From a beating spot in a hen's egg to IVF babies in Oldham and Kolkata: how people learned where life begins.
For most of history people could only guess how a new life starts. Microscopes in the 1600s revealed sperm and follicles, and in the 1800s scientists finally found the mammal egg and watched one sperm fertilise it. The 1900s brought chromosomes, hormones, ultrasound and IVF, and public health turned that knowledge into safer births, including in India, where far fewer mothers now die in childbirth.
Durga (Kanupriya Agarwal), Kolkata; Dr Subhas Mukhopadhyay
c. 350 BCEBig ideas, few tools
350 BCE – 1660
Big ideas, few tools
Thinkers open hens' eggs, name the tubes and argue that every animal comes from an egg, without being able to see one.
350 BCE
c. 350 BCE
Watching a chick grow inside an egg
AristotleLesbos and Athens, Greece
Aristotle opened hens' eggs day after day and wrote down what he saw. By about the third day a tiny red spot appeared that beat like a heart. He argued that the body's parts form one after another, not all at once.
Why it mattered. It was the first careful, step-by-step record of how an embryo develops.
The Italian anatomist Gabriele Falloppio described the two slender tubes that run from the uterus towards the ovaries, with their fringed, trumpet-like ends. His book Observationes Anatomicae was printed in Venice in 1561.
Why it mattered. We still call them fallopian tubes, although nobody then knew that eggs travel along them.
William Harvey, famous for showing how blood circulates, studied chicks and deer embryos. In his book On the Generation of Animals he argued that all animals, including humans, begin from some kind of egg. The phrase ex ovo omnia, everything from an egg, became linked to his work.
Why it mattered. It pointed scientists towards the egg long before anyone had seen a mammal's egg.
Microscopes reveal follicles and sperm, a wrong idea about tiny people is overturned, and the mammal egg is finally found.
1672
Bubbles in the ovary
Regnier de GraafDelft, Netherlands
The Dutch doctor Regnier de Graaf studied the ovaries of rabbits and other mammals and described small fluid-filled bubbles on their surface. He thought each bubble was an egg. In fact each one holds a far smaller egg inside. We still call a ripe one a Graafian follicle.
Why it mattered. He found the follicle, the bubble that ripens and releases an egg every month.
Antonie van Leeuwenhoek (with Johan Ham)Delft, Netherlands
Using his own tiny, powerful single-lens microscopes, the cloth merchant Antonie van Leeuwenhoek saw thousands of swimming cells with long tails in a sample of semen. A medical student, Johan Ham, had first pointed them out to him. He described them in a letter to the Royal Society in London.
Why it mattered. For the first time, people could see the cell that carries the father's half of a new life.
The Dutch microscope maker Nicolaas Hartsoeker drew a tiny curled-up person, a homunculus, inside the head of a sperm. He did not claim to have seen it; he drew it to show an idea many people then held, that a miniature person was already formed and only had to grow.
Why it mattered. It is a famous example of a wrong idea that microscopes and careful experiments later overturned.
In his thesis Theoria Generationis, the German scientist Caspar Friedrich Wolff showed from chick embryos that organs such as the gut form from simple, unshaped layers. Nothing was ready-made: the body builds itself in stages, an idea called epigenesis.
Why it mattered. It replaced the tiny-person idea with the picture of development that biology still uses.
The Italian priest and scientist Lazzaro Spallanzani showed that frog eggs only develop after they touch sperm-containing fluid. When he filtered the sperm out, the fluid no longer worked. He also carried out the first successful artificial insemination, in a dog.
Why it mattered. Experiments, not just looking, showed that both the egg and the sperm are needed.
Karl Ernst von BaerKönigsberg, Prussia (now Kaliningrad, Russia)
Karl Ernst von Baer opened a follicle from a dog's ovary and found a tiny yellowish speck floating inside it. It was the real egg, far smaller than de Graaf's bubble. He published the discovery in a short Latin book.
Why it mattered. It settled a 150-year-old question: mammals, including humans, do begin from a single egg cell.
Handwashing, trained doctors, ultrasound and photographs make pregnancy and birth safer and better understood.
1847
May 1847
Clean hands save mothers
Ignaz SemmelweisVienna General Hospital, Austria
Ignaz Semmelweis noticed that far more mothers died of childbed fever on the ward run by doctors, who came straight from dissections, than on the ward run by midwives. He made staff wash their hands in chlorinated lime, and deaths on his ward dropped sharply.
Why it mattered. Handwashing became one of the simplest and most powerful ways to keep mothers and babies safe.
Anandibai Joshi lost her baby son days after birth, and resolved to study medicine. She sailed to the United States and graduated from the Woman's Medical College of Pennsylvania with a thesis on obstetrics among Hindus.
Why it mattered. She showed Indian women could become doctors, and she chose care for mothers and babies as her subject.
Ian Donald, John MacVicar and Tom BrownGlasgow, Scotland
A Glasgow obstetrician, Ian Donald, worked with a doctor and an engineer to adapt an ultrasound machine used for finding cracks in metal. Their paper in The Lancet showed pictures of the inside of the belly made with sound echoes. Soon ultrasound could show a growing baby safely, without X-rays.
Why it mattered. Ultrasound scans became a routine, safe way to check a baby's growth.
The Swedish photographer Lennart Nilsson spent years taking pictures of human embryos and fetuses with special cameras and lenses. Life magazine printed them as Drama of Life Before Birth, and millions of copies sold within days.
Why it mattered. For many people it was the first time they saw how a baby develops.
Scientists watch fertilisation happen, count chromosomes, find the X and Y, and discover the hormones that run the cycle and puberty.
1876
Watching one sperm enter an egg
Oscar HertwigMediterranean coast (sea urchin eggs); based at Jena, Germany
Oscar Hertwig studied the clear eggs of a Mediterranean sea urchin, which are easy to see through. He mixed eggs and sperm and watched a single sperm enter an egg. About ten minutes later the sperm's nucleus had travelled to meet the egg's nucleus and joined with it.
Why it mattered. It showed that fertilisation is the joining of one sperm and one egg, nucleus with nucleus.
Working with the eggs of a roundworm that has very few chromosomes, Edouard van Beneden showed that the egg and the sperm each bring the same number of chromosomes, half of what the body's cells carry, and that they come together at fertilisation.
Why it mattered. This is the idea behind 23 + 23 = 46 in humans.
Nettie StevensBryn Mawr College, Pennsylvania, USA
Studying mealworm beetles, Nettie Stevens found that females had pairs of large chromosomes, while males had one large and one small one. She concluded that the sperm's chromosome decides whether the young is female or male. Edmund Wilson reached a similar conclusion the same year.
Why it mattered. It explained why the sperm, carrying an X or a Y, sets a baby's sex.
Edgar Allen and Edward Doisy extracted a substance from pig ovary follicles that made the lining of the uterus grow and brought animals into their breeding cycle. It was oestrogen. Doisy later purified it, and progesterone was found a few years afterwards.
Why it mattered. It showed that the menstrual cycle is run by hormones from the ovary.
For thirty years textbooks said humans had 48 chromosomes. Using better ways to spread cells out on a slide, Joe Hin Tjio counted 46 again and again, and he and Albert Levan published the result.
Why it mattered. It fixed the number at the heart of this box: 23 from each parent, 46 in all.
Andrew Schally and Roger Guillemin (separate teams)New Orleans and La Jolla, USA
Working with extracts from hundreds of thousands of pig and sheep brains, Andrew Schally's team worked out the structure of GnRH, the hypothalamus hormone that tells the pituitary to release LH and FSH. Roger Guillemin's team confirmed it. They shared the 1977 Nobel Prize with Rosalyn Yalow.
Why it mattered. It explained how the brain switches on puberty and runs the menstrual cycle.
IVF babies are born in England and India within months of each other, and new methods help more couples.
1978
25 July 1978
Louise Brown, the first IVF baby
Patrick Steptoe and Robert Edwards (with Jean Purdy)Oldham, England
After years of work, a gynaecologist and a scientist joined an egg and sperm in a lab dish and placed the early embryo in the mother's uterus. Louise Brown was born healthy. Robert Edwards received the Nobel Prize in 2010.
Why it mattered. It gave hope to millions of people with infertility.
Dr Subhas Mukhopadhyay (with Sunit Mukherji and Saroj Kanti Bhattacharya)Kolkata, India
Just 70 days after Louise Brown, a baby girl named Durga, later known as Kanupriya Agarwal, was born in Kolkata. Dr Subhas Mukhopadhyay and his colleagues had used their own methods and simple equipment. A government committee refused to believe him, and he died in 1981. Years later, experts reviewed his notes and recognised his work.
Why it mattered. India was only the second country with an IVF baby, and Mukhopadhyay is now honoured as a pioneer.
Dr Indira Hinduja, with T. C. Anand Kumar's ICMR teamMumbai, India
A baby boy named Harsha was born at KEM Hospital in Mumbai after IVF by Dr Indira Hinduja and a team from the Indian Council of Medical Research's Institute for Research in Reproduction.
Why it mattered. It started IVF as a medical service in India, which now has thousands of fertility clinics.
Doctors in Brussels reported the first pregnancies after injecting a single sperm directly into an egg with a very fine glass needle. The method is called ICSI.
Why it mattered. It helped many couples where the male partner has very few sperm.
Laws protect girls, schemes bring births into hospitals, and maternal deaths fall by more than three-quarters.
1994
20 September 1994
A law against sex selection
Parliament of IndiaNew Delhi, India
India passed the Pre-Natal Diagnostic Techniques Act, later renamed the PCPNDT Act. It bans using scans or tests to find out or choose the sex of a baby before birth.
Why it mattered. It protects girls, because the sperm, not anyone's choice, decides a baby's sex.
Janani Suraksha Yojana, National Rural Health MissionIndia
The Government of India launched Janani Suraksha Yojana (JSY), which gives cash help to poorer mothers who give birth in a hospital or health centre, supported by community health workers called ASHAs.
Why it mattered. Births in health facilities rose steeply, to 88.6% by 2019–21.
The Ministry of Health and Family Welfare launched PMSMA, which offers every pregnant woman in her second or third trimester a free check-up by a doctor on the 9th day of every month at government health centres.
Why it mattered. Regular check-ups catch problems like high blood pressure and anaemia before they become dangerous.
Sample Registration System, Registrar General of IndiaIndia
The Sample Registration System, which tracks births and deaths in a large national sample, reported a maternal mortality ratio of 88 deaths per 100,000 live births for 2020–22. In 1997–98 it had been 398.
Why it mattered. It is a fall of more than three-quarters in about 25 years, though some states still have far higher rates.
India's maternal mortality ratio from the Sample Registration System, plotted at the middle year of each period. It fell from 398 in 1997–98 to 88 in 2020–22.
1998 1997–98: 398
2005 2004–06: 254
2008 2007–09: 212
2011 2010–12: 178
2012 2011–13: 167
2015 2014–16: 130
2016 2015–17: 122
2017 2016–18: 113
2019 2018–20: 97
2020 2019–21: 93
2021 2020–22: 88
Did you know?
The human egg, about 0.1 mm across, is the largest cell in the body and only just visible without a microscope.
A girl is born with about 1 to 2 million immature eggs, but only about 400 to 500 are ever released.
For about 30 years, textbooks wrongly said humans have 48 chromosomes.
Durga, India's first IVF baby, was born just 70 days after Louise Brown, the world's first.
In 2019–21, 77% of young women in India used a hygienic method during their periods, up from 58% in 2015–16.
The people
Who figured it out
RG
Regnier de Graaf
1641 – 1673 · Physician and anatomist · Netherlands
Described the ovarian follicle that still carries his name.
AL
Antonie van Leeuwenhoek
1632 – 1723 · Microscopist · Netherlands
Built his own microscopes and was the first to describe sperm cells.
KE
Karl Ernst von Baer
1792 – 1876 · Biologist · Estonia (then Russian Empire), worked in Prussia
Found the mammalian egg and helped found embryology.
IS
Ignaz Semmelweis
1818 – 1865 · Obstetrician · Hungary
Showed that handwashing prevents deadly infections after childbirth.
OH
Oscar Hertwig
1849 – 1922 · Zoologist · Germany
First to watch a sperm and egg nucleus join.
AJ
Anandibai Joshi
1865 – 1887 · Physician · India
India's first woman doctor of Western medicine; wrote her thesis on obstetrics.
NS
Nettie Stevens
1861 – 1912 · Geneticist · USA
Showed that X and Y chromosomes decide sex.
JH
Joe Hin Tjio
1919 – 2001 · Cytogeneticist · Indonesia, worked in Sweden and the USA
Counted the human chromosomes correctly: 46.
ID
Ian Donald
1910 – 1987 · Obstetrician · Scotland
Brought ultrasound into pregnancy care.
RE
Robert Edwards
1925 – 2013 · Physiologist · England
Developed IVF with Patrick Steptoe and Jean Purdy; Nobel Prize 2010.
SM
Subhas Mukhopadhyay
1931 – 1981 · Physician and scientist · India
Led the team behind Durga, India's first IVF baby, in 1978.
IH
Indira Hinduja
born 1946 · Gynaecologist · India
Delivered Harsha, India's first scientifically documented IVF baby, in 1986.