Integrators! Mount Up

Editor in Chief at BioEssays, Andrew Moore, recently called for greater recognition of what he calls "integrators."

These are scientists who earn fewer grants, churn out fewer results, and publish fewer papers than their peers. Instead, they synthesize and contextualize the work of others, often with a cross-disciplinary perspective, and often coming up with new tunes of their own.

Both kinds of contributions are crucial but the former tend to earn higher scientific regard than the latter. Moore asks us to drop this bias against this second level of analysis. No matter what it looks like, integrators are creators too and they're not taking the easy way out either.

Plus, as data and results pile up--as it becomes increasingly impossible to keep up in lock step with the output of highly specialized fields and for specialists to keep up with what others are doing--integrators are needed more than ever.

But they can't be any geeks off the street; Moore suggests that universities take an active role in training integrators. Perhaps anyone interested in training integrators should look to their local anthropology department. There, they might find some nice role models because of the cross-disciplinary, context-aware, and synthetic nature of the research.

A new curriculum for Introduction to Biological Anthropology

A naturalist’s approach in the molecular age

[Update June 11, 2014: Here's how far this project has come.]

Brief Description

This is a curriculum that teaches introductory human origins and evolution the same way that humankind came to understand it-- from a naturalist’s perspective. This framework has historically worked quite well (witness Charles Darwin), yet it’s foreign to many undergraduate students who feel removed from nature. 

Background and Rationale

This spring 2012 semester marks about the 12^th time that I’ve taught Introduction to Biological Anthropology (which is called APG 201: Human Origins where I am now).

For my first stint, I did my best to ape Jeffrey Kurland’s Penn State course because I had TA’d for him in grad school and he was phenomenal. This also means that I ripped-off various activities that TAs had developed and contributed to the curriculum over the years. I was also heavily influenced by Susan Anton’s late 90s version that I experienced while an undergraduate at UF.   But ever since then my course has gradually developed its own distinct flavor and I’m now at the point where it looks so different from its ancestors that even Milford Wolpoff might consider it a separate species. (To the uninitiated, welcome to bioanth humor.)

The changes I’ve made are due in no small part to new findings in genetics, primatology, paleontology, biology, forensics, archaeology, etc. that constantly accumulate. 

But mostly I’ll blame the changes I’ve made on a complete shift in pedagogical perspective thanks to finally identifying my two biggest teaching goals:

(1) Students should get as strong a handle on evolution as possible, shedding as many misconceptions as possible, so that they can best comprehend the biological, ecological, and cultural significance of human variation and evolution.

(2)  Students should achieve as much of this evolutionary understanding on their own as possible, by thinking creatively, synthetically, and critically about the evidence.

Number one means that I probably take more time with evolutionary theory  than most of my colleagues. But because this course is the only college-level exposure to evolution (let alone biology) that many undergraduates have, it’s important that it's strong. Once they’re out your door, they’re consuming, producing, and voting based in no small part on their understanding of their place in nature and their (and others') place in the human species. This one chance that we get to represent evolutionary theory and human ecology and biology is crucial make-or-break time for us biological anthropology professors.

Number two means that I have to deviate pretty far from the conventional format for this course, which plays out exactly the same way in all the textbooks. 

Here's why. My best guess for how to get students to achieve number two is to lead them through the steps that have worked for naturalists through history. This means having students walk in Darwin’s shoes (wearing modern science's goggles and gloves, of course). A lot of evolutionary evidence is plainly obvious if you just look around and read up on things like Darwin did. No need for fancy protein-coding machinery that students would be lucky to use if they got into the right grad school, let alone if they go work in a cubicle after graduation. What’s more, a lot of the biology and ecology (variation, heredity, inter-connectedness of all things) that was once obvious to so many people because they grew their own food in their backyard is now far from obvious to students who only grow their waistlines at Taco Bell.  I want students to see it for themselves because, while it engages them in higher level thinking, it is just so satisfying to discover things about the world. Why take that pleasure away from students?

Unfortunately, that's what all the mainstream textbooks in introductory biological anthropology do. Every single one begins the course by spoon-feeding the students evolutionary theory and smacking them in the face with molecular and cellular processes, hardly any of which have been specifically identified to be causally linked to the locomotor, dietary, cognitive and social traits that are the foci of subsequent chapters. [See Jurmain et al. (Cengage), Boyd and Silk (WW Norton and Co.),  Park ( McGraw Hill), Larsen (WW Norton and Co), Relethford (McGraw Will), Stanford et al. (Pearson)] 

For the most part, the popular textbooks present the material as a tour of what biological anthropologists do. But why do this to hundreds of students a year who aren't going to be biological anthropologists? Those students are, however, going to continue to be humans. So while the content is very important, it's just the presentation that's off.

Frontloading the course with complex theory and molecular concepts before making any comparative observations or discussing any of the evidence for human evolution is simply backwards. It also leaves some students feeling like they’re just memorizing factoids with little hope as to how to bring them all together to answer larger questions about where we come from and why we vary. And this method also creates the potential for students to believe evolution merely because someone with authority said it is so. But, by definition, evolutionary theory does not require dogma to endure. Anyone can see for themselves the evidence for human evolution all around them. This is what my approach encourages. (For more, see my last post on pedagogy here.) 

A New Curriculum

For my curriculum to work, it means that I assign readings out of order of the textbook.  So, to start the course, students are reading up on comparative anatomy and behavior from the middle and sometimes end of the textbook.  This is far from ideal considering these textbooks are written to progressively build upon previous knowledge. Having students read chapters out of order can be confusing, but it’s the only way to do it. (That is, until I write my own book (heh) or until enough resources that I can piece together become available like, for example, this draft list.)

In my reorganized curriculum we ask a chain of questions that progress in a logical manner and that foster a natural sequence of discovery. Here’s the unit-by-unit breakdown.

Unit 1. What is the scientific approach to understanding human origins? Provides perspective for the rest of the curriculum and provides essential tools for interpreting and evaluating evidence and understanding the science of human origins and evolution.

Units 2 & 3. What is a human and what are human traits? Students compare and contrast human biology and behavior with other organisms and learn how observations of living organisms support their evolution from common ancestors over deep time.

Units 4 & 5. How did human traits evolve? Theories and principles used to explain the evolutionary processes responsible for the observations made above. Students decide how evolutionary hypotheses can be tested and they make predictions for what is contained in the fossil, archaeological, and genetic records. Molecular evidence is evaluated here; fossil and archaeological evidence comes later.

Unit 6. Why did our ancestors diverge from those of other animals? Evaluate hypotheses for human-chimpanzee divergence. Testing evolutionary hypotheses in the fossil and genetic records.

Unit 7. When did our ancestors diverge from those of other animals? The importance of context. Geological dating methods. Molecular clocks.

Unit 8. How were early hominins similar to and different from apes? Testing evolutionary hypotheses in the fossil, archaeological, and genetic records.

Unit 9. When did early hominins start behaving like us? Testing evolutionary hypotheses in the fossil, archaeological, and genetic records.

Unit 10.  When and where did the first humans live and how did they disperse around the globe? Testing evolutionary hypotheses in the fossil, archaeological, and genetic records.

Unit 11. How and why do humans vary? Explaining human variation with and without evolutionary forces. Understanding race.

Unit 12. Why is human evolution misunderstood and why is it controversial? Facing denial and misconceptions and their dangers.

Unit 13. Are we still evolving? From this newly acquired, informed perspective we consider the evolutionary sciences and their role in our lives today. We also consider our place in nature today and in the future.

(c) Holly Dunsworth
Note: I know it's a blog, but this is where I chose to publish. That means, if you use this then find a way to cite it, please. Thanks and welcome to the future!

Principles of life, in action

We presented a list of principles last week that we think are generic and help explain much of what goes on in life -- during development, between organisms, and over evolutionary time.  They won't tell you which gene is turned on when, or where the enhancer is that controls its expression -- to answer questions such as these, you need different sets of principles.  But, they do, we think, comprise a list of basic observations about life that are shown over and over again to be true.  The proof of that is the gold standard in science: the principles are, implicitly and explicitly, routine underpinnings and assumptions of daily research in the life sciences.

A couple of papers in last week's Science describing how bacteria adapt to changing environments illustrate this nicely. In their paper, Nicholas et al. undertook to explore changes in the 'transcriptome' (suite of genes expressed at any given time) when the bacterium, Bacillus subtilis, underwent environmental changes, 104 in all, in controlled conditions in their lab.  That is, they set out to characterize 'transcriptome plasticity' in this critter.  They catalogued the genes expressed in every set of conditions, and found 'highly correlated changes in expression', in response to conditions.

Of the previously annotated coding sequences (CDSs), only 186 (4.4%) were not expressed under any condition. Most of these CDSs were of unknown function and predicted to originate from horizontal transfer (SOM 3 and table S3). The 30% of the CDSs most highly expressed under each condition were defined as “highly expressed” (SOM 3). Eighty-five percent of all CDSs were highly expressed in one or more conditions (fig. S3A), but only ~3% (144) of all CDSs were highly expressed under all conditions, indicating that most B. subtilis genes are differentially expressed. Genes in the latter group encode proteins with essential functions and enzymes involved in glycolysis, iron sulfur metabolism, and detoxification pathways.

That is, a small percentage of genes were always expressed, another small percentage of genes never expressed, and the large majority of genes were highly expressed in at least one environment.  These facts show the modularity of genomes and differential combinatorial context-specific usage,  which implies various kinds of internal compartmentalization (effectively, the sequestration of components), even in  simple bacteria.

They also analyzed promoter regions, and discovered that about 46% of all genes can be transcribed from more than one promoter.  And:

We comprehensively mapped transcription units (TUs) and grouped 2935 promoters into regulons [reglators of groups of genes] controlled by various RNA polymerase sigma factors [transcription initiation factors in bacteria that facilitate RNA polymerase, the enzyme that enables the stringing together of nucleotides into RNA, to bind to gene promoters], accounting for ~66% of the observed variance in transcriptional activity. This global classification of promoters and detailed description of TUs revealed that a large proportion of the detected antisense RNAs arose from potentially spurious transcription initiation by alternative sigma factors and from imperfect control of transcription termination.

That is, a considerable amount of transcription is imprecise (what we've called 'slop').  For example,  transcription of coding regions often extended beyond the boundary of the gene, and this produced antisense RNA (asRNA), rather than protein-coding RNAs.  But, they propose that these 'spuriously' produced asRNA's may actually have a biological role, sometimes in gene regulation.  Thus, slop turns out to be an important part of life.  And gene regulation is a combinatorial phenomenon that involves some sorts of context-specific balance among factors.  Combinatorial causation (one can say via 'Boolean' logic if one is familiar with computerese) is fundamental even to bacterial life and eology.

Among other things, the authors conclude that their analysis "revealed that asRNAs generated by inefficient control of transcriptional events might be a drawback of [transcriptional plasticity], though they might contribute to the creation of previously unknown regulatory functions."

Buescher et al. also analyzed changing conditions on Bacillus subtilis, in their case, food -- glucose and malate, sources of carbon for these bacteria -- to try to understand the interaction of regulatory and function networks in the cell.  As described in the commentary to these two papers, Buescher et al found that:

Most genes were differentially expressed, and 127 out of 154 transcription factors changed their activity during one or both shifts. Changes in carbon metabolism during both shifts were mediated largely by altering the abundance of a small number of proteins. Although both nutrients are preferred carbon sources for B. subtilis, adaptation to glucose availability was slow and largely controlled transcriptionally, whereas adaptation to malate was fast and primarily regulated posttranscriptionally.

And,

To achieve adaptation, B. subtilis makes some compromises. The observations of Nicolas et al.suggest that transcriptional plasticity is often associated with imperfect control, leading to the generation of antisense RNAs. This may arise due to aberrant termination of transcription, or spurious transcription initiation while using alternative sigma factors. Similarly, the results from Buescher et al.suggest that, depending on the prevailing environmental condition, the preferential uptake of one carbon source over the other might confer condition-specific evolutionary advantages in growth. This is achieved by active regulation or constitutive expression of several genes—two distinct strategies, neither of which is advantageous per se. Thus, to adapt to changing environments, B. subtilis makes a trade-off between the implementation of complex regulatory programs and imprecise regulation.

So, how does this illustrate our principles?  Here's the list again, briefly, but the annotated list is here.

1. Inheritance with memory
2. Modularity
3. Sequestration
4. Coding and interaction
5. Contingency
6. Chance
7. Adaptability
8. Cooperation

Inheritance with memory is why B. subtilis, as any organism, are what they are generation after generation, and why they have predictable responses to environmental changes. Modularity is obvious throughout; regulatory regions, genes, cells themselves are all modules.  And cells are sequestered, but not completely, which is why they can detect the environment and respond to changes.  Coding and interaction are fundamental aspects of gene expression,  of course, and which genes are expressed is contingent upon environmental conditions.  Chance comes into the picture in how reliably gene transcription takes place (not always reliably), and indeed, in what environment the bacteria must respond to when.  And it all involves cooperation among genes, regulatory elements, and so on.

We think it's important and worthwhile to try to itemize principles like these, not because we feel we have made any sort of 'discovery', but because in the search for principles of life, there are twin thrusts, one being molecular biological reductionism, and the other being overly simplistic deterministic effectively one-gene or gene-for causal and evolutionary thinking.  The latter leads to a focus on competition when the principles in the format that we try to enunciate them show how much more life depends on cooperative (coordinated, jointly functional) rather than competitive interactions.

An apt description of how life works: slop! Part III

Is life sloppy or not?  Our last two posts discussed reasons to think it is, that it's orderly in many ways, but not so precise as to be characterized by laws like those of physical sciences.  Yet, if we're just molecules interacting, how can life not be just as law-like?  And isn't its law, or at least one of its laws, that evolution works by making every trait tightly adapted to its circumstances, just as Darwin argued and as many if not most life scientists (including those with scant real evolutionary training who plow the seas of biomedical genetics) routinely say it is?

Many years ago, I was doing some epidemiological research in Panama.  During a break in data collection, I took a stroll along a path that wound up into the rain-forested hills out of the small town where we were working.  I was watching parrots flying across the searing tropical sun overhead, and the lush tropical vegetation, which I'd never seen before, when I stopped to look at a butterfly sitting on a nearby leaf.  Admiring its black eye and curvy antenna, I moved to get a closer look, which made the butterfly dart off....backwards!

Well, it didn't really fly backwards, and in fact it was I who was thinking backwards.  I'd been tricked by a 'false' eye spot on its hind wing, thinking that was the head end.  It was a remarkable example of the effect of protective coloration, and I felt like the predatory bird that such eye spots had evolved to trick, so that the butterfly could live to mate another time.  At the time, I did not question the explanation, so impressed was I by my gullibility.  Evolution in action!

Then, a few years ago, I had a somewhat kindred experience.  Walking a long a path on the south rim of the Grand Canyon, I noticed a butterfly that landed on the sandy path.  Its coloration was remarkably like that of the stones and sand.  I could hardly see it, til it then flew off.  Again, I mused, this is just what the textbooks say about one of the most clear-cut examples of adaptation.

But I've thought about these experiences since, and wondered how accurately they reflect the dogma of evolution as it is so often held, explicitly or implicitly.  For example, while I did see the effectiveness of protective coloration in these two instances, I also did, after all, see the butterflies.  I wasn't completely fooled.  For the moment let's assume that the standard argument for protective adaptation is correct, even though it's based on our human abilities to recognize patterns, not those of the actual predators the butterflies have to deal with.

In the first case, had I been a predator, I'd have missed that butterfly.  But I'd not have been tricked a second time!  Likewise, while I marveled at the mottled butterfly largely hidden on the sunlit sandy path, I did after all, see it.  Had I been hungry, I'd have had my meal.

Sill, one can see the potential that protective coloration gives the prey so that at least sometimes it will escape being eaten and live to reproduce.  Even if it's not perfect protection, if it raises fitness just a tad, over the long haul it could represent a force-like, systematic genetic advantage that would work as Darwin said and as any biologist with physics-envy could want.

But then I wondered why most species in my surrounds did not have protective coloration.  If it's so force-like and obvious, why are most birds and beasts easily seen?  Why hasn't protective coloration worked so perfectly, as in a sense a Darwinian point of view would hold, that the ecosystem breaks down because predators can't find anything to eat?  Or, put another way, why is each species' adaptations, whatever they be, different?  Why isn't an ecosystem just one huge mottled pattern of camouflage?

Well, the Darwinian fundamentalist argument would say that each species has its own adaptations or it wouldn't be here.  That is not much different from saying "God made it that way", except that an adaptationist (that is, one who assumes that every trait must be the result of systematic natural selection) says that there is a physical reason for the traits that relates to its having out-competed other variants in its past. Our job in science is just to find out what the reason was.

So some species, the story goes, fly irregularly in a way that distracts the pursuing bat or bird, or makes it hard to catch.  Some have protective coloration.  Some only come out at night.  Some herd together so predators have a hard time finding which one to pursue and end up missing all of them, except maybe the elderly who are past reproduction anyway (and don't cost the prey species any fitness).  Some species taste bad so birds avoid them while others taste good but mimic their bitter contemporaries.  Some run fast or fly or climb to escape predators, while others freeze and appear dead to avoid detection.  And so on.

Or, because species move around and environments change, some non-camouflaged butterflies might do well to become so, but are recent immigrants from a zone where they didn't need camouflage or perhaps had it in that environment.  Of course, they'll now have to undergo adaptation in their new environment if they're to survive and persist there.  

Why are there so many kinds of sparrows, or grasshoppers, or grass just in my back yard?  The idea that each has its own specific 'niche' sounds good, but is often hard to accept, even just on the face of it.

Now, within each of these stories would be sub-stories of how the individual aspects of the traits mentioned evolved, piece-meal, over long time periods.  Think how many changes it makes to make a bird out of a non-flying reptile.  Or just to mold and color a butterfly's wing to give it the right sort of eyespot and antenna-like tail shape.  And similar ad hoc, or perhaps better described as post hoc, stories need to be told about how the predator hones its detection and pursuit skills so it doesn't just starve into extinction first.

The gist of the point here is that each story is so different that it becomes in a way self-fulfilling in terms of overall adaptation arguments.  One can, literally, always concoct some adaptationistic story about every trait in every species in every environment.  That is the sense in which evolution is either essentially tautological or so ad hoc as not to reflect the kind of law-like rigor we see in physics.

The strange fact is that at some level these stories seem to be true!  

Even if each story is in essential ways completely true--and many of them seem so plausible that one needn't doubt their truth--living nature is much more pixillated and less unitary in its evolution: each story is of the here and now, the factors and forces changing over time and place.  Each story is different and indeed is changing all the time.  That is an essence of an evolutionary principle.  It is, in a sense, the common basis of evolutionary theory.  It isn't controversial at all.  But it is very far from the kinds of forces we see in physics and chemistry, or the precision of mathematics.

The problem is that most of these stories cannot directly be confirmed. Among other reasons, whether you're eaten, or catch prey, is highly probabilistic--has a high level, even a fundamental, component of chance.  Since the difference at any given time between most genetic variants related to some aspect of the evolutionary race are usually very slight, having their purported effect over thousands of generations, the difference at the gene level can be essentially undocumentable:  we could not, perhaps even in principle, detect the differences with samples that we could actually obtain.

For the same reason, the outcomes themselves are also unpredictable even in principle.  This is so even if one assumes, as many biologists explicitly or implicitly do, that nothing in our makeup or genomes is without function, and natural selection detects all functional variation (a key point in Darwin's own thinking).  But that is an assumption and it makes adaptation explanations often unfalsifiable and to a great extent just stories empty of scientific content.

In fact, referring back to our series on whether probability exists, it is impossible in such a probabilistic world to show that something in life has exactly zero effect, or indeed to show that small effects are different from zero.  That means that much of our supposedly force-like story can't be confirmed except by using subjective judgments about statistical results in our studies--and that directly implies that Nature isn't doing what we say it's doing either.

Even if every aspect of the stories were true, and even if demonstrably so, it means that much in life is unique and that any law that applies is itself going to have to be ad hoc, different for each pixel at every time.  Indeed, and perhaps strangely, this is the essence of life, and is squarely within evolutionary theory if we but think carefully about it.  But that's very different from laws like gravity or the ideal gas law.  The foundations of modern science include repeatability and the similarity of observations underlying a law of nature.  But life is all about local, contingent, accumulating dissimilarity.

Causation in life is a kind of spectrum, with some causes so systematic and obvious that classical theory applies very well to anybody's satisfaction, and that fact is indeed the addictive hook that makes us think it will apply everywhere.  But they are the relatively rare exceptions to the general, more pixillated story, where the story seems to fit but really isn't nearly so clearly observed.

In that latter sense, the laws of life are about difference and things not being exactly repeatable.  That's why I can spot a camouflaged butterfly....but only sometimes.

Pander Bear: how much should we tolerate?

So now the Hype-O-Mat is in full force, with the media hacks taking stories from the science panderers about how the new (Exciting! Transformative!) gorilla whole genome sequence will (Finally!  At Last!) tell us everything you (or your friends, neighbors, and relatives) ever wanted to know about humans.  Your every thought explained by one hairy beast's DNA!  The BBC, usually or at least sometimes a tad more responsible than other media, is the vehicle for perpetuating enough hype about this Nature paper to make you want to reach for the air-sickness bag, especially when you look at the video that accompanies their story. (Just the first of many statements demonstrating deep misunderstanding about evolution: "In the distant past, humans were not very different from gorillas."  What were they actually trying to say?  That humans were once gorilla-like, as though gorillas have not changed through evolutionary time, but humans have?  Or, to give them the benefit of the doubt, that humans and gorillas share a common ancestor?  Unclear.)  Maybe this is getting such play because it's largely a UK sequencing effort that generated the new data.  But you can be sure Nature is eating it up -- and indeed you don't need a subscription to see the gorilla story touted on the front page above the fold this week.

Scientists are expert at toeing the line between responsible reporting and hype.  In print.  We cover our bets so we can't easily be found wanting by our peers.  So, the authors of the paper can argue that they aren't hyping their results when they write things like this: "The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution."  No over-promising there, they'll say.  But, on tape it's a different story.  They say things such as that gorillas don't get dementia, and their genomes will tell us why, and lead to a cure in humans.  And so on.  Oddly enough, the chimpanzee genome sequence hasn't told us why humans are human, or lead to miracle cures, and they're even closer to humans.

Indeed, the argument is that the human genome is only 2% different from our closest ape relatives. Close enough to let us figure out what makes us human.  But this is drivel.  Think about it.  Humans are closer to humans than any other ape, but each copy of our genome differs from each other copy by a few million bases, a fact well and specifically documented with modern sequence data.  Can we use those to tell us what makes one person different from another?  Or what about comparing Chinese and French genomes to see what makes the former use soy sauce and the latter eat truffles (that's culture, after all!).  Or why one person is good at math and another at play writing?

Never mind complex diseases (like dementia). And in fact if you don't just compare two copies, but ask how many nucleotides vary in someone in our species, the answer is probably nearly all of the 3 billion.   The tiny 2% difference people talk about between humans and other apes means 6 million base pair differences, again only comparing one copy from each species. Now we know that many traits like disease can be caused by a single base-pair change, so that playing the number game is, well, just a marketing game. 

These nucleotides (could) "hold the key to the human condition", if what we are is in our genome and if a gorilla sequence alone can tell us what the meaningful differences are.  Now, it is OK to say that a gorilla sequence will be potentially useful and will be interesting in understanding aspects of evolution of primates and that includes humans, and indeed, that is said in the paper.  Since we're clearly a bit more closely related (with more recent descent from common ancestry) to chimps than gorillas, it is not totally obvious how this will "hold the key" to our entire condition.  But what might it hold?

Of a set of genes that someone finds, or imagines they've found, that relate to our behavior or intelligence (our "language, culture, and science"), one could see whether orangs, chimps, or gorillas share variants that we have as well but that are different from the corresponding sequence in monkeys.  That would suggest that those variant states are not responsible for our language, culture, or science.  Or a candidate gene's sequence might be shared between gorilla and chimp, but not us (or, say, Neanderthal fossils).  Such variants would have arisen specifically in our lineage.

Conserved sequence elements, that is, elements that haven't changed among ape species are potential indicators of things too important for change to have been tolerated.  But those reflect what has had to stay the same, not what makes our culture.  And much hasn't changed because, given mutation rates and population sizes, there just hasn't been enough time, whether or not there's an important function.  And if a single nucleotide change could be favored by selection, and there are countless millions of differences, well, you ask yourself how such hype ever makes it past an editor's desk.

This is the most rosy, positive kind of spin one can put on such findings but of course the hype machine, and those driven to prematurely announce 'the' gene responsible for our language, culture, and science are eager to indulge.  Such preposterous nonsense should be resisted, first of all by the scientists, very skilled at their job, to make sure that they do not seem to be endorsing such silliness (one gene to explain the human condition?  Or is it 3 genes?  17?).  As long as it seems likely to encourage the sponsors to keep their wallets open (NIH and in this case the Wellcome Trust--a pharmaceutical foundation that is supposed to be supporting health-related research), investigators can't resist the cuddly Pander Bearing opportunity.  Without accountability, who can blame us?

There are so many other reasons to object to the hype that we won't bother to continue, and the points have been made by us and many others.  It is the over-selling of what is interesting, potentially useful knowledge as if it represents something transformative.  It transforms science into bullshit (to use a technical term).

The gorilla genome sequence represents another bit of data we have to work with in studying our evolution and genetics.  Like many other kinds of knowledge, it could contribute to important advances in understanding.  But that's true of almost any kind of data about life.  Claims like this story's are close to the line of outright lying by otherwise respectable scientists, or else by journaists who are either unqualified or dishonerable.  The pander bears cry wolf so often that we in genetics will have richly deserved to have our funding deeply cut, if the austerity police come round looking for fat.

We bet that even a gorilla has genes, somewhere in its now revealed genome, that make it smart enough to see through such posturing.  Chest-beating is one of the tricks in their genomes, after all!

An apt description of how life works: Slop! Part II

In defense of our working description of life as slop, which we posted about yesterday, we suggest here a few principles that we believe apply to life at all levels, and along all time spans, from the immediate to the evolutionary.  The immediate, cellular, developmental level; the organismal level, including interacting organisms; and the evolutionary level, spanning eons.  Hence, the EcoDevoEvo of our blog URL, and which we discuss at length in our book, The Mermaid's Tale.

Evolutionary biologists like laws, models, theorems or rules that explain biological observations and can be used to predict future observations.  Thus, Hamilton's Rule (which we blogged about a few days ago) which explains the perplexing (to a strict Darwinist) behavior of altruism, and which invokes the kinship assessing all-seeing eye of natural selection lest a simple act of kindness go by insufficiently rewarded by the beneficiary.  Likewise almost every trait of an organism from its color to its organ structures is given, or forced to have, a specific selectionistic explanation for its origin.  And of course the theory of natural selection has been used, refined and re-refined to explain all manner of traits and behaviors of individuals and even societies since Darwin's time.  But, despite their rigorous precision in principle, that resemble laws an Einstein would admire, none of these laws/models/rules can explain every instance of X, and often require some hand waving to apply at all.

We think this is because the most general rule, one that applies to all of life, is 'whatever works, works'.  That is, evolution follows no single rules.  As a result, life is a sloppy process, and when you think you've found a rule that works in one instance, life defies you to apply it again in another. It doesn't sound like proper science, but if the shoe fits.....

So, in writing our book and in other things we've written, we've come up with a list of general principles that we think apply very broadly, even given that life is a sloppy process, and even if the principles are very vague or generic by comparison with the formulas for chemical reactions or the action of gravity on the Moon.   And you don't have to take our word for it.  These general principles are used explicitly or implicitly every day in genetics and developmental biology laboratories around the world.  If you are a biologist, you will recognize right away that some or all of them guide your work, even if in an informal way.  We didn't invent these principles, we have simply compiled them -- and we discuss them at length in our book.

1. Inheritance with memory: life is one continuous history, from the beginning 4 billion years ago to now, and cells 'remember' what they've inherited and carry it forth (except for changes, such as mutations in DNA);

2. Modular organization; life is constructed in LEGO mode, with repeated units, like segments, hairs, leaves, and the like.  We have referred in earlier posts to the importance of polymers, long molecules made of different subunits (modular units), whose arrangement contains the 'information' of life.

3. Sequestration: the modules in life are isolated from each other, at least in part.  If life is a history of divergence from common origin, from the beginning, that was possible only because of local, isolated compartments that can be separated enough from other compartments to become different.  Parts of DNA are isolated from each other, cells are, organs are....and you are an organism all your own for the same reason.

4. Coding and interaction;  Life is organized as above, generally because of the signaling interactions among units within and between cells (and beyond).  The key to all of this is combinations of molecules present together in time and place within an organism.  Combinations represent one of many kinds of 'codes', of which the genetic code is only one example.  The dance of such interactions is what causes differential organisms.  

5: Contingency: what's here tomorrow works only from what's here today.  This is the hierarchical nature of combinatorial interactions that we mentioned yesterday.

6. Chance: action without direction.  It is fundamental to life that there is a major component of chance in most aspects of what happens.  Mutation in DNA or the chance transmission of variants from parent to offspring ('Mendel's rules'), and the chance aspects of birth and death, or of winning and losing competition (such as natural selection) are examples at various levels. 

7. Adaptability in the face of changing circumstances.  DNA reacts to its environment (genes are used, or not, depending on whether the DNA is grabbed near them by proteins or other molecules), cells react to conditions via signals of various sorts that they are primed to detect, and so on, up to you, who react to your environment and decide what to eat, when to hold 'em and when to fold 'em, who to woo and who to fear, and so many other things.  Your brain is a hyperactive environment-sensor and decision-maker, and we're all familiar with that (and why some of our closest friends can't ever seem to make up their minds!).  But every cell in your body is doing it all the time, and so are structures within them.

8. Cooperation.  The above phenomena are, as we use the term, examples of cooperation, that is, co-operation, working jointly together.  Sometimes, as among social organisms, this is the kind of socially supportive interactions we usually use the word 'cooperation' for, but the myriad interactions that involve multiple partners (signal, signal detector, cells in organs, and so on) are examples of cooperation in the mechanical and more literal, rather than emotional sense of the term.

Not the least aspect of life that is very general is the lack of precision in these general principles of life:  no matter what might be 'read' in the genes, development makes mistakes -- DNA gets wrongly copied during cell replication, e.g, or during gene expression, or a gene is expressed at the wrong time or place ('wrong' according to what we think are the rules; e.g., A's always pair with T's, and G's with C's in nucleic acids, or this gene is 'for' that, and only expressed here, or there's only one way to build a given trait).  From cell to cell there is variation if you look closely, and the only reason we tend to overlook that variation is what can be called the central tendency, of many cells of a given type, no matter that they vary, together generally produce an acceptable structure (or the individual dies aborning).

Work-arounds have evolved for some of these 'mistakes' -- some DNA copying mistakes are repaired, but not all by any means, which is a good thing for biodiversity.  But others, that aren't repaired, are either fatal to an embryo or survivable, and of the survivable ones, eventually they can even come to look like good ideas; another good thing for biodiversity.  Or, an embryo can survive the mistake, but that same mistake might well spell doom later on, in an unforgiving environment.

These principles provide a logic to explain why traits have come about.  Yes, you might say wings are naturally selected, and maybe they are (that is, proto-birds had more offspring than animals that weren't airborne at all, and so wings got trendy), but that doesn't tell you anything about how wings came about.  And anyway, maybe wings weren't advantageous at all, they just happened, so your theory of natural selection tells you nothing at all about wings in the end.

Now none of these generalizations are secret or unknown, they are as simple as can be, and they're rather obvious.  There's so much to say about them to show the point that one could, well, write a whole book on the subject.  That's what we did, but even the fact that these general ideas are all around us and easy to perceive, people persist in pushing hard for very precise and rigorous 'laws' that it is almost just as easy to show don't work that way.  We are too wedded to that kind of Galileo/Newton/Einstein science, for historical if not other reasons.

Tomorrow -- er, Monday -- we will take this kind of slopistry from a somewhat different perspective.....

An apt description for how life works is: Slop! Part I

From Darwin's time to the present, theories advanced to explain the nature and evolution of life have generally attempted something that is law-like, precise, mathematical, and universal.  But they all have essentially failed--not as apt descriptions of aspects of life or instances of evolution, but as generalizations with the kind of precision expected of 'science'.

Genetics, being molecular, strikes many as the underlying domain where the precise laws of life occur.  If molecules and energy are the fundamental constituents of all of existence, then this must be so about life as well.  It seems to many to be a reasonable deduction that whole organisms must therefore be complex embodiments of the diktats of their genomes.  What is written in the DNA is often treated, even despite some casual caveats to the contrary, as written in stone: your fixed destiny!

But upon close examination this is just not how things generally are.  The causal aspects of life comprise a spectrum, a panorama ranging from very strong causation that largely fits the dreams of simple theoretical biology, to a large amount (we would say certainly the majority) of causation that is aggregative, cooperative, weak, statistical and hence probabilistic, and for which we do not have rigorous theory of the kind that chemists do.

In fact, since life began just as some sort of bubbling chemical reaction in the primeval 'soup', it has become 'life' rather than just a chemical reaction, because it developed sequestered regions (that eventually became cells, organs, organisms, and species) that internally had various interactions but became both isolated and different from other such regions.  The patterns of difference were generated by the evolutionary processes whose key characteristics include that it has no plan, and no pre-set direction.  There is no theory for what will evolve, only some generic processes.

At the level of individual molecules, molecule A interacts with molecule B just as is taught in chemistry class.  There is no violation, that we know of, of the laws of chemistry just because the molecules are found in a living cell.  Molecules are molecules.  The same individual biochemical reactions can in fact be produced in the proverbial test tube, and those of us in life science research achieve such miracles routinely every day.  But there are so many different types of molecules, at different concentrations, times, and locations even within a single cell, that the net results are not so simple.  They don't just add up like the sums of the prices on your grocery list.

For one thing, there are always chance aspects to whether two molecules will bump into each other or interact (as taught in chem class).   But things are not uniformly distributed even within a cell, the way they are in class.  Unlike a soup, there's nobody to stir them to make them mix evenly.  Life is in a sense about not mixing evenly.  So a very large number of probabilistic aspects of chemistry are relevant to the net result.

The overall result is different from a simple sloshing solution for very key reasons that go beyond just differences in concentration of ingredients.  This is that living reactions are hierarchical: what happens now depends on what happened just before, which depends on what happened just before that, in a chain that goes back 3.8 billion years of continuous contingencies!  Some individual reactions are, again as they teach in chem class, reversible.  But the hierarchy from conception to death, or differentiation of cells from one state to the next, is typically not reversible (for example, making stem cells from other types of cells is a form of such reversal, but engineered from the outside, not by the cell itself).

Any major biological function is a mix of such hierarchies with their own complexities, time relationships, and contingencies.  In some situations there are ways of going back, but in many this is not the case.  In particular, it's generally not the case with evolution: commitments get made, hierarchies get established, and they are too interwoven for Nature to do much backpedaling.  But the origin of these complex, hierarchical wefts and warps was haphazard in that, unlike a human weaver, it had no pattern or future use in mind (it had no mind!).  Hierarchies build up over time, that become too complex to be viable if they were to 'try' to reverse course.

Then why do things seem so orderly -- so tempting to develop nice, neat equations for life the way Einstein had a ridiculously simple equation for the entire universe (e=mc^2)?  Or the simple formula for water (H2O), so simple that we can tell where in the vastness of space water may exist just by knowing the formula?  The reason, in a phrase, is that while life is sloppy in the above ways, it is divided into units with enough members, and the members are closely related enough, that there are what can be called 'central tendencies'.  Individuals who are each a mix of huge numbers of components, like molecules of a certain kind, or copies of a protein coded by some gene, each variable but only up to an extent, can themselves vary among each other, but only up to an extent.  Humans vary, but not enough to ever be confused with rabbits.  Body temperature varies but only within a recognizable mammalian range (and when too far off, we can understand why it is a 'disease').

So, orderly slop is the order of the day for much of life.  The orderliness is rather loose, not at all like the orderliness of water molecules, the speed of light, or the pull of gravity.  It follows general principles generally, and at various levels follows basic physical and chemical principles rigidly.  But life is an evolutionary phenomenon based on divergence and difference.  It is not like a crystal that may grow, but only within very constrained bounds.

This is why, unsatisfying as it may seem to someone suffering from physics envy, the laws of life are frustratingly elusive--even if there are such 'laws'.  And yet, if one stops expecting and starts understanding, life is very orderly and understandable, taken on its own terms.  That's what makes it life!

What one would expect, and what one sees very clearly, is that the soup became slop:  very organized in some ways, wholly consistent with the laws of physics and chemistry, but not orderly and rule-following in the way of the physical sciences.  Tomorrow we'll offer some general principles, that we think go a long way toward explaining -- and predicting -- the orderliness as well as the slop in life.