The FIRSTS: Dinosaurs and reputation (1842)

‘Dinosaur’ is a common noun in most languages of the Globe and, in its weak sense, it means “extinct big-sized reptile-like animal that lived a long-time ago”. The word has been in usage for so long that it can be used also for describing something “impractically large, out-of-date, or obsolete” (Merriam-Webster dictionary). “Dinosaur” is a composite of two ancient Greek words (“deinos”, “sauros”) and it means “terrible lizard”.

But, it turns out that the word hasn’t been in usage for so long, just for a mere 175 years. Sir Richard Owen, a paleontologist that dabbled in many disciplines, coined the term in 1842. Owen introduced the taxon Dinosauria as if it was always called thus, no fuss: “The present and concluding part of the Report on British Fossil Reptiles contains an account of the remains of the Crocodilian, Dinosaurian, Lacertian, Pterodactylian, Chelonian, Ophidian and Batrachian reptiles.” (p. 60). Only later in the Report does he tell us his paleontological reasons for the baptism, namely some anatomical features that distinguish dinosaurs from crocodiles and other reptiles.

“…The combination of such characters, some, as the sacral ones, altogether peculiar among Reptiles, others borrowed, as it were, from groups now distinct from each other, and all manifested by creatures far surpassing in size the largest of existing reptiles, will, it is presumed, be deemed sufficient ground for establishing a distinct tribe or sub-order of Saurian Reptiles, for which I would propose the name of Dinosauria.” (p.103)

At the time he was presenting this report to the British Association for the Advancement of Science, other giants of biology were running around the same halls, like Charles Darwin and Thomas Henry Huxley. Indisputably, Owen had a keen observational eye and a strong background in comparative anatomy that resulted in hundreds of published works, some of them excellent. That, in addition to establishing the British Museum of Natural History.

Therefore, Owen had reasons to be proud of his accomplishments and secure in his influence and legacy, and yet his contemporaries tell us that he was an absolutely vicious man, spiteful to the point of obsession, vengeful and extremely jealous of other people’s work. Apparently, he would steal the work of the younger people around him, never give credit, lie and cheat at every opportunity, and even write lengthy anonymous letters to various printed media to denigrate his contemporaries. He seemed to love his natal city of Lancaster and his family though (Wessels & Taylor, 2015).

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Sir Richard Owen (20 July 1804 – 18 December 1892). PD, courtesy of Wikipedia.

Owen had a particular hate for Darwin. They had been close friends for 20 years and then Darwin published the “Origin of Species”. The book quickly became widely read and talked about and then poof: vitriol and hate. Darwin himself said the only reason he could think of for Owen’s hatred was the popularity of the book.

Various biographies and monographers seem to agree on his unpleasant personality (see his entry in The Telegraph, Encyclopedia.com, Encylopaedia Britannica, BBC. On a side note, should you be concerned about your legacy and have the means to persuade The Times to write you an obituary, by all means, do so. In all the 8 pages of obituary written in 1896 you will not find a single blemish on the portrait of Sir Richard Owen.

This makes me ponder on the judgement of history based not on your work, but on your personality. As I said, the man contributed to science in more ways than just naming the dinosaur and having spats with Darwin. And yet it seems that his accomplishments are somewhat diminished by the way he treated others.

This reminded me of Nicolae Constantin Paulescu, a Romanian scientist who discovered insulin in 1916 (published in 1921). Yes, yes, I know all about the controversy with the Canadians that extracted and purified the insulin in 1922 and got the Nobel for it in 1923. Paulescu did the same, even if Paulescu’s “pancreatic extract” from a few years earlier was insufficiently purified; it still successfully lowered the glicemic index in dogs. He even obtained a patent for the “fabrication of pancrein” (his name for insulin, because he obtained it from the pancreas) in April 1922 from the Romanian Government (patent no. 6255). The Canadian team was aware of his work, but because it was published in French, they had a poor translation and they misunderstood his findings, so, technically, they didn’t steal anything. Or so they say. Feel free to feed the conspiracy mill. I personally don’t know, I haven’t looked at the original work to form an opinion because it is in French and my French is non-existent.

Annnywaaaay, whether or not Paulescu was the first in discovering the insulin is debatable, but few doubt that he should have shared the Nobel at least.

Rumor has it that Paulescu did not share the Nobel because he was a devout Nazi. His antisemitic writings are remarkably horrifying, even by the standards of the extreme right. That’s also why you won’t hear about him in medical textbooks or at various diabetes associations and gatherings. Yet millions of people worldwide may be alive today because of his work, at least partly.

How should we remember? Just the discoveries and accomplishments with no reference to the people behind them? Is remembering the same as honoring? “Clara cells” were lung cells discovered by the infamous Nazi anatomist Max Clara by dissecting prisoners without consent. They were renamed by the lung community “club cells” in 2013. We cannot get rid of the discovery, but we can rename the cells, so it doesn’t look like we honor him. I completely understand that. And yet I also don’t want to lose important pieces of history because of the atrocities (in the case of Nazis) or unsavory behavior (in the case of Owen) committed by our predecessors. I understand why the International Federation of Diabetes does not wish to give awards in the name of Paulescu or have a Special Paulescu lecture. Perhaps the Romanians should take down his busts and statues, too. But I don’t understand why (medical) history books should exclude him.

In other words, don’t honor the unsavories of history, but don’t forget them either. You never know what we – or the future generations – may learn by looking back at them and their actions.

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By Neuronicus, 19 October 2017

References:

1) Owen, R (1842). “Report on British Fossil Reptiles”. Part II. Report of the Eleventh Meeting of the British Association for the Advancement of Science; Held at Plymouth in July 1841. London: John Murray. p. 60–204. Google Books Fulltext 

2) “Eminent persons: Biographies reprinted from the Times, Vol V, 1891–1892 – Sir Richard Owen (Obituary)” (1896). Macmillan & Co., p. 291–299. Google Books Fulltext

3) Wessels Q & Taylor AM (28 Oct 2015). Anecdotes to the life and times of Sir Richard Owen (1804-1892) in Lancaster. Journal of Medical Biography. pii: 0967772015608053. PMID: 26512064, DOI: 10.1177/0967772015608053. ARTICLE

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Midichlorians, midichloria, and mitochondria

Nathan Lo is an evolutionary biologist interested in creepy crawlies, i.e. arthropods. Well, he’s Australian, so I guess that comes with the territory (see what I did there?). While postdoc’ing, he and his colleagues published a paper (Sassera et al., 2006) that would seem boring for anybody without an interest in taxonomy, a truly under-appreciated field.

The paper describes a bacterium that is a parasite for the mitochondria of a tick species called Ixodes ricinus, the nasty bugger responsible for Lyme disease. The authors obtained a female tick from Berlin, Germany and let it feed on a hamster until it laid eggs. By using genetic sequencing (you can use kits these days to extract the DNA, do PCR, gels and cloning, pretty much everything), electron microscopy (real powerful microscopes) and phylogenetic analysis (using computer softwares to see how closely related some species are) the authors came to the conclusion that this parasite they were working on is a new species. So they named it. And below is the full account of the naming, from the horse’s mouth, as it were:

“In accordance with the guidelines of the International Committee of Systematic Bacteriology, unculturable bacteria should be classified as Candidatus (Murray & Stackebrandt, 1995). Thus we propose the name ‘Candidatus Midichloria mitochondrii’ for the novel bacterium. The genus name Midichloria (mi.di.chlo′ria. N.L. fem. n.) is derived from the midichlorians, organisms within the fictional Star Wars universe. Midichlorians are microscopic symbionts that reside within the cells of living things and ‘‘communicate with the Force’’. Star Wars creator George Lucas stated that the idea of the midichlorians is based on endosymbiotic theory. The word ‘midichlorian’ appears to be a blend of the words mitochondrion and chloroplast. The specific epithet, mitochondrii (mi.to′chon.drii. N.L. n. mitochondrium -i a mitochondrion; N.L. gen. n. mitochondrii of a mitochondrion), refers to the unique intramitochondrial lifestyle of this bacterium. ‘Candidatus M. mitochondrii’ belongs to the phylum Proteobacteria, to the class Alphaproteobacteria and to the order Rickettsiales. ‘Candidatus M. mitochondrii’ is assigned on the basis of the 16S rRNA (AJ566640) and gyrB gene sequences (AM159536)” (p. 2539).

George Lucas gave his blessing to the Christening (of course he did).

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Acknowledgements: Thanks go to Ms. BBD who prevented me from making a fool of myself – this time – on the social media by pointing out to me that midichloria are real and that they are a mitochondrial parasite.

REFERENCE: Sassera D, Beninati T, Bandi C, Bouman EA, Sacchi L, Fabbi M, Lo N. (Nov. 2006). ‘Candidatus Midichloria mitochondrii’, an endosymbiont of the tick Ixodes ricinus with a unique intramitochondrial lifestyle. International Journal of Systematic and Evolutionary Microbiology, 56(Pt 11): 2535-2540. PMID: 17082386, DOI: 10.1099/ijs.0.64386-0. ABSTRACT | FREE FULLTEXT PDF 

By Neuronicus, 29 July 2017

The FIRSTS: Increase in CO2 levels in the atmosphere results in global warming (1896)

Few people seem to know that although global warming and climate change are hotly debated topics right now (at least on the left side of the Atlantic) the effect of CO2 levels on the planet’s surface temperature was investigated and calculated more than a century ago. CO2 is one of the greenhouse gases responsible for the greenhouse effect, which was discovered by Joseph Fourier in 1824 (the effect, that is).

Let’s start with a terminology clarification. Whereas the term ‘global warming’ was coined by Wallace S. Broecker in 1975, the term ‘climate change’ underwent a more fluidic transformation in the ’70s from ‘inadvertent climate modification’ to ‘climatic change’ to a more consistent use of ‘climate change’ by Jule Charney in 1979, according to NASA. The same source tells us:

“Global warming refers to surface temperature increases, while climate change includes global warming and everything else that increasing greenhouse gas amounts will affect”.

But before NASA there was one Svante August Arrhenius (1859–1927). Dr. Arrhenius was a Swedish physical chemist who received the Nobel Prize in 1903 for uncovering the role of ions in how electrical current is conducted in chemical solutions.

S.A. Arrhenius was the first to quantify the variations of our planet’s surface temperature as a direct result of the amount of CO2 (which he calls carbonic acid, long story) present in the atmosphere. For those – admittedly few – nitpickers that say his views on the greenhouse effect were somewhat simplistic and his calculations were incorrect I’d say cut him a break: he didn’t have the incredible amount of data provided by the satellites or computers, nor the work of thousands of scientists over a century to back him up. Which they do. Kind of. Well, the idea, anyway, not the math. Well, some of the math. Let me explain.

First, let me tell you that I haven’t managed to pass past page 3 of the 39 pages of creative mathematics, densely packed tables, parameter assignments, and convoluted assumptions of Arrhenius (1896). Luckily, I convinced a spectroscopist to take a crack at the original paper since there is a lot of spectroscopy in it and then enlighten me.

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The photo was taken in 1887 and shows (standing, from the left): Walther Nernst (Nobel in Chemistry), Heinrich Streintz, Svante Arrhenius, Richard Hiecke; (sitting, from the left): Eduard Aulinger, Albert von Ettingshausen, Ludwig Boltzmann, Ignaz Klemenčič, Victor Hausmanninger. Source: Universität Graz. License: PD via Wikimedia Commons.

Second, despite his many accomplishments, including being credited with laying the foundations of a new field (physical chemistry), Arrhenius was first and foremost a mathematician. So he employed a lot of tedious mathematics (by hand!) together with some hefty guessing along with what was known at the time about Earth’s infrared radiation, solar radiation, water vapor and CO2 absorption, temperature of the Moon,  greenhouse effect, and some uncalibrated spectra taken by his predecessors to figure out if “the mean temperature of the ground [was] in any way influenced by the presence of the heat-absorbing gases in the atmosphere” (p. 237). Why was he interested in this? We find out only at page 267 after a lot of aforesaid dreary mathematics where he finally shares this with us:

“I certainly not have undertaken these tedious calculations if an extraordinary interest had not been connected with them. In the Physical Society of Stockholm there have been occasionally very lively discussions on the probable causes of the Ice Age”.

So Arrhenius was interested to find out if the fluctuations of CO2 levels could have caused the Ice Ages. And yes, he thinks that could have happened. I don’t know enough about climate science to tell you if this particular conclusion of his is correct today. But what he managed to accomplish though was to provide for the first time a way to mathematically calculate the amount of rise in temperature due the rise of CO2 levels. In other words, he found a direct relationship between the variations of CO2 and temperature. Today, it turns out that his math was incorrect because he left out some other variables that influence the global temperature that were discovered and/or understood later (like the thickness of the atmosphere, the rate of ocean absorption  of CO2 and others which I won’t pretend I understand). Nevertheless, Arrhenius was the first to point out to the following relationship, which, by and large, is still relevant today:

“Thus if the quantity of carbonic acid increased in geometric progression, the augmentation of the temperature will increase nearly in arithmetic progression” (p. 267).

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P.S. Technically, Joseph Fourier should be credited with the discovery of global warming by increasing the levels of greenhouse gases in the atmosphere in 1824, but Arrhenius quantified it so I credited him. Feel fee to debate :).

REFERENCE: Arrhenius, S. (April 1896). XXXI. On the Influence of Carbonic Acid in the Air upon the Temperature of the Ground, The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science (Fifth Series), 49 (251): 237-276. General Reference P.P.1433. doi: http://dx.doi.org/10.1080/14786449608620846. FREE FULLTEXT PDF

By Neuronicus, 24 June 2017

The FIRSTS: Magnolia (1703)

It is April and the Northern Hemisphere is enjoying the sight and smell of blooming magnolias. Fittingly, today is the birthday of the man who described and named the genus. Charles Plumier (20 April 1646 – 20 November 1704) was a French botanist known for describing many plant genera and for preceding Linnaeus in botanical taxonomy. His (Plumier’s) taxonomy was later incorporated by Linnaeus and is still in use today.

Plumier traveled a lot as part of his job as Royal Botanist at the court of Louis XIV. Don’t envy him too much though because the monk order to which he belonged, the Minims, forced him to be a vegan, living mostly on lentil.

Among thousands of other plants described was the magnolia, a genus of gorgeous ornamental flowering trees that put out spectacularly big flowers in the Spring, usually before the leaves come out. Plumier found it on the island of Martinique and named it after Pierre Magnol, a contemporary botanist who invented the concept of family as a distinct taxonomical category.

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Excerpts from the pages 38, 39 and plate 7 from Nova Plantarum Americanum Genera by Charles Plumier (Paris, 1703) describing the genus Magnolia.

Interestingly enough, Plumier named other plants either after famous botanists like fuchsia (Leonhard Fuchs) and lobelia (Mathias Obel) or people who helped his career as in begonia (Michel Begon) and suriana (Josephe Donat Surian), but never after himself. I guess he took seriously the humility tenet of his order. Never fear, the botanists Joseph Pitton de Tournefort and the much more renown Carl Linnaeus named an entire genus after him: Plumeria.

Of interest to me, as a neuroscientist, is that the bark of the magnolia tree contains magnolol which is a natural ligand for the GABAA receptor.

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REFERENCE: Plumier, C. (1703). Nova Plantarum Americanum Genera, Paris. http://dx.doi.org/10.5962/bhl.title.59135 FULLTEXT courtesy of the Biodiversity Heritage Library

By Neuronicus, 20 April 2017

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The FIRSTS: Melatonin (1958)

By the late 18th and beginning of 19th century, some scientists were busily investigating how animals get their colors and how do they change colour in response to the environment. They identified several types of chromatophores, i.e. cells that contain pigments. Biological pigments are called melanins (don’t confuse them with melatonin). One of these cells is the melanophore which contains black pigments, called this way in the very typical scientist unimaginative style because “melas” in Greek means black or dark and “phoros” means carrier.

A couple of these scientists, McCord & Allen (1917), thought that the pineal gland from the brain might contain some substance that might interact with the melanophores. How did they get this idea is unclear from their paper; seems like a logical outcome of their contemporaries’ discussions and experiments, though they do not explain it in detail. They hint of other experiments where various glands have been fed to amphibians and then noticed their color change. So McCord & Allen obtained cow brains, extracted the pineal glands and fed them to tadpoles. Within 30 to 60 minutes, depending on the concentration, the tadpoles fed with pineal extract changed color from dark to light (see picture).

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Excerpt from McCord & Allen (1917, doi: 10.1002/jez.1400230108) showing the change in tadpole skin appearance after application of bovine pineal gland extract.

Fast forward now to 1958 when an MD PhD called Aaron B. Lerner with an interest in dermatology thought that whatever was responsible for the skin color changes in the McCord & Allen (1917) paper might be useful in treating skin diseases. But first he had to extract the substance from the pineal glands and he and his colleagues had better tools for this task than the mere alcohol and acetone of his brethren of 40 years ago.

Lerner et al. (1958) made full use of the then-recently discovered paper chromatography and some standard biochemistry techniques for the time like Soxhlet extraction and fluorescence spectroscopy and discovered a substance that can lighten frog skin color and can inhibit the melanocyte stimulating hormone (MSH). “It is suggested that this substance be called melatonin” (p. 2587). Lerner and his colleagues also isolated the MSH and cryoglobulin.

Changing skin color is one of melatonin’s minor roles; its main function is to regulate circadian rhythms like sleep and awake cycles in animals (it has an oxidative stress protection in plants). Melatonin, in animals, is produced by the pineal gland only, more during the night, less during the day. Pineal gets information about the day/night cycles from the eyes. In some countries melatonin is sold as an over the counter soporific, i.e. sleeping pill.

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REFERENCES:

1) McCord CP & Allen FP (Jan 1917). Evidences associating pineal gland function with alterations in pigmentation. Journal of Experimental Zoology, Part A, 23 (1):  207–224, DOI: 10.1002/jez.1400230108 ARTICLE 

2) Lerner AB, Case JD, Takahashi Y, Lee TH, & Mori W (May 1958). Isolation of Melatonin, the Pineal Gland Factor that Lightens Melanocytes. Journal of the American Chemical Society, 80 (10), p. 2587–2587, DOI: 10.1021/ja01543a060 ARTICLE (although JACS gives access only to the first page of a paper, the fact that this article is only half a page makes their endeavour useless in this case)

By Neuronicus, 18 March 2017

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100% Effective Vaccine

A few days ago I was reading random stuff on the internet, as is one’s procrastination proclivity, catching up after the holiday, and I exclaimed out loud: “They discovered an 100% effective Ebola Vaccine!”. I expected some ‘yeay’-s or at least some grunts along the lines of ‘that’s nice’ or ‘cool’. Naturally, I turned around from my computer to check the source of unaccustomed silence to the announcement of such good news or, at least, to make sure that everybody is still breathing and present in the room. What met my worried glare was a gloom face and a shaking head. That’s because news like that are misleading, because, duh, it finally dawned on me, there is no such thing as ‘100% effective vaccine’.

And yet…, and yet this is exactly what Henao-Restrepo et al. (2016) say they found! The study is huge, employing more that 10 000 people. Such a tremendous endeavor has been financed by WHO (World Health Organization) and various departments from several countries (UK, USA, Switzerland, South Africa, Belgium, Germany, France, Guinea, and Norway) and, I’m assuming, a lot of paid and unpaid volunteers. I cannot even imagine the amount of work and the number of people that made this happen. And the coordination required for such speedy results!

The successful vaccine in rodents and non-human primates, called the recombinant, replication-competent, vesicular stomatitis virus-based vaccine expressing the glycoprotein of a Zaire Ebolavirus (rVSV-ZEBOV) has been taken to the Republic of Guinea and rapidly administered to volunteers who were in contact with somebody that had Ebola symptoms. And their contacts. I mean the contacts and the contacts of contacts of the Ebola patient. Who were contacted by the researchers within 2 days of a new Ebola case based on the patient’s list of contacts. And of contacts of contacts. Is not that complicated, honest.

After vaccinations, the “vaccinees were observed for 30 min post-vaccination and at home visits on days 3, 14, 21, 42, 63, and 84” (p.4). Some volunteers received the vaccine immediately, others after 3 weeks. No one who received the vaccine immediately developed Ebola, which lead the researchers to claim that the vaccine is 100% effective. Only 9 from the delayed vaccination group developed Ebola within 10 days of vaccination, but the researchers figured that these people probably contacted Ebola prior to the vaccination, since the disease requires typically about 10 days to show its ugly  horns.

So this is great news. Absolutely great. Even if, as always, I could nitpick thorough the paper, squabble over the “typically” 10-day incubation period, and cock an eyebrow at the new-fangled ring vaccination design as opposed to the old-fashioned placebo approach. Even after these minor criticisms this is – I repeat – GREAT NEWS!

P.S. Don’t ever say that the UN didn’t do anything for you.

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Reference: Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, Carroll MW, Dean NE, Diatta I, Doumbia M, Draguez B, Duraffour S, Enwere G, Grais R, Gunther S, Gsell PS, Hossmann S, Watle SV, Kondé MK, Kéïta S, Kone S, Kuisma E, Levine MM, Mandal S, Mauget T, Norheim G, Riveros X, Soumah A, Trelle S, Vicari AS, Røttingen JA, Kieny MP. (22 Dec 2016). Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. pii: S0140-6736(16)32621-6. doi: 10.1016/S0140-6736(16)32621-6. PMID: 28017403 [Epub ahead of print] ARTICLE | FREE FULLTEXT PDF | Good Nitpicking in The Conversation

By Neuronicus, 18 January 2017

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The FIRSTS: The Name of Myelin (1854)

One reason why I don’t post more often is that I have such a hard time deciding what to cover (Hint: send me stuff YOU find awesome). Most of the cool and new stuff is already covered by big platforms with full-time employees and I try to stay away of the media-grabbers. Mostly. Some papers I find so cool that it doesn’t matter that professional science journalists have already covered them and I too jump on the wagon with my meager contribution. Anyway, here is a glimpse on how my train of thought goes on inspiration-less days.

Inner monologue: Check the usual journals’ current issues. Nothing catches my eye. Maybe I’ll feature a historical. Open Wikipedia front page and see what happened today throughout history. Aha, apparently Babinski died in 1932. He’s the one who described the Babinski’s sign. Normally, when the sole of the foot is stroked, the big toe flexes inwards, towards the sole. If it extends upwards, then that’s a sure sign of neurological damage, the Babinski’s sign. But healthy infants can have that sign too not because they have neurological damage, but because their corticospinal neurons are not fully myelinated. Myelin, who discovered that? Probably Schwann. Quick search on PubMed. Too many. Restrict to ‘history”. I hate the search function on PubMed, it brings either to many or no hits, no matter the parameters. Ah, look, Virchow. Interesting. Aha. Find the original reference. Aha. Springer charges 40 bucks for a paper published in 1854?! The hell with that! I’m not even going to check if I have institutional access. Get the pdf from other sources. It’s in German. Bummer. Go to Highwire. Find recent history of myelin. Mielinization? Myelination? Myelinification? All have hits… Get “Fundamental Neuroscience” off of the shelf and check… aha, myelination. Ok. Look at the pretty diagram with the saltatory conduction! Enough! Go back to Virchow. Does it have pictures, maybe I can navigate the legend? Nope. Check if any German speaking friends are online. Nope, they’re probably asleep, which is what I should be doing. Drat. Refine Highwire search. Evrika! “Hystory of Myelin” by Boullerne, 2016. Got the author manuscript. Hurray. Read. Write.

Myelinated fibers, a.k.a. white matter has been observed and described by various anatomists, as early as the 16th century, Boullerne (2016) informs us. But the name of myelin was given only in 1854 by Rudolph Virchow, a physician with a rich academic and public life. Although Virchow introduced the term to distinguish between bone marrow and the medullary substance, paradoxically, he managed to muddy waters even more because he did not restrict the usage of the term mylein to … well, myelin. He used it also to refer to substances in blood cells and egg’s yolk and spleen and, frankly, from the quotes provided in the paper, I cannot make heads or tails of what Virchow thought myelin was. The word myelin comes form the Greek myelos or muelos, which means marrow.

Boullerne (2016) obviously did a lot of research, as the 53-page account is full of quotes from original references. Being such a scholar on the history of myelin I have no choice but to believe her when she says: “In 1868, the neurologist Jean-Martin Charcot (1825-1893) used myelin (myéline) in what can be considered its first correct attribution.”

So even if Virchow coined the term, he was using it incorrectly! Nevertheless, in 1858 he correctly identified the main role of myelin: electrical insulation of the axon. Genial insight for the time.

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I love historical reviews of sciency stuff. This one is a ‘must-have’ for any biologist or neuroscientist. Chemists and physicists, too, don’t shy away; the paper has something for you too, like myelin’s biochemistry or its birefringence properties.

Reference: Boullerne, AI (Sep 2016, Epub 8 Jun 2016). The history of myelin. Experimental Neurology, 283(Pt B): 431-45. doi: 10.1016/j.expneurol.2016.06.005. ARTICLE

Original Reference: Virchow R. (Dec 1854). Ueber das ausgebreitete Vorkommen einer dem Nervenmark analogen Substanz in den thierischen Geweben. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin, 6(4): 562–572. doi:10.1007/BF02116709. ARTICLE

P.S. I don’t think is right that Springer can retain the copyright for the Virchow paper and charge $39.95 for it. I don’t think they have the copyright for it anyway, despite their claims, because the paper is 162 years old. I am aware of no German or American copyright law that extends for so long. So, if you need it for academic purposes, write to me and thou shall have it.

By Neuronicus, 29 October 2016

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The FIRSTS: the von Economo neurons (1881, 1904, 1926)

A von Economo neuron, also known as a spindle neuron, is a unique cell with several interesting characteristics:

1) It has a long axon and on the opposite side of the cell body has only one long dendrite, resembling a spindle and hence the nickname.

2) It is to be found only in humans, apes, elephants, dolphins, whales, and a few other animals known for their intricate social structure.

3) In humans, they exist only in the frontal part of the brain.

4) It is thought to be important for social awareness.

In all fairness, these cells should be called Betz cells, or at least Ramón y Cajal cells because these neuroanatomists mentioned their existence in 1881 and 1904, respectively. But Betz already has his own neurons, and Ramón y Cajal, well… his fame is established already. But von Economo “made a more complete description of their morphology and mapped their specific locations in human cortex” (Allman et al., 2011)

So what do we know about von Economo? Quite a lot, thanks to Triarhou, an excellent biographer. Constantin von Economo (1876–1931) was born in Brăila, Romania to a wealthy family of Greek descent. Shorty after his birth, the family moved from Romania to Austria where the father acquired a “von” in front of his name by way of elevation to the rank of baron.

Von Economo went to medical school  in Vienna, traveled a lot across the globe, graduated, spent some more time here and there learning psychiatry, physiology, neurology and such with some Big Names, then returned to Vienna where he followed the classic academic path (for his time). He was a prolific writer, having published at least 139 scientific works in a relatively short time.

Besides the spindle neurons, he is also known for publishing an awesome brain atlas in 1925 (with Georg Koskinas) and for investigating in detail a mysterious and weird disease, encephalitis lethargica (the ‘von Economo disease’). This disease has unknown causes to the day, partly because it is very difficult to study, having virtually disappeared form the face of the Earth after a furious epidemic in 1926.  But about that enigma some other time.

For now, enjoy von Economo’s drawings.

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Composite image of the four drawings by von Economo (1926) in doi:10.1007/BF02970950.

Notes: 1) One last thing. Although according to Springer’s website the copyright for the von Economo paper I’m citing should have expired, Springer still charges a lot of money to obtain it (if you don’t have an institutional license like some of us, the fortunates, that is). I have attempted to contact Springer about it with no luck. Anyway, if you want it, email me at scientiaportal@gmail.com. It’s been more than 70 years since the death of the author, so it should be public domain.

2) I have no idea why people reference the Ramón y Cajal’s Textura del Sistema Nervioso del Hombre y de los Vertebrados as published in 1889. I got it from Google Books and it says 1904 on it.

References:

  1. von Economo, C. (1926). Eine neue Art Spezialzellen des Lobus cinguli und Lobus insulae (‘A new kind of special cells in the cingulum and insula’). Zeitschr. Ges. Neurol Psychiatr (Berlin), 100: 706–712. DOI: 10.1007/BF02970950. ARTICLE
  2. Allman JM, Tetreault NA, Hakeem AY, Manaye KF, Semendeferi K, Erwin JM, Park S, Goubert V, & Hof PR (Apr 2011). The von Economo neurons in the frontoinsular and anterior cingulate cortex. Annals of the New York Academy of Sciences, 1225:59-71. PMID: 21534993. PMCID: PMC3140770. DOI: 10.1111/j.1749-6632.2011.06011.x. ARTICLE | FREE FULLTEXT PDF 
  3. Triarhou, LH (14 Apr 2006, Epub 28 Feb 2006). The signalling contributions of Constantin von Economo to basic, clinical and evolutionary neuroscience. Brain Research Bulletin, 69 (3): 223–243. PMID: 16564418, DOI: 10.1016/j.brainresbull.2006.02.001. ARTICLE

By Neuronicus, 25 September 2016

Who invented optogenetics?

Wayne State University. Ever heard of it? Probably not. How about Zhuo-Hua Pan? No? No bell ringing? Let’s try a different approach: ever heard of Stanford University? Why, yes, it’s one of the most prestigious and famous universities in the world. And now the last question: do you know who Karl Deisseroth is? If you’re not a neuroscientist, probably not. But if you are, then you would know him as the father of optogenetics.

Optogenetics is the newest tool in the biology kit that allows you to control the way a cell behaves by shining a light on it (that’s the opto part). Prior to that, the cell in question must be made to express a protein that is sensitive to light (i.e. rhodopsin) either by injecting a virus or breeding genetically modified animals that express that protein (that’s the genetics part).

If you’re watching the Nobel Prizes for Medicine, then you would also be familiar with Deisseroth’s name as he may be awarded the Nobel soon for inventing optogenetics. Only that, strictly speaking, he did not. Or, to be fair and precise at the same time, he did, but he was not the first one. Dr. Pan from Wayne State University was. And he got scooped.98.png

The story is at length imparted to us by Anna Vlasits in STAT and republished in Scientific American. In short, Dr. Pan, an obscure name in an obscure university from an ill-famed city (Detroit), does research for years in an unglamorous field of retina and blindness. He figured, quite reasonably, that restoring the proteins which sense light in the human eye (i.e. photoreceptor proteins) could restore vision in the congenitally blind. The problem is that human photoreceptor proteins are very complicated and efforts to introduce them into retinas of blind people have proven unsuccessful. But, in 2003, a paper was published showing how an algae protein that senses light, called channelrhodopsin (ChR), can be expressed into mammalian cells without loss of function.

So, in 2004, Pan got a colleague from Salus University (if Wayne State University is a medium-sized research university, then Salus is a really tiny, tiny little place) to engineer a ChR into a virus which Pan then injected in rodent retinal neurons, in vivo. After 3-4 weeks he obtained the expression of the protein and the expression was stable for at least 1 year, showing that the virus works nicely. Then his group did a bunch of electrophysiological recordings (whole cell patch-clamp and voltage clamp) to see if shining light on those neurons makes them fire. It did. Then, they wanted to see if ChR is for sure responsible for this firing and not some other proteins so they increased the intensity of the blue light that the ChR is known to sense and observed that the cell responded with increased firing. Now that they saw the ChR works in normal rodents, next they expressed the ChR by virally infecting mice who were congenitally blind and repeated their experiments. The electrophysiological experiments showed that it worked. But you see with your brain, not with your retina, so the researchers looked to see if these cells that express ChR project from the retina to the brain and they found their axons in lateral geniculate and superior colliculus, two major brain areas important for vision. Then, they recorded from these areas and the brain responded when blue light, but not yellow or other colors, was shone on the retina. The brain of congenitally blind mice without ChR does not respond regardless of the type of light shone on their retinas. But does that mean the mouse was able to see? That remains to be seen (har har) in future experiments. But the Pan group did demonstrate – without question or doubt – that they can control neurons by light.

All in all, a groundbreaking paper. So the Pan group was not off the mark when they submitted it to Nature on November 25, 2004. As Anna Vlasits reports in the Exclusive, Nature told Pan to submit to a more specialized journal, like Nature Neuroscience, which then rejected it. Pan submitted then to the Journal of Neuroscience, which also rejected it. He submitted it then to Neuron on November 29, 2005, which finally accepted it. Got published on April 6, 2006. Deisseroth’s paper was submitted to Nature Neuroscience on May 12, 2005, accepted on July, and published on August 14, 2005… His group infected rat hippocampal neurons cultured in a Petri dish with a virus carrying the ChR and then they did some electrophysiological recordings on those neurons while shining lights of different wavelengths on them, showing that these cells can be controlled by light.

There’s more on the saga with patent filings and a conference where Pan showed the ChR data in May 2005 and so on, you can read all about it in Scientific American. The magazine is just hinting to what I will say outright, loud and clear: Pan didn’t get published because of his and his institution’s lack of fame. Deisseroth did because of the opposite. That’s all. This is not about squabbles about whose work is more elegant, who presented his work as a scientific discovery or a technical report or whose title is more catchy, whose language is more boisterous or native English-speaker or luck or anything like that. It is about bias and, why not?, let’s call a spade a spade, discrimination. Nature and Journal of Neuroscience are not caught doing this for the first time. Not by a long shot. The problem is that they are still doing it, that is: discriminating against scientific work presented to them based on the name of the authors and their institutions. Personally, so I don’t get comments along the lines of the fox and the grapes, I have worked at both high profile and low profile institutions. And I have seen the difference not in the work, but in the reception.

Personally, so I don’t get comments along the lines of the fox and the grapes, I have worked at both high profile and low profile institutions. And I have seen the difference not in the work, but in the reception.

That’s my piece for today.

Source:  STAT, Scientific American.

References:

1) Bi A, Cui J, Ma YP, Olshevskaya E, Pu M, Dizhoor AM, & Pan ZH (6 April 2006). Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron, 50(1): 23-33. PMID: 16600853. PMCID: PMC1459045. DOI: 10.1016/j.neuron.2006.02.026. ARTICLE | FREE FULLTEXT PDF

2) Boyden ES, Zhang F, Bamberg E, Nagel G, & Deisseroth K. (Sep 2005, Epub 2005 Aug 14). Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neuroscience, 8(9):1263-1268. PMID: 16116447. DOI: 10.1038/nn1525. doi:10.1038/nn1525. ARTICLE 

By Neuronicus, 11 September 2016

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The FIRSTS: Theory of Mind in non-humans (1978)

Although any farmer or pet owner throughout the ages would probably agree that animals can understand the intentions of their owners, not until 1978 has this knowledge been scientifically proven.

Premack & Woodruff (1978) performed a very simple experiment in which they showed videos to a female adult chimpanzee named Sarah involving humans facing various problems, from simple (can’t reach a banana) to complex (can’t get out of the cage). Then, the chimps were shown pictures of the human with the tool that solved the problem (a stick to reach the banana, a key for the cage) along with pictures where the human was performing actions that were not conducive to solving his predicament. The experimenter left the room while the chimp made her choice. When she did, she rang a bell to summon the experimenter back in the room, who then examined the chimp’s choice and told the chimp whether her choice was right or wrong. Regardless of the choice, the chimp was awarded her favorite food. The chimp’s choices were almost always correct when the actor was its favourite trainer, but not so much when the actor was a person she disliked.

Because “no single experiment can be all things to all objections, but the proper combination of results from [more] experiments could decide the issue nicely” (p. 518), the researchers did some more experiments which were variations of the first one designed to figure out what the chimp was thinking. The authors go on next to discuss their findings at length in the light of two dominant theories of the time, mentalism and behaviorism, ruling in favor of the former.

Of course, the paper has some methodological flaws that would not pass the rigors of today’s reviewers. That’s why it has been replicated multiple times in more refined ways. Nor is the distinction between behaviorism and cognitivism a valid one anymore, things being found out to be, as usual, more complex and intertwined than that. Thirty years later, the consensus was that chimps do indeed have a theory of mind in that they understand intentions of others, but they lack understanding of false beliefs (Call & Tomasello, 2008).

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References:

1. Premack D & Woodruff G (Dec. 1978). Does the chimpanzee have a theory of mind? The Behavioral and Brain Sciences, 1 (4): 515-526. DOI: 10.1017/S0140525X00076512. ARTICLE

2. Call J & Tomasello M (May 2008). Does the chimpanzee have a theory of mind? 30 years later. Trends in Cognitive Sciences, 12(5): 187-192. PMID: 18424224 DOI: 10.1016/j.tics.2008.02.010. ARTICLE  | FULLTEXT PDF

By Neuronicus, 20 August 2016