Reproduction

Reproduction: timeline of key events

Known as the father of modern physiology, von Haller was a physician who discovered the autonomous nature of the heart and the mechanism of respiration. He also discovered that bile helps digest fats and made many contributions to understanding the distinction between nerve impulses and muscle contractions. During his time he put forward different theories about the nature of embryological development, one of which proposed that the new individual exists within the maternal egg prior to conception. He also put forward an accurate model of fetal growth during gestation, showing that the growth was faster at the beginning than later on. 1708-10-16T00:00:00+0000Known as the father of modern physiology, von Haller was a Swiss physician who discovered the autonomous nature of the heart and the mechanism of respiration. He also discovered that bile helps digest fats and made many contributions to understanding the distinction between nerve impulses and muscle contractions. During his time he put forward different theories about the nature of embryological development, one of which proposed that the new individual exists within the maternal egg prior to conception. He also put forward an accurate model of fetal growth during gestation, showing that the growth was faster at the beginning than later on. 1777-12-12T00:00:00+0000von Baer was a biologist who helped found the discipline of embryology and developmental biology. Much of his early work was on chick embryology. In 1827 he published the first description of the mammalian egg cell. This was based on his investigations of the structure of the ovum in the dog. He found it to be a small yellow spot floating in follicular fluid. von Baer developed the germ-layer theory which holds that four layers of cells are formed in vertebrate eggs and that each layer always gives rise to certain tissues in the adult organism. Based on his research he also showed that while the early development of embryo of one species resembled that of other species, it passed through a number of states that became progressively different from each other so that the adult never resembles other species.1792-02-17T00:00:00+0000Hertwig was a biologist who determined that fertilisation starts when the nuclei of sperm and ovum cells fuse. This he proved in 1876 through experiments with sea urchins. Eight years later he demonstrated, through investigations of frog eggs, that the cell divides along its long axis. He was also prescient in predicting, in 1885, that the nucleic acid is the substance responsible for fertilisation and the transmission of hereditary traits. This phenomenon was proven in 1944. 1849-04-21T00:00:00+0000Loeb was a physiologist and biologist who demonstrated the possibility of reproduction without male fertilisation, parthenogenesis, in sea urchin eggs. He found it was possible to stimulate embryonic development in the eggs of sea urchins without sperm by making slight chemical changes to the water where the eggs were kept. This he discovered while conducting experiments at the Marine Biological Laboratory in Woods Hole, Massachusetts. His results were published in 'Activation of the unfertilized egg by ultra-violet rays', Science, 40/1036 (1914), 680-1. While Loeb was nominated for the Nobel Prize many times he never won. 1859-04-07T00:00:00+0000von Baer was a Prussian-Estonian biologist who helped found the discipline of embryology and developmental biology. Much of his early work was on chick embryology. In 1827 he published the first description of the mammalian egg cell. This was based on his investigations of the structure of the ovum in the dog. He found it to be a small yellow spot floating in follicular fluid. von Baer developed the germ-layer theory which holds that four layers of cells are formed in vertebrate eggs and that each layer always gives rise to certain tissues in the adult organism. Based on his research he also showed that while the early development of embryo of one species resembled that of other species, it passed through a number of states that became progressively different from each other so that the adult never resembles other species. 1876-11-28T00:00:00+0000Julian was a chemist who was a renowned pioneer of pharmacological synthesis. He was the first African-American granted a doctoral degree in chemistry and the first to be inducted into the National Academy of Sciences. In 1935 he achieved the first synthesis of physostigmine. This he produced from soybean oil. The drug is used to treat glaucoma and delayed gastric emptying. A year later he joined the Gidden Company in Chicago where he oversaw the development of the industrial large-scale chemical synthesis of the human sex hormones progesterone, oestrogen and testosterone from soybean plant sterols. This work laid the foundation for the industrial production of cortisone, other corticosteroids, and the oral contraceptive pill. Julian left Gidden in 1953 to found his own company, Julian Laboratories Inc. 1899-04-11T00:00:00+0000Butenandt was a biochemist. In 1931 he managed to extract estrone and other primary female sex hormones from urine. Three years later he extracted progeterone and testosterone a year later. He was awarded the Nobel Prize for Chemistry in 1939 for his discovery of sex hormones. Initially Butenandt rejected the Prize in accordance with Nazi government policy, but accepted it in 1949. His involvement with the Nazi regime and science to aid its war efforts led to criticism after World War II. He served as the president of the Max Planck Society for the Advancement of Science between 1960 and 1972. 1903-03-24T00:00:00+0000Pincus was a biologist. He first came to public attention in 1934 when he announced the creation of baby rabbits with in vitro fertilisation. His technique involved the removal of an ovum from the mother rabbit, soaking it in a solution with a mixture of saline and estrone and then placing it back in the rabbit. The experiment could not be repeated by other scientists and prompted wide-scale condemnation. It cost him his tenure position at Harvard University. In order to continue his research Pincus helped found the Worcester Foundation for Experimental Biology in 1944, where he led the development of the first contraceptive pill in the early 1950s. 1903-04-09T00:00:00+0000Studying the mealworm, Stevens found that males made reproductive cells with both X and Y chromosomes whereas the females made only those with X. NM Stevens, 'Studies in spermatogenesis with special reference to the accessory chromosome', Studies in Sermatogenesis (Washington, DC, 1905), 1-32. 1905-01-01T00:00:00+0000Mazia was a cell biologist whose passion was to understand how cells reproduce. As a doctoral researcher he was one of the first to establish the role of calcium in the egg activation in the process of fertilisation. Following this worked on the process of cell division, structure and division. He is best known for the work he did in 1931 which helped identify the cell structure responsible for mitosis, the process when a eukaryotic cell divides chromosomes into two identical daughter cells. Mazia also determined how the nucleus and chromosomes change during the cell cycle.1912-12-18T00:00:00+0000Steptoe was an obstetrtician and gynaecologist who co-pioneered in vitro fertilization, the technique that produced the first test tube baby, Louise Brown, in 1978. This involved collecting ova from Louise's mother using laparoscopy. While Steptoe faced a lot of criticism for his work, many clinics began offering IVF following the birth of Louise. 1913-06-09T00:00:00+0000Hertwig was a German biologist who determined that fertilisation starts when the nuclei of sperm and ovum cells fuse. This he proved in 1876 through experiments with sea urchins. Eight years later he demonstrated, through investigations of frog eggs, that the cell divides along its long axis. He was also prescient in predicting, in 1885, that the nucleic acid is the substance responsible for fertilisation and the transmission of hereditary traits. This phenomenon was proven in 1944. 1922-10-25T00:00:00+0000Loeb was a German-American physiologist and biologist who demonstrated the possibility of reproduction without male fertilisation, parthenogenesis, in sea urchin eggs. He found it was possible to stimulate embryonic development in the eggs of sea urchins without sperm by making slight chemical changes to the water where the eggs were kept. This he discovered while conducting experiments at the Marine Biological Laboratory in Woods Hole, Massachusetts. His results were published in 'Activation of the unfertilized egg by ultra-violet rays', Science, 40/1036 (1914), 680-1. While Loeb was nominated for the Nobel Prize many times he never won. 1924-02-11T00:00:00+0000Miramontes was a chemist. He is best known for having helped synthesise noresthindrone, one of the first compounds used as an oral contraceptive. This he did in 1951 when he was 26 years old. He did the worlk while based at Syntex, a small Mexican company that first made its name in the production of steroids. 1925-03-16T00:00:00+0000Pincus was a biologist. He first came to public attention in 1934 when he announced the creation of baby rabbits with in vitro fertilisation. His technique involved the removal of an ovum from the mother rabbit, soaking it in a solution with a mixture of saline and estrone and then placing it back in the rabbit. The experiment could not be repeated by other scientists and prompted wide-scale condemnation. It cost him his tenure position at Harvard University. In order to continue his research Pincus helped found the Worcester Foundation for Experimental Biology in 1944, where he led the development of the first contraceptive pill in the early 1950s. 1967-08-22T00:00:00+0000Julian was a chemist who was a renowned pioneer of pharmacological synthesis. He was the first African-American granted a doctoral degree in chemistry and the first to be inducted into the National Academy of Sciences. In 1935 he achieved the first synthesis of physostigmine. This he produced from soybean oil. The drug is used to treat glaucoma and delayed gastric emptying. A year later he joined the Gidden Company in Chicago where he oversaw the development of the industrial large-scale chemical synthesis of the human sex hormones progesterone, oestrogen and testosterone from soybean plant sterols. This work laid the foundation for the industrial production of cortisone, other corticosteroids, and the oral contraceptive pill. Julian left Gidden in 1953 to found his own company, Julian Laboratories Inc.1975-04-19T00:00:00+0000The baby, Louise Joy Brown, was born after her mother, Lesley, received treatment for infertility that resulted from blocked fallopian tubes. She had been trying to conceive for 9 years. Later known as in vitro fertilisation (IVF), the procedure Lesley received involved removing an egg from her ovary, fertilising it a Petri dish and then having it replanting it into her, The technique was developed by Patrick Steptoe and Robert Edwards. Four years after Louise was born, Lesley gave birth to another daughter, Natalie, the world's 40th child conceived with IVF. 1978-07-25T00:00:00+0000The technique was developed by Martin Evans and Matt Kaufman. They showed that by delaying implantation it was possible to obtain slightly enlarged mouse blastocysts and that cells taken from these blastocysts could be used to establish mouse embryo stem cell cultures. The work was published in MJ Evans, MH Kaufman, 'Establishment in culture of pluripotential cells from mouse embryos', Nature, 292/154 (1981), 154-56.1981-07-09T00:00:00+0000A team led by John Buster at UCLA Medical Center successfully non-surgically transferred an embryo from one human to another. The procedure was used to help an infertile woman. She received the embryo donated by another woman. In contrast to the in vitro procedure as was used in the Louise Brown case—in which the mother’s egg is fertilised by the father’s sperm outside the womb—the transplant pregnancy started with in vitro fertilisation.1984-02-03T00:00:00+0000Steptoe was an obstetrtician and gynaecologist who co-pioneered in vitro fertilization, the technique that produced the first test tube baby, Louise Brown, in 1978. This involved collecting ova from Louise's mother using laparoscopy. While Steptoe faced a lot of criticism for his work, many clinics began offering IVF following the birth of Louise. 1988-03-21T00:00:00+0000Butenandt was a German biochemist. In 1931 he managed to extract estrone and other primary female sex hormones from urine. Three years later he extracted progeterone and testosterone a year later. He was awarded the Nobel Prize for Chemistry in 1939 for his discovery of sex hormones. Initially Butenandt rejected the Prize in accordance with Nazi government policy, but accepted it in 1949. His involvement with the Nazi regime and science to aid its war efforts led to criticism after World War II. He served as the president of the Max Planck Society for the Advancement of Science between 1960 and 1972.1995-01-18T00:00:00+0000Mazia was an American cell biologist whose passion was to understand how cells reproduce. As a doctoral researcher he was one of the first to establish the role of calcium in the egg activation in the process of fertilisation. Following this worked on the process of cell division, structure and division. He is best known for the work he did in 1931 which helped identify the cell structure responsible for mitosis, the process when a eukaryotic cell divides chromosomes into two identical daughter cells. Mazia also determined how the nucleus and chromosomes change during the cell cycle. 1996-06-09T00:00:00+0000Miramontes was a Mexican chemist. He is best known for having helped synthesise noresthindrone, one of the first compounds used as an oral contraceptive. This he did in 1951 when he was 26 years old. He did the worlk while based at Syntex, a small Mexican company that first made its name in the production of steroids. 2004-09-13T00:00:00+0000W Hu et al, 'p53 regulates maternal reproduction through LIF', Nature, 450 (2007), 721–4.2007-11-01T00:00:00+0000NIH issued its ban after researchers in China announced experiments altering the gene in non-viable zygotes. 2015-04-15T00:00:00+0000S. Ellys Harrison, B. Sozen, N. Christodoulou, C. Kyprianou, M. Zernicka-Goetz, 'Assembly of embryonic and extra-embryonic stem cells to mimic embryogenesis in vitro', Science, DOI: 10.1126/science.aal1810 2017-03-03T00:00:00+0000M. Hong, N. Marti-Gutierrez, S-W Park, et al, 'Correction of a pathogenic gene mutation in human embryos', Nature, doi:10.1038/nature233052017-08-02T00:00:00+0000UK scientists modified 41 embryos shortly after fertilisation. N.M.E. Fogarty et al, 'Genome editing reveals a role for OCT4 in human embryogenesis', Nature, doi:10.1038/nature240332017-09-20T00:00:00+0000P. Liang, et al, 'Correction of beta-thalassemia mutant by base editor in human embryos', Protein and Cell (2017), doi.org/10.1007/s13238-017-0475-6.2017-09-23T00:00:00+0000The work was undertaken by a group of researchers at the University of Edinburgh led by Evelyn Telfer. It involved taking tiny pieces of ovarian tissue from 10 women undergoing elective caesarean surgery extracting priorial follicles, small structures that have the potential to release an egg, which were then placed in a nutrient-rich liquid to grow. The team then carefully removed the fragile, immature eggs and some surrounding cells from the follicles and placed them on a special membrane with the addition of growth-supporting proteins so that they could grow to become the size you would see of an egg during ovulation. Most of the eggs failed to grow, but 10% completed their journey to maturity - that is they were able to divide and halve their chromosomes so they were ready to be fertilised by sperm. The work was published in M McLaughlin, DF Albertini, WHB Wallace, RA Anderson, EE Telfer, Molecular Human Reproduction, 24/3 (March 2018) 135-42. DOI: 10.1093/molehr/gay002. 2018-01-30T00:00:00+0000He Jiankui, a genome-editing researcher at Southern University of Science and Technology of China, reported transplanting embryos into a woman that he had edited with CRISPR-Cas9 to disable a gene called CCR5, to disable the genetic pathway HIV uses to infect cells. More than 100 Chinese biomerical researchers condemned the experiment and called on Chinese authorities to investigate the case and introduce strict regulations. 2018-11-24T00:00:00+0000
Date Event People Places
16 Oct 1708Albrecht von Haller was born in Bern, Switzerlandvon HallerUniversity of Gottingen
12 Dec 1777Albrecht von Haller diedvon HallerUniversity of Gottingen
17 Feb 1792Karl Ernst von Baer was born in Piep estate, Governorate of Livonia, Russian Empire (now Piibe, Estonia)von BaerSt Petersburg Academy of Sciences
21 Apr 1849Oskar Hertwig was born in Friedberg, GermanyHertwigFriedberg, Germany
7 Apr 1859Jacques Loeb was born in Mayen, Germany LoebRockefeller University
28 Nov 1876Karl Ernst von Baer diedvon BaerSt Petersburg Academy of Sciences
11 Apr 1899Percy Lavon Julian was born in Montgomery, Alabama, USAJulianHarvard University
24 Mar 1903Adolf F J Butenandt was born in Bremerhaven, GermanyButenandtMax Planck Institute
9 Apr 1903Gregory Pincus was born in Woodbine, NJ, USAPincusHarvard University, Worcester Foundation for Experimental Biology
1905Nettie Stevens showed that sex is inherited by a chromosomal factor and that males determine the gender of offspringStevens 
18 Dec 1912Daniel Mazia was born Scranton, PA, USAMaziaUniversity of California Berkeley
9 Jun 1913Patrick Steptoe was born in Oxford, United KingdomSteptoeOxford, United Kingdom
25 Oct 1922Oskar Hertwig diedHertwig 
11 Feb 1924Jacques Loeb diedLoebRockefeller University
16 Mar 1925Luis Ernesto Miramontes was born in Tepic, Nayarit, Mexico MiramontesSyntex
22 Aug 1967Gregory Pincus diedPincusHarvard University, Worcester Foundation for Experimental Biology
19 Apr 1975Percy Lavon Julian diedJulianHarvard University
25 Jul 1978First test-tube baby was bornEdwards, Steptoe 
9 Jul 1981Mouse embryonic stem cells first isolated and cultured in the laboratoryEvans, Kaufman, MartinCambridge University
3 Feb 1984First human embryo-transfer baby bornBusterUniversity California Los Angeles
21 Mar 1988Patrick Steptoe diedSteptoe 
18 Jan 1995Adolf F J Butenandt diedButenandtMax Planck Institute
9 Jun 1996Daniel Mazia diedMaziaUniversity of California Berkeley
13 Sep 2004Luis Ernesto Miramontes diedMiramontesSyntex
November 2007p53 shown to be required for embryo implantationHu, Feng, Teresky, LevineCancer Institute of New Jersey
15 Apr 2015National Institutes of Health declared it will not fund any use of genome editing technologies in human embryos 
3 Mar 2017Cambridge scientists report the development of an aritificial mouse embryo using stem cellsUniversity of Cambridge
2 Aug 2017Research published demonstrating possibility of editing gene defect in pre-implanted human embryos for preventing inherited heart diseaseHong, Marti-Gutierrez, Park, Mitalipov, Kaul, Kim, Amato, BelmonteOregon Health & Science University, Salk Institute, Center for Genome Engineering, Seoul National University, China National GeneBank,
September 2017DNA of human embryos edited using CRISPR-Cas9 to study cause of infertilityFogarty, McCarthy, Snijders, Powell, Kubikova, Blakeley, Lea, Elder, Wamaitha, Kim, Maciulyte, Kleinjung, Kim, Wells, Vallier, Bertero, Turner, NiakanFrancis Crick Instiitute, Cambridge University, Oxford University, Seoul National University
23 Sep 2017Chinese researchers report correction of gene linked to beta thalassaemia, inherited blood disorder, in human embryos using base editing techniqueLiang, Ching, Sun, Xie, Xu, Zhang, Xhiong, Ma, Liu, Wang, Fang, Songyang, Zhou, HuangSun Yat-sen University, Baylor College of Medicine
30 Jan 2018First human eggs grown in laboratoryTelfer, McLaughlin, Albertini, Wallace, AndersonUniversity of Edinburg
24 Nov 2018First gene-edited babies announced by Chinese scientistJiankuiSouthern University of Science and Technology of China

16 Oct 1708

Albrecht von Haller was born in Bern, Switzerland

12 Dec 1777

Albrecht von Haller died

17 Feb 1792

Karl Ernst von Baer was born in Piep estate, Governorate of Livonia, Russian Empire (now Piibe, Estonia)

21 Apr 1849

Oskar Hertwig was born in Friedberg, Germany

7 Apr 1859

Jacques Loeb was born in Mayen, Germany

28 Nov 1876

Karl Ernst von Baer died

11 Apr 1899

Percy Lavon Julian was born in Montgomery, Alabama, USA

24 Mar 1903

Adolf F J Butenandt was born in Bremerhaven, Germany

9 Apr 1903

Gregory Pincus was born in Woodbine, NJ, USA

1905

Nettie Stevens showed that sex is inherited by a chromosomal factor and that males determine the gender of offspring

18 Dec 1912

Daniel Mazia was born Scranton, PA, USA

9 Jun 1913

Patrick Steptoe was born in Oxford, United Kingdom

25 Oct 1922

Oskar Hertwig died

11 Feb 1924

Jacques Loeb died

16 Mar 1925

Luis Ernesto Miramontes was born in Tepic, Nayarit, Mexico

22 Aug 1967

Gregory Pincus died

19 Apr 1975

Percy Lavon Julian died

25 Jul 1978

First test-tube baby was born

9 Jul 1981

Mouse embryonic stem cells first isolated and cultured in the laboratory

3 Feb 1984

First human embryo-transfer baby born

21 Mar 1988

Patrick Steptoe died

18 Jan 1995

Adolf F J Butenandt died

9 Jun 1996

Daniel Mazia died

13 Sep 2004

Luis Ernesto Miramontes died

Nov 2007

p53 shown to be required for embryo implantation

15 Apr 2015

National Institutes of Health declared it will not fund any use of genome editing technologies in human embryos

3 Mar 2017

Cambridge scientists report the development of an aritificial mouse embryo using stem cells

2 Aug 2017

Research published demonstrating possibility of editing gene defect in pre-implanted human embryos for preventing inherited heart disease

Sep 2017

DNA of human embryos edited using CRISPR-Cas9 to study cause of infertility

23 Sep 2017

Chinese researchers report correction of gene linked to beta thalassaemia, inherited blood disorder, in human embryos using base editing technique

30 Jan 2018

First human eggs grown in laboratory

24 Nov 2018

First gene-edited babies announced by Chinese scientist