Just like last week, I have scheduled this post to appear at the time when I am actually teaching this very lab again. If there are any notable difference, I’ll let you know in the afternoon.
When teaching the lecture portion of the course, I naturally have to prepare the lectures in advance, and each lecture has to cover a particular topic. This makes biology somewhat fragmentary and I try to use various strategies to connect one lecture to another, one topic to another, one area of biology to another, and especially each area of biology to evolution, as it is the unifying principle of all biology. As I have written before, I often use diseases, especially my favourite (what – you don’t have a favourite disease?) – malaria.
On the other hand, teaching the lab is a great opportunity to introduce mini-lectures that appear almost like streams of consciousness, touching on several different topics in succession, veering off on tangents, yet actually serving as unifiers – demonstrating how evolution, ecology, physiology, behavior, genetics etc. are all connected. Teaching adults makes this even easier because they do not expect me to be a Perfect Human Being, and are capable of laughing with me. I can also use more real-life examples and they are not squeamish to talk or hear about sex.
In my lab yesterday, I did something like that. But I had a great starting point – the jigsaw puzzle excercise that I have described before here (also here, and check a long discussion thread here). I kept talking on and on and on. Here is, roughly, what I said and what the students said:
“A-ha, I see what all of you are doing first – turning all the pieces right side up. You know that each piece has a dull grey side and a colorful side. You also know that the colorful side is much more informative than the grey side. The grey side gives you only the information about shape, and even that only as a mirror image, while the other side also gives you information about color and pattern. You knew to do this because this is not, for any of you, a new excercise. You’ve all done jigsaw puzzles when you were kids and now you are doing them again with your own kids. This, as far as solving puzzles, gives you experience and prior knowledge. If you think of science, this is an equavalent of 6 or 8 or 10 years of grad school. You have background knowledge, you have experience, and you have perfected the use of the puzzle-piece-flipping technique. It is like being really good at using a microsope, something that you learned last week and will again use later today.
So, what are you doing first? Looking at the pieces – that is observation. You still have absolutely no idea what the Big Picture is going to be, but you are looking for a good starting point, so you are soaking in all the information that you can glean from all the jumbled pieces on the table. So you are taking prior knowledge and using it to make sense of observed phenomena.
What are you doing next? You are trying to put some pieces together. Those are experiments. Every time you pick up two pieces and try to put them together you are testing a hypothesis – that the two pieces will fit. Most of the time your experiment fails at the first try, so you try again by rotating the pieces a little bit at a time and trying again. If it does not work, you drop the pieces and leave them for later, as obviously you need additional information. If it works, you publish your findings in a scientific journal and move on to the next hypothesis.
I see that different people have different approaches. Some look for edge pieces and try to put them together. Others are looking for any two pieces that may have shape, color and pattern similar enough that they may fit together, yet others are looking for key pieces – those with most interesting pieces of information, like an eye or a nose.
This is just like personal styles of different scientists. Some start with easily gleaned information – the edges – and systematically build on it, piece by piece. They know that this approach is slow and tedious, but will certainly, over time, build the whole picture. Others do something more risky – go for the most interesting information although it is difficult to study it or to place it in a broader context. They are more likely to fail, but if they get it right, the returns on the investment are enormous – they have figured out what the big picture is going to be without doing all the detailed boring work.
Does anyone already know what the big picture is going to be? No? Any hints and hunches so far? Perhaps a chicken over here, but you are not sure. So, this is still a hypothesis and not yet a theory. The same here with deer? OK.
Do you ever try to force a piece in its place although it does not fit and keep it there?
A-ha. But later, once you find the correct piece that fits there, will you stubbornly resist removing the right piece?
No, I’d replace it.
Good. That is just like scientists work. Sometimes you tentatively accept wrong data because they serve as place-holders – they help drive the future research. And although everyone is aware that the data are flawed, everyone tolerates it until better data come along.
We seem to be missing a piece!
A corner piece. Actually, all corner pieces.
Good. It took you about 10 minutes to discover that. I guess there was nobody here who always starts a jigsaw puzzle by looking for corner pieces. Do you really need the corner pieces in order to figure out what the big picture is?
No, not really…
Correct, the key information is unlikely to be at the periphery. But, you are humans, so it drives you nuts that the corner pieces are missing, so here they are – you can have them.
But, those are not our corner pieces they are theirs!
That’s fine. I made sure when I bought the puzzles that the pieces have exactly the same shapes. You can use the wrong corner pieces as place-holders. They fit by shape, although they do not fit by color and pattern. By putting them in, it can help you add a couple of more pieces together. But in the end, you will not be happy with semi-correct data and will put a lot of effort into solving that problem. Perhaps, as science is collaborative, international, and does not recognize borders, you can negotiate with the other group to exchange the corner pieces later on in order to get a more perfect picture. It is like sharing data or sending each other laboratory reagents, or publishing all your findings in reputable journals for all to see.
In the same vein, I could have ruined some pieces by removing the colorful top layer. You would have only shape to work with as there is no more color or pattern to it. You would still be able to fit it into the puzzle and although it may look ugly and incomplete, it would help you build the rest of the puzzle by adding more pieces to it, and it is unlikely to affect the Big Picture. This is equivalent of incomplete data. You can reconstruct a piece of history from an ancient manuscript although it is partially burned. You can reconstruct the evolutionary history of a particular group of organisms by working with an incomplete fossil record – after all, there are other puzzle-pieces supporting your theory, for instance the data from genetics, embryology, comparative anatomy and physiology, etc.
Any ideas yet what the big picture is going to be?
We are going to have a bird – not the chicken as we first thought, but more something like a duck, as well as a cat, we think…
We thought at first it was going to be a deer, then we thought for a while that it was going to be a squirrel, now we are back to deer.
OK, so you have changed your minds over time. How easy or hard was it for you to change your minds?
Good. So, you did not have a great emotional need to stick to your first guess and, once new information came in – when you placed a number of new pieces, you adapted your thinking to fit the new information. How sure you are that it is going to be a deer? Or a cat and a duck?
100%? Do you think it is possible that you may change your mind again as you place more and more pieces.
Perhaps, but unlikely.
OK, so now you have moved from the hypothesis stage to the theory stage. You are quite confident that you have a correct solution for the whole puzzle, although you are still missing many, many pieces and some modifications of the theory are still possible without changing the main gist of things.
Ha! Now this was interesting! You just put together an eye piece together with a nose piece and both to a group of green grass edge pieces. This is a relatively small amount of work: just two pieces being put together and placed in the context of the whole theory, but it is huge in terms of information content. This is something you would publish in a major journal, like Science or Nature or Journal of American Medical Association. On the other hand all those green edge pieces, as many as you have already put together after a lot of tedious work, as important they are for building the whole picture, are just not that interesting – they say little about the Big Picture or if your theory is correct. That is kind of stuff you would publish in the American Journal of Green-Grass Jigsaw-Puzzle Research – a lower-tier journal for sure.
Putting together pieces that fit well with your theory is sometimes called “normal science”. Putting in the pieces that result in your changing your mind on what the Big Picture is going to be is sometimes called a “paradigm shift”. So, you work within a paradigm that it is a squirrel and keep looking for pieces that have squirrel-like properties and putting them in, until you run out of such pieces and it looks less and less likely that it is a squirrel. Then, you find a couple of pieces that persuade you that you were wrong and that the Big Picture is the deer. You have experienced a paradigm shift, and now you are going to do some normal science within the new paradigm – adding more and more pieces with the assumption that it is going to turn out to be a deer.
We have a paradigm shift right now! It is not an adult deer but a fawn!
Great. It is a pretty big change. Although a fawn is technically a deer, there is a difference that is important in the description of your theory. You are now going to call it the Fawn Theory instead of The Grand Theory of Deer. Sometimes theory changes a lot, sometimes a little. Even if you think that the piece that will fill this hole is going to be just grass, if it turns out that it also contains a little flower, this is change in the theory. It does not overturn the whole theory – it is still going to be a fawn, but it will be a change in details. It is like adding sexual selection and neutral selection to the natural selection – the theory of evolution is not overturned – it just gets more detail and sophistication.
How about now? Do you think there is a possibility that adding another few pieces can make you completely change your mind on what the Big Picture will be? No? You are completely sure that you are correct although so many pieces are still missing from the puzzle? You would place it at 100% now? Yes? OK. But you, if you were a scientist, would never say that out loud, because, technically, this may happen no matter how sure you are. In well-supported theories, like relativity, plate-tectonics or evolution, chances of overturning the whole theory are practically zero, but it is considered bad form, philosophically incorrect, to state that a theory is Truth with capital T. Every new piece of the puzzle just confirms that all of life on Earth evolved out of a single common ancestor. Every new piece confirms that natural selection is the major mechanism of evolutionary change. Not a single piece of new information is at odds with those notions and have not been for the past 150 years of thousands and thousands of scientists looking really hard.
It is not one fawn – we have two! It was kinda hidden in one of the corners so we missed it at first.
Great. So, you get to keep the original theory of the fawn and get to add a second fawn. It is like keeping natural selection but adding sexual selection into the theory, something that Darwin himself did a couple of decades after he published the Origin of Species.
OK, how much your understanding of the whole picture changed since you just started the puzzle? A lot? Well, the science changes the same way. Theory of evolution from 1860s is not the same as the theory of evolution in 1900s, or the theory of evolution of 1940s, or 1960s, or today. We cannot use Origin of Species as a textbook today because so many details are different. Darwin got many details wrong, and in cases in which he got things correctly, he did not have much supporting evidence – his puzzle was based on too few puzzle pieces which we now have. But what Darwin got right was the Big Picture. He said it was going to be a Duck and the Cat and we still agree that it is a Duck and a Cat, although we now also known which flowers are growing around them and that the cat is very young and grey and looks like it may be an Abyssinian and the duck is also very young – just a duckling really and it is yellow and really cute. Darwin was right, but our knowledge is much more complete.
Also, if I was going to be really mean to you I would have also removed all the edge pieces. That way, you can never finish your puzzles, just like the work of science is never finished – there are always more details to uncover and more hypotheses to be tested. Also, no scientific theory lives in isolation. If I left the edges out, you would be able to connect one whole puzzle to the next puzzle to the next puzzle. A century or two ago, it was easy to ditinsguish what was biology, what was astronomy, what was physics, or chemistry or geology. Today, we know so much, the borders between disciplines are blurred. We have physical chemistry connecting physics and chemistry, biochemistry spanning biology and chemistry, biophysics in-between biology and physics – it’s all connected. Not to mention how much one field uses the techniques developed by another field or is based on the knowledge developed by another field.
Now quit doing the puzzle.
What? Why groaning? I bet if I asked you 15 minutes ago you would have had no problem quitting. You, just like all scientists, are kids at heart. At the beginning you may have wondered what on earth are we doing playing jigsaw puzzles in college, but now you really like doing it. Fine, you may continue and finish the puzzles. Happy? Just like scientists, more you know about something, more you want to know. It is so hard to get scientists to retire – many work until the day they die. There is always another experiment to do, another hypothesis to test, another piece of information to collect. More you know, more you realize how much more there is to know, and more you want to learn more. It is a positive feedback loop…wait, do you remember what a positive feedback loop is? You all have had lecture portion of the course at some point in your careers. Can anyone give me an example of a positive feedback loop from human physiology – the way the human body works?
When you cut yourself, the way the blood clots and makes a scar.
Excellent, that is a very good example. The cut makes a molecule act on another molecule which energizes another molecule and that molecule may recruit more copies of the first molecule so the whole process works faster and faster over time. Let’s make a more general description of a positive feedback loop. A process A triggers a process B which, in turn, triggers process A again. Moreover, it multiplies over time as A may trigger 10 instances of process B which in turn trigger 10 instances of process A each, so very soon you have both processes happening thousands of places simultaneously. Does anyone know any other examples of positive feedback loops in the human body?
OK, here’s one. Breast-feeding. You all have children so you should know this one. When a baby is hungry it latches onto the nipple. There are receptors in the nipple that sense that and send a signal to the brain – more specifically the part of the brain that you may remember from the lectures called the posterior pituitary gland – which secretes a hormone called oxytocin – no, not Oxycontin, that is what Limbaugh is taking. Oxytocin makes the milk glands eject milk. The baby gets the milk and is prompted to suckle on the nipple some more which releases more oxytocin which releases more milk which makes the baby suckle more etc etc the process reinforces itself until the baby is not hungry any more and quits eating. How about another example? Also has to do with babies?
OK, giving birth is a positive feedback loop, too. When the baby is ready to be born it signals the mother, which makes the uterus contracts. At that moment you know the baby is coming that day and you get in the car and go to the hospital. That first contraction of the uterus pushes the baby down a little bit. That movement stretches the uterus a little which results in release of more, again, oxytocin, which makes uterus contract again, which pushes the baby a little bit more out, which stretches the uterus more, which tirggers release of more oxytocin, which makes the uterus contract again….over and over again, faster and faster, until the baby is completely out. Good, how about another example? It also has to do something with babies. Anyone? Come on – you all have children – you should all know this outside of biology class, just from real life!
[eyes glazed over]
OK, here it is. It is making babies. Sex is a positive feedback loop. Just like doing the puzzle, it is easy to stop at the beginning, and much harder farther along you go. More you do it, more you want to do it and faster you go, until the orgasm in the end.
All right. Right off the top of my head I cannot think of another example of a positive feedback loop in the human physiology. Those are really rare. Most of the events are negative feedback loops. Can anyone give me an example?
Walking. It is loosing and regaining balance. You lean forward and you catch yourself from falling by stepping out.
Good. That is a pretty good example. Pretty much every time something goes away from the optimum, there are mechanisms that bring it back to the optimum. Put more formally, an event A triggers an event B which supresses the event A. For instance, if a hormone surges, there will be mechanisms that inhibit further synthesis and release of that hormone.
This whole concept of negative feedbcak loops keeping everything in the body at an optimum is called homeostasis and it can be depicted like this:
Let’s say you exercise or go out in the hot sun. Your body temperature rises. As a response, you start sweating, perhaps lower your metabolic rate, there are changes on the sub-cellular level that we will discuss next week, you wil also try to find a shade and drink something cold. Thus, there are biochemical, physiological and behavioral mechanisms that will drive your elevated body temperature back towards its normal level. Likewise, if you go out in the cold and your temperature starts dropping, your metabolism gets cranked up, you shiver, you put on more clothes, go inside, light up the fireplace and drink hot chocolate – again biochemical, physiological and behavioral mechanisms that will drive the temperature back up to the optimum level.
Now, all this is correct, but this graph is correct only if the X-axis spans time in the range of minutes, e.g., from 0 to 60 minutes for the whole length of the graph. How does it look like if the X-axis spans 24 hours? It looks more like this:
This does not mean that homeostatic mechanisms do not work very well – they do. It just shows that the optimal values – those defended by the homeostatic mechanisms – are not static. They are dynamic. They change predictably over the course of the day. For instance, your body temperature is lowest just before dawn and highest in late afternoon. On the other hand your cortisol levels in the blood are the highest early in the morning, preparing your body to wake up and seize the day! This controlled dynamic change in optimal values is called rheostasis. The daily rhythms are called circadian rhythms and there is a small area at the bottom of the brain which contains a few thousand brain cells that act as a clock, a circadian clock, which acts a relay – telling other parts of the brain and other parts of the body when – over the course of a single day – to raise and when to drop the optimal values of whatever processes they govern.
[Update: Here I spent some more time describing two functions that do not show rhythms – blood levels of Calcium are constant and blood pH is constant because the optimal values have an extremely narrow range. I talked about parathormone here, etc.]
Let’s take a break now. Please break down the puzzles and put them in these boxes here. By the time we come back, the slides you prepared first thing this morning will be dry and we can stain the bacteria and look at them under the microscope. This is obviously not hypothesis-testing. You are just learning a technique – how to flip the puzzle-pieces right side up so you can make observation of shapes, colors and patterns of…bacteria. Once you know how to do it, you can go on and make your own further obeservations and make predictions and test hypotheses. We’ll do that, too. You will press your thumbs on the agarose in these petri dishes that I poured this morning and next week we are going to see what kinds of critters live on your fingers.
Finally, at the end today, we are going to dissect owl pellets. By using the charts I give you, you will try to figure out which pellet comes from a Northwestern owl and which one from a Southeastern owl. Your homework will be to explain the results and the methodology you used to figure it out and then, next week, we will talk about this some more.”
And that is what we did. Wow – what a roller-coaster. From philosophy and sociology of science (no need to critique Kuhn at that level of instruction), through various areas of physiology to circadian rhythms, just to be continued with some microbiology and ecology in the second half of the lab. This is so much fun!