The Scientific Method?

August 29, 2010

This is very much on my mind lately as I start my first semester of an assistant professor-ship at a community college. This semester I am teaching 2 different introductory biology courses for non-majors and an important question is “what exactly do they NEED to know?”. Of course, covering your college’s curricula is a good start, but what do you do with The Scientific Method? Is it really so important that non-scientists be able to list each distilled “step” (and will they even remember them after the class?)? I show them (and test on) the standard minimalist list of steps (Observations, form a question, etc etc) and then tell them that this is a gross oversimplification and that, while it DOES happen at times it is embedded in a much much much larger and more complicated process. I then show one of the really complicated scientific method figures you can find on the internet that includes “collaboration”, “manuscript rejections”, “being scooped” and “blind stabs in the dark”. I then emphasize that the important part is that, when science is being done “at its best” (don’t ask me what I mean by this) the scientists are willing to give up what they know as “facts” if new observations pop up that contradict it. I said willing, not that they always do (or even should). The other thing I emphasize is the difference between hypothesis and theory, and how “theory” definitions outside of science differ from the formal scientific word. Any feedback/suggestions for how I should teach The Scientific Method – I mean aside from using the basso profundo echoing voice when I say it (they just LOVE that)? I was a researcher for almost 15 years, but its interesting how little researchers think about the process they are using while doing it.

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ATP is a molecule used by every cell known to temporarily store the energy derived from the food you eat. Just how temporary is my question.  The beauty of ATP is that it is a pretty high energy molecule, and most processes in cells that require energy get it from ATP.  So it connects the energy harvesting reactions of a cell to the energy spending ones.  The analogy I use while teaching is that its like the cash in my wallet.  I harvest money at work and spend money at stores, cash is the intermediary, and cash is not very stable in my wallet.  Its not a great analogy (especially because I don’t rip two-inches off of the bills while holding them really close to the register and I generally pay for everything with credit, which doesn’t fit into the analogy at all) but it works.

There are a lot of energy spending reactions, and most of the test tube reactions I have done in the lab require the addition of ATP (else your reaction will not go).  It comes as a white powder, and every researcher I have ever known considers it to be a very unstable molecule, meaning that it is a high enough energy molecule that it sort of just “falls apart”.  We keep it on ice, we freeze it in ultra cold freezers, instead of freezing 1 ml of it in one tube we break that 1ml into 10 tubes so as to avoid freeze/thawing it.  I had never thought about it too much, but had always considered ATP to be unstable and that made a certain amount of sense to me given its role as a temporary energy storage molecule (if it stored the energy stably, it would be hard to get the energy back out for the energy spending reactions).  But this isn’t the kind of thing that we measure, none of the labs I have worked in cared specifically about the stability of ATP so long as there was enough of it in your tube to make your reaction go.

This thinking has even leaked out during my teaching… I don’t remember, but I am fairly sure that I have told classes that ATP IS a very temporary place to store energy and that once the ATP is made, that it doesn’t last very long.  However I have never actually seen data that actually asks the question: “how long does a molecule of ATP last?”.  All compounds fall apart at some rate, some faster than others, but I had always assumed that ATP’s stability would be measured in hours, if not minutes.  Well, snake research to the rescue.

According to a 1997 study (1) looking at NTP levels (ATP is an NTP (there are three others, CTP, GTP and TTP) in snake red blood cells, you can leave ATP in a beaker for 24 hours with no drop in levels.  I am sure this is underwhelming to many many people, but to me its an important fact when thinking and teaching about cellular metabolism: if ATP is very unstable, then it can not be an energy storage molecule, if it IS truly that stable, then it can.  Probably in our mammalian cells this is never an issue – as endotherms we are constantly burning though energy to keep ourselves warm, but it COULD possibly be more of a real issue for ectotherms (which is to say, most animals (don’t be fooled, mammals are actually a very small subset of animals)).  As an ectotherm cools down, could its metabolism slow down to the point where it is actually relying on the “stability of ATP”??. Given the known ability of mitchondrial electron transport chains to generate free radicals, I would think that it would be advantageous to bank on ATPs stability in order to slow ETC as much as possible. Which naturally leads me to question: is there any indication that the mitochondrial genomes of ectotherms is LESS damaged than those of endotherms??

And yes, I know that a cell isn’t a beaker of buffer and that there are many ATPases in every cell just waiting to lay waste.  But come on, isn’t anyone else even a little bit surprised that ATP is THAT stable on its own?  How many times have YOU saved that tube of NTPs floating in your ice bucket the next morning?

1. Ingerman et al 1997 J. Exp Biol “Stability of nucleoside triphosphate levels in the red cells of the snake”

I am preparing for the transition to full time teaching and the jump to light speed that is involved in teaching a subject for the first time.  I find the light speed jump is eased somewhat by actually reading the textbook and taking notes, even though the annoying PhD part of my brain keeps spoiling the plot by completing the sentences before I finish reading them.  Sometimes though, that PhD part of my brain is wrong, and thats a big reason why I teach.  I also think better if I can either talk or walk, or talk and walk.  Since typing is a form of speech these days, I am probably going to be subjecting both readers (thanks Pete and whoever that other person is!) of this blog to a fair amount of  “thinking”.  If you stumbled on this because you saw me post it on Facebook and haven’t learned that both my writing and the subjects I choose to write on are nerdy and boring to all some most people (except Pete and that other person!), well, I just warned you.

Evolution is a really big thing when you are teaching Biology, both because it so obviously ties all life (I do mean all there) together and is as obvious as gravity, but also because there is quite a debate going on in our country about how we should talk about it to students.  At the moment, I am thinking about a statement in the textbook I am to teach from (I am intentionally not mentioning the subject or book, it really isn’t important):

“…eventually though, evolution selected the cell as the best structural solution for supporting the fundamental characteristics of life.”

While I do believe the data suggesting that self-replicating RNAs eventually became housed within a membrane (the first cell!), this statement has a couple of big problems.  First, evolution does not select anything.  Evolution is a word the describes a process. Evolution is the process of something changing.  A situation can evolve, a person can evolve, a hopelessly boring blog can evolve. Cooking is also a process, but cooking does not DO anything; it doesn’t select the ingredients, mix the ingredients, put the ingredients in the oven or prevent the kids from sticking their hands in the uncooked ingredients and then painting the walls with them.  Cooking is the term that describes the process.  Getting back to evolution, environments can select, diseases (which are technically a part of your environment) can select, even humans can select – but evolution does not.  If you think I am quibbling over terms, substitute the word “God” for “Evolution” in the above quote – it fits far to well. (thin ice! thin ice! move on Jeff, move on!).  Natural selection is what does the selection (and even that isn’t the only mechanism of evolution).  Simply put, ANY genetically determined feature in a population of organisms that results in more or less grandchildren in that population will over time result in that feature becoming more or less common in the individuals of that population.  Longer arms, shorter arms, extra arms, baldness, blue eyes, green eyes, one eyes – if even one individual in a population has one of these features (and the feature is genetically determined) and the feature affects, even indirectly, their ability to have babies, its a good bet that in a million years either everyone or no one in the population will have it.  Natural selection baby, along with genetic drift and gene flow its how our eyes got moved to the front of our skulls, how we started walking upright and lost our tails.

Second, to say that evolution results in the selection of  “the best” anything is dangerously close to being  flat wrong.  The misconception that evolution results in better and better solutions is extremely common when students walk into my classrooms (hopefully less so when they walk out), and its something that is far more problematic than than saying “evolution selected for a better phrase in this paragraph”.  To put it flatly, evolution not only doesn’t necessarily result in the best solution to a problem, like government work – “good enough” is all it can do.  Literally.  As a thought experiment, imagine a population of cheetahs and a population of penguins living in the African savanah.  The penguins obviously can not defend themselves well against the cheetahs (unless one of them is born with a claw on their wing (happens in other birds) and that armed penguin (there’s a pun there) successfully breeds) so they must run.  Imagine that these penguins can run fast, fast enough that 50% can outrun the cheetahs.  Now imagine that 10% of the penguins are faster runners (more fast twitch muscles, it happens in other species) and over millions of years, that 10% tends to get eaten less frequently, so the average speed of this penguin population increases.  For slower cheetahs, this could be the end.  As the average speed of the slowest penguin herd surpasses the top speed of the slowest cheetah, well, cheetah eats less, cheetah has less babies.  Over time, the cheetah herd’s average speed could increase as well.  But here is the important point: natural selection does not select the fastest cheetah – as long as a cheetah is fast enough to catch enough penguins so that it can have rock hard abs and impress the cheetah ladies, its fine.

Need a more concrete example?  Ok, off the top of my head, I pick male pattern baldness.  Given the amount of money spent* on keeping a man’s coiffure thick and luxurious, you would think that MPB (which is genetically determined), if given millions of years would gradually recede from the population.  However, my two healthy children at home give me a concrete reason to doubt that.

*Extra bonus points: how long would it take all of these creams, gels and plugs to remove male pattern baldness from the human population?  Assume that every male thinks this is important.

I will admit that I was taken in by the dramatic descriptions of the Ventner Insitute’s recent claims of having made “synthetic life”, but after reading the paper and then talking to people that are smarter than me (thanks Donna, Andrew) I have to say: this is a load of crap.  Impressive crap, but still crap.  I would love nothing better than to bore you with details of why (1) there is nothing synthetic about what they made and (2) they did not “reboot” anything.  Perhaps if enough of you hold your lighters in the night air I will.  For now, I think Jim Collins at Boston University says it best:

Frankly, scientists do not know enough about biology to create life. Although the Human Genome Project has expanded the parts list for cells, there is no instruction manual for putting them together to produce a living cell. It is like trying to assemble an operational jumbo jet from its parts list — impossible. Although some of us in synthetic biology may have delusions of grandeur, our goals are much more modest.

The organismMycoplasma mycoides

The disease:  Bovine pleuralpneumonia

Symptoms: respiratory distress, cough, cessation of rumination, anorexia, and severe pleuritic pain.  In cattle, buffalo and yaks.    How it works:  The genus mycoplasma contains many species, some that “infect” humans and cause disease.  So why am I writing about a bovine pathogen?  Primarily because scientists announced today (well, yesterday) that they made a “synthetic bacterial cell” and this is the species that whose DNA they used. It was manually copied, plunked into a dead cell from a different species and walah, that dead cell comes back to life as M. mycoides (que Vincent Price laughter).  I am waiting to read what smarter people say about this paper before I commit premature ejaculation, however I will say that this is big.  Huge.  Bigger than huge.  Secondarily, mycoplasma are fascinating because they have just about the smallest genome of any known living organism – to the point where they do not have the genes to make the four building blocks of DNA like every other cell can.

Where is it in your house: It probably isn’t.  But you might want to encourage the yaks in the back yard to cover there coughs.  Of the human-colonizing species: M. genitalium is, well, its all over your gentitalia.  M. orale is doing the breast stroke in all of our mouths (and ends up contaminating *many* laboratory cell cultures).

What you can do to protect yourself:  Don’t buy into what I predict will be histrionic responses of anti-science types about this “synthetic cell” being something to be worried about. Worry more about why I could probably find M. genitalium on the doorknobs in your house. And please, wash your hands.

Synthetic cell paper by Gibson et al.

A mycoplasma testing service

The organismToxoplasma gondii
The disease: Toxoplasmosis
Symptoms: Immunocompentent adults -some flu-like symptoms, possibly increased risk taking behavior, rarely schizophrenia.  Fetuses: hydrocephalus (“water on the brain”), inflammation of the retina, and later in life: blindness, deafness, mental retardation.
How it works:  T. gondii is a eukaryotic (meaning that genetically it is more related to us than to bacteria), single celled organism that appears to prefer infecting cats.  Because any one organism is guaranteed at some point to assume room temperature, T. gondii hitches a ride into the cat’s poop in a hardy spore-like form that can infect just about any mammal that ingests it, including us.  It appears to have a special liking for forming cysts in either skeletal muscle or brain.  Here is where it gets REALLY creepy. Once in the brain, T gondii can actually change that animal’s behavior (sound crazy? see here).  For instance, infected rodents are less fearful of cats.  Cat eats stupid/brave mouse and T. gondii has itself a new mobile home.  Studies have clearly shown that 15-40% of humans have been infected and that the bug does appear to change human behavior too.  Don’t believe it?  Google “Toxoplasma gondii and Schizophrenia”
Where is it in your house: Your cat, the catbox or anything that has touched your cat’s feces (water, the floor, your dog’s mouth etc) and potentially the meat in your refrigerator.  Given that so many people have clearly been infected, millions of new infections are probably happening every year, probably from infected farm animals.
What you can do to protect yourself:  Buy and learn how to correctly use a home irradiator for your food.  Short of that, cook your food well and keep pregnant mothers and babies away from cats and their end products.  Resist the temptation to rub catfood on yourself and lie down in front of your cat (but such a temptation suggests that its too late for you.)
Above all, please, wash your hands.

Toxoplasma entry at MicrobeWiki