Rapid diagnostic tests have saved many lives around the world thanks to their simplicity, speed and affordable price. The most widespread are the antigenic tests, which we were all able to benefit from during the Pandemic of Covid-19. Other antigenic tests exist, such as those detecting dengue or chikungunya, two tropical viral infections, or malaria, the most fatal disease in the world in children under the age of 5.
These types of tests are recognized as public utility by the World Health Organization (WHO). The antigenic influenza test is used for example routine. Although the interest in these self-tests emerged during the COVVI-19 pandemic, we were already familiar with antigenic tests without realizing it. Pregnancy tests, oh how much involved in our personal stories are the first rapid diagnostic tests created. We owe this discovery to Margaret Crane, whose invention has contributed to the considerable improvement in the general diagnostic field.
Pregnancy tests through the ages
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Detecting a pregnancy has always been of importance for female health, family management and social issues. An Egyptian medical papyrus dating from around 1350 BCE, called the Carlsberg papyrus, details a simple method. Grains of barley and wheat, each locked in a small bag or a container, were moistened daily with the woman’s urine to test. The lack of germination diagnosed the absence of pregnancy. The germination of barley provided for the birth of a boy, when that of wheat presage that of a girl.
In 1963, a research team decided to try this technique of ancient Egypt, at first glance rudimentary. Surprisingly, even if the prediction of sex was disappointing, the Egyptian method had a very high sensitivity: 70% of pregnancies were confirmed! This is probably due to the fact that hormones in the urine of pregnant women mimic the action of phytohormones, vegetable hormones.
The first tests presented time, costs and animal use constraints, which motivated the search for faster and less invasive methods.
In 1927, the British zoologist Lancelot Hogben obtained a research chair to study animal hormones at the University of Cape Town, in South Africa. He discovers the CAP “toe” to the claws “(Xenopus laevis), whose females have the capacity to lay the year. Professor Hogben contributes to the creation of a pregnancy test that bears his name. Its principle? Inject pregnant woman urine into a female toad. Due to the hormones contained in the urine, this injection spontaneously triggered the laying. The test presented a sensitivity greater than 95%!
A specimen of “claws toad” from CAP or smooth xenope (Xenopus laevis), spotted in Chimanimani (Manicaland), in southern Zimbabwe, in December 2012. | Brian Gratwicke / CC by 2.0 / Flckr
Although this protocol became a routine test in the 1940s, the majority of women still did not have easy access to pregnancy tests. Other similar tests existed, using female mice or rabbits, consisting in examining the ovaries for forty-eight to seventy-two hours after the injection of urine, to see if it had induced ovulation. These tests had time, costs and animal use constraints, which motivated the search for faster and less invasive methods.
The discovery of the HCG hormone
In the early 1930s, the American endocrinologist Georgeanna Seegar Jones discovered that the placenta produced a hormone, called the human chorionic gonadotrophin, whose abbreviation is HCG. This discovery has made it an early marker of pregnancy. To test it, it only remained to detect it.
In 1960, the Swedish biochemist Leif Wide Immunisa animals against human HCG and purified antibodies. We therefore had molecules available, antibodies, capable of detecting HCG, it was still necessary that the antigen-anticorps reaction (in this case, the HCG is the antigen recognized by antibodies) could be visible to confirm a pregnancy from urine.
Professor Leif Wide developed a pregnancy test, according to a technology called the inhibition of hemagglutination. It is based on the use of red blood cells, whose color allows an analysis with the naked eye. If antibodies are binded to red blood cells, they tend to agglutinate and this forms a “red spot” at the bottom of the test. In case of pregnancy, the urine sample contains HCG: antibodies react with HCG and cannot link red blood cells. The absence of a red spot indicates a pregnancy. This test was revolutionary, because, unlike others and in addition to being much less expensive, the result was only obtained in two hours.
The invention of Margaret Crane
In 1962, the American company Organon Pharmaceuticals marketed this pregnancy test, for medical analysis laboratories. In 1967, Margaret “Meg” Crane was a young 26 -year -old designer without any scientific baggage, employed by this pharmaceutical company in New Jersey, to create the packaging of her cosmetic branch. One day when she visits the company’s laboratory, she attended the execution of one of the tests. A laborantin explains the long procedure to him, consisting of the debit of urine by the doctor and sending to an analysis laboratory. It took about two weeks for a woman before having a result.
Despite the theoretical complexity of technique, Margaret Crane then achieves both the simplicity of reading the test and the protocol: it was enough to have tubes, a bottle of antibodies and a color indicator (red blood cells). Back home in New York, she launched experiences, inspired by a box of paper clips on her desk. It designs an ergonomic case – with all the equipment and a simplified user manual – intended for direct use at home by users. Margaret Crane shows his prototype to organnon pharmaceuticals, who refuses the idea, judging that a woman would not be able to read the result alone [PDF]as simple as it is …
The predictor, the pregnancy test invented by Margaret Crane. | National Museum of American History / CC by
The perseverance of Margaret Crane
Shortly after the proposal of Margaret Crane, a man employed by Organon Pharmaceuticals inspires it and launches the same idea. He is listened to. She then decides to take advantage of the situation, attending the meetings where she was the only woman. Several tests, prototyped by male designers, are presented there: in the shape of a chicken egg, either pink, or decorated with rhinestones …
Without any hesitation, it is that of Margaret Crane who is chosen for her practicality, because she had thought it so that her use is as easy as possible. Margaret Crane filed his patent in 1969, but Organon Pharmaceuticals hesitated to market it immediately, for fear that consumers will be dissuaded by conservative doctors or their religious community.
The predictor was put for the first time on the market in 1971 in Canada, where abortion had just been legalized. Although credited on the American patent, Margaret Crane did not perceive any remuneration, because organnon pharmaceuticals ceded the rights to other companies.
The story of Margaret “Meg” Crane, now 85 years old, illustrates a fascinating course, where empirical observation meets industrial design. His contribution was finally recognized in 2014 by the National Museum of American History. Its founding concept, that of a simple, intuitive and autonomous test for the user, opened the revolutionary path to pregnancy tests in the form we know today and antigenic tests, essential especially during health crises.
Valérie Lannoy is a postdoctoralizing in microbiology at Sorbonne University.
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