INDIA AND CALCUTTA LOST A NOBEL LAUREATE

HOW WE LOST A ‘’NOBEL LAUREATE’

Dr Mukhopadhaya [January 16, 1931-19June1981] graduated (1955) from the Calcutta National Medical College, earned doctorate from

the University of Calcutta [1958 in reproductive physiology] and the University of Edinburgh [1967 in reproductive endocrinology]

WHO laboratory manual for the examination of human semen came out in 1980. But in 1978 , Dr Subhash Mukhopadhaya, aware of the

diagnostics value of semenograms , diagnosed Durga’s father to be having a low sperm count and felt that such a condition can he

effectively treated with gonadotropins.

On 19-10-1978,he treated Mrs Agarwal with hMG[human menopausal gonadotrophin] as following regimen – 76 ampoules twice a day

and on alternate days and starting from day 3 to day 9 of the cycle. 6000 I.U. of hCG on day 11 of the cycle . 48 hr later , he aspirated as

many as 5 follicles [oocytes] from her .

Today Ovarian hyperstimulation is a standard work before IVF but it was only 1981 when other scientists first attempted ovarian

stimulation to extract ovum for IVF [Australians used clomiphene citrate in 1981 and Norfolk group in USA used hMC and hCG in 1982

in their IVF programmes]

Stimulated ovaries enlarge and drop down towards the Pouch of Douglas and by a small

incision on the posterior vaginal wall, Dr

Mukhopadhaya collected 5 oocytes in a couple of minutes. Note that the British team had used a laparascope to harvest oocytes [Others

aspirated oocytes transvesically under ultrasound guidance] and presently oocytes are aspirated per vaginum under ultrasound guidance

The oocytes were incubated for 4 hours before inseminating with the husband’s semen that was processed in protein-supplemented

Tyrodes solution -- exactly what is done even today. After 24 hours , it was incubated in a mixture of cervical-uterine fluids [use of such

fluid is not described elsewhere] for another 72 hours. Subsequently it was frozen slowly to about –196 degreeC after stepwise treatment

with dimethyl sulfoxide. One such frozen embryo was subsequently thawed slowly and transferred into the uterus

Dr Mukhopadhaya reported the successful cryopreservation of a eight cell embryo, storing it for 53 days, thawing and replacing it into the

mother’s womb, resulting in a successful and live birth as early as 1978 -- a full five years before anyone else had done so. [Report of first

cryopreservation of human embryos appeared as late as 1981 and first successful transfer of thawed human embryos in 1983]. Source -

Current Science, Vol .72. No. 7, 10th april1997

On 18 November 1978 , an ‘expert committee’ was appointed by the Government under a Radio physicist , a gynecologist, a

psychologist, a physicist and a neurologist whose verdict read as “Everything that Dr. Mukhopadhyay claims is bogus”. He was punished by being transferred to eye department sealing his prospect to work on hormones. He was denied passport by Indian  Govt.   to go to Japan where he was invited to speak on  his  invention  [IVF & ET]. Facing social ostracization, negligence, insult and refusal of the Government to allow him  a  passport  to  go  to attend international conferences, he committed suicide at age of 50 [ 19 June 1981]

On 1987 , T.C Anand Kumar, Director of IRR (ICMR) made the “first” test tube baby of India [Harsha - born 16 August 1986]. In 1997,

This  T.C. Anand Kumar   went to Kolkata for participating in the Science Congress ,  where  he was  shown  the  document  of  Dr  Mukhopadhaya. On rediscovering the research documents of Late Dr Mukhopadhyay,  T.C. Anand  Kumar  took the initiative to sacrifice his crown and officially proclaim Dr Mukhopahdhyay as the architect of first test tube baby  of  India  [“Durga” alias Kanupriya Agarwal]

The ‘Dictionary of Medical Biography,’ published by World Foundation, that enlists 1100 Medical Scientists contains only three names from Kolkata - Sir Ronald Ross, U.N. Bramhachari and Dr. Mukhopadhyay

Dr Mukhopadhaya’s test tube baby came only 68 days after the world’s first test tube baby and that also with few apparatus and a refrigerator in his small southern avenue flat.This would have been sufficient to be credited as independent invention and to claim a share of the Nobel Prize 2010 [medicine ] with Robert Edwards  [who  ,  with  Steptoe ,  made  the first  test tube baby – Louise  Brown] , were he alive today

INDIA REJECTED ANOTHER CHANCE OF MEDICINE/CHEMISTRY NOBEL PRIZE

Indian may have missed Nobel by a whisker

Press Trust of India  [http://www.expressindia.com/news/fullstory.php?newsid=37290]
Posted online: Friday, October 15, 2004 at 1528 hours IST


New Delhi, October 15: Krishnamoorthy Kannan, a protein chemist at the Guru Gobind Singh Inderprastha University in Delhi, may have missed his share of this year's Nobel Prize in chemistry by a whisker because of government's failure to recognise a discovery he made 12 years ago.


This year's chemistry prize was shared by two Israelis and an American for their discovery of the function of a molecule called "ubiquitin".
They showed that ubiquitin gives the "kiss of death" to unwanted proteins inside the cells by marking them out for destruction thereby defending the body from certain types of cancer.

While the trio were the first to demonstrate the role of this molecule "inside" the cells, Kannan was the first to identify an equally important function of ubiquitin "outside" the cells. He was then working at Span Diagnostic Research Centre, a little known laboratory at Udhna, in Surat

In a seminal paper published in 1993 in the British Journal of Hematology, Kannan and his student K.S. Parakh showed for the first time that ubiquitin homes in and binds to the so-called "haemopoetic" stem cells - the mother of all cells that make up the blood.
By staining it with a dye, he showed he could use ubiquitin as a probe to seek out stem cells and separate them outside the body -- a discovery that opened exciting possibilities for treatment of leukaemia and even aids.

The experiments were extremely tough performed as they were in ill-equipped laboratories. "I feel happy that sitting in India we could establish the first extra-cellular function for ubiquitin as well as stain the progenitor stem cells without using antibody specifically," said Kannan.

But working in a low profile laboratory, Kannan's efforts to get funding to continue the work failed. "We applied for a grant from the department of biotechnology but I was upset when it was turned down  [.by  Indian  Govt.]  ," he said. "I feel more upset now when work on the function of ubiquitin was selected for Nobel Prize."

Though ubiquitin's intracellular role got the Nobel recognition, Kannan -- who was general manager of research at Ranbaxy Laboratory before setting up the School of Biotechnology at the Indraprastha University -- said that ubiquitin has a bigger role outside the cell than inside the cell. Kannan's only regret is that he was unable to carry on his work due to lack of funds.

But Kannan's interest in ubiquitin never died. Next month he and his student Anjana Nityanandam will be presenting at Goettingen University in Germany their work on ubiquitin as a novel tool to study early stages of brain development.

"Our work on chick embryo shows it is quite possible that extra-cellular ubiquitin actually gets to interact with neural stem cells just as it was shown to do in the case of haemopoetic stem cells," he said. "If this is so, ubiquitin might find use as a marker in studies related to neural stem cell

HOW CAN WE STIMULATE AND PROMOTE CREATIVITY IN SCIENCE?

HOW CAN WE STIMULATE AND PROMOTE CREATIVITY IN SCIENCE?

By providing lab facility to those who want it irrespective of whether he has passed msc or phd or not .............. allow lab and guide to undergrad student also [there r many undergrads with innovative idea but not being able to culture in want of a mere sds page appartus or 2or 3 mice ]

The technical--course students like MBBS and BE or b tech -- they get very low ....very .. to basic science lab facilities. Whatever is given , that are 4 BSc orMSc pupils

I insist it is not high quality instrument that is needed out always..

A simple mice or flow cytometer \ guide \ electrophoresing or chromatography or pcr are not very high tech instruments dat need great funding. Instrument are lying in dust in lab.s under bossy-supervisor who ud create 1000 harrasment before allowing u touch them .. Why i know giants in their field in my domicile city ....one of them waste hours to talk over ramkrishna , the other over hrs,read newspaper and the 3rd spend much of time scolding undergraduates .... but when i requested 10min from them to hear and comment my proposal.............. they showed me to some assistant professor without even hearing a word fromMe.And one of them, literally drove me away with slang word .. when his assistant professor ATTEMPTED TO forward my proposal2him. Mind Mr, i did not request them fund, guide or instrumnt ..........i told them to hear..........and all these 3 people are head of their respective departments. As for some other ppl .......... i have found them helplessly groaning that the rules STOP any lab to allow an INDEPENDENT RESEARCH by an undergraduate. I agreed to fund my expt my self ......i told no one has to be my regular guide if they r busy .... but i do need the instrument and animal. Some were agreeing to give instrument but no one could agree on animal .........becos that needs a ethical certification and that z tough to get for an undergraduate 's research ........ unless it is beautified by name like ICMR-STS / KVPY

And as for doing work under the above 'beautiful' names..........

there r 2 problems.

The kvpy cover only 1st and 2 nd year student ............. but by the time a student learn hos subject n think independently ....he has reached the end of 2nd yr or may be 3rd yr;

And icmr or kvpy .. both expect a research that cover 2 month study!! What d hell inventive work can be done in 2 months ? relation between cigar and cancer? datz what they expect. If u apply for a inventive one, that ud take more than 2 month , then icmr sts shall reject

Rhythmic shine [21-3-2003 }

The shining of victory is rhythmic .. it is there sometime and at other time , the shine is gone .. everything is dark..

THE RHYTHMIC SHINE [ 21-3-2003 }

When I am gone and no more on Earth

Finally blowing off all candles of my birth

Life shall move and no one shall care

That yet one more’s life cycle is over.

As smoke shall haze the air

And no more the wet eyes stare

At my dying funeral flame,

The Earth shall scarcely care .. deletion of yet another name.

Amid the haze shall be writ all memories

Amid the haze shall be spoken all the glorious stories ….

“All the tittles those I won , all the battles fought.

My defuncted spirit was how much crimson hot.

How much beloved was I , how much bonhomie,

How many endeavours were accomplished by me.

How they praised me , what respect;

What awe , fear and honour could I always expect.

How sweet I used to sing

When it was the yellow spring;

How would not I ever fear

Even the whitest of winter….

And how sudden did D Day did come to pass

When untimely Death my life did trespass

They would curse Death but finally accept the “fateful” day --

When amid tears and sobbing,their Hearts robbing ,I would go away.”

Yes I would go away evacuating all the well fought shrines,

The Earthly Halo would be no more there , but Heavenly halo shines..

“Fateful”? do I hear they to “Death” call ?

What rejuvenating eternal sleep,from all the earthly gall.

When I win , people applause and unwanted praise is mine,

And when mine is loss, they would be so gross and gone is the Rhythmic Shine.

And tears? and broken hearts ? they would never be the same..

The Earth would scarcely care,deletion of just one name.

And do not sigh , that all is gone to waste ,all that I won through strife,

‘Coz the Throne is always dynamic and that”s the way of life.

AH .. WHAT A SLEEP ! NO RUSH FOR WEALTH .. FOR UPHOLDING MY NAME..

DEPRIVING MILLIONS OF MY FELLOWS , NO RUSH FOR THE RHYTHMIC SHINE OF FAME

THIS RHYTHMIC SHINE , IT”S EARTHLY WINE , IS THE GIFT OF TYRANT LIFE;

I AWAIT SERENE DEATH TO END UP ALL MY SUPERFICIAL STRIFE.

To those youth who committed suicide to academic pressure

To those youth who committed suicide to academic pressure

.

.

AN EPITAPH

Thy life lies motionless on the bed,

On thy face serenity unabated.

As who should say that thy head,

[Now resting a little tilted on a white pillow] made

Ingenious ideas that could thwart --

All thy rivals , however clever they wert.

Thy face is now the picture of peace profound.

Thy soul has completed another cycle round;

Of birth and death, on Earth and Heaven ,

A far way thee are gone , amid the constellations seven.

Far, far , leaving us behind,

Farther than where any mortal can find.

farther than the farthest of me to bring thee back;

I can only sob , die heart –broke and follow thy track.

“Wake up dear friend , prove wrong thy early end”

Fulfill this only prayer of each of thy friend.

But now I realize that it can never be –

Dark voids and memoirs shall take place of thee.

Thy eyes so curious , has closed so young;

So fresh are martyred , thy prospects strong.

In heaven above , in God”s love , there is no time;

no ‘Past’ , nor Future, only ‘Preset’ ‘s regime.

But ‘Past’ stabs us , here , on Earth

Thy memories sad ,creeps into all our mirth.

I know you would love to see my eyes merry and dry

To see me smile gay, I’m failing whatsoever I try.

Now that the coffin is nailed , now that it is lowered;

Now that the last chunk of soil is delivered --

I fight against it , whatsoever --

It deeply impresses me , thee are gone .. FOREVER

pathogenesis autoimmunity

Why does autoimmunity occur? In RHD,the antigenic epitope [against which anti streptococcus antibody and anti heart antibody are created after streptococcal pharyngitis } is always there in heart valve and is always exposed to APCs and lymphocytes. Then why suddenly antibody [ against heart] is produced only when this antigenic epitope is presented by streptcocci?

Immediately after antigenic stimuli, there is production of plasma cells that produce IgM [primary immune response] and 7-10day later , the mRNA [of these plasma cells } producing the IgM, undergoes splicing and the spliced mRNA now produces IgG [instead of IgM}[secondary immune response] . However the variable region [i.e. antigen binding site , Fv ] of these IgG remains same as that of the original IgM.

Now the plasma cells produced during primary immune response are monoclonal or almost monoclonal -- i.e. the antibodies [Ig M } produced by them have a unique paratope. I mean that these Ig M antibodies can bind to one specific antigen only -- and NOT to the other SIMILAR antigens. In eg of RHD , the plasma cells [ that are produced during primary immune response due to stimulation by say M-5 protein of streptococcus cell wall} can produce antibodies [obviously Ig M and NOT Ig G } that have the capability to bind to ONLY streptococcal M-5 protein ........ and neither to even streptococcal M-6 protein , nor to cardiac myosin Protein.

Now as time of about 7-10 days goes, two things happen-
[i] The plasma cells produce Ig G, instead of IgM [mechanism discussed already]

[ii] In these 7-10 days , the plasma cells undergo numerous cell divisions and with every cell division, there is the chance of a mutation in the DNA coding for that specific immunoglobulin. As a result of these mutations, m RNA also alters a bit, and the resultant Ig G molecule has a variable region [antigen binding site ..i.e. Fv } that is slightly different from the variable region of the original IgM. This process results in a polyclonal production of Ig G [ as opposed to the monoclonal nature of the initial Ig M molecules } that serve dual result—

[i] it protects body from the other antigenic mutant types of the attacking pathogen [like from streptococci bearing M-6 , M-8 etc and not only from those bearing M- 5]
[ii] it makes a chance that the antibody molecule may acquire a paratope against an epitope of a closely resembling host tissue . [e.g. cardiac myosin and streptococcal M protein]