evolgen

Best Biology Experiment/Discovery

Chad at Uncertain Principles, one of my ScienceBlogs siblings, is requesting his co-bloggers suggest the most important experiment or discovery in their field. There are a disproportionate amount of “bio-bloggers” — though we each have our own niche — and he’s asking us to nominate “the most important experiment or observation in biology”. I’m expecting that because of our diverse interests, you’ll see some differences in how we interpret “important”. This leads me to wonder why we have so many life-sciences types at ScienceBlogs and so few math/physics/chemistry types, but that’s a discussion better left for another time.

I’d guess PZ Myers (who is probably thought of as “Pee-Zee” in the US, and “Pee-Zed” elsewhere) will suggest a classic embryology discovery (Haeckel’s embryos or some other pretty picture), something from the early days of developmental genetics (probably from Nusslein-Volhard’s group), an early zebra fish paper (another by Nusslein-Volhard?), or maybe something evo-devo from Sean Carroll or West-Eberhard. I’ll bet Razib will come up with a better classic population genetics paper than I ever would; and, besides, he’s really into the theory and human genetics stuff, wereas I prefer experimental studies of non-human populations. Some of my other fellow ScienceBloggers are harder to predict. I have a general idea of what Tara would consider the greatest biology discovery, but I don’t know enough about her field to make a solid prediction. Your guess is as good as mine when it comes to Hedwig the Owl (aka, Grrl Scientist . . . aka, Living the Scientific Life) and John Lynch.

My nominations are below the fold . . .

I’m going to divide this up into different categories because it’s hard to compare Darwin’s Origin of the Species with shotgun sequencing. Here are the best discoveries in somewhat non-arbitrary categories (basically, I gave the greatest discoveries their own category that explains why they are so great), along with links to the papers (or books) that go along with the best discovery in that field.

Best pre-20th Century Discovery: Natural selection as presented by Charles Darwin in The Origin of Species. Enough said.

Best 20th Century Re-Discovery: Mendelian genetics. Not much to say here, other than it’s hard to imagine any biological sub-discipline without Mendel’s important contribution.

Most Important Study of the Early 20th Century: Alfred Sturtevant‘s genetic maps. The seminal paper would have to be Sturtevant’s 1919 publication “The Linear Arrangement of Six Sex-Linked Factors in Drosophila, as Shown by Their Mode of Association” (available as a pdf here). Sturtevant’s work in the Morgan lab (as an undergraduate) made up a large part of the base on which classical and molecular genetics was built. He also was an important player in population genetics, publishing multiple papers with the also influential Theodosius Dobzhansky. Sturtevant managed to unite the concept of a gene with the idea of a linear chromosome, which was essentially the first step towards sequencing a genome.

Most Important “Discovery” of the Late 20th Century: Whole genome sequencing’s not really a discovery, but it’s pretty damn important. It’s hard to give a single person credit for this; it really was the product of a merger between technology, biology, and business (for a good review, check out James Shreeve’s The Genome War). Craig Venter gets a lot of the credit for the shotgun approach to whole genome sequencing, but the actual algorithm was implemented by computer scientists who also had to the code all of the assembly algorithms that put together the genomic fragments. Of course, without the biotechnology industry, we never would have been able to generate reads at the high-throughput pace required for whole genome sequencing. You can point to the first shotgun sequenced genome, the first eukaryotic shotgun sequenced genome, or the human genome as the single paper to symbolize this innovation, and it would be hard to argue against any of them. The technology behind contemporary sequencing may be going by the wayside with even faster sequencing methods, but the concepts behind the shotgun approach are still quite important.

Biggest Technological Innovation: I’d group the Sanger sequencing method together with the Polymerase Chain Reaction (PCR) as a single technological innovation. (Should we include molecular cloning in here as well?) These innovations essentially paved the way for whole genome sequencing, and it’s hard to imagine one without the other (and it’s hard to imagine CSI without either of them). PCR allows us to amplify DNA, either randomly or focusing on a specific region, for further analysis. This comes in handy when working with small amounts of DNA or if we only want to look at certain sequences. It also allows us to build up enough DNA to implement the Sanger method of DNA sequencing, whereby one of the four nucleotides is used to terminate DNA polymerization. Kary Mullis’s Cold Spring Harbor Symposium contribution (the PCR paper) can be found here and the PubMed entry is here. Sanger’s publication is available here.

Others to Consider: Here are a few other important discoveries I considered, but did not write about because it would take forever to discuss everything I think of as important:

  • Microarrays: These are being used for more and more different things every month, from gene expression, to genotyping, to who know what’s next.
  • The Central Dogma of Molecular Biology: Beadle and Tatum earned a Nobel prize for the important discovery that genes encode proteins. This one is more of a discovery than most of the discoveries I discussed above, but I was running low on free time and didn’t want to write another entry filled with links (I could write about this stuff forever, and maybe I’ll write an entry on this later).
  • Dobzhansky’s Genetics of Natural Populations: One of the greatest collections of science, but I’m a bit biased. The whole collection is a great contribution to evolutionary genetics.
  • R.A. Fisher: Yes, I know that’s a person and not a discovery or idea, but the man was so influential within population genetics (and statistics) that he deserves mention.

Please leave any suggestions in the comments section. If you disagree with me, let me know why I’m wrong. But please beware, this list is biased toward genetics (especially evolutionary genetics and genomics), so any suggestions in these fields (or closely related disciplines) would be especially appreciated.

Comments

  1. #1 S. C. Hartman
    January 17, 2006

    The seminal event in molecular biology was the identification of the genetic material as a chemical substance, and specifically as DNA; hence, my nominees in this category are Avery, Macleod, & McCarty, and Hershey & Chase.

  2. #2 Paul Orwin
    January 17, 2006

    Ms. or Mr. Hartman beat me to it (I’d have picked Avery, Macleod and McCarty). Others in this vein include the obvious (Watson and Crick et al), the pretty obvious (Pauling, Chargaff), and the less obvious (Berg, for the demonstration of recombinant DNA, or Baltimore, retroviruses). Going beyond that, how about Barbara (?) McClintock for the discovery of transposons.

    Here’s a thought question – it seems that biology is less amenable to breakthrough experiments. My opinion (feel free to add adjectives like “arrogant” and “uninformed”) is that biology is orders of magnitude more complex than physics and chemistry (after all, biological systems are built from physics and chemistry parts), so the experiments necessary to figure it out are bigger, more complex, and more piecemeal. No one will figure out a general relativity for biology (although I suppose you could argue for natural selection as the general relativity of biology), or a quantum mechanics (although I suppose you could argue for the Central dogma of molbio as quantum mechanics for biology).

    Wonderful question to start the new blog off with, and much better than work!

    Interesting followup – what current research will be the basis for the next revolution in biology?

  3. #3 Mike the Mad Biologist
    January 17, 2006

    I’m not sure I agree with this myself, but I’ll put this out there for discussion: Kimura’s work on neutral theory. So much of pop gen and phylogenetics is built around this. I don’t think we would have anywhere near as good as handle on DNA sequence variation without him.

    Feel free to tell me why I’m wrong…

  4. #4 Chad Orzel
    January 17, 2006

    That’s great stuff, thanks. The only ones I would’ve guessed were Darwin and Mendel.

    (As an aside, I recall hearing that some people think Mendel fudged his results in a way that would be problematic these days. Is that accurate?)

    Paul Orwin: My opinion (feel free to add adjectives like “arrogant” and “uninformed”) is that biology is orders of magnitude more complex than physics and chemistry (after all, biological systems are built from physics and chemistry parts), so the experiments necessary to figure it out are bigger, more complex, and more piecemeal.

    General Relativity and Quantum Mechanics are both theories more theoretical achievements than experimental discoveries, though QM at least grew out of a number of fundamental experiments. But even by the time you get to Rutherford’s discovery of the nucleus, the great physics experiments are starting to be awfully complex and hard to figure out.

    You may be onto something here, though. There weren’t many people nominating particle physics experiments as the Greatest Ever when I asked, and the complexity may be an issue there. Most of the real classics have a sort of elegant simplicity.

    It’s an interesting question.

  5. #5 RPM
    January 17, 2006

    Kimura’s a good one, but we also need to credit King & Jukes for that one, and we should also mention Ohta for her contribution (the nearly neutral theory, which I think is far more important). That said, I don’t know whether the neutral theory deserves to be in the same class as these others “discoveries” (not at the same scope).

    I probably should have included one of the findings regarding the structure of DNA, but I’m not familiar with this field. Good suggestions, thanks.

    I really have nothing to say about the comparisons between biology and chemistry/physics. Ok, one thing: notice how your university has one chemistry department and one physics department, but a biochemistry department, biology department, and a bunch of other “life-sciences” departments. Interpret it as will.

  6. #6 Paul Orwin
    January 17, 2006

    Chad,
    You are quite right about GR and QM, obviously. What I meant (and didn’t really say) is that the fundamental theories are well studied. I put up some (obvious) suggestions for fundamental theories in biology that should and do lead to experiments. Nevertheless, it is harder, I think, to see an experiment in a single organism as fundamental because the tree of life is so full.

    I thought of another experiment (or a series of them). I had to look up the name of the experimenter (Nirenberg), but the discovery that UUU encodes phenylalanine, which lead to the deciphering of the genetic code (i.e. what triplets encode what a.a.’s), and also to figuring out the mechanisms of transcription and translation.

    One pt here is that there are, I think, lots and lots of nominees. Which goes back to my original pt, sort of. Any physics student will come up with Rutherford’s nucleus experiment, or the two-slit interference experiment, or the Michelson-Morley speed of light experiment (I hope I got all those right!), but if you picked a biochemist, a microbiologist, a developmental biologist, a geneticist, etc together, you’d probably get 10 different sets, with Darwin, Watson and Crick, and Mendel as the commonalities. Or maybe I’m wrong?

    How about Paul Ehrlich (the german immunologist)? Louis Pasteur? Robert Koch? etc etc etc Any one of us could go on and on, which I guess goes to the point of how amazingly fruitful biological sciences research has been in the last 150 or so years (physicists and chemists manage to do the odd interesting experiment as well :) )

  7. #7 razib
    January 17, 2006

    As an aside, I recall hearing that some people think Mendel fudged his results in a way that would be problematic these days. Is that accurate?

    he worked before Statistical Methods for Research Workers, The Design of Experiments by r.a. fisher, so give him a break :)

    paul

    1) are you blogging again?

    2) r.a. fisher, whose training was in statistical mechanics after his undergraduate degree in mathematics, once envisaged a ‘ideal gas law’ for the dynamics of gene frequencies (that is, the ascending of genetic frequencies up the adaptive landscape via gradual change toward fixation). that is the sort of grand theoretical framework which is common in the physical sciences. i don’t think that will happen in the near future in evolutionary biology, at least, because i think epistasis, wrinkly adaptive landscapes and the elusiveness of fitness is a lot more intractable of a ‘problem’ than fisher believed they were. but, i hope i’m wrong!!!

  8. #8 Paul Orwin
    January 18, 2006

    Razib,
    No, I’m not blogging again-I occasionally find something I want to say something about, but mostly people like PZ, Tara, Orak, etc say it better and faster (all while being more successful professionally than I, so there you go!). I still hang around and contribute, every so often.

    Your Fisher point brings up another interesting and counterintuitive idea – the math in biology is too hard! Not, I hasten to add, the straightforward stuff used in mol bio classes, entry level microbio, or statistics, but the math necessary to model biological systems, as we see in the nascent field of systems biology, is really, really tough. Thus, the following conundrum – pick an oversimplification of limited applicability, or an accurate depiction that is unsolvable. I’ve oversimplified the issue, but it’s definitely there. I say it is counterintuitive, because most people think of the rank order of mathiness as physics – chemistry – biology – social sciences. This is true in the sense that physicists use mathematical models most readily to describe their work, followed in order more or less by the others. However, the difficulty of the modeling problem is the inverse. Hope that makes sense! Cheers all

  9. #9 coturnix
    January 18, 2006

    I did not think the question was about great revolutionary discoveries, but great experiments. I would pick simple, chepa things that were creative at the time and resulted in change in the way we think about stuff.

    When Jacque Manceau de Mairan put the mimosa in the closet…
    When Darwin scraped the mud off of birds’ legs and planted the seeds from it…
    When Niko Tinbergen moved the pine-cones away from the wasp’s nest…
    When Ingeborg Beling (though her PI, Karl von Frish got the Nobel for it) placed dishes of sugar water for the bees at different times of day…
    When Knut Schmidt-Nielsen gave seabirds salt water to drink (and later kept a camel in the isolation chamber)…

    Those are the kinds of creative, thought-provoking, ground-breaking experiments that moved biology in quantum leaps. Techniques are fine, but they do nothing without creative individuals who think outside the box.

  10. #10 razib
    January 18, 2006

    paul, biology is big, huh? many molecular type people i run into are pretty inummerate cuz they can be (at least beyond basic arithmetic and algebra). it seems that some of the physiology and molecular development people use diff eq to model flow, etc. but some of the statistical genetics stuff is rather nasty (even some of the really interesting evo genetics stuff by h. allen horr requires a lot of math). but a physicist friend of mine recently said, ‘it doesn’t explore much of hilbert space’ (he’s getting into kimura and crow’s work). most people can get the gist with discrete different equations where the algebra isn’t very gnarly i think though. i think that the rank order is overall correct in terms of the mathiness of the fields, that is, physics – chemistry – biology – social sciences. but, though the expectation of mathiness does follow that order, i think that the variance is greatest in biology and the social sciences, as economics and quantitative genetics are rather mathematical, if not as wild as theoretical physics, at least as mathy as a lot of chemistry (and bio and organic don’t require a lot of math, at least to the level i’ve explored those fields). fisher and haldane were mathematically trained, j.m. smith had an engineering background, lewontin has a m.s. in mathematical statistics.

  11. #11 Paul Orwin
    January 18, 2006

    I’m sorry that this isn’t more clear. I’m not saying you need to be great at math to do biology (far from it!). I’m saying that to do the things equivalent to what has been done, for example, to understand the physics of particle accelerators, analogously to understand the biology of an ecosystem, requires math beyond most people’s ken (and indeed, beyond the ken of all the people you mentioned, and me, and you). Our understanding of ecosystems, or even of a single celled organism, is comparable (IMHO) to Newton’s understanding of the universe as a clockwork. Wonderful for “simple” problems, but falls apart on the toughies (some of which you and I and your former? counterparts at GNXP have discussed before :) ). I hope that makes sense. In some ways, (and this sounds very bad, i suspect), the math orientation of the sciences is the way it is because the math people can do is useful in simplified systems like physics experiments (sorry, Chad!), but not in the complex systems like organisms. I hope that makes more sense.

  12. #12 razib
    January 18, 2006

    yes paul, i took your point, but what do you suggest, back to aristotelian science by analogy? :) i look forward to the emergence of the AI gods, then we will see some real cogito, gods willing.

  13. #13 Paul Orwin
    January 18, 2006

    Not at all, not at all. I’m all for the pre-eminence of experiment. I am, in fact, a hard core experimentalist (I love the playing with theories and math concepts etc,but I don’t confuse it with science). (Yeah, I saw the smiley)

    My overall idea was simply to recognize that there is a funny inversion between the field that attracts the mathematically inclined (physics) and the field in which the math is most intractable (biology, or perhaps the social sciences). However, it is explainable by the fact that the math is useful in physics, whereas deep concepts in biology often represented allegorically or heuristically (exceptions abound, of course).

    BTW, if you read Wilson’s Consilience, that probably gets at my point better than I can. I don’t agree with everything he had to say, but it was an interesting read.

  14. #14 RPM
    January 18, 2006

    This is a bit off topic from Razib and Paul’s discussion, but back on topic with the original discussion. I’m looking back at the list, and I think we should consider the coalescent, for both the elegance of the model and the fruitful research it has spawned (for example, what would the HapMap analysis look like without coalscent theory?). Dick Hudson is considered “Mr. Coalescent”, but I don’t know if you can give credit to a single person. Needless to say, this was an extremely important development in population genetics theory.

    Maybe I should create a new list: greatest population genetics developments (they’re not really discoveries).