Monday, 13 January 2020

Congratulations to Sofie Lykke Møller

Sofie Lykke Møller's Ph.D. Thesis
Sofie Lykke Møller successfully defended her Ph.D. thesis last week. It was my privilege to be one of her examiners. This is part of an ambitious project conducted in rural Tanzania by researchers from the University of Copenhagen (here). Sofie examined the vasculature of placenta at term and related her findings to a history of anaemia (here) or malaria (here) at various stages of pregnancy.

After the oral exam: Anthony Carter, Sofie Lykke Møller,
Annetine Staff and Peter Damm
This involved a sophisticated stereological analysis with random sampling of the placenta in the field and random orientation of the tissue blocks for sectioning in the laboratory.

Anaemia or malaria in the second half of pregnancy led to adaptive responses that included increases in the length and surface area of the capillaries in the terminal villi. 

Malaria infection before 14 weeks of gestation was reflected in changes at term including a reduction in the volume of intermediate villi and thickening of the endothelial component of the interhaemal barrier. Thus even though entry to the intervillous space is limited at this time, the surface proteins on infected erythrocytes seem able to hinder normal placental development.

Friday, 15 November 2019

Can invasive placentation be linked to oxygen requirements of the brain?

Skull of a male Western Gorilla
By Didier Descouens CC BY-SA 4.0
Three years ago (here) I reported a study suggesting the metabolic rate of the brain had increased during hominin evolution. This conclusion was reached by extrapolating from measurements of the carotid foramina in fossil skulls of adults (here). I asked whether there was an increasing demand for oxygen during fetal development and whether this could have driven an increase in the depth of trophoblast invasion of the placental bed.

Now Seymour and colleagues return to the fray (here). First, they address criticisms of their previous reliance on an equation for shear stress and introduce a modified approach for estimating blood flow in the internal carotid artery. This replicated their previous findings.

Second and more important, they applied their methods to the great apes Pongo, Pan and Gorilla. A surprising finding was that estimated brain metabolic rate was higher in these apes than in the hominin ancestor Australopithecus. (Brain volume was about the same in extant great apes and australopithecines.)

Decidual myometrial junction in placental bed
of a Western Gorilla with trophoblast stained red
From Carter et al. 2015 (here)
We have shown that the pattern of trophoblast invasion is similar in chimpanzee, gorilla and human (here). This is consistent with an improved oxygen supply to the fetal brain compared to gibbons and Old World monkeys. However, unless this represents convergent evolution, one would infer that the pattern was present in Australopithecus

Perhaps the oxygen supply needed to support the brain of the term fetus was present in the human ancestor, but brain development more complete at birth. The human newborn is secondarily altricial, i.e. highly dependent on parental care (previous post). The only clue we have about Australopithecus is that breastfeeding lasted for a shorter time than otherwise expected (here).

Thursday, 15 August 2019

Women Physiologists in the Naughty Nineties

A group portrait of physiologists and embryologists awarded honorary doctorates by Cambridge University in 1898 was the subject of a previous post (here). A friend noted there were no women among them. The Fourth International Congress of Physiology did, however, have several female participants listed in the proceedings. In addition, research by an Oxford physiologist was presented by Gustav Mann and the findings of four Russian scientists by Hugo Kronecker. In trying to identify them some interesting stories emerged.

Miss J. Brinck, London. Julia Maria Brinck (1854-1926) was born in Helsingborg, Sweden. She trained initially as a physiotherapist and then studied medicine at the London School of Medicine for Women (later the Royal Free Hospital). She could not obtain a licence to practice in the UK but obtained one from Dublin in 1886. She worked in Berne under Kronecker and received an M.D. degree in 1887, the first Swedish woman to obtain a higher degree in medicine.

Miss M. Greenwood, Lecturer in Physiology, Newnham. Marion Greenwood later Bidder (1862-1932) read Natural Sciences at Girton College Cambridge. As a woman she was denied a degree due to a policy confirmed by a vote in 1897 and not reversed until 1947. She was Director of Studies in Biology at Newnham and Tutor in Physiology. From 1890 to 1899 she was Director of the Balfour Biological Laboratory for Women (see here). Greenwood was one of the first women to do independent research at Cambridge and published several papers in Journal of Physiology. In 1899 she married marine biologist George Parker Bidder.

Ordre des Palmes (Officier d'Académie)
Miss H. J. Hutchinson, Nottingham. Harriet Jane Hutchinson (1860-1946) was Lecturer in Physiology and Histology and Warden of Foreign Students at University College, Nottingham. She retired in December 1934 after more than 35 years of service and in the following year was made an Officier d'Académie of the Ordre des Palmes in recognition of her support of French students attending the College. 

Miss Sowton, London. Sarah Charlotte March Sowton (1853-1929) was among the first six women admitted to the Physiological Society (see here). She studied the effects of carbon dioxide on skeletal and cardiac muscle at St. Mary’s Hospital, London. At the 1898 meeting, she read a paper on the current of injury in medullated nerve and, with Alice Waller, another on the action of muscarine, choline and neurine on isolated nerve.

Miss M. C. Tebb, London. Mary Christine Tebb later Rosenheim (1868-1953) read physiology at Girton College, Cambridge. Like Marion Greenwood, she was not awarded a degree. She worked in Cambridge and later at King’s College London, where she met and married a German physiologist, Sigmund Otto Rosenheim. She published a paper on the hydrolysis of glycogen in the same year as the Congress.
The Augustus Desiré Waller Family
Wellcome Collection CC BY 4.0
Mrs A. D. Waller, London. Alice Mary Waller née Palmer (1859-1922) is here listed with her husband’s initials. She studied at the London School of Medicine for Women where she was a student of her husband, Augustus Desiré Waller FRS, who created the first practical ECG machine. One of his biographers wrote, “the wife helped her husband in his work and her name appears with his on some of his published work.” At the 1898 meeting she read a paper on the influence of salts on the electrical mobility of medullated nerve.

Miss F. A. Welby, Demonstrator in Physiology, Women’s School of Medicine, London. Frances Alice Welby (1862-1947) was then a demonstrator at that institution. She is best known as an author and translator of physiological and other texts.
(Mary) Edith Pechey-Phipson by Frank Meadow Sutcliffe
albumen cabinet card 1870s NPG x12740
(C) National Portrait Gallery
Mrs E. Pechey Phipson Bombay. As Edith Pechey (1845-1908) she was one of the Edinburgh Seven, the first women to matriculate at any British University. Despite this achievement, they were not allowed to proceed to a degree (they were awarded posthumous medical degrees by Edinburgh University in July 2019). Edith Pechey therefore completed her education at Berne where she also achieved an M.D. for a thesis on uterine catarrh (endometritis). Like Julia Brinck she got a licence to practice at Dublin. She practised for six years in Leeds before going to Bombay as Senior Medical Officer at the Cama Hospital for Women and Children. She married Herbert Musgrave Phipson, a wine merchant who was Secretary to the Bombay Natural History Society.  After her return to England in 1905, she was active in the suffragette movement.

Miss M. B. Wilson, Instructor in Physiology at Women’s College Infirmary, New York. Margaret Barclay Wilson (1863-1945) was born in Dunfermline but migrated to the United States with her parents. She studied at the Normal College of the University of New York (later Hunter College) and received her M.D. from the Women’s College Infirmary and M.S. from New York University. She later taught physiology and hygiene at Hunter College, where she was Head of the Department of Physiology.


Nadine Lomakina, Bern, paper on innervation of heart in dog and horse read by H. Kronecker. Nadezhda Lomakina (1873-?) was from Moscow and read medicine at Bern 1893-1899. She was awarded her doctorate in 1900.

Pélagia Betschasnoff, Bern, paper on heart rate of the frog read by H. Kronecker. Pélagia Beschasnova (1860-?) was from St. Petersburg and read medicine first at Zurich then at Bern but did not graduate.

Julia Devine, Bern, paper on respiration of the toad heart read by H. Kronecker. Juliia Devine (1868-?) was born in Moscow but had a British family background. She read medicine at Bern 1893-1899.

Ludmila Schilina, Bern, paper on Ludwig’s kymograph and Hürthle’s tonometer read by H. Kronecker. Liudmila Schilina (1872-?) was born in Krasnoyarsk, Siberia and read medicine at Bern 1893-1898.

An account of the Russian scientists in Kronecker’s laboratory is given by Creese, M. R. S. Ladies in the Laboratory IV: Imperial Russia’s Women in Science, 1800-1900; Lanham MD: Rowman and Littlefield, 2015.

Lily H. Huie, Oxford, paper on the gland cells of Drosera read by Gustav Mann. Eliza Henrietta (Lily) Huie (1862-1930) was a botanist and Drosera is the sundew. She worked at the Physiological Laboratory in Oxford 1896-1898 and later at the Royal College of Physicians, Edinburgh.

There is a brief mention of Lily Huie in Creese, M. R. S. Ladies in the Laboratory? American and British Women in Science, 1800-1900, Lanham Maryland: Scarecrow Press, 1998.

Wednesday, 17 July 2019

Networking in the Naughty Nineties

Group Portrait outside the Old Schools, Cambridge 1898
A. J. Allen Wellcome Collection CC BY 4.0
In August 1898 Cambridge hosted both the International Congress of Physiology and the International Congress of Zoology. The group portrait was no doubt taken on 25 August 1898 after conferment of honorary doctorates on the physiologists (Franklin 1938) as well as Haeckel and Hubrecht from the zoology meeting. The ceremony was at the Senate House adjacent to the Old Schools that forms the backdrop to the portrait. Franklin mentions the Vice-Chancellor Alex Hill is in the background (recognizable from the droopy mustache).

Those shown (left to right) are:

Étienne-Jules Marey (1830-1904) French cardiovascular physiologist also known for using chronophotography (a forerunner to cinematography) to study animals in motion. He collaborated with Anton Dohrn to document the movements of fishes.

Anton Dohrn (1840-1909) German entomologist and marine biologist who studied with Virchow, Haeckel and Gegenbauer at Jena. He was the founder and first director of the Zoological Station at Naples.

Camillo Golgi (1843-1926) Italian neuroscientist and biologist who also made a significant contribution to renal physiology. He discovered the Golgi apparatus a finding dismissed as an artefact by many contemporary scientists. He received the Nobel Prize in Physiology or Medicine 1906.

Ernst Haeckel (1834-1919) German zoologist whose work was hugely influential. His many interests included embryology and he famously argued that ontogeny recapitulates phylogeny.

Ambrosius Hubrecht (1853-1915) Dutch zoologist and embryologist. He described placentation in insectivores (sensu lato) and a major paper on the placentas of tree shrew and tarsier was published in the Proceedings of the Fourth International Congress of Zoology (pp. 343-411).

Wilhelm Kühne (1837-1900) German muscle and nerve physiologist. He also studied the physiology of digestion and coined the term "enzyme."

Henry Pickering Bowditch (1840-1911) American physiologist who was the founding President of the American Physiological Society and Dean of Harvard Medical School. He had worked beside E. J. Marey in Claude Bernard's lab in Paris and later with Carl Ludvig in Leipzig. 

Alexander Hill (1856-1929) Vice-Chancellor of University of Cambridge 1897-1899 had been Hunterian Professor at the Royal College of Surgeons. He was a lecturer in physiology and in addition to his ceremonial rôle was a scientific member of the physiology congress.

Hugo Kronecker (1839-1914) German muscle physiologist then at Berne, Switzerland. Like Bowditch he had worked under Carl Ludwig. 

Franklin KJ. A short history of the International Congresses of Physiologists. Ann Sci 1938; 3: 241-335 with 15 Plates. 

Wednesday, 12 June 2019

Placentation in sloths

Placenta and fetal membranes of Hoffmann's Two-toed
Sloth (Choloepus hoffmanni) from Turner 1872
Two recent papers cast light on the evolution of sloths. Delsuc and colleagues obtained mitochondrial genomes from living and extinct sloths (here) while Presslee and colleagues used proteomics to describe Type I collagen - likewise from extant and extinct species (here). They agree that notions of sloth evolution based on morphology need revision. 

It was confirmed that two-toed and three-toed sloths are not closely related and group with different forms of ground sloths. A third group with a suspensory life style was found to have diverged even earlier. These sloths crossed a land bridge to the Greater Antilles and went extinct just a few thousand years ago.

Interhaemal barrier of the pale-throated three-toed sloth
(Bradypus tridactylus) Courtesy of Allen C. Enders
Together with anteaters and armadillos, sloths belong to the ancient superorder Xenarthra. Armadillo placenta has been studied in some detail. It is villous haemochorial (discussed here). Anteater placentation is rather similar (previous post). Sloths are different. As shown by Turner, the placenta is lobulated in appearance. It is labyrinthinre and endotheliochorial (here).

Given current opinion on the relations between sloths (Folivora), anteaters (Vermilingua) and armadillos (Cingulata), parsimony dictates that their common ancestor would have had a villous haemochorial placenta. Thus the sloth placenta represents a derived state. The most recent common ancestor of two-toed and three-toed sloths lived >25 million years ago whereas sloths diverged from anteaters >50 mya. 

Tuesday, 14 May 2019

Epiblast from the past

Mouse blastocyst with epiblast (EPI), trophoblast (TE)
and primitive endoderm (PE) or hypoblast from Selenka 1883
The three cell lineages of the blastocyst are trophoblast, hypoblast (primitive endoderm) and epiblast. The epiblast creates the embryo and contributes extra-embryonic mesoderm to the fetal membranes. An insightful review by Guojun Sheng (OA here) traces epiblast evolution across reptiles/birds, monotremes, marsupials and eutherians.

First he summarizes early development in the mouse as known since Selenka and Sobotta and now understood in terms of gene expression. Some of this translates to early human development (previous post). Yet the behaviour of the epiblast is very different in mammals as diverse as rabbit, pig, cattle and dog. As an example there is loss of the polar trophoblast to expose the epiblast. There are also important differences in gene expression as known from cattle (OA here). 

Meroblastic cleavage of the platypus egg
From Hughes 1993 (here)
Monotremes are more like birds and reptiles starting with the incomplete (meroblastic) cleavage of the yolky egg. Guojun Sheng suggests how the monotreme and reptile/bird patterns of epiblast epithelialization could each have evolved from a hypothetical amniote prototype.

Embryonic and trophoblastic areas of the marsupial
blastocyst as envisaged by Hartman 
Marsupials have a blastocyst-like stage with no inner cell mass (previous post) and it is not fully clear how the cell lineages segregate. Guojun Sheng thinks it can be seen as an intermediate in evolution from a hypothetical therian prototype. 
Serial sections through the blastula of the lowland streaked tenrec
Hemicentetes semispinosus) from Bluntschli 1937
Finally, he suggests that the blastula stages described in tenrecs by Bluntschli and elephant shrews by van der Horst (discussed here) may reflect the early eutherian prototype.

Altogether a very good read.

Friday, 18 January 2019

Lagoa Santa skulls still perplex Danes

Peter Wilhelm Lund (1801-1880)
Danish National Library (public domain)
When Peter Lund excavated human remains from Sumidouro Cave he was thoroughly perplexed. Not least because they were jumbled together with the bones of an extinct megafauna. This was in 1840 so well before Darwin had published On the Origin of Species (which cites Lund's work).

The skeletons were shipped to Copenhagen and examined there by several distinguished anthropologists (Lund never returned to Denmark). The consensus that arose was that "Lagoa Santa Man" was unrelated to present-day Native Americans. 

Springer 2017: ISBN 978-3-319-57465-3
Research and debate was renewed in the last century with new excavations in the caves near Lagoa Santa (now a suburb of Belo Horisonte). A key find was Luzia, a skull feared lost in the recent fire at the National Museum in Rio de Janeiro (previous post) (it survived but suffered heat damage). This skull was dated to 11,000 years ago.

Comparisons have been drawn between the features of the Lagoa Santa skulls and those of Australasian peoples such as Andaman Islanders. What can genomics tell us? A first set of clues hinted at an early wave of migrants designated "Population Y" who left a genetic signature that is strongest in some isolated Brazilian communities (see my review of David Reich)

Skull from Sumidouro Cave excavated by Peter Lund
Now a Dane has ventured into the Lund Collection and extracted ancient DNA from a 10,400 year-old skull. The results appeared in Science last December (here). Eske Willeslev and his group found a clear Australasian genomic signature that was absent in other ancient remains from the Americas. They concluded this signal, "implies that an early group possessing it had disappeared or that a later-arriving group passed through North America without leaving any genetic trace." A conclusion echoed by the lead author, José Victor Moreno-Mayar, who simply said (here), "How did it get there? We have no idea."

It seems the Lagoa Santa remains are just as perplexing to Willerslev as they were to Lund and for a similar reason: they do not neatly fit into the scheme of things.


The Willerslev paper is really worth reading. It builds on earlier work to confirm that Native Americans (other than Inuits) derived from a group that split from East Asians and resided in Beringia (Ancient Beringians). As they advanced into the Americas at the end of the Ice Age there was an early split into Northern (NNA) and Southern Native Americans (SNA). The SNA dispersed rapidly south of the remaining ice some 14,000 years ago. In a later phase there was admixture from a population in Mesoamerica that migrated both north and south. Another paper on ancient DNA from the Reich group also found evidence for rapid expansion into South America (here), but did not have Lagoa Santa in the data set.