All those little LGP (Little Green People) out there: A space fantasy

Ah, yes, the highly publicized, if not hyped, search for planets with life 'out there'!  A promotor's dream, because how can you ever falsify the idea that we're not in this alone?  NASA and other funding-hungry semi-sci-fi agencies continue to drop hints about habitable planets and so on.  You know the patter, and the promises almost as flagrant as those of 'precision' genomic medicine.

Well, forget the hype, promise and 'artist' impressions, and let's take a little look at what is in a sense being promised.....

First, let's go back to Aristotle's time and before, and imagine space as a crystal sphere in which the Earth is centered. That is, what we can see is the encircling sky dome.  There we peer into the stars, galaxies, and so on.

Now let us suppose that there really is 'life' out there, and as a short-cut for our purposes here let's further suppose that what we mean by 'life' is living organisms that are advanced enough to use and/or transmit electromagnetic waves strong enough to reach Earth detectably.  Now, to make the SETI (search for extra-terrestrial intelligence) effort easier, let's imagine that these particular emanations can be discriminated from all other sources of electromagnetic radiation in the skies, like light from stars, microwave background from the Big Bang, and so forth--that is, so we can specifically visualize the life-signals' beams by their being green.  I pick green so we can think of them as being (intentional or not, but at least direct evidence) from the Little Green People (LGP) that are out there--if any of them are. That we exist suggests that thinking that life of interesting sorts exists elsewhere is not particularly surprising, and it must have many forms we might not even recognize.

So, let's grant NASA's and the ESL's (and sci-fi writers) wishes and assume that not just life but LGP are out there.  Indeed, let's make our effort to contact them really, really easy, and simply assume that there are millions of planets, even just in the visible universe, that have such LGPs on them.  That's at least plausible; whether it's probable can't be said because we have no way to evaluate what 'probable' would mean.

The figure very schematically suggests what I mean.  The ring around the Earth represents what we can see today. Again, we assume we can discriminate the 'green' radiation from all the other radiation coming in.  The length of each arrow represents the length of time the civilization out there was sending a signal, and let's allow these to be for millions of years (note I'm being very generous: for example, any human-sent signal emanating from Earth would only be about 100 years' long, since radio signaling is only that old).  The place of origin will usually millions or billions of light years away, way, way, way beyond this figure, and the signal has taken that number of years getting here, as it's doing just now when we see it.  After the end of an arrow, that civilization was no longer sending, probably no longer exists, but we don't know that until the end of the signal arrives.  Before the arrowhead, the civilization hadn't developed appropriate signaling technology, so we can't know it is (or was) there.   Incoming signals outside of that ring are not yet visible to us--we don't know they're on their way here and have no way to know those LGP civilizations even exist.

The green-dappled sky
OK, envision our celestial globe, with its hundreds of billions of stars in the Milky Way, and the hundreds of billions of similar galaxies we know are in the heavens, again, just considering our 14 billion year old universe's visible horizon, which is I think tens of billions of light-years in diameter. If life is here on Earth, why not all over the place out there?  There are similar environments, presumably, in countless planets.  At any given moment, we would see green dots on the celestial sphere wherever an LGP signal was incoming.

So, let's say, just to be as favorable to the LGP search as possible, that we see a million such dots. That's not implausible, and let us assume, again to be generous, that each emitting population actively disseminates electromagnetic radiation for a million years, from the time they developed the technology until they evolved on to extinction or disinterest or whatever.

This should mean rich hunting grounds.  But I think it does no such thing.

By far most, if not essentially all such LGP emanations will be from more than a million light years away from Earth.  That means that by the time we can detect them, the emanations will have stopped and the people probably become extinct (many reasons, such as their local star blew up, they evolved to some other species, they damaged their environment beyond sustainability, they overpopulated themselves into starvation....).  And of course, we have no idea just by seeing a dot whether it's one of those, or one from a still-living source.

Even if such a source were still viable, and even if we guess right about which one that may be at the time we mount an expedition or sent a 'Hello!' message, it would likely take 'us' so long to reach them, with either generations of astronauts in transit or just a radio signal, that the LGP would be done-for by the time we or our signal got there.  A manned expedition would take hugely more generations than have ever existed for our species, of course.  And, of course, no matter how clever they were, the LGP wouldn't be able to detect us for millions of years after we sent our message to them, assuming they were still alive at that time so distant from when we received their emanation.  And, of course, we'd be extinct or would have polluted the Earth out of life, by the time any such contact occurred.

So, it is essentially hopeless to wave around vague suggestions of finding 'life in space'.  In fact, most of the universe isn't just a few millions of light years away from us, it's billions of them.  Even hinting at connecting with LGP borders on fraud by those who want our attention, and funds, to explore these possibilities.

The hopeful (sort-of) side
However, there is, surprisingly (sort of), a hopeful side.  That's because if there in fact are LGP out there, most of their signals won't be visible to us at any given time.  Millions or billions or even trillions of little green dots may be approaching us from any or all directions, but just haven't gotten here yet.  That would only be expected if we can see a million of them at our particular time today.

Out of all of those incoming signals, maybe some are close enough to us to constitute something to be excited about....except that once we see their blip, it will at best have been sent at the beginning of their signal-generating lifespan and we'll have no idea how long ago that happened, and hence whether they're still there and sending, so we can't know how long the blip will keep appearing, and most of the time the signal will be millions if not billions of years old, and as above, the senders long-gone.

If some movie or video game outfit develops a real tele-transporter or wormhole traversing system, we might dream of going 'there', wherever there is.  Even then, we'll have to choose which of the million green dot sources to travel to, and just hope the senders are still there.  Of course, they're not really green, so choosing light blips to pursue won't be easy!

There are enough fascinating things about space, and enough real, not imaginary, needs right here on our green earth.  We should keep fantasies to the world of fiction.

Many more words are extinct than those we get to read

I'm starting a new human evolution book project. Technically I've already started it but I've got the greenlight from my agent so it's for real. 

So much writing, at least for me, is just exploratory, organizational vomit that I never times infinity wish to see on the printed page. 

But, here, let me show you my vomit from this morning:

High heels are sexy because they change a woman’s posture so that her boobs and butt stick out and that’s attractive because boobs and butts and because waist hip ratio. 

Wait, no, they’re sexy because they make a person taller and taller is universally attractive. 

What if they’re a handicap or a fitness indicator like a risky bird call or a peacock’s tail? The hampered, painful locomotion signals to potential mates how badass the high heel wearer is. “We will have badass kids!” say high heels. 

source

Or they keep women from being able to escape too quickly if ambushed by aroused men, but that’s too macabre for me to consider further and pisses me off. 

How about, they’re sexy because we decided they are. Culture is weird and powerful: neck lengthening rings, circumcision, Taco Bell. 

Or they’re sexy because they make a woman’s feet look small for her height and this is sexy because … Fibonacci? (Must do calculations.) I don’t know. "Hold me closer tiny footed," isn’t how the song goes. 

But, wait, high heels change a woman’s locomotion. Women who walk in them have an exaggerated female-stereotyped gait. Ask those biomechanists who said so. That’s why heels are sexy, then, they heighten femininity and project its signal further out across the savannah, and into the gaze of more men for longer in each of their numerous salivating minds. 

But why are swinging hips sexy? Because they’re opposite of a man’s? 

But there’s something else that heels do to gait. They make a person unstable, careful, as if they're just learning to walk. One slips into those torture slippers and they're suddenly precious, adorable, in need of rapt attention. Like a toddler, walking for the very first time. 

The idea’s out there, somewhere, that heels make a woman helpless and that’s attractive to men who want to rescue women. This toddler idea is just a fraction of a degree away from that one. Is male attraction to helpless women the same thing that drives them to be doting fathers? Gawd. If that’s true, that means I shouldn’t be as annoyed when they want to rescue full grown women, and when full grown women want to be rescued, because, after all, it’s just good fatherly mojo. But, we’re not babies, dammit. 

High heels. Sexy for so many reasons, but also because they make women into babies and, hey, wait a second...

We don’t think babies are sexy. What the bleep am I talking about? Back up: what we prefer in babies can be preferred in adults for fundamentally similar reasons but those preferences can result in different outcomes. 

Attractive helpless babies get cared for and not sexualized (too much) and attractive helpless women do too but that affection includes bleeping. 

It all makes perfect sense. How on earth did our lineage survive this long without high heels?

FAS - Fishy Association Studies

           

                                  On Saturday, July 19, 1879, the brilliant opera 

                                  composer, Richard Wagner, "had a bad night; 

                                  he thinks that...he ate too much trout."  

                                             Quoted from Cosima Wagner's Diary, Vol. II, 1878-83.

As I was reading Cosima Wagner's doting diary of life with her famous husband, I chanced across the above quote that seemed an appropriate, if snarky, way to frame today's post. The incident she related exemplifies how we routinely assign causation even to one-off events in daily life. Science, on the other hand, purports to be about causation of a deeper sort, with some sufficient form of regularity or replicability.

Cause and effect can be elusive concepts, especially difficult to winnow out from observations in the complex living world.  We've hammered on about this on MT over the years.  The best science at least tries to collect adequate evidence in order to infer causation in credible rather than casual ways. There are, for example, likely to be lots of reasons, other than eating trout, that could explain why a cranky genius like Wagner had a bad night.  It is all too easy to over-interpret associations in causal terms.

By such thinking, the above figures (from Wikimedia commons) might be interpreted as having the following predictive power:
     One fish = bad night
     Two fish = total insomnia
     Many fish = hours of nightmarish dissonance called Tristan und Isolde!

Too often, we salivate over GWAS (genomewide association studies) results as if they justify ever-bigger and longer studies.  But equally too often, these are FAS, fishy association studies.  That is what we get when the science community doesn't pay heed to the serious and often fundamental difficulties in determining causation that may well undermine their findings and the advice so blithely proffered to the public.

We are not the only ones who have been writing that the current enumerative, 'Big Data', approach to biomedical and even behavior genetic causation leaves, to say the least, much to be desired.  Among other issues, there's too much asserting conclusions on inadequate evidence, and not enough recognition of when assertions are effectively not that much more robust than saying one 'ate too much trout'.  Weak statistical associations, so typically the result of these association studies, are not the same as demonstrations of causation.

The idea of mapping complex traits by huge genomewide case-control or population sample studies is a captivating one for biomedical researchers.  It's mechanical, perfectly designed to be done by huge computer database analysis by people who may never have seen the inside of a wet lab (e.g., programmers and 'informatics' or statistical specialists who have little serious critical understanding of the underlying biology).  It's often largely thought-free, because that makes the results safe to publish, safe for getting more grants, and so on; but more than being 'captivating' it is 'capturing'.... a hog-trough's share of research resources.

The promise, not even always carefully hedged with escape-words lest it be shown to be wrong, is that from your genome your future biomedical (and behavioral) traits can be known.  A recent article in the July 28 issue of the Journal of the American Medical Association (JAMA), Joyner et al. describes the stubborn persistence of under-performing but costly research that becomes entrenched, a perpetuation that NIH's misnomered 'precision based genomic medicine' continues or even expands upon. Below is our riff on the article, but it's open-source so you can read the points they make and judge for yourself if we have the right 'take' on what they say.  It is one of many articles that have been making similar points....in case anyone is listening.

The problem is complex causation
The underlying basic problem is the complex nature of causation of 'complex' traits, like many if not most behavioral or chronic or late-onset diseases. The word complex, long-used for such traits, refers not to identified causes but to the fact that the outcomes clearly did not have simple, identified causes.  It seemed clear that their causation was due mainly to countless combinations of many individually small causal factors, some of which were inherited; but the specifics were usually unknown. Computer and various DNA technologies made it possible, in principle, to identify and sort through huge numbers of possible causes or at least statistically associated factors, including DNA sequence variants.  But underlying this source for this approach has been the idea, always a myth really, that identifying some enumerated set of causes in a statistical sample would allow accurate prediction of outcomes.  This has proven not to be the case nearly as generally as has been promised.

To me, the push to do large-scale huge-sample, survey-based genomewide risk analysis was at least partly justified, at least in principle, years ago when there might have been some doubt about the nature of the causal biology underlying complex traits, including the increasingly common chronic disease problems that our aging population faces.  But the results are in, and in fact have been in for quite a long time.  Moreover, and a credit to the validity of the science, is that the results support what we had good reason to know for a long time.  The results show that this approach is not, or at least clearly no longer the optimal way to do science in this area or contribute to improving public health (and much of the same applies to evolutionary biology as well).

I think it fair to say that I was making these points, in print, in prominent places, starting as long ago as nearly 30 years, in books and journal articles (and more recently here on MT), that is, ever since the relevant actual data were beginning to appear.  But neither I nor my collaborators were the original discoverers of this insight: instead, the basic truth has been known in principle and in many empirical experimental (such as agricultural breeding) and observational contexts, for nearly a century! Struggling with the inheritance of causal elements ('genes' as they were generically known), the 1930s' 'modern synthesis' of evolutionary biology reconciled (1) Darwin's idea of gradual evolution, mainly of quantitative traits, with the experimental evidence of the quantitative nature of their inheritance, and (2) the discrete nature of inheritance of discrete causal elements first systematically demonstrated by Mendel for selected 2-state traits.  That was a powerful understanding but in too many ways it has thoughtlessly been taken to imply that all traits, not just genes, are usefully 'Mendelian', due to substantial, enumerable, strongly causal genetic agents.  That has always been the exception, not the rule.

A view is possible that is not wholly cynical 
We have been outspoken about the sociocultural aspect of modern research, which can be understood by what one might call the FTM (Follow the Money) approach, in some ways a better way to understand where we are than looking at the science itself.  Who has what to gain by the current approaches?  Our understanding is aided by realizing that the science is presented to us by scientists and journalists, supplier industries and bureaucrats, who have vested interests that are served by promoting that way of doing business.

FTM isn't the only useful perspective, however.  A less cynical, and yet still appropriate way to look at this is in terms of diminishing returns.  The investment in the current way of doing science in this (and other areas) is part of our culture.  From a scientific point of view, the first forays into a new way or approach, or a theoretical idea, yield quick and, by definition, new results.  Eventually, it becomes more routine and the per-study yield diminishes. We asymptotically approach what we can glean from the approach.  Eventually some chance insight will yield some forms of better and more powerful approaches, whatever they'll be.

If current approaches were just yielding low-cost incremental gain, or were being done in well-off investigators' basement labs, it would be a normal course of scientific-history, and nobody would have reason to complain.  But that isn't how it works these days.  These days understanding via FTM is important: the science establishment's hands are in all our pockets, and we should expect more in return than the satisfaction that the trough has been feeding many very nice careers (including mine), in universities, journalism, and so on.  How, when, and where a properly increased expectation of science for societal benefits will be fulfilled is not predictable, because facts are elusive and Nature often opaque.  However, simply more-of-the-same, at its current costs, with continuing entrenched justification, isn't the best way for public resources to be used.

There will always be a place for 'big data' resources.  A unified system of online biomedical records would save a lot of excess repeat-testing and other clinical costs, if every doctor you consult could access those records.  The records could potentially be used for research purposes, to the (limited) extent that they could be informative.  For a variety of conditions that would be very useful and cost-effective indeed; but most of those would be relatively rare.

Continuing to pour research funds into the idea that ever more 'data' will lead to dramatic improvements of 'precision' medicine is far more about the health of entrenched university labs and investigators than that of the general citizenry. Focused laboratory work that is more rigorously supported by theory or definitive experiment, with some accountability (but no expectations nor promises of miracles) is in order, given what the GWAS etc. era, plus a century of evolutionary genetics, has shown. There are countless areas, especially many serious early onset diseases, for which we have a focused, persuasive, meaningful understanding of causation and where resources should now be invested more heavily.

Intentionally open-ended beetle collecting ventures joined at the hip to promises of 'precision' without those promising even knowing what that word means (but hinting that it means 'perfection'), or glorifying the occasional seriously good findings as if they are typical or as though more focussed, less open-ended research wouldn't be a better investment, is not a legitimate approach.  Yet that is largely what is going on today.  The scientists, at least the smart ones, know this very well and say so (in confidence, of course).

Understanding complex causation is complex, and we have to face up to that.  We can't demand inexpensive or instant or even predictable answers.  These are inconvenient facts few want to face up to.  But we and others have said this ad nauseam before, so here we wanted to point out the current JAMA paper as yet another formal and prominently published realization of the costly inertia in which we are embedded, and by highly capable authors. In any aspect of society, not just science, prying resources loose from the hands of a small elite is never easy, even when there are other ways to use those resources that might have better payoff for all of us.

Usually, such resource reallocation seems to require some major new and imminent external threat, or some unpredicted discovery, which I think is far more likely to come from some smaller operation where thinking was more important than cranking out yet another mass-scale statistical survey of Big Data sausage.  Still, every push against wasteful inertia, like the Joyner et al. JAMA paper,  helps. Indeed, those many whose careers are entrapped by that part of the System have the skills and neuronal power to do something better if circumstances enabled it to happen more readily.  To encourage that, perhaps we should stop paying so much attention to Fishy stories.

In Memoriam: Al Knudsen, a modest, under-recognized founder of cancer genetics (and more)

My first job was a young faculty member was in the Graduate School of Biomedical Sciences, at the University of Texas Health Science Center in Houston.  Our small Center for Demographic and Population Genetics was part of the Graduate School, and it was small enough that we got to know, and interact with, the Dean.  And what a dean he was!

The great, and good Al Knudsen (1922-2016).  Google images.

It was a small graduate school, so Dr Knudsen still was active in research, cancer research. One of the first talks I heard down there in Houston, when I still didn't have my first pair of cowboy boots, y'all, was an interesting idea about the causes of cancer.

Radiation was a known carcinogen, as were some chemicals, and there were various ideas about how carcinogenesis worked at the gene level. The basic idea was that these agents caused genetic mutations that led cells to misbehave, and though abnormal, escape detection by the immune system. More mutations meant more cancer risk, and this was consistent with 'multi-hit' ideas of cancer. More mutations took longer to accumulate, which was consistent with the increasing risk of cancer with age.  But genetics was still very rudimentary then, compared to now, direct testing primitive at best. And there were some curious exceptions.  An interesting fact was that some cancers seemed familial, arising in close relatives, and typically at earlier ages than the sporadic versions of what seemed to be the same type of tumor.  Why?

One example was the eye cancer retinoblastoma which arose in children or young adults, mostly in isolated cases; but there were affected families in which Rb was often present at birth.  Knudsen's idea was that in affected families one harmful allele was being transmitted, but the disease did not arise until a second mutation occurred.  Al published a quantitative mutational model of the onset age pattern in a PNAS paper in 1971, just before I myself had arrived in Houston, but by chance I had heard him present his work at the time of my job interview.

The basic idea was a 2-hit hypothesis, in which you could inherit one Rb mutation, and then only had to 'wait' for some one of your embryonic retinal cells to suffer the bad luck of a hit in the normal copy in order for a cancer to develop.  That waiting time accounted for the earlier onset of familial cases, because they only had to 'wait' for one mutation, whereas sporadic cases needed to experience two Rb hits in the same cell lineage.

This was a profound insight.  It allowed for cancer genetic findings, in which some forms of cancer clustered in families (e.g., some breast and colorectal cancers). Yet most cases were sporadic.  It was shown roughly at that time, by clever work in those crude days of human genetics, that tumors were clonal--the tumor, even when it had spread, was the descendant of a single aberrant (mutated) cell.

It did not take long for this sort of thinking, along with various methods for detection, to find the Rb gene....and other genes related to cancer.  This eventually included genomewide tests for loss of detectable variation based on microsatellite sites, continued to confirm the idea, far beyond those types of cancer that seem to be caused largely by changes in a single gene. The idea of somatic mutation caused by environmental factors, was complemented by the idea that it is common to inherit genotypes that are partially altered but insufficient by themselves to cause cancer, so that the tumor only arises later in life, after environmentally-caused (or stochastic) further mutations occur.

Knudsen's basically 2-hit idea was quickly generalized to 'multi-hit' models of cancer, and the discovery that cancers in a given individual were clonal led to models in which combinations of inherited mutations (present in every cell) and those that occurred somatically, seemed to account for the basic biology of cancer.  Many of the individual genes whose mutation puts a person at very elevated risk of one or more forms of cancer have since been identified, and newer technology has allowed their functional nature (and reason for their role in cancer) to be found.  Some are involved in DNA repair or control of cell division, and it's understandable why their mutational loss is dangerous.

The sources of variation in these genes may vary, but cancer as a combination of inherited and somatically generated mutations is a, if not the, prevailing general model for its biological nature and epidemiology, and shows why tumors are somatic evolutionary phenomena at the gene level.  But his nugget of an idea triggered much broader work in human genetics that, once technology caught up to the challenge, led to our understanding (and, too often, convenient ignoring) of the role of combined inherited and somatically induced variation as a major cause of the common, complex disorders for which genomewide mapping has become a routine approach.

I was still in Houston when Dr Knudsen moved to the Fox Chase Cancer Center in Philadelphia.  We missed him, but over the following decades he continued to contribute to the understanding of cancer.  His inspiring, gentle, and generous nature was an exception in the snake-pit that has become so common in the 'business model' of so many biomedical research circles.

Al's foundational work earned him many honors.  But he didn't get one that I think he richly deserved: his quiet, transformative role in understanding cancer, and the much broader impact on human genetics that followed as a result, deserved a Nobel Prize.

When scientific theory constrains

It's good from time to time to reflect on how we know what we think we know.  And to remember that, as it has been in any time in history, much of what we now think is true will sooner or later be found to be false or, often, only inaccurately or partially correct.  Some of this is because values change -- not so long ago homosexuality was considered to be an illness, e.g.  Some is because of new discoveries -- when archaea were first discovered they were thought to be exotic microbes that inhabited extreme environments but now they're known to live in all environments, even in and on us. And of course these are just two of countless examples.

But what we think we know can be influenced by our assumptions about what we think is true, too. It's all too easy to look at data and interpret it in a way that makes sense to us, even if there are multiple possible interpretations.  This can be a particular problem in social science, when we've got a favorite theory and the data can be seen to confirm it; this is perhaps easiest to notice if you yourself aren't wedded to any of the theories.  But it's also true in biology. It is understandable that we want to assert that we now know something, and are rewarded for insight and discoveries, rather than more humbly hesitating to make claims.

Charitable giving
The other day I was listening to the BBC Radio 4 program Analysis on the charitable impulse.  Why do people give to charity?  It turns out that a lot of psychological research has been done on this, to the point that charities are now able to manipulate us into giving.  If you call your favorite NPR station to donate during a fund drive, e.g., if you're told that the caller just before you gave a lot of money, you're more likely to make a larger donation than if you're told the previous caller pledged a small amount.

A 1931 advertisement for the British charity, Barnardo's Homes; Wikipedia

Or, if an advertisement pictures one child, and tells us the story of that one child, we're more likely to donate than if we're told about 30,000 needy children.  This works even if we're told the story of two children, one after the other.  But, according to one of the researchers, if we're shown two children at once, and told that if we give, the money will randomly go to just one of the children, we're less likely to give.  This researcher interpreted this to mean that two is too many.

But there seem to me to be other possible interpretations given that the experiment changes more than one variable.  Perhaps it's that we don't like the idea that someone else will choose who gets our money.  Or that we feel uncomfortable knowing that we've helped only one child when two are needy.  But surely something other than that two is too many, given that in 2004 so many people around the world donated so much money to organizations helping tsunami victims that many had to start turning down donations.  These were anonymous victims, in great numbers.  Though, as the program noted, people weren't nearly as generous to the great number of victims of the earthquake in Nepal in 2015, with no obvious explanation.

The researcher did seem to be wedded to his one vs too many interpretation, despite the contradictory data.  In fact, I would suggest that the methods, given what were presented, don't allow him to legitimately draw any conclusion.  Yet he readily did.

Thinness microbes?
The Food Programme on BBC Radio 4 is on to the microbiome in a big way.  Two recent episodes (here and here) explore the connection between gut microbes, food, and health and the program promises to update us as new understanding develops.  As we all know by now, the microbiome, the bug intimates that accompany us through life, in and on our body, may affect our health, our weight, our behavior, and perhaps much more.  Or not.

Pseudomonas aeruginosa, Enterococcus faecalis and Staphylococcus aureus on Tryptic Soy Agar.  Wikipedia

Obesity, asthma, atopy, periodontal health, rheumatoid arthritis, Parkinson's, Alzheimer's, autism, and many many more conditions have been linked with, or are suggested to be linked with, in one way or another, our microbiome.  Perhaps we're hosting the wrong microbes, or not a diverse enough set of microbes, or we wipe the good ones out with antibiotics along with the bad, or with alcohol, and what we eat may have a lot to do with this.

One of the researchers interviewed for the program was experimenting with a set of identical twins in Scotland.  He varied their diets having them eat, for example, lots of junk food and alcohol, or a very fibrous diet, and documented changes in their gut microbiomes which apparently can change pretty quickly with changes in diet.  The most diverse microbiome was associated with the high fiber diet. Researchers seem to feel that diversity is good.

Along with a lot of enthusiasm and hype, though, mostly what we've got in microbiome research so far is correlations.  Thin people tend to have a different set of microbes than obese people, and people with a given neurological disease might statistically share a specific subset of microbes.  But this tells us nothing about cause and effect -- which came first, the microbiome or the condition?  And because the microbiome can change quickly and often, how long and how consistently would an organism have to reside in our gut before it causes a disease?

There was some discussion of probiotics in the second program, the assumption being that controlling our microbiome affects our health.  Perhaps we'll soon have probiotic yogurt or kefir or even a pill that keeps us thin, or prevents Alzheimer's disease.  Indeed, this was the logical conclusion from all the preceding discussion.

But one of the researchers, inadvertently I think, suggested that perhaps this reductionist conclusion was unwarranted.  He cautioned that thinking about probiotic pills rather than lifestyle might be counterproductive.  But except for factors with large effects such as smoking, the effect of "lifestyle" on health is rarely obvious.  We know that poverty, for example, is associated with ill health, but it's not so easy to tease out how and why.  And, if the microbiome really does directly influence our health, as so many are promising, the only interesting relevant thing about lifestyle would be how it changes our microbiomic makeup.  Otherwise, we're talking about complexity, multiple factors with small effects -- genes, environmental factors, diet, and so on, and all bets about probiotics and "the thinness microbiome" are off.  But, the caution was, to my mind, an important warning about the problem of assuming we know what we think we know; in this case, that the microbiome is the ultimate cause of disease.

The problem of theory
These are just two examples of the problem of assumption-driven science. They are fairly trivial, but if you are primed to notice, you'll see it all around you. Social science research is essentially the interpretation of observational data from within a theoretical framework. Psychologists might interpret observations from the perspective of behavioral, or cognitive, or biological psychology, e.g., and anthropologists, at least historically, from, say, a functionalist or materialist or biological or post-modernist perspective. Even physicists interpret data based on whether they are string theorists or particle physicists.

And biologists' theoretical framework? I would suggest that two big assumptions that biologists make are reductionism and let's call it biological uniformitarianism. We believe we can reduce causation to a single factor, and we assume that we can extrapolate our findings from the mouse or zebrafish we're working on to other mice, fish and species, or from one or some people to all people. That is, we assume invariance rather than that what we can expect is variation. There is plenty of evidence to show that by now we should know better.

True, most biologists would probably say that evolutionary theory is their theoretical framework, and many would add that traits are here because they're adaptive, because of natural selection. Evolution does connect people to each other and people to other species, it has done so by working on differences, not replicated identity, and there is no rule for the nature or number of those differences or for extrapolating from one species or individual to another. We know nothing to contradict evolutionary theory, but that every trait is adaptive is an assumption, and a pervasive one.

Theory and assumption can guide us, but they can also improperly constrain how we think about our data, which is why it's good to remind ourselves from time to time to think about how we know what we think we know. As scientists we should always be challenging and testing our assumptions and theories, not depending on them to tell us that we're right.

Mammoth ego above all

From time to time our genetics colleagues propose projects that perhaps belong more to Hollywood or the video industry.  At least that way no inadvertent harm could be done.  But, hell, a big ego splash or some book royalties might make one a bit reckless.

I refer here to ideas about cloning extinct animal species from DNA rescued from preserved bone or tissues. Some recent species, like Dodos, might be directly clonable in some way, and in some senses could have some value--assuming that making one or a few of them is good for someone--themselves, that is, not just zoo-goers.

However, how do you do this?  The best idea would be to take an entire cell, re-set its DNA/RNA status to that of a fertilized egg, and let 'er rip.  But how?  Unless you can make that cell develop all by itself in a Petri dish, the answer isn't obvious.  The usual idea, at least for mammals, is to find a surrogate mother.

Generally the approach has been, for mammals at least, to extract a complete nuclear genome from a fossil specimen, take a surrogate mother's egg cell (from its ovary), remove its nuclear DNA, replace it with the fossil's DNA, and inject it into a hormonally prepared mother for gestation.  This is basically the 'Dolly' approach and to my (clearly incomplete) knowledge it is still the basic idea.  But there are problems with this, if you really want to revive a species as opposed just to getting a farm-worthy sheep or the like.

One problem is that you need the host-species' egg, and that means its mitochondrial DNA (mtDNA, which is not in the nucleus) and the RNA and other contents of the host egg cell.  Even if you can use an entire intact nuclear genome, the resulting new individual is necessarily a hybrid between its mother and the other exogenous DNA.  For agriculture, there are some well-known problems such as the fact that the host's cell will reflect some aspects of the host, like mutations in mtDNA or the RNA from its nucleus, and so on.  The new individual is in some senses already a bit old, for example.

These problems can probably be dealt with, or perhaps have already been.  But with extinct species there are other problems.  Among them is that the DNA is usually not entirely intact in any cell. From fossils or extinct species, it may be degraded into very small fragments.  By sequencing currently living relative species, we can identify roughly what part of the genome those fragments come from, and if we have several samples we could perhaps find in some sample each necessary fragments.  That's still not the same as having intact chromosomes, and almost certainly some large subset will be missing.  Then, however, you have to find the surrogate mother, and if the species is extinct you have to use a current, similar species to do this.

Mammoths and Neanderthals . . . . 
Let's for the moment ignore the fact that the cloned individual in these cases really won't be a cloned individual of its original species, but some kind of hybrid or chimera.  Suppose the attempt were made.  What then?

Two of the favorite species that the raw, I'd say cruel Frankenstein egotism and its simplistic portrayal of the idea to the public, are Neanderthals and mammoths.  Maybe the suggestions have only been publicity stunts, given the real issues in the world that serious geneticists could address, but they seem to have been offered seriously, and they show to me how science needs to be kept under control.

Neanderthals and mammoths are social beings.  Real ones were gestated in mothers of their own kind, eating their natural diet, in their natural social (and hence hormonal, physiological) circumstances, and born to families and nurturing, educating, protecting, natural social groups.  Once born, they were incorporated into the group in a way that they presumably evolved to be.

How should a cloned Neanderthal be treated?  It would be basically human: recall that we all carry some Neanderthal inheritance through extensive inter-mating way back then. Would it have civil rights, such as to education, a home, voting?  Could one experiment on it, to test aspects of its physiology? Could it be put on display in a zoo or some university museum?

What about mere mammoths?  One leading Mary Shelly imitator has suggested that cloned mammoths could be plunked back into 'natural' conditions in the Arctic, where there aren't (currently) too many humans around to destroy their environment--assuming, in a fantasy way, that commercial tour groups would not be immediately organized, to go gawk at them (including by 'scientists' who want then to publish papers in Nature on their behavior), and that they wouldn't be kept in zoos or labs in our august universities.  Such innocent-sounding ideas as cloning these extinct beings are far more egotism and ignorance--or willful avoidance of realities--than any sort of sound proposal.

Like humans, mammoths are social beings.  The Arctic today would not be a hospitable or normal place for a mammoth.  A surrogate elephant mother would not gestate a normal mammoth, in ways large or small that we can't really anticipate or even know.  It would be plunked down by itself or in a pack of clones that didn't have normal social life to be raised in.  Even if it had a mother who loved it rather than rejecting it as a freak, it would not be a mammoth mother, nor would its life  replicate the mammoth's natural existence as a herd species.  It is cruelty to suggest otherwise.

In memoriam, or a lesson never learned?
Let's not forget one Ota Benga, an African man, obtained from a slave trader, and exhibited at the St Louis World Fair in 1904 and then put on display--is there a better way to state this?--in the Bronx zoo!

From Benga Wikipedia page

Baartman, from her Wikipedia page

Nor let us forget poor Saartjie Baartman, a southern African native, put on display, naked, around Europe to exhibit her exaggerated private parts, in early 19th century Europe  Traveling freak shows, might one say?

It is to be noted that the people involved were leaders of their time, and people responsible for such dehumanizing practices have included prominent scientists at major universities.  Anthropologist Franz Boas requested that explorer Robert Peary bring an Inuk back from the Arctic, to be studied by scientists at Columbia.

Minik Wallace (also called Minik or Mene ) (ca. 1890 – October 29, 1918) was an Inuk brought as a child in 1897 from Greenland to New York with his father and others by the explorer Robert Peary. The six Inuit were studied by staff of the American Museum of Natural History, which had custody. The adults and one child died soon of tuberculosis (TB), and one young man was returned to Greenland. After deceiving Minik by a staged burial, the museum put the skeleton of his father on exhibit. Adopted by the museum's building superintendent, William Wallace, Minik did not return to Greenland until after 1910. A few years later, he came back to the United States, where he lived and worked until dying of influenza in the 1918 pandemic.  (Wikipedia)

. . . . . and nobody to defend them
In our age of science, the idea of cloning extinct species seems exciting and appealing on the surface, a kindly sort of rescue--until you think about it carefully.  As you can tell, I feel quite strongly about this.  It's playing games with other sentient organisms' lives for no seriously justifiable purpose.  If it's hard enough to justify or excuse what we allow to be done with mice and other species for research purposes (and I include myself among the accused), this is beyond beyond.

To me, personally, these juicy cloning suggestions reflect the cold, selfish, arrogance of science, and scientists in leading universities.  The poor target species have nobody to defend them, and that is why these proposals, irresponsibly presented in the media, can get off the ground.  One sees little censure of these ghoulish proposals, whose presumptive nature is essentially a continuation of the eugenics movement.

The video industry is as close as we need to get to these notions.  Let us not forget our history.

Full-scale Disneyland (with canals!), and sustainability issues

We recently returned from a 2-week trip to Italy.  Two of our children and their spouses live in Europe.  One couple lives in a small town in northern Italy, the other in central Switzerland.  The latter drove down to Italy where we all enjoyed seeing each other, which is not easy given the distances.  But while this vacation/family gathering was very pleasant and, to us, important, it raises some less pleasant thoughts about sustainability in our time in history.

My concerns are personal, but in a sense also global, and to some extent they relate to societal inequity: not everybody can just drop a few thou and travel across the ocean for a couple of weeks' dinners with family.  But beyond unfairness, my concerns are about other issues.  This was a very energy-bad vacation, and we weren't alone!

We flew from the east coast to Venice, the most convenient airport for our purposes.  We flew on a large plane, maybe 2/3 full of passengers. As we all know, one of the worst ways to contribute to global warming is to fly. The aircraft was largely filled with people taking cruises in the Mediterranean.  The trip was about 3700 miles each way, not including the various train and car junkets we took during those two weeks.

And then there's Venice itself.  We stayed a couple of days there to recover from jet lag, and to see the sites.  We'd been there for a science meeting once before.  Bella Venezia!  Once home to a world-leading trade empire, and to many great cultural and architectural wonders and of course its romantic lacework of canals.  The glory days were then, but what is the city today?  Venice takes in something like 100,000 tourists a day, well more than the number of people who actually live there.  The piazzas, side streets, walkways, and bridges--and they are very scenic indeed--are often a shoulder-to-shoulder river of tourists.  They (and we) sightsee in museums, shop, eat, shop, stay in hotels, eat, and shop.  It is obvious that a huge amount of money pours into the city, every day, all year, and has been doing so for decades if not centuries.

Even forgetting their thought-provoking historical value and more trivial entertainment value, and just thinking of them as Disneyesque curiosities for selfie-ops, these museums, shops, and hotels are staffed by an army of people who earn their living from the tourist trade.  So while Venice is in a sense unique and beautiful, it is also in a perhaps deeper sense something of a fake, a touristic Potemkin village, a hyper, full-time, full-scale Disneyland entertainment park, there today mainly to pluck the pockets of the relatively idle affluent and wasteful denizens of our planet (I certainly include myself in that category!).

St Mark's Square, Venice; By Nino Barbieri - Own work

Venice is but one rather small city on the global tourist map.  If you think about the amount of fuel used to transport everyone to, from, and around Venice (and even take into account that the gondolas don't require fossil fuel!), and then multiply that by the hundreds of tourist sites around the world, you have to wonder what hope there is for containing global warming.  There is no sign of self-restraint of any kind here--even on departure to return home, the airport luxury shops do a booming business as tourists part with whatever dollars they've not yet spent.

But what can one seriously do?

It is easy to chastise people who take such totally needless trips, even if accompanied by a self-incorporating mea culpa.  After all, this really is a nearly total luxury.  For most of human history those relatives who moved or sailed far away never saw their family again and corresponded by mail (if at all, if there was such a thing as 'mail').  That was just how life was!  Our family get-togethers are a new, pure luxury.  In a seriously conservation-dedicated world, we could dispense at least with the purely sightseeing, self-indulging kinds of global vacationing.  That would seem like something trivial, a luxury that a resource-conscious world could easily forego.  But even if we all were so equitable, fair, future-aware, and so on, things aren't nearly so simple.

The world is crowded with people and much of it is industrialized, with the number of people who live on the land, as subsistence farmers, declining every year.  We have hugely diverse economies, in a sense creating occupations that earn money so we can swap that for food and so on.  Most of it isn't really necessary.  Among these non-food related activities is tourism, which is huge because so many people are now wealthy and idle enough to take global junkets.

In turn that means that much of the world depends on travel and sightseeing.  Countless peoples' livelihoods are involved.  This is in a sense quite antithetical to global sustainability.  If we seriously slowed down travel to save fossil fuels and reduce warming, then tourism, air travel, cruise ships, and the people involved in the manufacture and operation of planes, ships, trains and buses, their ports and terminals, would lose their jobs. The manufacturers of tourist-related goods, including Venetian carnival masks, post-cards, luxury shopping goods, hotel supplies, restaurant foods, chefs, waiters, menu printers, clerks, etc. would be hit.  Venice, already a shell of its former self, would cease to have a reason to exist.  Even those who deliver all these goods during the night, and those who remove the trash, invisible to the tourists sleeping quietly in their beds, would be affected.  Society would somehow have to do something about their employment needs.  

This means that the idea of just paring back on consumption really is a dream--or, as every even mild economic depression shows, a nightmare.  And just the one example of tourism, essentially a luxury trade, involves countless thousands of people.  Needless to say, all of this is grossly unfair to the huge majority of people living on or below the margins.  It shows the inadvertent implications, even the distanced cruelty, of those idealists who want quick changes in sustainability directions.

It is difficult to have a non-selfish moral position on these issues.  If we say "let's change things slowly so as not to be too disruptive to too many people", the normal human tendency is to think the problem isn't so real, and not even go along with 'slowly' with much dedication. That's why car companies begin making and hawking, and consumers purchasing, bigger cars and trucks the moment gas prices drop.  [I insert this post-posting editorial change because today's NY Times had a story about the return of gas-guzzlers, in the same spirit of what this post is about]

If we say 'we must rush' then too many will find rationales for not going along ('OK, it's a good idea, but I can't do it--I have to see my family overseas!').  So where is a feasible ground to be found, and to what extent should we personally expect to be affected by it?  What will we give up for the cause?  The question, for me, is not abstractly how much one must cut out of what one does, but how much I must cut!  That gets pretty close to home, so to speak.

I can't help but add a rather gratuitous, if snide, side comment. The problems are compounded in an ironic way.  We have agricultural sustainability issues, as everyone by now should know.  The 'developed' world suffers common diseases largely due to bad nutrition and that means to over-eating. So while much of the world barely scrapes by, many in the rich world waddle along largely over-weight (these are not the minority of people struggling with genetic or epigenetic problems that make weight control a real challenge).  The obesity epidemic is why we hear complaints about airplane seats being too small!  So I remark snarkily that, as a consequence, one reason air travel is so environmentally unfriendly is the countless tons of human bulk that are being transported daily across the oceans in tourist-filled aircraft.  One thing leads to another.

We just took what was clearly a very energy-bad trip, no matter how understandable our desire to be with family and our decision to go.  We could, of course, have talked with our family members via Skype--indeed, we already do that often.  I complain that leaders in sustainability and climate change, including the very organization that documents it for the UN, fly all over the world and meet in fancy hotels to discuss the problem and tell everyone what they (that is, they) must do to 'save the planet'. The leading spokespersons for sustainability and climate-change avoidance could set a very public example and work only via Skype! 

In the context of global conservation, sustainability, and climate issues, who should feel guilty about what?  If do as I say not as I do is not acceptable, then what justifies our personal exceptionalism? For me, the answers are far from clear.