Mendel's Garden #13

 
 

Mendel's Garden #13 has been posted by Alex Palazzo at The Daily Transcript. Read the articles and learn about fish flakes at the same time!

Home Schooling in Missouri

 
I just don't get home schooling. How can parents think they know everything about everything? Why don't they value different points of view? I always wanted my children to be exposed to other ways of thinking and not just my way of thinking. Isn't that what education is all about?



[Hat Tip: Greg Laden]

Blood Clotting: The Basics

 
When blood vessels are damaged the leak must be sealed as rapidly as possible to prevent excess blood loss. The first response is formation of a blood clot at the site of damage. The clot is made up of cross-linked fibers made from a protein called fibrin.

The fibrin network is formed from a precursor of fibrin called fibrinogen [hear it]. Fibrinogen is a large protein that circulates freely in the blood stream. The key to understanding the mechanism of blood clot formation is in understanding how fibrinogen is converted to fibrin and why this only occurs at the site of damage to the lining of the blood vessel.

The activation mechanism is very complicated and highly regulated. The disruption of a blood clot when it is no longer needed is also complicated and highly regulated.

We'll start by looking at the basics of clot formation and dissolution.

Fibrinogen is composed of three different polypeptide chains or subunits. Each one is present in two copies (α₂β₂γ₂). The α, β, and γ chains wrap around each other to form a coiled coil triple helix. Two of these coiled coil complexes are joined head-to-head at the N-terminal ends of the polypeptides to make the complete molecule.


The complete fibrinogen molecule, which is very large as far as proteins go, consists of two domains. The central region where the N-terminal ends (N) are located forms the E domain. The outside ends where the C-terminal (C) ends are found are called the D domains.

Fibrinogen is soluble in blood plasma and the molecules show very little tendency to aggregate to form blood clots. Aggregation is prevented in large part by the N-terminal tails of the α (red) and β (blue) subunits projecting out of the central E domain. Blood clotting is initiated when these tails are chopped off by a specific protein-cutting enzyme (protease) called thrombin. Thrombin converts fibrinogen to fibrin and fibrin spontaneously aggregates to form a clot.

The activation takes place in two stages. In the first stage thrombin cleaves the α subunit releasing fibrinogen peptide A (FpA) and creating fibrin. The resulting fibrins can interact through their E domains to form filaments.

In the slower second step, the β subunit is cleaved releasing fibrinogen peptide B (FpB) and this permits aggregation of filaments to form complex networks. The resulting clot is called a soft clot. It is converted to a hard clot by Factor XIIIa (the "a" stands for "activated"). FXIIIa catalyzes the formation of covalent cross-links between fibrin molecules. The activated cross-link enzyme (FXIIIa) is formed from an inactive precursor (FXIII) by the action of thrombin. Thrombin not only cleaves fibrinogen, it also cleaves a number of clotting factors, like FXIII, to create active forms.

The initiation of clotting depends on thrombin activity. Thrombin is formed by proteolytic cleavage of inactive prothrombin to create the active protease (thrombin). This activation of prothrombin takes place at the site of injury and it's the way clotting is regulated. We'll cover it later on. You're probably getting the idea—blood clotting is controlled and regulated by a cascade of protein cleavages.

Once a clot is formed it eventually has to be dissolved once the injury is healed. This step is called fibrinolysis. The enzyme that dissolves clots is called plasmin. It chops aggregated fibrin fibers in the coiled coil region thus breaking up the clot. Can you guess how active plasmin is formed?

That's right. It's formed from a precursor called plasminogen by proteolytic cleavage. The enzyme that activates plasminogen is called tissue plasminogen activator (TPA). Plasminogen has a high affinity for fibrin clots but not for free fibrinogen. TPA also binds to fibrin and it only cleaves plasminogen when a complex of fibrin clot+plasminogen+TPA forms. The scheme on the right is a summary of what we've covered so far.

You may have heard of TPA. It's an enzyme that's given to heart attack patients but it must be delivered as soon as possible in order to prevent death. Here's what The American Heart Association says about TPA.

We strongly urge people to seek medical attention as soon as possible if they believe they're having a stroke or heart attack. The sooner tPA or other appropriate treatment is begun, the better the chances for recovery.

Tissue plasminogen activator (tPA) is a thrombolytic agent (clot-busting drug). It's approved for use in certain patients having a heart attack or stroke. The drug can dissolve blood clots, which cause most heart attacks and strokes.

Studies have shown that tPA and other clot-dissolving agents can reduce the amount of damage to the heart muscle and save lives. However, to be effective, they must be given within a few hours after symptoms begin. Administering tPA or other clot-dissolving agents is complex and is done through an intravenous (IV) line in the arm by hospital personnel.

There are very few textbooks that do a good job of summarizing and simplifying blood clotting. One of the better ones is Textbook of Biochemistry with Clinical Correlations 6th ed. edited by Thomas H. Devlin. This is an excellent book for those interested in biochemistry with a medical slant. I recommend it very highly as a reference text. It ain't cheap.

Devlin, T.H. (ed.) (2006) Textbook of Biochemistry with Clinical Correlations 6th ed., Wiley-Liss, Hoboken, N.J. (USA)

Wolberg, A.S. (2007) Thrombin generation and fibrin clot structure. Blood Reviews Jan. 5 2007. [PubMed]

Monday's Molecule #20

 
Name this molecule. The figure doesn't show the precise structure of the complete molecule but there's enough of a hint for you to figure it out. In this case we don't need a precise scientific name.

As usual, there's a connection between Monday's molecule and this Wednesday's Nobel Laureate but this one is very indirect. Nobody will be able to guess it. The bonus lunch date will be awarded to the first person to make the connection between this molecule and the University of Toronto.

Comments will be blocked for 24 hours. Comments are now open.

Latest Poll on Evolution in America

 
Here's the result of the latest Newsweek Poll published on March 31, 2007. The poll was conducted by Princeton Survey Research Associates International.


These numbers don't make a lot of sense. For example, 39% of non-evangelical protestants think that God made humans only 10,000 years ago. But only 24% think that evolution is not well-supported by scientific evidence. Does that mean 15% think that evolution could be well-supported but they don't believe it anyway?

And what about the 58% of Catholics who think that evolution is supported by evidence? How did those Catholics answer the previous question? How 'bout those atheists/agnostics! Wouldn't you like to meet the 27% who think that God guided evolution or the 13% who think that humans were created quite recently? Does this mean that the "agnostics" include a significant number of believers? If so, then it suggests that calling yourself an agnostic in America is compatible with belief in the literal truth of genesis. Maybe these people have a truly sophisticated, philosophical, definition of "agnostic" in mind when they answered this question.

Public Scientific Debates

 
Sean Carrol has posted an article about pubic debates over the validity of string theory [String Theory is Losing the Public Debate]. You should read the article in order to get some idea of the "controversy." Sean thinks that string theory is in much better shape than most people realize, it's just that the supporters of string theory aren't getting their message out.

The article has attracted a number of comments including some from John Horgan and Peter Woit, both of whom are skeptical of string theory. The issue has prompted some discussion about whether public debates of scientific controversies are useful. Sean says yes,

In their rush to find evidence for the conclusion they want to reach, everyone seems to be ignoring the fact that having public debates is actually a good thing, whatever the state of health of a particular field might be. The existence of a public debate isn’t evidence that a field is in trouble; it’s evidence that there is an unresolved scientific question about which many people are interested, which is wonderful. Science writers, of all people, should understand this. It’s not our job as researchers to hide away from the rest of the world until we’re absolutely sure that we’ve figured it all out, and only then share what we’ve learned; science is a process, and it needn’t be an especially esoteric one. There’s nothing illegitimate or unsavory about allowing the hoi-polloi the occasional glimpse at how the sausage is made.

I agree, but I'd like to make an additional point. In the biological sciences there are a number of controversial issues that are not openly debated. I'm thinking of things like evo-devo, punctuated equilibria, adaptionism, RNAi, Neutral Theory, and junk DNA. What happens is that one side gets far more attention that the other so that the very existence of a controversy is buried deep in the scientific literature. Thus, it is possible to get a major grant on genomes based on the idea that Neutral Theory is wrong and there's no such thing as junk DNA. The applicant doesn't even have to justify these assumptions because the controversy isn't visible. This is wrong.

We should have more public debates on some of the topics that really are controversial in biology. (By "public" I'm usually thinking of open debates at scientific meetings.) This is becoming increasingly necessary because there are too many scientists who aren't paying attention and they don't realize that there's more than one side to a story (e.g., Animal Chauvinism, Evolution of Mammals, The Three Domain Hypothesis).

What about the downside? There is a downside and we're much more aware of it than the physics community is. We know that the public loves the debate between evolutionary biologists and Creationists because that's taken as evidence of a controversy. Evolution must not be "proven," otherwise scientists wouldn't be debating with creationists. This is a problem.

One the one hand, I think there should be much more open debate over real controversies in biology. On the other hand, I don't think we should legitimize the Creationist nonsense by debating it. I was recently invited to speak at a meeting with Michael Behe, Marcus Ross, and Paul Nelson. The topic was Intelligent Design Creationism. After some agonizing, I declined because it was apparent that these were not scientific debates in any meaningful sense of the word. How could they be when both Ross and Nelson are Young Earth Creationists? There's no scientific controversy over whether the Earth is only 10,000 years old.

So, the way I resolve this problem is to encourage public scientific debate over real science controversies but discourage public scientific debate over bogus controversies. Let's leave the non-scientific debates to the lawyers.


Via: VideoSift

Animal Chauvinism

 
There's much to criticize in the field of evolutionary developmental biology or evo-devo. Some of the "theories" are little more than wide-eyed speculation. I'm thinking particularly of The Plausibility of Life by Marc Kirschner and John Gehart.

The thing that bugs me more than anything else is the attempt to create a general theory of evolution based entirely on a subset of living species; namely multicellular animals. Most proponents of evo-devo seem to be entirely unaware of the the fact that there are other species where genes are developmentally regulated.

This strange bias is spectacularly illustrated in a recent review in Nature Reviews: Genetics. The authors, Ronald Jenner and Matthew Wills, say,

Study of the model organisms of developmental biology was crucial in establishing evo–devo as a new discipline. However, it has been claimed that this limited sample of organisms paints a biased picture of the role of development in evolution. Consequently, judicious choice of new model organisms is necessary to provide a more balanced picture. The challenge is to determine the best criteria for choosing new model organisms, given limited resources.

Great! I couldn't agree more. When I used to teach this stuff I would begin with development in bacteriophage lambda where there is a beautiful example of a genetic switch. I then described development during sporulation in the bacterium Bacillus subtilis where there's a nice simple example of communication between the mother cell and the developing spore. Both of these examples made it into my textbook back in 1993.

Yeast development got a lot of play in my courses and it still does in the courses that are taught here. I would also look for examples of plant development since that's where I first learned about development as an undergraduate. We need to teach more plant development.

So, as you can imagine, I was excited to read the abstract of this paper. Jenner and Wills bemoan the fact that most of the work in the field is based on just six model organisms: Caenorhabditis elegans, Gallus gallus, Xenopus laevis, Mus musculis, Danio rerio, and Drosophila melanogaster. How right they are. The evo-devo crowd needs to expand their horizons to cover bacteria, protists, fungi, and plants.

So I eagerly read on to see which organisms they would name. Here are their choices: sea urchin, dung beetle, water flea (Daphnia), and sea anemone. All animals.

Evo-devo is never going to gain widespread respectability among evolutionary biologists unless the proponents abandon their animal chauvinism and start to recognize that development is important in four other kingdoms. [Press Release from the University of Bath]

Jenner, R.A., Wills, M.A. (2007) The choice of model organisms in evo-devo. Nat Rev Genet. 8:311-314. Epub 2007 Mar 6.

University Classes Doubled in Size when Grade 13 Was Abolished in Ontario

Friday's Urban Legend: FALSE

Back in the 20th century Ontario had a unique education system where students spent an extra year in high school. They didn't graduate until they had completed Grade 13.

This system was abolished in order to bring Ontario into line with the rest of the civilized world. There didn't seem to be any logical reason to force Ontario students to stay in high school for an extra year. When they entered university they ended up being a year older than students from every other country and every other province in Canada.

The new system began with an overhaul of the high school curriculum so that five years worth of material could be taught into four years. Some voluntary breadth courses were abandoned. On implementation day all students entering grade nine were going to graduate at the end of grade 12.

This created a double cohort of graduating students since those completing the new four year program were graduating at the same time as the class ahead of them who were the last to finish grade 13. Naturally, the universities in Ontario were expected to accommodate the double cohort so that students in the first year of the new system would not be penalized. It was widely believed that the "double cohort" really meant there would be twice as many students entering university at some point.

Newspapers published articles about the double cohort as though the class sizes would double. Parents believed that classes would double in size and so did students. Even today, after we have seen the result, it is still widely believed that there were twice as many students in the double cohort year.

It never happened. The universities knew that their enrolment would not double and they published lots of data to explain why. As it turned out they were right and they publicized that too. Still the myth persists. An article in this week's Toronto Star show how little we've learned (see below the fold).

Let's start with a little quiz. Here's some data on the size of first year science classes at the University of Toronto. The red bars represent students enrolled in our first year biology class. Green is for chemistry, blue is calculus, and yellow is physics. I haven't told you when the so-called "double" cohort entered university. See if you can guess by looking at the data.


The double cohort class entered university in the Fall of 2003. The universities predicted that class sizes in that year would increase by about 20-25% over those of the previous years. They also predicted that class sizes would remain at that level for several years. The double cohort hit universities at the same time that applications were expanding because of the echo boom and because of increases in participation rates. The chart below shows the increase in university students throughout Canada over the past decade. You can see that the numbers grew from 2000 to 2005 and this has nothing to do with the double cohort in Ontario. Even without a double cohort there was a predicted increase in enrolment during this time frame.

Why was the "double cohort" increase only 25% and not 100%? There are many reasons but the most obvious one is that universities attract students from all over Canada and from many foreign countries as well. The double cohort only affected graduates from Ontario high schools. If only half the students at the University of Toronto are from Ontario, for example, then the expected increase would only be 50% assuming that the double cohort really was twice the size and assuming that all qualified applicants were accepted.

The reason it was less than that had to do with other, predicted, events. First, a significant number of students in the last year of the five year program were allowed to "fast-track" in order to finish in four years and get ahead of the double cohort. A significant number of students in the first year of the new four year program took an extra year in order to fall behind the double cohort. Many more students than normal in the double cohort went to universities in other provinces.

Let's look closely at the actual numbers by normalizing the class size to that of 1997-98.


Now we see that the largest increase was in 2002-03, the year before the double cohort entered university. This increase is entirely due to expanded enrolment in anticipation of further increases that are due to increased participation. It had the added benefit of accommodating the fast-trackers. The actual enrolment increase in the double cohort year was only 10-15% higher than that in the previous year and it was less than the numbers in the following year. This is an important point. The real increase in that particular year (2003-04) was no more than 20% and in most cases was considerably less. Part of the increase (about 20%) in this period was due to demographic factors unrelated to the double cohort as demonstrated in the chart for Canada as a whole.

This brings me to the Toronto Star article [Double cohort graduating again].

There was much concern when the last Grade 13s and the first graduating-year Grade 12s combined to create the largest group to finish high school en masse in the province's history.

The decision was designed to cut public education costs and bring Ontario in line with the rest of the continent, where 12 grades were already the norm, but it left educators facing serious challenges.

Would universities and colleges have enough staff and classroom space? What about residences? Would crowded schools affect the quality of education? Would thousands of students fall through the cracks just because they happened to be born in the wrong year?

Four years later, the Ontario government is again straining to accommodate the double cohort. Apart from concern about a flood of entries to the labour force, the province has to provide an extra $240 million a year to create 14,000 graduate school spaces by 2009.

The Star interviewed three students. I'd like to quote the remarks on one of them in order to illustrate the double cohort mythology.

As part of the double cohort's older half, Allard regrets not having fast-tracked her way through high school.

"In high school, I thought it was no big deal. Now I've come to realize that for the rest of my life, this group is going to follow me wherever I go. Whether it's grad school, medical school or work, there will be twice as many people trying to do everything I'm trying to do. If I'd fast-tracked, I could have gone to university a year earlier."

As a double cohort student, I presume Allard was interested in the numbers. She probably read the predictions and she probably read about the actual increase in class size. I can't imagine that she didn't. At some point she must have been exposed to the fact that her class was less than 20% larger than the one ahead of her and smaller than the one behind her.

She has just spent four years in university were one hopes she learned how to think critically. She must have noticed that her classes weren't twice as large as other classes. So why does she say that she will always be competing with twice as many people? I can't help but feel that we've failed to do a good job of educating if there are so many out there who believe in things that are easily refuted by facts and observations.

Young will graduate with a degree in political science from the University of Western Ontario next month. A good student in high school, he had no trouble getting into his university of choice. In fact, he liked being in the double cohort.

"It was fun," he says. "I was in the younger year of the cohort, so I got to spend my year with twice as many students, and half of them were older than me."

Hmmm ... one wonders just how much attention he was paying in class. A good many of his classmates were not from Ontario so they were the same age. The class was only 20% bigger than the previous class so where did he get the idea that there were twice as many students?

Young's plans were also affected by the double cohort. Had it not been for the increased competition for graduate school positions, he says he likely would have continued his education.

"In a different year, I probably would have worked a bit, then considered getting my master's, which would have helped me land the kind of job I want."

The data is clear. His "competition" is no greater than most other years. This is because the actual increase in the graduating class this year will be less than 20% and the number of graduate positions has increased significantly. We must not have done a good job of teaching critical thinking in this case either. Maybe it's not a requirement in political science?

Thanks to Brenda Bradshaw in our office for gettng some of the data on very short notice.

Blogging with Bush

 
This is cool. President George Bush reads blogs and he even quotes them in his speeches. These bloggers were from Iraq. They say America is winning [Blogging with Bush].

[Hat Tip: Canadian Cynic]

Evolution of Mammals

 
A paper in this week's issue of Nature presents a nice summary of recent work on mammalian evolution. Bininda-Emonds et al. (2007) have combined a lot of data from various studies in order to construct a supertree of mammalian evolution. The study incorporates fossil data with molecular sequence data to arrive at estimates of divergence times for 4,510 species of mammal out of a total of 4,554 extant species (99% complete).

This is a study of macroevolution. The authors are addressing questions about the mode, tempo, and pattern of speciation over a period of more than 150 million years. The main questions are when did mammals diversify and did it have anything to do with the mass extinction event at the Cretaceous/Tertiary (K/T) boundary. This is the event that resulted from an asteroid impact 65 million years ago.

The results are presented in the form of a large phylogenetic tree showing the major groups of mammals. The first split in the mammalian tree occurred 166 million years (My) ago when monotremes such as platypus and echidnas (black) split off from the other mammals. Marsupials such as opposums, kangaroos, and koalas (orange) separated from placental mammals 148 My ago.

Within the placental mammals, all of the extant orders appeared by 75 My ago. This includes the clades labelled on the outside of the circle plus other. For a compete list and a description of the species, see the NCBI Taxonomy website [Eutheria].


All of these orders were established at least 10 Myr before the mass extinction event (dashed circle on the circular tree). This is one of the main conclusions of the meta-analysis. The most significant diversification of mammals takes place well before the extinction of non-avian dinosaurs.

The other conclusion is that subsequent radiations at the level of families were not significant until after 50 Myr ago. This period of diversification lasted until about 10 Myr ago. There is no evidence to suggest that the radiations within each order were synchronous, ruling out global climate change as a mechanism.

Furthermore, the data clearly shows no connection between the mass extinction event at the K/T boundary (65 Myr ago) and subsequent radiations of mammalian groups. This effectively rules puts an end to the long held belief that mammals diversified after the devastation in order to fill up the niches left by dinosaurs. This is not the first paper to refute that belief but it may be the final nail in the coffin.

This summary serves as a warning to those who continue to associate evolution with environmental change. At this level of analysis there does not seem to be a connection between rates of speciation and climate change. This is most obvious with respect to the asteroid impact of 65 My ago. While it led to mass extinction, it did not lead to increases in the rate of evolution of the survivors. The branching pattern of cladogenesis in the figure is hardly affected by the cataclysm.

Similarly, there are no other speciation events that correlate with known climate change over the past 150 million years, including recent ice ages. There is growing recognition among evolutionary biologists that rates of speciation cannot be attributed to large-scale environmental change. (The data has not prevented speculation. Many reports on this paper attempt to manufacture some correlation between global environmental change and speciation. The old idea of a link between them is too entrenched to give up so easily.)

There's an interesting sidebar to this story. The paper clearly states the two main conclusions,

... the pivotal macroevolutionary events for extant mammalian lineages occur either well before the boundary (significant decrease in diversification rate at approximately 85 Myr ago, after establishment and initial radiations of the placental superorders and major orders at approximately 93 Myr ago) or well afterwards, from the Early Eocene onwards (when net diversification began to accelerate)....

Therefore, the demise of the non-avian dinosaurs, and the K/T mass extinction event in general, do not seem to have had a substantial direct impact on the evolutionary dynamics of the extant mammalian lineages.

However, in the title of the paper, The delayed rise of present-day mammals, the authors focus attention on the second conclusion at the expense of the first. Some of the press releases picked up on this emphasis, leading to the false impression that mammalian evolution is more recent than scientists thought [Did the Dino Die-Off Make Room for Mammals?] while others got it right [Mammals not such late developers, after all].

The point about early diversification is emphasized in the Nature News & Views commentary that's published with the article in the March 29th issue. David Penny and Matthew J. Phillips begin with a summary of the evidence for early evolution,

On page 507 of this issue, Bininda-Emonds and co-authors1 present an evolutionary tree of more than 4,500 mammals, and conclude that more than 40 lineages of modern mammals have survived from the Cretaceous, some 100 million to 85 million years (Myr) ago, to the present. This is paralleled by Brown and colleagues' analyses for birds, just published in Biology Letters: they claim that more than 40 avian lineages have likewise survived from before the extinctions at the Cretaceous/Tertiary (K/T) boundary 65 Myr ago. These numbers of surviving lineages push back the evolutionary history of many mammals and birds much further than earlier estimates based on smaller data sets. But strong claims need strong evidence to support them.

Later on they re-emphasize this point,

But the most challenging aspect of the phylogeny is the inference that more than 40 lineages of living mammals (and of birds, as described by Brown et al. 2007 ) survived from the Cretaceous to the present.

There are some quibbles about the data. Personally, I think the estimates for early divergence are too recent rather than too late . It all depends on the first fixed data point which is the separation of monotremes. This date (166 Myr ago) is a minimum estimate and there's evidence for an older date. The popular report on the Nature website [Disappearing dinos didn't clear the way for us] mentions this possibility. Mark Springer of the University of California, Riverside (USA) is interviewed and the article states,

"This is a reasonable first approximation," he [Springer] says. "Some of the dates and relationships are probably right on, and some are probably going to move around."

For example, says Springer, the team estimates that the deepest split in the mammals' family tree, between the egg-laying monotremes (such as the duck-billed platypus) and the rest happened 166 million years ago. But some molecular analyses suggest it happened more than 200 million years ago; Springer thinks this earlier date is probably closer to the truth. If that fundamental point changes, he notes, other things will have to shift too. "That date influences everything else through the tree," he says.

I suspect he's right and all the dates will move back in time. One wonders whether the late radiation at 50 My will then shift closer to the K/T boundary.

It's clear that more work needs to be done but the significance of this paper is that it assembles a lot of evidence into one place and publicizes a debate that's been smoldering among evolutonary biologists for over adecade.

Bininda-Emonds, O.R.P., Cardillo, M., Jones, K.E., MacPhee, R.D.E., Beck, R.M.D., Grenyer, R., Price, S.A., Vos, R.A., Gittleman, J.L., and Purvis, A. (2007) The delayed rise of present-day mammals. Nature 446: 507-512. [PDF]

Penny, D. and Phillips, M.J. (2007) Evolutionary biology: Mass survivals. Nature News & Views, Nature 446: 501-502. [PDF]

Some Days I Feel Really Old

 
The students in my biochemistry course are also taking a course called Molecular Cell Biology. They use the textbook Molecular Biology of the Cell by Bruce Alberts et al.

I was showing several students my copy of the older 3rd edition. It has this picture (below) on the back cover so I asked them to name the street they were crossing. None of them had a clue.


The street is only two blocks from the house in St. John's Wood where the authors meet to work on the book. I've been there and I crossed the street at that very crosswalk. For people my age the street and the crosswalk (and the white building in the background) are holy places. For students born after 1988 they aren't. I feel really old.

The Largest Single Organism on Earth

 
The largest known organism is not some giant squid or other cephalopod. It's a stand of quaking aspen in Utah known as Pando. What seem to be individual trees are actually just the visible expression of a gigantic underground organism. Every "tree" is connected via the root system. The individual "trees" are genetically identical. (Erroneously referred to as "clones.")

The total size and weight of this organism isn't known with certainty but it's surely more than 6,000,000 kg. The Wikipedia article mentions that Pando is probably the oldest known organism as well, dating back 80,000 years. I'd like to confirm this, if possible. Does anyone know how accurate this date is and whether there is anything older?

Lots of plants are bigger than cephalopods. There are even some mushrooms that are bigger!

Nobel Laureates: Dam and Doisy

 

The Nobel Prize in Physiology or Medicine 1943.


Henrik Carl Peter Dam (1895-1976): "for his discovery of vitamin K"

Edward Adelbert Doisy (1893-1986): "for his discovery of the chemical nature of vitamin K"

Henrik Dam and Edward Doisy won the Nobel Prize in 1943 for their contributions to the understanding of blood clotting, especially the role of vitamin K.

Dam was working at the Biochemical Institute in Copenhagen during the 1930's. He was studying diet in chickens and noticed that his flock was suffering from frequent hemorrhages. After eliminating the most obvious causes, including lack of vitamin C, Dam proceeded to isolate the missing factor that caused the deficiency in blood clotting. The effort is described in the presentation speech.

In cooperation with F. Schønheyder, it was found by Dam in 1934 that an addition of hempseed to the food prevented the bleedings. This forced him to the conclusion that hempseed must contain a still unknown substance which has a protective effect against certain hemorrhages. This substance, which was found to be necessary for the coagulation of the blood, is termed by Dam the coagulation vitamin or vitamin K. Dam moreover found that this vitamin occurs not only in the vegetable kingdom, for example in the seeds of cabbage, tomatoes, soya beans and lucerne, but also in certain animal organs, especially in the liver. Dam and the American investigator Almquist showed almost simultaneously that activity follows the non-saponifiable lipoid fraction. Vitamin K is formed also by bacteria in the intestinal canal, as was shown in 1938 by Almquist and his co-workers. The organism's need of this vitamin may thus be satisfied either by supply with the food, or by its formation in the intestinal canal.

Dam was able to show that a lack of vitamin K led to a deficiency in prothrombin, the precursor of thrombin. Thrombin is the enzyme that cleaves fibrinogen to create fibrin and it is fibrin molecules that interact to form a blood clot.

The nature of vitamin K remained a mystery until 1939 when Edward A. Doisy, Professor of Biochemistry at St. Louis University School of Medicine, determined its structure and synthesized it in the laboratory.


By 1943 it was apparant that vitamin K could relieve the symptoms of inappropriate hemorraging in humans and treatment with vitamin K became routine as described in the Nobel Prize presentation speech.

It was in fact soon found that this vitamin was to assume great importance in the treatment of hemorrhagic diseases in man. Certain diseases of the liver and gall ducts with jaundice are characterized by a marked tendency to hemorrhage, and it was found that this tendency, being due to a lack of prothrombin, could be remedied with vitamin K. In this way operative treatment in such cases has become much less risky than before. Also in certain protracted intestinal diseases there is a hemorrhagic tendency, due to insufficient absorption of vitamin K through the intestine. These cases too have been successfully treated with vitamin K.

It is, however, in the checking of hemorrhages in newborn babies that this vitamin has assumed its greatest practical importance. At this early age, hemorrhages - sometimes involving menace to life - occur far oftener than in more advanced stages. A great many of these cases have proved to be due to deficiency of vitamin K and can be cured by the supply of that vitamin. What is more, by treating the mother shortly before delivery, or the newborn child immediately afterwards, it is possible also to prevent the occurrence of such hemorrhages. Even if there are also neonatal hemorrhages which are not due to a lack of vitamin K and therefore cannot be cured by the supply thereof, the number of cases of such deficiency in the neonatal stage is rather large, and then vitamin K often conduces to save life. Indeed, it may be said that the discovery of vitamin K has revolutionized the treatment of these not uncommon cases.

Nowadays the role of vitamin K is so well understood, and the compound is so easily available, that it's rare to encounter deficiencies.

Most Metabolic Diseases Affect Unimportant Genes

 
Okay, so the title is a little bit disingenuous. Obviously metabolic diseases like cystic fibosis, thalasemia, phenylketonuria, and Huntington's Disease are not trivial. They cause devastating problems for patients and family. Many metabolic diseases are lethal. That's not "unimportant."

The point isn't that the genes are "unimportant" in that sense. What I meant is that defects in essential genes—the ones are part of core metabolism—do not usually show up as metabolic defects. The reason is that any defects in, say, RNA polymerase, will usually be embryonic lethals and we will never see them [RNA Polymerase Genes in the Human Genome].

The defects that are most likely to show up as metabolic diseases are those where the defect is not so severe as to prevent embryonic development. Thus, a defect in adult hemoglobin (thalasemia), for example, will only be manifest after birth and even then there are compensating genes that can prevent death. Same with cystic fibrosis. Not to minimize the consequences of the disease, but we only see it as a metabolic defect because it isn't immediately lethal.

The point of this little note is to correct a widespread misconception. Many people think that metabolic diseases identify the most important genes in humans. The ones that are essential for life. In fact that's not usually the case. The really important genes do not have associated metabolic diseases. As a general rule, it's only the second tier of important genes that are associated with metabolic disease. The ones that are not essential for cell survival during fetal development.

Vitamin K

 
Vitamin K (phylloquinone) is a lipid vitamin found in plants as K₁, or phytylmenaquinone, and in bacteria as K₂, or multiprenylmenaquinone. Vitamin K is related to ubiquinone [Monday's Molecule #10]. Ubiquinone serves as an electron carrier in reactions such as membrane-associated electron transport [Ubiquinone and the Proton Pump]. Related cofactors in plants (plastoquinone) and bacteria (menaquinone) can be absorbed in the intestine and converted to vitamin K.


Although we can't synthesize vitamin K ourselves, we usually get enough of it from intestinal bacteria. Vitamin K deficiency is not common for this reason. The most common symptom of vitamin K deficiency is hemorraging due to a defect in blood clotting. The symptoms are frequently seen in newborn babies, especially those born prematurely because they lack intestinal bacteria. This is why premature babies are given vitamin K.

Vitamin K is a cofactor in reactions required for the synthesis of some of the proteins involved in blood coagulation. It is the coenzyme for a mammalian carboxylase that catalyzes the conversion of specific glutamate residues to γ-carboxyglutamate residues. The reduced (hydroquinone) form of vitamin K participates in the carboxylation as a reducing agent.