Wednesday, April 15, 2015

The Virtual Cell Animation Collection

I'm interested in science education in general and teaching biochemistry and molecular biology in particular. A recent publication in PLoS Biology caught my eye ...
Reindl, K.M., White, A. R., Johnson, C., Vender, B., Slator, B.M., and McClean, P. (2105) The Virtual Cell Animation Collection: Tools for Teaching Molecular and Cellular Biology. PLoS Biology 13(4): e1002118 DOI: 10.1371/journal.pbio.1002118
The paper focuses on the value of short animations for teaching biochemistry and molecular biology to advanced high school students and college students.

There's nothing in the paper about the scientific accuracy of the presentations or the pedagogical approach and this is unfortunate. The animations only show complex eukaryotic cells in spite of the fact that the American Society for Biochemistry and Molecular Biology recommends an evolutionary approach to teaching. The fact that the videos emphasize eukaryotes leads to some interesting descriptions of fundamental processes.

Look at the video on transcription regulation for example [Regulated Transcription]. The textbooks teach this using simple systems such as E. coli transcription then they move on to more complex prokarotic systems such as the lac operon. Then they cover the eukaryotic examples pointing out how they differ from the simple bacterial systems. This has always been a successful approach to teaching the basic concepts of transcription and transcription regulation. 1

Is the approach taken by the authors of The Virtual Cell Animation project better? I don't think so. What do you think? Does anyone out there teach transcription without introducing it first in bacteria?

Let's not forget my favorite example of biochemical misconceptions: the Citric Acid Cycle. Did you know that it's sometimes called the "tricarboxylic acid cycle" because three CO2 molecules are released for every pyruvate molecule? 2

The carboxylate groups on citrate, isocitrate etc. are shown as -COOH instead of COO- as in the textbooks. I don't know why they did this ... it leads to some extra protons being released in the reactions.

The authors make a very common mistake with succinate dehydrogenase. They show FADH2 as one of the products of the reaction whereas the IUBMB database shows that the real final product is QH2 [see Succinate Dehydrogenase]. I don't understand why biochemistry teachers can't check out a leading textbook (or the scientific literature) before producing a video.

Did you know that some of the reactions of glycolysis are irreversible? Check out the video on Glycolysis to find out which reactions have this interesting property. 3 There is no video on gluconeogenesis and that's surprising because the synthesis of glucose is far more important than glycolysis in most species.

I wonder if the editors of PLoS bothered to watch the videos or whether they just assumed that they were scientifically accurate and pedagogically sound? I'm guessing that they didn't see the need to review the videos and simply concentrated on whether all the words in the article were spelled correctly.


1. There's a separate video on the lac Operon. How many errors, flaws, or missed opportunities, can you spot?

2. Silly me. I always though it had something to do with the fact that two of the key intermediates (citrate and isocitrate) were tricarboxylic acids. Most of the others are dicarboxylic acids.

3. Maybe I'm quibbling. In my textbook I describe these reactions as "metabolically irreversible" because the activities of the enzymes are regulated. That's not the same as saying that the reactions are irreversible.

11 comments :

  1. I'm even more of a quibbler than you are, because I don't call it by any of the names you mention. I call it the tricarboxylate cycle. As you rightly point out, one shouldn't write -COOH for -COO-, and for the same reason one shouldn't call anions acids. I don't (usually) call it the Krebs cycle (1) because it wasn't the only or the first cycle that he described, and (2) because it's more important for students to know what things are than whose name is attached to them. No one talks about Harden and Young ester any more (except in articles about the history of biochemistry).

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    1. With respect to proper chemical formulae, why does this happen? My experience with many biochemistry instructors is that far too many of them think they know all they need to know without checking to see if they are correct. These guys are supposed to be scientists. Does it never occur to them to read a modern textbook?

      I really don't care what you call the pathway but that's not the point. The point was their explanation of "tricarboxylic." What were they thinking?

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    2. Why does it happen? I don't know, but it's long been a mystery to me why so many people are reluctant to write structures in their ionized forms. Many years ago, when I was a junior lecturer in a biochemistry department, and when nearly all common textbooks got it wrong, I tried to convince some my senior colleagues that students wouldn't be able to understand why, say, glycine looks like a salt (white crystalline solid) and behaves like a salt if their textbooks tell them that it has a -COOH group, suggesting a strongly smelling liquid, and an -NH2 group, suggesting that it might be a gas. I had no success: everyone knows, I was told, that amino acids are zwitterions, but it's more convenient (for whom? why?) to draw them with wrong structures. (They didn't say "wrong structures", of course, they talked about "neutral forms", as if the neutral forms really existed.)

      If you take a standard textbook of the 1960s and 1970s, say the 4th edition (1968) of White, Handler and Smith, you'll find that it defines all the amino acids with wrong structures, then several pages later there is a ritual mention of zwitterions, and then the authors make it clear that they don't believe a word of what they've just said because they go back to wrong structures for the rest of the book.

      The point was their explanation of "tricarboxylic." What were they thinking? Again, I don't know, but I expect they didn't think about it much at all, and didn't get a suitably critical person to read before they published it (and the editors of PLoS Biology didn't either).

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    3. Honesty compels me to add that I was a member of the committee that wrote the current (1983) IUPAC-IUB Recommendations on Nomenclature and Symbolism for Amino Acids and Peptides, in which you will find, in Table 1, the words "The systematic names and formulas given refer to hypothetical forms in which amino groups are unprotonated and carboxyl groups are undissociated. " This convention is useful to avoid various nomenclatural problems but should not be taken to imply that these structures represent an appreciable fraction of the amino-acid molecules." I tried but failed to convince the rest of the committee that "hypothetical" was a euphemism that should be replaced by "fictitious" or "nonexistent". After more than 30 years it's hard to be certain, but I think the second sentence had not originally been in the draft but was added in an effort to keep me quiet. To be fair to the committee, I think the rest of the document shows correct structures, except for lapse with glutathione.

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    4. Does it never occur to them to read a modern textbook?
      The point was their explanation of "tricarboxylic." What were they thinking?


      Tricarboxylic is a funny one. Despite all the misconceptions and errors out there, I have never heard that explanation before. As for reading textbooks, as you have pointed out many times before, they are also a source of erroneous information at times, esp matters pertainng to TCA cycle.

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    5. Athel Cornish-Bowden says,

      I tried but failed to convince the rest of the committee that "hypothetical" was a euphemism that should be replaced by "fictitious" or "nonexistent".

      Whenever I teach this stuff (e.g. last Fall) I ask my students to calculate the concentrations of the uncharged species (with -NH2 and -COOH) at various pH's. They certainly DO exist. There's just not very much of them.

      Here's the question from the end of Chapter 3 in my textbook.

      18. Generations of biochemistry students have encountered a question like the one below on their final exam.

      Calculate the approximate concentration of the uncharged form of alanine (see below) in a 0.01M solution of alanine at (a) pH 2.4 (b) pH 6.15 and (c) pH 9.9.

      NH2-CH(-CH3)- COOH

      Can you answer the question without peeking at the solution?

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    6. If you take a standard textbook of the 1960s and 1970s, say the 4th edition (1968) of White, Handler and Smith, you'll find that it defines all the amino acids with wrong structures, ...

      The first edition of Lehninger (1970) and the first edition of Styer (1975) drew them as zwitterions. The last edition of Garret & Grishom (2013) still draws the amino acids incorrectly.

      Lots of biochemistry is taught out of chemistry departments in the USA and those instructors prefer the uncharged structures.

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    7. Whenever I teach this stuff (e.g. last Fall) I ask my students to calculate the concentrations of the uncharged species (with -NH2 and -COOH) at various pH's. They certainly DO exist. There's just not very much of them.

      You're right, of course, the concentrations are not zero, just very small. It's the usual question of when you decide that some quantity is small enough to be treated as negligible. Can we say that the probability of intelligent design being right is zero? No, but we can certainly say that that it's small enough not to be taken as a serious possibility.

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    8. The first edition of Lehninger (1970) and the first edition of Styer (1975) drew them as zwitterions. The last edition of Garret & Grishom (2013) still draws the amino acids incorrectly.

      That, of course, is why the first edition of Lehninger seemed like a breath of fresh air when appeared. For the first time a book that got most things right, written in a way that made the subject seel interesting. Mahler & Cordes also got many things right, but not in a way that got many people excited.

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  2. re: lac operon ommissions, errors

    A large number, but most obviously it is allolactose not lactose that binds Lac repressor and no mention of the absolutely critical role of Crp and cAMP. Many more ommissions too, but I don't feel like typing right now.

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