How sad it is that inventors cannot control the eventual application of their work: The flipside of innovations in diagnostic and therapeutic technologies in medicine. Japheth Mati MD

It is fair to conclude that the technological revolution of the twentieth century was unprecedented in human history. Medicine was one area of tremendous progress, especially considering that at the dawn of that century Surgery, in particular, was a dicey procedure to undergo. It was before the arrival of safe anaesthesia, blood transfusion, antibiotics, and other life support paraphernalia we often take for granted. Admittedly, a lot of today’s surgical procedures predate the 20th century, but they were far from being safe. Take Caesarean section, for example, around 1860s the mortality rate associated with the operation in Great Britain and Ireland, was 85%[i]. Major strides in mortality reduction had to await advances, especially in three key areas: Anesthesia, Blood transfusion and Antibiotics.

Anesthesia: In the 20th century, the safety and efficacy of general anaesthesia was improved by the routine use of endotracheal intubation, advanced airway management techniques, and better anaesthetic agents that made “bite the bullet” become obsolete!  Blood transfusion: The discoveries by Karl Landsteiner, of human blood groups (1901) and the Rhesus factor (1937), markedly improved the safety of blood transfusion. Antibiotics: Antibiotics are a creation of the 20th century, starting with the sulpha drug Prontosil in1935; Penicillin[ii] (1942), Streptomycin (1943); Tetracycline (1955); Nystatin (1957); to be followed by others, including the semi-synthetic antibiotic Amoxicillin (1981).

As I marvelled over these and other 20th century great medical scientific and technological feats, one question kept nagging me: does the way we mainly use these inventions today conform to the original purpose of their creators?

Thinking slightly outside of medicine, one can for example compare the opposites in the employment of nuclear technology: on the one hand, its value as a source of efficient energy to drive industry, and on the other its use as a weapon of  mass destruction. Though not to the same degree of departure, in medicine, a considerable number of today’s most celebrated technologies are used in manner that is at variance with the inventor’s original intentions, to the extent that some inventors have had occasion to publicly express regret over the ‘misuse’ of their work.

It’s the intention in this post to review briefly selected diagnostic and therapeutic innovations that have exerted great impact on medicine in general, and the practice of obstetrics and gynaecology in particular, especially beginning the second half of the 20th century.

The review covers the following diagnostic and therapeutic techniques: amniocentesis and amniotic fluid sampling, prenatal cytological sex determination, prenatal blood DNA sex determination, obstetric ultrasound, and in-vitro fertilisation technique. Each one of the above innovations has performed beyond expectation, finding greater utilisation for purposes far removed from the original intention at the time of their discovery. These “other” uses are examples of what can be referred to as ‘the flipside of scientific and technological innovations in medicine’. In sympathy with their cause, we are left to wonder: “If only inventors were endowed with wisdom to foresee the ends to which their creation might end up being applied!”

 Amniocentesis

Amniocentesis is the process of removing a sample of amniotic fluid – the medium in which the fetus floats in the mother’s uterus, to be analysed for markers of certain disorders of the fetus. This procedure is credited to the work of Douglas Bevis, a British obstetrician and gynaecologist at St. Mary’s Hospital in Manchester in early 1950s. Later, following the discovery of ultrasound (see below) it became possible to undertake ultrasound-guided amniocentesis with greater accuracy and safety.

Amniocentesis ultrasound guided image

Ultrasound guided amniocentesis

Amniocentesis and amniotic fluid sampling (AFS) permits the monitoring of fetal wellbeing in utero, especially in the management of Rh-isoimmunisation. It is frequently used in the estimation of fetal lung maturation, and in the diagnosis of genetic disorders such as Down’s syndrome (mongolism) and sex-linked diseases such as haemophilia.

In 1949 Canadians Murray Barr and Ewart Bartram had discovered sex chromatin (a mass of chromosomes, also called “Barr Body”), which is found only in female cells. Thus, finding the sex chromatin in fetal cells obtained through AFS permitted identification of a female child. Later through tissue culture techniques it was possible to identify the actual male and female sex chromosomes in cells, thereby improving accuracy of sex determination using cytogenetic technique, which remains the gold standard. There are now over 500 hereditary diseases that can be diagnosed through amniocentesis and other diagnostic techniques[i].

The technique of amniocentesis reigned supreme till the tail-end of the 20th century when in 1997 Dennis Lo and colleagues (both in Oxford UK and Hong Kong, China) published their seminal paper[ii] reporting the presence of fetal DNA in maternal blood, thereby opening the door to a new non-invasive technique that avoided the risk (albeit very small) of abortion following amniocentesis. The new DNA test, which employs the more advanced Polymerase Chain Reaction (PCR), has the added advantage of being performed at an earlier gestational age- as early as 7 weeks, much earlier than was possible with ultrasound scan (see below) which could only demonstrate male fetus at 11 weeks earliest, and not so reliably. An important downside of DNA PCR test is the cost involved.

The potential to determine fetal sex has opened the door to abuse of these tests. The ‘flipside’ of prenatal sex diagnosis has been its utilization in selective abortion of female fetuses, to the extent sometimes, of posing demographic imbalance as has been feared for India[iii] and China[iv]. In this regard the test changes from enhancing the wellbeing of the fetus to selecting it for destruction. A complete turnaround!

Ultrasound scanning

Prof Ian Donald[v] (1910-1987), the Regius Professor of Midwifery at the University of Glasgow (1954 -1976), and a tough Scot who endured three open-heart valve-replacement operations, is the celebrated Father of Medical Ultrasound, a technology he pioneered beginning the late 1950s. His first major publication on the subject appeared in the Lancet in 1958, which contained the first ultrasound images of the fetus ever published[vi].

The potential to reveal information on the growing fetus in the womb was soon realised and the use of ultrasound spread quickly, improving the safety of pregnancy and childbirth, and allowing for the much more effective detection and treatment of fetal abnormalities. Since the 1970s ultrasound scanning has become a routine part of antenatal care. And as the science of ultrasound developed, so did its applications. Ultrasound scanning is now used in numerous other areas of medicine, with recent advances in technology enabling three-dimensional images to be produced.

Ian Donald hommedia

Professor Ian Donald

A less discussed dimension of Ian Donald’s work is what fundamentally may have driven him to develop the technology. In this regard, he seems to have considered obstetric ultrasound to be more than simply a means to visualise the fetus in utero; instead, he saw the technology as providing a chance to ‘individualise’ the fetus. The technology made it possible for the fetus to be recognised, or at least spoken of as, an individual, a reality. This view comes out clearly from the description he uses in the following 1978 presentation to a lay audience[i]:

Here’s the baby see how he jumps … This baby is about a 12 week pregnancy … She [the mother] certainly cannot feel these movements but there is no doubt about the reality, … now you see it move its hand up to its face you see his head is up here and his chest is down here then he throws his legs out and his arms … You see his hands come up like that. And you see his face here, the back of his head … It is rather like a child on a trampoline, tremendous strength, energy and vitality.)

Perhaps because of these experiences, Ian Donald came to hold quite strong views against abortion, being a lead campaigner against the 1967 Abortion Act in the UK. He is known to have employed the ultrasound imagery as a powerful persuasive resource in urging women to continue with their pregnancies. In his view the only indication for abortion was a very grossly deformed fetus; no consideration in cases of mild or moderate handicap. Indeed Ian Donald even went to the length of attempting to save a fetus in an ectopic pregnancy – a heroic surgical endeavour which failed miserably, but which nevertheless, justified an audience with Pope John Paul II, an occasion he described as ‘the crowning event of my life’[ii].

Personal idiosyncrasies apart, there is absolutely no argument that Ian Donald’s work has contributed immensely to better outcomes in many medical disciplines, away from his own field of obstetrics and gynaecology. However, in a rather ironical way, ultrasound scan happens to be the most reliable way of diagnosing not only early pregnancy, but also of ensuring the uterus has been completely evacuated, following both spontaneous abortion and induced abortion (especially medical termination of pregnancy).

By the 1970’s, Ian Donald had become aware of the truth, that the ends to which technology is put cannot be determined by its originators. He somewhat despairingly wrote, “My own personal fears are that my researches into early intrauterine life may yet be misused towards its more accurate destruction”[iii]. Indeed, Ian Donald had come face to face with the flipside of his own scientific and technological innovation in medicine!

 In vitro fertilization

Patrick Christopher Steptoe (1913 – 1988), a British obstetrician and gynaecologist, along with biologist/ physiologist Robert Edwards, were the pioneers of the technique of in vitro fertilization for infertility treatment. Louise Joy Brown, their first ‘test-tube baby’, was born on 25 July 1978, the product of great perseverance- it took them 10 years before they had their first successful birth. Edwards was awarded the 2010 Nobel Prize in Physiology or Medicine for this work, however because the Prize is not awarded posthumously, Steptoe was not eligible for consideration.

Since Louise Brown, there have been over 4 million babies worldwide conceived through IVF. Despite a steady stream of ethical and moral questions arising from IVF, to date, the lives of many women and couples across the globe have been enriched by a child conceived through one or other of the various modifications of the original IVF technique introduced by Steptoe and Edwards. This reproductive technology has made and continues to make tremendous advancements in basic reproductive biology and embryology. It has enabled us to understand the human reproductive processes and especially fetal development, in a way that has never been possible in the past[iv].

At the same time, the world of IVF almost everywhere has become a very competitive market-place, resulting in many treatment centres going to great lengths to ensure a pregnancy is achieved. The temptation is high to transfer large numbers of embryos to the uterus, which results in pregnancies of high multiples, some of which may be lost through spontaneous abortion, or subjected to ‘fetal reduction’ procedures (euphemism for abortion).

The technique of IVF has become an essential source of ‘spare embryo’ for stem-cell research, which gives hope to many people dying from today’s incurable diseases. But, still, this is far beyond Patrick Steptoe’s imagined application of their technique.


[i] I. Donald (undated but after 1978) ‘Predicting ovulation’, unpublished lecture, tape-recording in BMUS Archive).

[ii] Malcolm Nicolson, Ian Donald – Diagnostician and Moralist http://www.rcpe.ac.uk/library/read/people/donald/donald.php

[iii] I. Donald (1972) ‘Naught for your comfort’, Journal of the Irish Medical Association, 65, 279-89.


[ii] Lo YMD, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, et al. Presence of fetal DNA in maternal plasma and serum.Lancet1997;350:485-7.

[iv] en.wikipedia.org/wiki/Abortion_in_China

[v] Prof Ian Donald was my supervisor at the Queen Mother’s Hospital in Glasgow in 1969.

[vi] I. Donald, J. MacVicar, T. G. Brown (1958) ‘Investigation of abdominal masses by pulsed ultrasound’, The Lancet, 1, 1188-95.


[ii] Fleming, Florey, and Chain shared the 1945 Nobel Prize for medicine for their work on penicillin.

 

 

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