Tuesday, March 15, 2011

Science without hypotheses? Not exactly penis-spine tingling

I’m still a bit bewildered after attending an afternoon of talks at the American Academy of Forensic Sciences (AAFS) conference held in Chicago a few weeks ago.

For one, I was stunned by the practical use of “mongoloid,” “caucasoid,” and “negroid” which I thought were long ago shelved as artifacts of physical anthropology’s racist past. But, whatever.

There was another surreal aspect to the meetings. I attended five talks and not one had a hypothesis. Based on these few talks, the conventional format appeared to be: Show photos of dead things. For example, even if the stated aim is to find anatomical indicators or predictors of intentional animal abuse, it was clear that one need not provide a single hypothesis and that one can conclude a slide show of dog strangulations and gunshot deaths with a simple, “animal abuse happens.” And if you thought it was impossible to make a disappointing presentation about a tiger attack, you’d have been as surprised as I was.

So instead of learning anything new about how forensic science is practiced, I discovered something (that I’d hardly thought about before) about how science is presented to the public.

Science without hypotheses is boring. Hypotheses aren’t just critical to the scientific method, they’re crucial for telling captivating and satisfying science stories to other humans.

Without hypotheses, there is no mystery and there is nothing for your audience to do.

Without hypotheses there’s no engagement—that thing that we strive so hard to foster in the classroom because we have good reason to believe that it’s correlated to learning success.

And outside the classroom, it’s clear that people really dig engagement. Why do you think people read The Da Vinci Code in one sitting from cover to cover?

Because it beckons the reader to solve the riddles and puzzles before turning the page!

This is what hypotheses do for presentations of scientific research.

And for scientists, there’s no need to concoct or conjure anything. Doing science is writing the mystery itself. No need to take a weekend seminar in suspense writing from Stephen King or to even call your hypotheses “foreshadowing.” Scientists, by the very nature of their work, have all the tools to build a good mystery. And this is how they should present their research to others.

Just lay out your process for the listeners/readers and let them anticipate what comes next. Let them mentally guess which hypotheses will be supported or not and then allow them to be surprised or vindicated by the results.

I offer you an example. I’ve written two blurbs about a recent paper in Nature. In the first blurb, I offer hypotheses and leading questions. In the second blurb I do no such thing. Which one is better?
Number 1: With hypotheses and leading questions
Did you know that humans not only have unique brains but unique penises as well?

Compared to chimpanzees, our closest relatives, and other mammals we have large brains for our body size and we also have no spines on our penises.

There must have been genetic mutations during our evolution that contributed to these traits. But what kinds of mutations were they and what kinds of genes were affected?

For the loss of penis spines here are just four hypotheses, phrased as questions:
(1) Are we missing genes that code for penis spines?
(2) Or are there penis spine-coding genes in our genome but they’re nonfunctional?
(3) Are we missing genes that are involved in regulating penis-spine-coding genes?
(4) Or are there regulatory genes for penis-spine development within our genome but they’re nonfunctional?

According to McLean et al., it’s hypothesis 3… sort of. It’s a bit more circumvented than that. Humans have a deletion of a highly conserved region in chimpanzees and other mammals that’s in a noncoding region near genes involved in steroid hormone signaling. The deletion removes a penile spine enhancer from the human androgen receptor (AR) gene, a molecular change correlated with anatomical loss of androgen-dependent penile spines in the human lineage.

Okay, then what about the brain? What kind of mutations could have caused it to increase in size?

Here are just four hypotheses, phrased as questions:
(1) Do humans have additional genes linked to brain development that chimpanzees don’t have?
(2) Do we have mutated regulatory genes that supercharge our brain growth genes?
(3) Do we have mutated genes that code for growth hormones that affect brain growth uniquely in us?
(4) Are the regulatory genes for those growth hormone genes different in humans compared to chimps?

According to McLean et al., it’s none of these hypotheses! It’s actually another deletion, if you can believe that. A deletion that leads to more brains? Yep.

Humans have a deletion of a highly conserved region in chimpanzees and other mammals that’s in a non-coding region near genes involved in neural function. The deletion “removes a forebrain subventricular zone enhancer near the tumor suppressor gene growth arrest and DNA-damage inducible, gamma (GADD45G), a loss correlated with expansion of specific brain regions in humans.” In other words, the deletion removes something that inhibits growth.

And why put these two discoveries, one about penises and one about brains, in the same paper?

[Insert your favorite _______-head joke here.]

First of all, as you probably gathered by now, both discoveries are dealing with deletions. The team identified 510 of these in humans. They saw these deletions as hypothetical fertile ground for human-specific traits. And almost all of these deletions occur in non-coding regions and are “enriched” near genes involved in steroid hormone signaling (penis spines) and neural function (brain size). As they say in the abstract,
“Deletions of tissue-specific enhancers may thus accompany both loss and gain traits in the human lineage, and provide specific examples of the kinds of regulatory alterations– and inactivation events long proposed to have an important role in human evolutionary divergence.”
Also, both discoveries about brains and penises were achieved through the use of similar methods. Beyond the fancy computing and statistical techniques used to identify the deletions as candidates in the first place, both the brain and the penis stories required mouse embryos to check to see what these deletions do during development. According to the paper, the experiments with the mouse embryos supported these deletions as influencing the loss of penis spines and the enhancement of brain size (e.g. cortical expansion) in humans.

And there are further questions too. Most things we know about the genetics of the development of our bodies indicate that the genes are pleiotropic, meaning they are involved in more than one process. So did the loss of penis spines during development coincide with the loss of anything else? If so, what could that thing be? Something else to do with the penis? Something else to do with male-specific traits? Something that affects female reproductive organs?

It turns out, the same deletion that’s linked to loss of penis spines is linked to loss of whiskers (or “sensory vibrissae”). And it makes sense given that the development of both are dependent on androgen and the deletion has to do with androgen.

Okay, though. Which is it? Did natural selection prefer hominin males without penis spines? Or did natural selection prefer hominin males (or females) without whiskers? The latter seems silly. Why would natural selection favor the loss of something that provides sensory information to an organism?

It seems more likely that natural selection would favor the loss of penis spines and that whiskers were lost as collateral damage. But penis spines may be useful for scrubbing out a rival male’s sperm while inserting one’s own, right? So, again, why would natural selection favor the loss of such a seemingly useful trait as that? Hmmm? How could one survive and reproduce if you’ve lost the ability to scrub out unwanted semen to make room for your own swimmers? The environment would have to change. And the environment is not just trees and grasses, it’s also others within your own species.

Are you thinking what I’m thinking? Male-male competition changed. That’s where the authors go. Here’s how they explain the evolutionary loss of penis spines. (Heavily citing Dixson’s 1998 book Primate Sexuality and also citing Lovejoy’s 2009 piece at the end of Ardi’s special issue in Science.)
“Simplified penile morphology tends to be associated with monogamous reproductive strategies in primates. Ablation of spines decreases tactile sensitivity and increases the duration of intromission, indicating their loss in the human lineage may be associated with the longer duration of copulation in our species relative to chimpanzees. This fits with an adaptive suite, including feminization of the male canine dentition, moderate sized testes with low sperm motility, and concealed ovulation with permanently enlarged mammary glands, that suggests our ancestors evolved numerous morphological characteristics associated with pair-bonding and increased paternal care.”
So the loss of penis spines makes intercourse take longer which is better for bonding a male and a female together emotionally and that sort of bond helps them work together better to raise big, helpless, slow-growing offspring.

All right.

(But but but… what if extending the duration of intercourse is just another type of male-male competition? You monopolize a lady so long that other guys can’t have their chance. But I digress…Also, spineless (actually, "simplified") penises are linked to monogamy, but is duration of intercourse positively correlated with pair-bonding behavior as well? I think there are data for this...Again, I digress...)

But then they conclude…
“We cannot exclude the possibility that loss of AR and GADD45G enhancers has occurred because of relaxed selection following other genetic changes that have led to anatomical differences in the human lineage. However, based on the previously established role of AR in vibrissae and penile spine development, and of GADD45G in negative regulation of tissue proliferation, we think it probable that deletions of tissue-specific enhancers in these genes have contributed to both loss and expansion of particular tissues during human evolution.”
If you're like me, you're wondering, What other human-specific traits could be influenced by deletions in our genome? This is fun.

And this notion of adaptive deletion leading to brain expansion conjures up thoughts of this recent paper: "EXPERIMENTAL EVOLUTION, LOSS-OF-FUNCTION MUTATIONS, AND “THE FIRST RULE OF ADAPTIVE EVOLUTION.

Number 2: Without hypotheses
There are numerous deleted regions in the human genome that are conserved (i.e. not deleted) in chimps and other mammals. One such deletion is involved in the loss of whiskers and penis spines. Another such deletion is involved in the development of our large brain. In conclusion, genes were altered during human evolutionary history that affected human-specific brain size increase and the loss of whiskers and penis spines.

I can’t even bring myself to fill in the details in that second piece because it's so boring.

When scientists are speaking to a room of colleagues at a professional meeting (like at the AAFS), their hypotheses are well-understood by most listeners and will probably continue to be jettisoned from time-constrained talks. The same thing happens in page-limited publications, where hypotheses are often banished to the supplemental materials. The problem with all of this is that stating the hypotheses actually strengthens your study.

When scientists are presenting their research to broader audiences, leaving out the hypotheses is the biggest mistake they can make. Good teachers know that formulating and testing hypotheses are some of our strongest tools for student engagement. And good science writers, like Carl Zimmer, get this too and they write tantalizing yet responsible pieces.

There’s no harm in spicing up the presentation of your research with the thoughts and processes you’ve already gone through while you did your research in the first place! You really can make whatever it is that you do into a good story for the rest of us.

Scientific literacy—that thing we all want our students and neighbors to achieve—is not just about numeracy and rote memorization. It’s literally about literary literacy too… about stimulating the literature-lovers in us all.

So go ahead and tingle our spines, Scientists.

It’s not that hard.

(That’s what she said.)


Ken Weiss said...

Or maybe it didn't matter for either trait, so the lost enhancer was just lost and those who carried the mutation had no disadvantage (or some other advantage not yet known).

The problem with juicing up science stories is that the facts tend to be left behind as the titillation is stressed, and it can lead to too-easy acceptance of Just-So stories.

Often, what go as 'hypotheses' are just wild-guesses, and to me therein lies the problem. It should be fine to label such ideas as 'one can speculate that....', but even then our society tends to ignore the caveat and treat the ideas as having much more specific support than they actually do.

But making a story about a tiger ravaging some young damsel boring, that takes even _more_ skill, perhaps....

Holly Dunsworth said...

Ken, I quoted a passage from McLean at all that offers what you say in your first paragraph. (it's near the end of Number 1, above).

And I had a hunchpothesis that you'd take issue with my post today!! :)

Holly Dunsworth said...

I'm really truly referring to the actual hypotheses being tested in the research. That's what I want to see and that's what I believe spices up science presentation...

I'm NOT referring (at least not primarily) to the kinds of hypotheses that you're referring to, like their explanation for why humans lost penis spines. That's not a hypothesis that's being tested in their study.

Ken Weiss said...

Well, Holly, I think taking issue is a bit strong, but I would say that responsible speculation--that heeds what is known about evolution--is what's missing.

There are so many alternatives and obvious questions. You touched on a few. If big or 'hard working' organs (at either end) are important in humans for the reasons you mention, it seems very forced (to me) to argue that they would not be similarly important in many other species. This raises the question of our tendency to invoke human exceptionalism.

I know I tend to be a spoil-sport, but the integrity of science is important to guard. The issues are not at all new: showman-science goes back at least to the Enlightenment. Even at the time, Galileo published in Italian rather than Latin. He learned of telescopes when the early models were being used as toys in Holland. Boyle, Edison, and others I forget went around giving science shows, often for self-promotion.

On the other hand, this leads, in my view, to hyper-determinism and when that is mixed with evolution, you get eugenics. That is my main concern, and history shows it's not exaggerated.

History, being last November, for example, when the 91 year old just elected to the New Hampshire legislature argued that the weak and defective should be dispensed with because they're a burden on society: that is exactly the argument that fed the eugenics movement and, quite explicitly, the Nazi's.

So, it's not all just good clean fun, and all size-matters innuendos aside, there are legitimate reasons to be a stuffed...shirt.

Ken Weiss said...

The more serious and (to me) legitimate issues are the way in which relatively rapid evolution of seemingly complex traits can occur. Getting rid of penis spines may be simple, but what about not just bigger brains but 'smarter' ones... or is just bigger all it took for us?

In the early '70s King and Wilson argued, basically on principle (no data) that regulation rather than new construction would be responsible for things like human-chimp differences. Maynard Olsen in the genome-sequence age (about, say, 10 years ago) once said to me (maybe he published this, too, I can't recall but if he did it would likely have been in PNAS), that gene inactivation was likely to be responsible.

The underlying reason is that making up a new trait by having to assemble a bunch of new genes is very unlikely to explain major, rapid changes. Even then, it would almost have to be in some small, local population and almost impossible for us to reconstruct in terms of the proximate causes.

More likely is just knock out a gene or a context of its expression, and if it has a major effect, then selection could quickly favor it.

But even in that case, all other variation that affects the trait---and there's almost always a lot of it, as experimental breeding has clearly shown--will also be favored. But most of the genes involved will have so little individual impact as to be undetectable (see my comments about this in Evol. Anth. a couple of issues ago).

The simple-hypothesis hunters see the one or few genes that have a detectably strong effect, and make Big Stories out of that. But this could be a statistical artifact of the way selection works.

These issues are separate from ones like pleiotropy, drift, and so on.

I'm working on some simulations to try to show these things, but haven't got anything specific to cite at the moment. But I believe we will come to realize that they are relevant.

But the hunger for juicy stories won't stop wild hypothesizing even then, I predict.

Holly Dunsworth said...

Just in case any readers are totally confused.

(I'm sorry if my post was confusing.)

There actually are scientists out there who leave their hypotheses out of proposals, papers, articles, and presentations. I'm talking about the actual hypotheses that they're testing with their research.

And I think that's a mistake on many levels. Emphasized here is on the level of engagement with the public that's compromised if hypotheses are ignored.

I used the McLean et al article (on penis spines, whiskers, and brain size) as a tool to help illustrate two different ways of presenting research. I couldn't help but talk about the "why" for penis spine loss (as they did in their paper), but it's not directly to do with the point of my post. Also, I am not a geneticist (like Ken is), so I could not (and did not aim to) critique their methods in determining that the deletions were linked to these human-specific traits. And I didn't even attempt to touch on just how big or small the effects of these deletions are.

My point was to show how stating some hypotheses (from my imagination: see where I listed 4 items) makes a more engaging report than one without hypotheses.

And I thought that using a recent and interesting article was a great tool for that.

Ken Weiss said...

Yes, and you did a good job of it!