain to the lay audience what was going on! Both were interesting "experiences"!

..At this time in a career, the standard academic procedure takes hold; responsibilities pile up. Research is soon done only by graduate students and postdoctoral fellows. My group has been run in the "disorganized mode." Each individual has usually ended up doing what they wanted, but with no particular relation or coordination between the different projects. For grant purposes, of course, we have written up the applications as though they there were one or more clearly achievable goals and a logical set of experiments by which to obtain the necessary data. The title of the grant was very general and has not changed in 35 years: "Study of Proteins in Solution, Interfaces and Solids."

..In the early 1970s I was called for jury duty in New Haven. This citizenly chore turned out to be a blessing in disguise. In each court case either the prosecution or the defense did not want an academic on the jury. Thus for two or three months I spent each day in the jury room with no phone or other disturbance. This time permitted the rapid coding of the Voronoi procedure for calculating atomic volumes, which I had been put onto by John Finney from his work with JD Bernal. Each lunch recess I ran up the street to the computer center and put the morning's effort on punch cards and started the debugging. It all went well and produced quantitative estimates of the packing quality in proteins.

..If more individuals recognized the mileage that one gets by leaning over backwards to acknowledge the work of one's colleagues, a good segment of the turmoil over scientific misconduct would disappear overnight. Much of the rest could be handled by listening without jumping to immediate conclusions. A major culprit seems to be ego."

This is just a glimpse into Fred's world - one that was filled not just with fun science but with many other interesting events and people, some of which he has alluded to here and elsewhere. For scientists working in the area of protein structure or for those interested in the history of the past few decades of scientific research, the article is a wonderful read.

Sweet Sixty five!

A landmark British study - and its subjects reached the age of sixty five last month, and I hope it sees many more happy years ahead.  The 1946 British birth cohort study, initiated at a time when there was a great deal of interest in socio-economic planning and reform, is the only one of its kind in the world, in terms of number of years spent and amount of information gathered.

The post war years had an optimism and momentum that lent impetus to this ambitious study that was thought of by the Medical Research Council (MRC) and implemented by a physician, James Douglas, who had been studying effects of air-raid casualties during the war.  The study identified 16,695 babies that were born in the UK in one week of March 1946.  It then looked in more detail at 5000 of these babies and documented social, economic, physical and mental aspects of their lives over time.  The data collected was enormous, the cost and infrastructure considerable, but the study managed to proceed,uninterruptedly, under the leadership of three very different personalities over more than six decades.

Douglas's initial work demonstrated the vast economic gap that existed in society and its effect on health and lifestyle options.  He showed the disparity in medical facilities available for the care of the mother and infant and how these affected their health and survival.  Later on, he addressed the issue of the relative success of the educational system and how children from different socio-economic backgrounds fared in national school exams.  Several of his publications led to changes in parliamentary bills and policy regarding health care and education in Britain.

In 1979, when the project seemed to be stagnating, a social epidemiologist, Wadsworth, who was a part of Douglas's team, took over and steered it in a new direction.  He persuaded the MRC to fund the study to follow important medical parameters (heart, lung and general physical functions) and aspects of people's lifestyle for the next two decades.  He wanted to see if conditions of early life affected people's health and lifestyle when they were adults.  A large amount of data was obtained and several new correlations discovered.  The general impression seems to be that early life experiences do affect one's later choices and also affect one's susceptibility to specific kinds of health problems (though the researchers stress on the fact that one's fate is not ultimately determined by early experiences).

This study, being continued under the leadership of Diana Kuh, now looks to interpreting some of the medical correlations in molecular terms- the genetic variations of the people being studied and epigenetic changes that occur (small modifications of DNA that are induced by environment or stress of some kind and that change patterns of gene expression).

The study is conducted in a highly personalized fashion and several of the subjects, when interviewed, said they were happy to participate.  Obtaining consent in the mid-forties required much less effort (and red tape) than currently, which certainly helped a study of this magnitude.  However the nature and scope of investigations early on was more limited, mainly owing to social reservations about certain issues.  The research has evolved in an interesting way over time and I suspect it sheds light on many more aspects than it was originally intended to.  Other such cohort studies have since been initiated, but it will be many years before one sees whether they succeed in their stated aims.

This study has shown a link between cognition, hormones and aging, something people did not think about much.  The effects of lifestyle, environment (physical and emotional) and social trends on a person's life have been shown very clearly for thousands of people who were born within a few hours or days of each other.  This has made people begin to think about factors influencing life, health and aging.  The study is remarkable  not only in the quality and quantity of data collected but also because the data was not taken just when people were ill or facing difficult times, but periodically through their lives.  It would be wonderful if eventually one could look at alternate or traditional medical systems (several of which emphasize the maintenance of balance and prevention of illness) and incorporate aspects of these in the questionnaires and tests that such people are subjected to.

The MRC has made a small documentary recording to mark this 65th anniversary which can be viewed at http://www.nshd.mrc.ac.uk/nshd__65/about_the_nshd/the_douglas_children.aspx