In vitro fertilization and embryo transfer leading to a successful pregnancy was well established in experimental animals during the early part of the 20th century. It was such findings that led to the publication of early science fiction “Brave New World' by Aldous Huxley in the 1930's. In the Brave New World, Huxley envisaged a society in which babies were artificially procreated. Babies were ‘tailor made’ to fulfill specific tasks (was this a forecast of ‘Designer babies’ that appeared in the latter part of the 20th and early part of he 21st centuries?).
Fiction often precedes true events. The world's first ‘artificially created’ human baby, Louise Brown, was born on 28th of July 1978 by a process of removing an oocyte from the ovaries of a woman, fertilizing it in a petri dish with the husband's sperm, leaving the fertilized egg in the petri dish for a short period until it divided and replacing into the woman's womb leading to a live birth. This entire process has now come to be known as in vitro fertilization and embryo transfer (IVF-ET) as carried by the original investigators, Patrick Steptoe and Robert Edwards.1 This led to the birth of the world's first ‘test-tube baby’, a very popular terminology that is nevertheless a misnomer as test-tubes are not used for in vitro fertilization.
Following this success, a number of newer techniques were subsequently developed by others and given different terminologies. Briefly, these techniques aim to assist barren couples to parent a child through Medically Assisted Reproductive Technologies (MART).
Infertility is considered a curse in India and infertile couples often face social ostracism. Any method that improves the chances of barren couples bearing a child is therefore a very attractive proposition to Indians. While the world was experimenting with MART, India was not far behind as would be evident in the narrative given below. The aim of this chapter is to highlight events that led to the firm establishment of MART in India.
INDIA'S FIRST TEST-TUBE BABY
Exactly 67 days after the birth of the world's first test-tube baby, an Indian team, led by Subhas Mukherjee (physiologist) Sunit Mukherjee (cryobiologist) and Bhattacharya (a gynecologist) announced to the world, through the press and other media, the birth of ‘Durga’ conceived following the transfer of an embryo produced by fertilizing in vitro an oocyte aspirated from the mother, and transferring the embryo back to the mothers womb.2–4
Subhas Mukherjee was essentially a loner, much dedicated to his work and kept much of his work confidential as he was not sure of the outcome of his efforts. Following his announcement, his uninformed colleagues and others subjected him to great humiliation. He was ridiculed, professionally harassed by the authorities and he was ultimately driven to commit suicide.
Mukherjee however, left behind copious notes that have recently been collated and published in Kolkata. He also wrote an ‘official’ note to the Government of West Bengal describing the procedure he followed in some detail. This note was written at the request of the Government of West Bengal. He also published a very short note describing the procedure he followed. However, much of his work was not published as Mukherjee wanted to repeat his studies several times to confirm his finding. However, he was encouraged to publicize his achievement through the press and television and later at the Indian Science Congress when the world's first test tube baby was born.
His announcement elicited some very sharp inquiries by the Government which setup a ‘Star-Chamber’ committee to verify his claims. The committee did not have any expertise in the field of human reproduction to appreciate his contributions; it only ridiculed his claims and humiliated him at a public meeting in Kolkata. The Government of West Bengal asked him to submit a report of his work. A copy of this report, signed by all the three investigators on 19 October 1978, is available amongst the personal papers of Subhas Mukherjee. He, along with his colleagues, published a note in the Journal of Cryogenics 1979;3:80 on how to freeze embryos and recover them for intrauterine transfer at a later stage.5 His presentation at the Indian Science Congress in 1978 was reported in the New Scientist and his work received global publicity.6
The information presented, gathered over a period of a few years by the author here is based on his note to the Government, and his short publication. It was gathered through personal interviews with Kanupriya (the real name of “Durga”), her parents and some of the surviving people who were associated with the work, and a sworn affidavit from the parents stating their personal experience.7
Mukherjee had informed the parents that since the mother's tubes were blocked, he was going to attempt a novel way of getting her pregnant that involved taking out eggs from the mother and fertilizing them outside her body and replacing the embryo back into her womb. He also informed them that he was not sure of the outcome or even if the child would be normal. The parents agreed to try out anything but insisted that the whole matter kept confidential as they did not wish to be socially ostracized for having subjected themselves to an experiment that resulted in the birth of an abnormal child. When the baby girl was born they gave it a pseudonym—‘Durga’ In other words, this was a case where the patients' informed consent was obtained much before treatment was started. The girl, whose actual name is Kanupriya, is now a young lady and, at the moment of writing this document, is a student of Business Management in Pune.
Novel Techniques used by the Kolkata team based on the Report submitted by Mukherjee to the West Bengal Government (1978) and the Article published in the Journal of Cryogenics (1979)
There are many significant differences between the techniques used by the British and Indian teams as described below:
- Mukherjee was the first to successfully use human menopausal gonadotropins (hMG) for ovulation stimulation in an IVF program to ensure the availability of multiple ovarian follicles for aspiration. hMG is now routinely used all over the world in IVF Programs and the credit for its first time use has been given to Howard Jones (USA).8 Indeed Mukherjee's colleagues still have the old boxes containing gonadotropins manufactured by SERONO, that were routinely used by him.
- Mukherjee was the first to approach the ovaries via the vaginal route by posterior colpotomy. The transvaginal route is now the most widely used approach to the ovaries for follicular aspiration under ultrasonographic guidance.
- Mukherjee was the first person to have succeeded in freezing and thawing human embryos using a reagent (DMSO) that is now very commonly used for freezing embryos. The Australian team, headed by Trounson is credited for having first made this discovery in the 1980's using DMSO.9
- Mukherjee was the first to have aspirated oocytes in a stimulated cycle, fertilize them in vitro and freeze the embryos in that cycle; recover, thaw and transfer them into the uterus during the following, natural cycle. This procedure has since been used successfully and independently by several other clinics.
One must remember that the world was not yet ready to accept the reality of initiating life outside the body. Each and every pioneering work in this field faced great criticism once the work was reported starting from the British team, to the American and Australian teams. It is therefore not surprising that Mukherjee's colleagues also looked down upon Mukherjee's work; they had absolutely no idea of what was possible in the ‘Brave New World’ that had just dawned. The fate of Mukherjee is rather tragic. His public ridicule and humiliation by his colleagues, harassment by the West Bengal Government, led him to make the ultimate sacrifice with his life.
India' Second Test Tube Baby—The ICMR's Institute for Research in Reproduction (IRR) in Bombay undertook a project to produce a baby through in vitro fertilization and embryo transfer. The reason for undertaking such a project was to acquire skills in handling human gametes; gain an understanding of the physiological deficiencies causing infertility as such knowledge could lead to the development of better contraceptives. It was also thought necessary to have a method of reversing infertility caused by tubal sterilizations under the Family Planning Program in such rare instances where women, who have lost their child born before sterilization, desire to have another baby.
Under the advice of the Scientific Advisory Committee of the Institute, a project was mounted under the leadership of Professor TC Anand Kumar in 1982. He gathered a team comprising biologists from the IRR and a gynecologist from one of the collaborating institutions from the neighborhood, the King Edward Memorial (KEM) hospital. The protocol for undertaking this work was drawn up by the IRR based on what was possible. The entire project at the IRR was fully funded by the Indian Council of Medical Research. Patients with blocked tubes, as diagnosed by laparoscopy, were selected for IVF. Ovulation was induced with clomiphene citrate and hMG; ovarian response monitored by rapid estimations of estradiol levels at the IRR in daily serial blood samples. Semen analysis was carried out at the IRR according to the WHO semen analysis manual. The oocytes were aspirated in the KEM hospital, rapidly transported in a ‘warm’ (37°C) thermacool box to IRR, which was just a few hundred yards away from the hospital, where the biologists at the IRR carried out all the in vitro culture work, including the processing of semen. Resultant embryos were transferred into the patient's uterus at IRR. Conception following in vitro fertilization and embryo transfer led to the birth of Harsha on the 6th of August 1986.
This birth of Harsha did not go unheeded and without criticisms. The press gave ample coverage of the event. The Indian Parliament asked the ICMR to verify the claims made by IRR and whether the project was approved by the ICMR. The IRR had not only obtained the Scientific Advisory Committee's approval but had also obtained the institutional ethics committee's approval in accordance with the ICMR's Guidelines. It was because of such transparency in the IRR's work, by which all the members of the Scientific Advisory Committee had witnessed growth of embryos and their transfer into the patients uterus that eventually got pregnant, that the ICMR was able to substantiate IRR's claim and answer any criticism.
However, because the details of Subhas Mukherjee's work were not widely known, Harsha was termed as India's first ‘scientifically’ documented test tube baby. The scientific documentation was initially published in the Bulletin of the Indian Council of Medical Research.10
The birth of the first GIFT baby and the first baby born after embryo donation soon followed the birth of Harsha through the efforts of IRR and the KEM Hospital. MART had at last arrived in India and accepted by the public. Mushrooming of IVF clinics in India occurred thereafter.
The birth of Louise Brown in the UK and Durga in India raised many controversies ranging from disbelief to outright criticisms. Some libelous charges were made by the Press against Edwards and Steptoe that were successfully challenged in the court in favor of the scientists.
In India too, not only did Mukherjee face criticism but even the work carried out in Bombay was questioned by Parliament and even ridiculed by some.
All these are of the past. Today, over a million babies have been born the world over. Making babies is big business both commercially as well as in opening out new therapeutic modalities. A whole range of therapies are predicted to emerge from embryonic stem cells used for tissue or even organ repair in conditions such a diabetes, Parkinsonism, Alzheimer's, broken spinal cord, cardiovascular disorders and bone damage. The source of stem cells is spare and surplus embryos produced through MART.
As with every technological innovation, there is a good and a bad side to MART. Infertile couples especially in India are a gullible lot and are prepared to go to any extent just to have a child. There are also an equal number of capricious infertility clinics run by untrained staff, ill equipped and making tall claims on their success rates.
Recognizing this state of affairs, the Indian Council of Medical Research and the National Academy of Medical Sciences, have drawn up Guidelines for the Accreditation, Supervision and Regulation of Infertility Clinics in India. This Draft is intended to be a prelude to legislation.
- Steptoe PC, Edwards RG. Birth after the pre-implantation of a human embryo. Lancet 1978;ii:366.
- Staff Reporter, Amrita Bazar. October 6, 1978;1–7,
- Staff Reporter, Statesman. October 6, 1978.
- Staff Reporter, Statesman, October 17, 1978.
- Mukerji S, Mukherjee S, Bhattacharya SK. Indian J of Cryogenics 1978;3:80.
- Jayaraman KS. New Scientist 1978;80:159.
- Anand Kumar TC. Architect of India's first test tube baby: Dr. Subhas Mukerji (16 January 1931 to 19 July 1981) Curr Sci 1997;72:526–31.
- Jones W Jr, Jones GS, Andrews M et al. The program of in vitro fertilization at Norfolk. Fertil Steril 1982;38:14.
- Trounson AO, Mohr LR. Human pregnancy following cryopreservation, whawing and transfer of an eight-cell embryo. Nature 1982;305:707–09.
- Anand Kumar TC. ICMR Bulletin 1986;16.