How to find a biotech company's secret recipe

I have a story to share. I was a research scholar in Biotechnology in IIT Bombay few years back. I was doing an experiment on cell death by annexin V-Propidium Iodide (PI) assay. I was using a kit supplied by a commercial manufacturer. Incidentally after a series of lab mates used it and when my turn came the crucial buffer of the assay was finished though the annexin V antibody and PI was very much there. My advisor suggested me to not to depend on the manufacturer but to make my own buffer. I was clueless because the supplier did not provide the buffer composition. I searched in internet for a possible composition source. Ultimately a widely used cell biology laboratory protocol book came to my rescue. I found that a simple salt CaCl₂ and a HEPES buffer were the key components. I made the buffer according to the instruction laid in the book and voila! utilized that buffer for very many reactions later on.

I learnt this lesson to scour for the buffer composition because my buffer was finished and the company did not provide the ‘secret’ composition. If all company start doing this research will be hampered. Protocols and buffer compositions should be clearly mentioned. In fact earlier version of Maniatis’s Molecular Cloning – a bible for cloning had a nice preface urging the ‘Scientific Illiterates’ to know of the reaction components scientists were using.

Western Classical Music

I have forgotten Western Classical Music (WCM). Once it was so dear to me. I used to love, be happy to collect and be happier to learn the nuances….and now! It seems as if it beckons me from my past life…..as if a mist has separated the boat from the shore……Oh! Calcutta……that city gave me so much……For a long time I lost touch. May be for past 7 years….till I left Calcutta for Haldia, then Aurangabad, then Bombay, then Hyderabad. I might have heard occasionally some Dinu Lipatti or Maria Callas or some best of Mozart, Beethoven CD (presented by my friends staying in US)…and some in Youtube (getting irritated when it takes long to buffer while I wait for my Perlman or Horowitz or Oistrakh or Richter……)………and……..and…..that’s all in last 7 years. Nothing more…….

But who but I remember once I used to live and breathe Western Classical Music(WCM), visit concerts in Calcutta School of Music(CSM) and scour the music stores (my favorite was Rhythm in Lindsay street, a friendly avuncular Sardarji owner used to copy CDs into cassette for me those days….God!) in search of cassettes (those days I did not have CD player though I had some CD presented by my friend and presented to my father by his friend……) and Max Mueller Bhavan library…the heaven for Western Classical Music lovers in Cal….so many cassettes I borrowed and copied…so many talks I attended in the music appreciation classes  by my guru Kishore Chatterji ( one on comparison of WCM and Tagore songs on the theme of death….ah ! girls from Santiniketan sung those songs and Mr.Chatterji played his choicest collection…lachrymosa from Mozart, Gluck’s Orpheus and Eurydice…..) and unforgettable talks by Adi Gazdar (he was a doctor, friend of Ray, and played wonderful piano, he played in the class. Helped Jennifer Kapoor in playing piano in Ghare Baire duly acknowledged by Bijoya Ray in ‘Amader Kotha’), Bulbul Sirkar (of Calcutta radio, took memorable interview of Ray on WCM which I have recorded from radio), Proshanto Dutt (conductor of Calcutta School of Music), and then in CSM……pony tailed Neil Mukherji playing Segovia classical guitar (I never knew he played for  Mohiner Ghoraguli, a Bangla band !), my first concert attendance with Mr.Chatterji, then  listening to Robert Vijay Gupta, a 8 year old kid from Julliard, New York playing Vivaldi’s four seasons…I gate crashed into Gyan Manch that day in 1999 ……….I can still hear his pizzicato from Winter……Ah what delight! What a time I had…..and I used to record FM radio talks by Yehudi Menuhin or Gerald Moyer….I left no stones unturned to collect WCM….shops, library, radio…any reference of WCM in movies caught my attention, be it Gregorian chant from Ray’s Shakha Proshakha or Pachelbel Canon from Hollywood movies……and I used to remember WCM tunes from ad jingles and compile cassette out of them from our collection and present it to friends….we had more than 200 cassettes….collection started by my father in 1992……now with dismay I note how time and fungus damage and ruin my beloved collection….my father still lives on the remnant of those…..and I don’t have enough time to collect CDs…..What more disappointment could be that staying in Bombay I missed concerts by Zubin Mehta and Sir Colin Davis and I could only see a single performance by 4 years old National Symphony Orchestra of India ! So much work tied me up.

After so many years of non practice I tend to forget the tunes which I could once recollect instantly…..and which used to give me so much pleasure…I simply wait to regain that exquisite touch of WCM…I simply want to immerse myself into the sea of music which used to make me unbelievably happy….

My association with Kishore Chatterji who single-handedly had been popularizing WCM through his newspaper articles (The Statesman is an institution of Calcutta and only newspaper in the country to carry a weekly authoritative article on WCM by Mr.Chatterji) and his books needs another article. It was because of his book that I started listening to WCM while I was bedridden and recovering from a bike accident …It all started in 1993. My doctors told me I recovered sooner because I was in good mood despite lying on bed for 7 long months…..and what but WCM made me happier those gloomy days! But readers, that’s a different story…..I will write that in a different time. Oh! Calcutta!

The journal of misfit papers

My article is about how I found two journals who accept papers vetoed by other journals in the field, or results for which there are no takers, or when you question current practices. This sprang from the frustration a scientist feels when his or her paper is summarily overruled, or after thorough peer review and its remedy. When overcoming the dejection of having my first paper being returned by a journal, a colleague kindly counselled me by saying, “Welcome to the real world of science, you have just arrived.” Later on, when I had eventually published my work in another journal, I tried to seek avenues for publishing an unaccepted paper per se. Voila! I found these two unusual journals.

One such journal is ‘Rejecta Mathematica’.(1) It publishes mathematics papers. It has a nice editorial on the rejection-acceptance cycle predominating scientific publications in its inaugural issue†. Their requirements are that “submitted research manuscripts must have been previously rejected from a peer-reviewed journal in the mathematical sci­ences,” and that the manuscript must accompany an open letter from the authors stating the full procedure of peer review and final rejection by the previous journal. If you are very disgruntled with your field of research, then they are ready to help you to start a ‘Rejecta’ journal in your field!

Another is the ‘Journal of Negative Results in Biomedicine’.(2) As the name suggests, it publishes articles on clinical trials or pharmaceutical sciences. This journal is published by BioMed Central, an open-access publisher of 220 peer-reviewed journals. The impact factor of this journal is 1.10. The impact factor of a journal indicates how many times an article is cited by readers in a given time. The higher the impact factor of a journal, the better its acceptability. This journal publishes failed clinical trials as well as existing or promising drug molecules which fail to live up to their expectations.

An example of such a paper is on the lack of effect of anti-cholesterol drugs Statins are cholesterol-lowering drugs used to treat patients with cardiovascular diseases.(2) However, this particular article published in this journal of negative results in 2011 showed that continued use of statins in Swedish populations between 1998 and 2002 did not lower any incidence of cardiovascular diseases or mortality rate. It is to be noted that this journal has been FEATURE

publishing such papers for the past ten years.

You may find their approach surprising, amusing or weird, but don’t forget that sometimes, there is no balm more soothing for your bruised ego than a publication to announce your efforts in science.

But the purpose of publishing negative results goes deeper. Sometimes the negative results obtained by the researchers can prevent others from redoing the same experiments or alert others about futility of certain medicines. Any failures of medicines in clinical trials need to be known by the doctors and scientists to avoid future use. Many potential drug molecules in clinical trials show severe side-effects in patients. It is also very frequently seen that pathogens develop resistance to antibiotics, anticancer, anti-parasitic or antifungal drugs. Bacteria resistant to antibiotics after rampant use or cancer cells resistant to anticancer drugs are not unknown. Quite often, transgenic plants carrying pesticide genes grow resistant to the pests over the time.

Journals for publishing negative results in life science or medicine can successfully make the scientific commu­nity aware of these particular failures discussed above, such as side effects, or the development of resistance. Sometimes journals specialising in printing rejected pub­lications can offer a contrarian view of present models to the scientific community, and also alert fellow scientists which way to go or avoid.

Journals which publish rejected papers or negating results about medical or biotechnological use of drugs or proteins can carve a niche in the widely-expanding repertoire of scientific journals.

References:

†. Letter from the editors. (2009) Rejecta Mathematica Vol. 1, No. 1, pp. 1-3

‡. Nilsson S, Mölstad S, Karlberg C, Karlsson JE and Persson LG. (2011) No connection between the level of exposition to statins in the population and the incidence/mortality of acute myocardial infarction: An ecologi­cal study based on Sweden’s municipalities. Journal of Negative Results in BioMedicine , 10:6 (24 May 2011)

1. http://math.rejecta.org/

2. (http://www.jnrbm.com/)

Note: This article written by me appeared first in campus magazine of IIT Bombay in 2011.

Anandibai Joshi-the first lady doctor of India

Today in any Indian hospital, presence of a lady doctor is not an unusual occurrence. Even the CMO of IIT Bombay hospital is a lady. It is my general perception that in India lady doctors usually takes up softer subjects like gynecology, pediatrics, psychiatry, pathology, biochemistry - subjects where they are expected to be because they are ladies. Their presence is largely absent from super-specialty subjects namely orthopedic surgery, neurosurgery, plastic surgery, cardiology etc. Reasons for ladies not joining these may be several. Working mothers may not be able to do odd hours at emergency; male dominated society may be reluctant to get treated by female doctors. Lack of trust on a woman doctor’s capability is still a major mental block of patients. But even then, the present role of lady doctors in India is undeniable. The Indian lady doctors have come a long way. They started the process of entering medical profession in our country in the 2^nd half of nineteenth century which I am going to recount in the following pages. And what a journey it was! Due to initial struggle of few lady doctors in pre-independence era, today we see an emboldened India. This article is a tribute to an undaunted spirit who thought of joining medicine- a typical male bastion.

Let us take a quiz. Who was the first woman doctor in India? Who was the first lady surgeon in India? Dr.Anandibai Joshi became the first lady doctor in 1886 and Dr.Anjali Mukherjee passed M.S. from Calcutta University in 1954. It has to be remembered that introduction of Western medicine in India was not without resistance and took some time to flourish. The prevailing system of Indian medical practice-Ayurveda and Unani could not be overruled. When the British government started medical colleges in 1835 Hindus and Muslims had resistance to the idea of dissection of corpses due to religious reasons and crossing the seas to study medicine in England was regarded as quite sinful. So when Madhusudan Gupta performed dissection in Calcutta Medical College for the first time, the British government saluted him with 21 cannon shots from Fort William, Calcutta.  If it was difficult for Indian men to study allopathic medicine then it was doubly difficult for Indian women to do so.

And Anandibai Joshi holds that honor of being the first woman doctor in India in a time when education for women was unthinkable. Women were not allowed to go outside their home to schools and colleges. They were home-bound and their life revolved around marriage, children and happy domesticity. Purdah system in hindu and muslim households did not allow the girls and ladies of the family to mix with men. Even male doctors were not allowed to treat female patients in many cases. Childbirth was mostly taken care of by untrained midwives. Due to unhygienic practices of these midwives, death of the newborn or the mother was pretty common because of septicemia. In fact, Indian women needed the female doctors badly. But who would be bold enough to go against the male-dominated society to learn medicine?

Anandibai Joshi was one such bold lady. She was born in 1865 in Kalyan in Maharshtra in a staunch Brahmin family. In those days going to school from such a family was equivalent to be outcaste. And following the tradition she was married at the tender age of 9 to Gopalrao Binayak Joshi. Gopalrao was educated, progressive and wanted Anandi to learn English. Gopalrao got a job in Postal department and shifted to Kolhapur. Anandi’s education was going on inside home under the tutelage of her husband. She was extremely lucky to have such a nice husband and without her husband’s active help her medical studies would not have been possible. Being meritorious she learnt Sanskrit, English, Math, History, and Geography in no time. In the meanwhile she gave birth to a baby boy. But the child died due to lack of appropriate medical treatment. Maybe this sad turn of event propelled the couple to make Anandi a doctor. And Gopal left no stones unturned despite his poor income. He kept on writing letters to foreign newspapers to raise funds for Anandi’s medical education. After two years his efforts paid off. A letter to a Christian missionary was published in Christian Review magazine in 1878 which drew the attention of Theodora Carpenter, an American philanthropist. Being a Quaker, Mrs. Carpenter reached out to help her. Anandi went to America in 1883, all alone. Even that was quite a feat at that time for a woman from a Hindu Brahmin family to cross the sinful seas. She started studying medicine in Women’s Medical College of Pennsylvania (now known as Drexel University College of Medicine) and got her M.D. degree in 1886. In front of the bewildered American audience an Indian lady, all of 22 years, received a medical degree from the first all-women medical college of the world. It cannot be forgotten in this context that women doctors were rare in those days even in developed and rich industrialized countries. World’s first woman doctor was Elizabeth Blackwell who passed degree in Medicine in 1849 in USA. And another Elizabeth- Elizabeth Garrett Anderson passed medicine in England. Sophia Jex-blake started London School of Medicine for women in 1874. Lady doctors were laughed off as ‘Physicians in Petticoats’ and reviled in the world famous medical journal The Lancet. So in view of these difficult times, achievement of Anandibai was nonetheless praiseworthy.

All poised to serve the ill, Anandi came back to India in 1886. But the time after she returned proved unfortunate. She became ill and contracted TB due to long sea journey and harsh living condition in US due to poverty. Though she joined Kolhapur hospital to serve them, she took ill and passed away in February, 1887 at an early age of 22. Her wish of serving the nation by treating the ill died untimely and thus unsung was finished, Anandibai Joshi, the first lady doctor of India. It is a pity that she was such short lived and could not blossom into a full-grown doctor. Later-on S.J.Joshi wrote a historical novel called Anandi Gopal on her life which became immensely popular in Maharashtra. A short film and a TV serial  was made on her life too.

The idea of Indian lady doctors did not trickle-off after Anandibai. History says it gained a momentum. Dr.Kadambini Ganguly became the first lady physician from Calcutta Medical College in 1886.  Bidhumukhi Basu was the first lady to be awarded the MB degree from Calcutta Medical College. Allen D’abrew became first MBBS degree holder from Madras Medical College in 1888. As Lady Dufferin Hospital and Lady Hardinge colleges were established in Calcutta and Delhi in the end of nineteenth century and beginning of twentieth century, more and more ladies got enrolled for studying medicine.

Today a significant number of students of medicine in India are girls. Lady doctors are no way behind their male counterparts. In fact, National Family Planning and Child Health programme would have failed without their participation. But today it is a different world. In urban India women are not prevented for studying or making a career. Girls are given equal opportunity as boys. The world in 1870s was a far cry from present day. In a time when women’s education was unthinkable, Anandibai Joshi stood up, took the challenge and fought against all odds to become a doctor. She justifiably took the first step which paved the way for Indian women to study medicine. A lot more change is needed in the outlook of Indian society so that our women doctors can go on in their mission undeterred and rise to greater heights. Time has come that we should put our full trust on our lady doctors so that they do not shy away from cardiac surgery, neurosurgery, and plastic surgery and restrict their career growth.

Reference :

1. Mohila daktar Bhin groher basinda- a Bengali book on history of Indian women doctors by Chitra Deb. Publisher :- Ananda Publishers,1994.

      ISBN 81-7215-283-3

      2.    Women in Colonial India: Essays on Politics, Medicine, and Historiography

             By Geraldine Hancock Forbes

             Published by Orient Blackswan, 2005

       ISBN 8180280179, 9788180280177

3.   Madhusudan Gupta written by Debashish Bose. Indian J Hist Sci. 1994 Jan-    Mar;29(1):31-40.

On increasing use of plasticware in life science and biotech research

I think the time has come to replace the word in vitro to in plasto. I have been working in Molecular biology, microbiology and protein biochemistry and cell biology fields in different capacities for the past decade. It is remarkable to note how glassware has been replaced with plastic ware. Starting from centrifuge tubes (Eppendorf, Falcon etc) to Petri plates, dispensing pipette tips to measuring cylinder – every usable item is made up of plastic these days. Even chemicals come packed in plastic bottles. Tissue culture flasks, dishes and 96, 24, & 6 well plates used in cell culture are also made of plastic. In fact most of the experiments in molecular or cell biology, biochemistry or microbiology are conducted inside plastic tubes or containers. Only glaring omission from this ever-increasingly plastic world are glass coverslips or glass slides used in microscopy.

In vitro literally means ‘inside glass’. When plastic was unknown experiments performed in glassware i.e. outside the living system were called in vitro. But everything is done in plastic today. And there is remote chance that glass will replace plastic in future.So isn’t it high time that we, the scientists change the terminology of in vitro to in plasto?  In ‘The Graduate’ - the cult Hollywood movie of the sixties starred by Dustin Hoffman, the film hero’s father’s friend whispers the word ‘Plastic, plastic’ into his ears to reiterate the fact  where the future business and money lie in. It is truly a plastic-filled world now and the scientists (chemists, molecular and cell biologists, biochemists and microbiologists) should take note of this.

An outsider’s view on Mumbai

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Few weeks back, Amitabh Bacchan wrote a special article in an esteemed daily that chronicled Big B’s experience of making it big in Mumbai after initial struggle. He was also an outsider in Mumbai and his view on Mumbai reflects that of a very famous outsider.

Let me share my views-the views of an unknown outsider. To me, Mumbai is the New York of India. It is the most cosmopolitan city in this country, which does not ask your caste or creed; rather it asks for your talent, determination and hard work. It is the city of opportunities; you can make a living without any snide remarks from your neighbor if you know how to work hard. Every profession is respected here and if you know tricks of the trade, then sky is the limit. Due to the endless job opportunities, it is jokingly said ‘Hum do hamara do, teesra hua to Mumbai bhej do’.

The skyscrapers of marine drive are nothing short of Manhattan skyline. Coming from Calcutta, the cultural capital of India, I had a highbrow attitude toward culture. I thought Mumbai would be a departure from my Pablo Neruda-craving, Satyajit Ray-loving intellectual style. Rather, I found it even better. The NCPA, Prithvi theatre, Kala Ghoda festival bowled me over. Best of meaningful theatres and movies, both national and international are showcased in Mumbai. Jehangir art gallery is a place where painters would vie for an exhibition. And where else would you find a National Symphony Orchestra and Mehli Mehta foundation playing the western classical music to the discerning masses?

 Due to its inclusive nature, Mumbai is for all. Today, in this globalized world, you cannot keep one outside. Who knows where the next big idea is coming from? And who other than the Mumbaikars know it better that in Mumbai transcending all religions and ideologies only one deity is worshipped-the deity of wealth. And where is the leisure time in this city running at breakneck speed to pause and think who is an outsider and who is not? The city is always on the run; the local train bogeys seem to me a big escalator, which churns out thousands in every station endlessly. Where is the time to stop and think? I have not seen a single day of strike (Bandh, as we call it in Kolkata, which is a regular phenomenon there) after coming here. Hats off to Mumbai.

Note: This article written by me was first published in Times of India, Mumbai edition, on 31st May 2008.

Rabindrasangeet I like

It was winter of 1996. Cable TV had made entry into our household then. We were slowly getting used to plethora of channels. One late night I was watching Star Movies. Suddenly a Rabindrasangeet started while an English movie began. It was “Majhhe Majhe Tobo dekha pai” sung mellifluously by recently departed Ritu Guha. The backdrop was fitting well with the song. A young lady was waiting at a port to meet his beloved. In the distant sea we see a ship approaching towards the port. Now we hear the soulful strains of that Rabindra sangeet exemplifying the feeling of the lady…..Majhe majhe tabo dekha pai, chirodin keno paina…Keno megh ashe hridoy akashe tomare dekhite dei na……..(Why don’t I see you more often ? Why don’t I see you forever? Why the clouds eclipse you inside the sky of my soul?)………The song stayed with me forever…..The movie was ‘Island ‘by Australian director Paul Cox.

I associate my favourite Rabindrasangeets with people. I learnt ‘Ganer surer asonkhani’ from my mother, Sadhana Chatterji in class VII which I never forgot. She was very particular about the tune and notations because she was a trained singer. Three songs ‘Jene shune tobu bhule achi’ , ‘Amar ja ache ta sokoli dite parini tomai’ and ‘Hridoye tomar daya jeno pai’ by her are unforgettable. She sang them with heart.

Harisadhan Dasgupta, India’s pioneering documentary filmmaker was my room partner in SSKM hospital of Kolkata. He narrated a tragic incident of his life associated with a Rabindrasangeet. His brother Bulu Dasgupta died of a lightning strike when filming ‘Panchthupi’ in a Murshidabad village. He brought his dead body back to Kolkata in his car. All the while he was singing ‘Keno chokher jol e bhijie dile na sukno dhula joto’ wishing that his brother will come to life! He sang this song to me and I remember him whenever I hear it.

I will end with other personal favorites 'Amar Bela je jai sanjh belate' and ‘Diner seshe ghumer deshe ghomta pora oi chhaya’. My maternal grandfather Dr. Murari Mohon Mukherjee used to put me to sleep singing thiese. I was raised by him. I always  asked him their  meaning. He used to say “You will understand this when you grow up”. He was right. With advancing age  I realize we will all go to ‘Diner seshe ghumer deshe….’ someday!