Subhash Mukhopadhyay (physician)
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Subhash Mukhopadhyay (Bengali: সুভাষ মুখোপাধ্যায় Shubhash Mukhopaddhae) (died June 19, 1981) was an Indian physician from Calcutta (now called Kolkata) in India. He was educated at the Scottish Church College and later, at the Calcutta Medical College which was then affiliated to the University of Calcutta.
His life and death has been the subject of countless newspaper reviews and inspired the Hindi movie Ek Doctor Ki Maut (Death of a doctor), directed by Tapan Sinha.
He created history when he became the first physician in India (and second in the world after British physicians Patrick Steptoe and Robert Edwards) to perform the In vitro fertilization resulting in a test tube baby "Durga" (alias Kanupriya Agarwal) on October 3, 1978.
Facing social ostracization, bureaucratic negligence, reprimand and insult instead of recognition from the Marxist West Bengal government and refusal of the Government of India to allow him to attend international conferences, he committed suicide in his Calcutta residence on 19 June 1981.
His feat has been given belated recognition as the Indian physician who in 1986 was "officially" regarded as being the first doctor to perform in-vitro fertilization in India.
His recognition is attributable to TC Anand Kumar who is credited to be the mastermind behind India's second (officially the first) test-tube baby. Kumar took the crown off his own head after reviewing Subhash Mukhopadhyay's personal notes. He was ably helped by Sunit Mukherji, who was a one-time colleague of Mukhopadhyay.
Kumar is currently active in setting up a research institute in reproductive biology in memory of Mukhopadhyay.
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[edit] Experiment
[edit] Collection and evaluation of spermatozoa
Durga’s father was found to have a low sperm count, according to Mukerji who obviously was aware of the diagnostics value of semenograms as evidence by the papers he represented much before the WHO laboratory manual for the examination of human semen came out in 1980. Mukerji also knew that such a condition can he effectively treated with gonadotropins. Gonadotropins therapy is now routinely used to treat men with low sperm counts.
Ovarian stimulation.In his report dated 19-10-1978 to the DHS, Mukerji stated that he had treated Mrs Agarwal with hMG 76 ampoules given twice a day an don alternate days and starting from day 3 to day 9 of the cycle. She was given 6000 I.U. of hCG on day 11 of the cycle and she was subjected to oocyte aspiration some 48h later. Mukerji was able to aspirate 5 folicle by this method. In todays context this ovarian protocol will not sound outrageous because controlled ovarian hyper stimulation is the standard procedure for all women subjected to IVF. However, until 1980 december ‘conventional wisdom’ in Britain, Australia and USA dictated that stimulated cycles were unsuitable for oocyte collection and therefore oocyte aspiration was restricted to natural cycles. It was only in 1981 that other scientists resorted to ovarian stimulation. The Australians who were the next to announce the birth of IVS babies, began to use clomiphencitrate for ovarian stimulation in 1981. the Norfolk group in the USA, who were the third to report the occurrence of an IVF baby, began to use with hMC and hCG in their IVF programme with success in 1982. It is noteworthy that Mukerji was far ahead of his time in successfully using an ovarian stimulation protocol before anyone else in the world had thought of doing so.
Ovum pick-up for IVF was a problem during the early days. The British team had used a laparascope to harvest oocytes. The advent of ultrasonography later on opened out a new avenue to aspirate oocytes transvasicaly under ultrasound guidance by making apercutaneous insertion of a long needle traversing the abdominal wall, the urinary bladder and finally the ovarian follicle. The advent of the transvaginal probe has made it possible to collect oocytes per vaginum and this is the standard procedure used now.
Mukerji’s originality was that he was able to access the ovaries by a very simple operation on the wall of the vagina. Stimulated ovaries enlarge and drop down towards the Pouch of Douglas. A small incision on the posterior wall of the vagina would allow the ovaries to fall through this opening. This reminds one of how a biologist gains rapid access to the ovaries of rats by a very simple lateral, abdominal incision. The entire procedure was accomplished within a couple of minutes. Mukerji’s research experience with rats and humans had helped him take this very simple and original approach of gaining access to ovaries by posterior colpotomy. One wonders why this very simple approach did not gain popularity. After all today oocytes are aspirated per vaginum under ultrasound guidance.
[edit] In vitro culture techniques
The freshly aspirated oocytes were incubated for 4 hours before inseminating them with the husband’s semen that was processed in protein-supplemented Tyrodes solution. This is exactly what is done even to this day in almost all IVF programmes to accomplish in vitro oocyte maturation; processing semen is essential for ‘sperm activation’. The oocytes were exposed to processed semen for a period of 24 hours and later incubated for another 72 hours in a mixture of cervical-uterine fluids. The use of such fluid is not described elsewhere. However, the use of a synthetic fluid, similar to that found in the human fallopian tube, has been described to be useful for in vitro embryo culture procedures.
The methods of in vitro fertilization and embryo growth are described in detail in Mukerji’s letter to the DHS dated 19 October 1978 as well as in a publication in an obscure journal. Mukerji’s stated ‘…It also appears that for cryogenic preservation of embryos with a relatively larger number of blastomeres (more than 8 cells) may be preferable’.
‘Few pre-ovulatory human oocytes collected from a married by surgery were fertilized with spermatozoa from the husbands and cleaved in vitro and subsequently frozen slowly to about 196oC after stepwise treatment with dimethyl sulfoxide. One such frozen embryo was subsequently thawed slowly and when transferred into the uterus of the woman apparently resulted in the production of a clinically normal female baby after normal period of gestation’.
Here is clear published evidence of how exactly Mukerji carried out his version of in vitro fertilization and embryo transfer.
Cryopreservation of embryos from mice, rabbits, sheep goats and was reported between 1971 and 1979. The first report on the successful cryopreservation of four to eight cells human embryos appeared as late as 1981 and Trounson and Mohr reported the first successful clinical outcome of the transfer of thawed human embryos in 1983. A WHO report states ‘embryo cryopreservation has now become a routine adjunct to IVF procedures, and various methods of freezing are employed. The method that has yielded the best results in terms of simplicity, efficiency and reproducibility is one that involves freezing of one to three-day-old embryos (one to eight cells) in a controlled biological chamber that cools the embryos to sub-zero temperatures in the presence of a cryoprotectant 1,2 propanediol. Other cryoprotectants that are used are dimethyl sulfoxide (the same cryoprotectant was used by Mukerji) and glycerol.
It may be noted that Subhas Mukerji 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. This small publication of Mukerji in 1978 clearly shows that Mukerji was on the right line of thinking much before anyone else had demonstrated the successful outcome of a pregnancy following the transfer of a 8-cell frozen-thawed embryo into human subjects transferring 8-cell cryopreserved embryos.” (Current Science, Vol .72. No. 7, 10th april1997)
[edit] End of experiment
18th November 1978. An ‘expert committee’ was appointed by the Government of West Bengal under the medical association to decide over the fate of a convict named Dr. Subhas Mukhopahyay. His charges are, one, he claims to be the architect of first human test tube baby named Durga.(3rd October, 1978). Secondly, he denounced the report to the media before being cleared off by the Government bureaucrats. Thirdly, he made this impossible possible with few general apparatus and a refrigerator in his small southern avenue flat while others cannot even think of it, although, having all the expensive resources in their hand.(in this research Mukhopadhyay was assisted by Sumit Mukherjee and S.K. Bhattacharya.). Fourth and most important allegation, he never let his head down by the Government Bureaucrats and his straightforwardness always attracted jealousy out of his peers. The committee was presided over by a Radio physicist and it was composed of a gynecologist, a psychologist, a physicist and a neurologist. None of them were having any knowledge about modern reproductive technology. “Where did you keep these embryos?”[citation needed] Mukhopahdhyay said “in sealed ampules.” Then he asked again “How did you seal an ampule?” Speechless Mukhopadhyay could only utter “pardon?” From here started a questioning and counter questioning session which need not to be mentioned was utterly meaningless.[citation needed] “Oh! Embryos do not die while sealing?” there were people who never saw embryos in the entire span of their lifetime.
The Committee put forward its final verdict, “Everything that Dr. Mukhopadhyay claims is bogus.”
Only 67 days earlier, on 25 July 1978, world’s first human test tube baby Louise Joy Brown was born at Oldham General Hospital in England. Architects were Robert Edward and Patrick Steptoe. In their procedure they collected Ovum By using Laparoscope. At first they observed the evolution and development of the Ovum for a long span of time and then collected it through a small incision. Ovum thus collected is then fertilized by sperm on a small disc. When it forms into an embryo scientists placed it into the womb. But Mukhopadhyay without using laparoscope collected ovum by performing a small operation in the vagina. He increased the number of ovum collected by using a hormone and developed embryo. Lastly, he placed it in the womb.
Thanks to his peers and Government bureaucrats he ultimately handed with a punishment. He had been transferred to ophthalmic department which sealed his prospect to work on hormones.
[edit] Late recognition
An insulting silence carried on with every passing day. Many of you know that according to the Scientific documents “Harsha”(16th August 1986) become the first human test tube baby of India. The invention went to T.C Anand Kumar, Director of ICMR. In 1997 he came to Kolkata for participating in Science Congress. It was when all the research documents of Mukhopadhyay were handed over to him. After meticulously scruitinising and having discussion with Durga’s Parents he became certain that Mukhopadhyay was the architect of first human test tube baby. This eminent scientist once mentioned in a journal on ‘A critique of Mukerji’s technique’: “The brief description given by Mukerji in his letter dated 19 October 1978 to the Director of Health Services, Government of West Bengal, the reports he gave over the television interviews and reported in the lay press describe how Mukerji carried out the procedure of in vitro fertilization.
In T.C. Anand Kumar’s initiative Mukhopahdhyay is mentioned as the architect of first Indian test tube baby in a document related to the subject of artificial intercourse in ICMR India’s first test tube baby “Durga” whose parental name is Kanupriya Agarwal works in a Multinational Company as a Marketing Executive in Delhi. On her 25th birthday she first time exposed her identity in a ceremony organize in the memory of Mukhopahdhyay. She spoke about her creator in front of media and proved once again that her creator’s claim was not bogus.
In the ‘Dictionary of Medical Biography’ published by World Foundation enlists names of 1100 Medical Scientists from 100 countries around the world for the path breaking contribution to the medical science. Only three names found there place in that dictionary from the city of Kolkata. The names are; Sir Ronald Ross, U.N. Bramhachari and Dr. Mukhopadhyay. What is more ridiculous is that after his death, in 1983, one by one three scientists Howard Jones, Gleichar and Tronson (Australia) in three separate research claimed the invention of Human test tube baby. All these three research were already successfully accomplished by Mukhopadhyay long before their time. One of these scientists even found his research published in famous Journal “Nature”.
[edit] References
- “The Great Scientist Dr.Subhash Mukhopadhyay”; Written By Bidyut Tantra; 11 February 2008 ; B.C.D.A Collage of Pharmacy & Technology
- Prof Sunit Mukherjee , Secretary—Dr.Subhas Mukherjee Memorial Reproductive Biology Research Center
- Architect Of India’s First Test Tube Baby- Dr.Subhas Mukherjee.Edited by- Prof Sunit Mukherjee & Dr. S.C.Lodh
- Kuntal Bhattacharya ( Human Resource Executive )
- Mr. Surajit Goon And Mr. T. R. Panigrahi ( Lecturer B.C.D.A Collage of Pharmacy & Technology )
- Times News Network 15 October 2003
