Tuesday, May 21, 2013

Microbiomes R Us -- another form of science marketing

The microbiome hits the big time 
A piece by food writer/journalist Michael Pollan, "Some of My Best Friends Are Germs", was the cover story of the New York Times magazine on Sunday.  Pollan says the interest he developed in fermented foods while he was writing his latest book -- beer, kimchi, cheeses -- naturally led into an interest in the fermentation that goes on in our large intestines with the help of resident microbes, and this led him to think generally about the interaction between microbes and us.

The current estimate is that microbial cells in and on our body outnumber our own cells ten to one.  The Human Microbiome Project, funded by the NIH, as yet another Big Science do it all and think about it later investment, was launched in 2008 with the goal of sequencing the microbes in the nasal passages, oral cavities, skin, and the gastrointestinal and urogenital tracts of a fairly small sample of men and women.  The project was completed last spring with sequences from samples from more than 240 people (completed means the authors can now go to the press and demand even more money because 'more research is needed' before we understand anything.....).

But, that's not the end.  In a drive to document the microbiome of America, The American Gut Project will sequence your microbiomes for $99.  It's an open source, open access project which allows participants to compare their data with data from people around the world. 

Why?  Because the microbiome is the new genetics.  Forget (our own) genes, the idea is that we are who we are, healthy or sick, because of the microbes we share our bodies with. Well, of course, it's the microbes' genes, so it's really just more genetics.  As Pollan puts it,
To the extent that we are bearers of genetic information, more than 99 percent of it is microbial. And it appears increasingly likely that this “second genome,” as it is sometimes called, exerts an influence on our health as great and possibly even greater than the genes we inherit from our parents.
Our microbiome may make us fat or keep us thin, predispose us to diabetes or heart disease or asthma and allergy. And, the microbiome apparently influences our immune system and trains it in how it responds to the world, and may be responsible for the increase in autoimmune diseases in the West. Indeed, Pollan writes of "an impoverished 'Westernized microbiome'" -- some researchers suggest that the microbiota in our gut should be restored to look more like the microbiomes of people who eat less processed food and take fewer antibiotics (and, by the way, are more likely to die early of infectious diseases than we are). 

But, happily for us, changing our second genome is going to be a lot easier than changing our first one.  We do it all the time, through our diet, the medicines we take, the people (and their microbes) we come into contact with.  Happily for Big Pharma and Big Food, once we know which microbes are best for us, they'll be able to sell you any number of products to reverse these changes and reduce your chances of getting all those diseases geneticists have been trying to find the causes of for so long.  You'll have personalized microbiomalgenomic medicine.  Enough to put another smile on Francis Collins' funds-securing face!

There has been a lot of talk lately about 'fecal transplants' which are just what they sound like -- the transfer of fecal bacteria from healthy people into the colons of unhealthy people, primarily people with Clostridium difficile infections, intestinal infections resistant to antibiotics.  And yes, there is a lot of information on the web for those who want to learn to do this kind of self-medicating at home.  

Overpromising yet?
Pollan (whose qualifcation for writing this piece is that he is a food journalist whose writing sells well) says a few times that people involved in researching the microbiome don't want to make the same mistake that geneticists did with the Human Genome Project, overpromising the extent to which their work will lead to the cure for everything that ails us.  But, if as Pollan claims, the microbiome community is actually talking about the Grand Unified Theory of Chronic Disease, there's apparently a fine line between hype and overpromising -- not to mention borrowing from physics' line that is used to justify Hadron.  And there are certainly plenty of 'probiotic' options in the grocery store these days, so someone's jumping the bandwagon. 

All satire aside, the point isn't that we doubt that there's a connection between microbes, health and disease.  Nor that there are indeed lots of nuggets of grain in the bin being described.  Instead, it's that these are early days yet, and the whole approach to this project is already sounding too reductionist for words.  Not only are microbiome researchers in danger of mimicking the genome project with overpromising to over-enumerate, but also by reducing everything to their favorite microbe (for 'microbe' we used to read 'gene'). The bugs for ability to play the bass or baseball, score well on IQ tests, or tolerate abuse with equanimity may be right around the corner.

Enough Just-So stories yet?
Indeed, the Just-So storytellers are already out in full force. Why are there complex carbohydrates in human breast milk, if babies can't digest them?  As Pollan puts it, "Evolutionary theory argues that every component of mother's milk should have some value to the developing baby or natural selection would have long ago discarded it as a waste of the mother's precious resources." So, it turns out they are there for a particular gut bacterium that breaks them down and uses them.  
“Mother’s milk, being the only mammalian food shaped by natural selection, is the Rosetta stone for all food,” says Bruce German, a food scientist at the University of California, Davis, who researches milk. “And what it’s telling us is that when natural selection creates a food, it is concerned not just with feeding the child but the child’s gut bugs too.”
And, we evolved this commensurate relationship with microbes because they evolve so much faster than we do, so can quickly evolve mechanisms to cope with new kinds of toxins in our environment and so forth.

And, the bacterium that causes ulcers and perhaps some stomach cancers, Helicobacter pylori, is an endangered species, writes Pollan.  But his informants tell him it shouldn't be.  H. pylori also has beneficial roles to play in our stomachs -- preventing acid reflux by regulating acidity, for example, which Pollan suggests they do to render the stomach inhospitable to competing microbes, or regulating levels of an appetite hormone -- and because they do these good things, they should be nurtured rather than killed off.  Why do they do both good and bad?  Well, they do the bad stuff when we're middle-aged or older, so Pollan's informant suggests "this microbe’s evolutionary role might be to help shuffle us off life’s stage once our childbearing years have passed."

Of course, among other curious aspects of this scenario, how something evolved to kill us off once we're no longer contributing genes to the human gene pool is not explained. In order for this to work, the fitness of the microbe that could do this would have to be increased by killing us, its host, and it doesn't work that way.

Stripping it down to the truth
Again, fine, it seems quite likely that our microbiome does make contributions to our health and disease.  That's interesting enough.  For various theoretical reasons, rapidly dividing microbes do present interesting evolutionary challenges, and there's no doubt that we, and our genomes, must respond successfully if we are to persist.  If infection, broadly defined, has early negative effects because of the host's genotype, then selection favoring the bacteria, and likewise selection favoring human resistance can both be strong.  Culture and climate and habits also contribute to this potentially very dynamic evolutionary mix.  Infectious diseases with strong effect on survival, like malaria and HIV and others have clearly demonstrable effects of this kind.

But that is not the same as invoking specific selective stories for complex, ephemeral, varying fluxes of bacteria, which must coexist as well as keep a host alive so they can stay alive.  It's not the same as inventing pat, closed Just-So stories about how this or that effect must have evolved, and it involves no subtleties that we know are applicable, including the range and mobility of humans, modes of transmission,  population size and so on.  We have had a difficult time, and often unsuccessful, in working out clear-cut examples of natural selection at work in humans, though our evolved defenses against malaria (which is not caused by bacteria but involve many relevant evolutionary issues) may be the best one. 

So why can't researchers, writers, the rest of us just concentrate on figuring out how and when microbes are harmful or beneficial, without the hyperbole, the suggestion that microbes now do everything that genes did not long ago, and the made-up stories about how this all evolved? 

This whole microbiome thing needs to slow down and let the science catch up.


James Goetz said...

This ten to one ratio is mind boggling. Are the microbial cells much smaller than mammalian cells? What is the mass ratio?

Unknown said...

To James Goetz: yes, the microbes are much smaller than mammalian cells.
To the main point: I was surprised by Pollan's restraint. He points out how much is not known ("early days" is his phrase) but captures the excitement, which is, I believe, justified. Recent results really have changed the thinking of scientists, and in justifiable ways. Immunology has indeed been revolutionized.
I dislike hype as much as you do, but unlike the ENCODE story, where the main take home (that almost all DNA is functional) was simply wrong, here the main take home is correct. I looked for errors and didn't find much. The just so story about Helicobacter pylori is a good point, complex carbohydrates not so much (http://ongen.us/16J6l8T).

isambard said...

I thought the article was restrained too. Didn't get a sense of hyperbole

Ken Weiss said...

The Tweet-O-Sphere has been active regarding this post this morning. One comment did not like our apparent critiquing of scientists whose work was referred to in the article, feeling that we should have cited the scientists' papers directly. Since this is a burgeoning area, and we're not microbiomics experts, that is not practical and was not the point of our post.

Scientists who speak to journalists should insist, as a condition of the interview, on being able to vet the resulting quotes (before publication) for accuracy. We always do. If not, or if the scientists approved what the article quotes them as saying, or let themselves speak in unmeasured terms or with minor caveats buried in the enthusiasm, then the scientists (as well as the science journalist) are either of misrepresenting or hyping the work etc. And the NY Times should not be publishing things that are not sufficiently vetted (though it does it all the time).

None of this being-careful easy to do, but if the scientists said what Mr Pollan quotes them as saying, then they merit the critique (though, of course, they might disagree with our take on the issues).

Understanding the complex, nuanced interactions between us and our microbial guests is important and clearly there are instances when these interactions are vital and/or reflect a selective history. And, surely there will be surprises. But not every story that comes down the news media deserves credence.

The nuances affect science journalism and public presentation just as the facts do. We realize that commenters may disagree with us, and certainly microbiomics, the latest form of 'omics' research, has its enthusiasts and when done in measured ways, its obvious merits. Hopefully it will achieve some successes that measure up to its promises. But it seems, to me, eerily like the costly excesses we've seen with the omics models the microibiomics community is following, in regard to the way that the problems of causal complexity are, in a sense, minimized.

To me personally, overstatement is marketing, and science has come uncritically to accept far too much of it. Pat causal or evolutionary just-so stories undermine careful, patient, critical thinking. They tend to confound plausibility with likelihood. Of course, we've said things like this many times. And, of course, others disagree with my own take on things.

Holly Dunsworth said...

This is such a choice quote:

"Evolutionary theory argues that every component of mother's milk should have some value to the developing baby or natural selection would have long ago discarded it as a waste of the mother's precious resources."

It will go down (for me at least) as an example of when evolutionism = creationism, of presentism, of panglossianism.

This is exactly why people think cavemen were imbecile knuckle-draggers who could barely put one foot in front of the other. This is why proto-Anyspecies can hardly see beyond its drooling face.

Holly Dunsworth said...

...^quote is not only incorrect but it negates the very thing it claims to be describing.

Anne Buchanan said...

Thanks for your comments, Steve and isambard. I certainly understand the enthusiasm for this field, and I hope it's clear that we are not criticizing the science here. Michael Pollan did point out that it's early days, and that scientists were working hard not to hype this field. I'll try to be more concise about why it seems like hype in spite of this.

Genetics is the perfect example because, as with the microbiome, it was said that once we had the genome deciphered, and knew the cause of every disease, we'd then be able to predict and eventually cure everything. There are many reasons that hasn't panned out, most of them known ahead of time. Yes, causal genes have been found for many diseases, but most of these diseases are rare pediatric diseases. Genes with major effect on most common chronic diseases haven't been found, except for rare familial cases (early onset dementia, say), and they won't be.

The same will, I predict, be true for the microbiome. There will be some early successes, which will be fantastic, and that will energize the field, and more and more people will talk hopefully about the Grand Unified Theory of Chronic Disease and so forth. But, as with genetics, it will turn out, I think, that everyone's microbiomes are different, they can be, and are, altered throughout life, it won't be clear when the right (or wrong) population of microbes needs to be resident (or not) to cause or prevent disease or for how long, it won't be clear what people need to eat/drink/put in their gardens to maintain the optimal microbiome and optimal will vary by individual, environmental exposures to dietary or other risk factors, and so on. As with genetics, all this complexity will mean that risk of disease will be difficult to predict at the individual level.

As for the evolutionary Just-So story telling, that just happens to be one of our pet peeves. People get away with completely making up evolutionary reasons for given observations all the time, with nothing but a belief that natural selection explains everything as evidence. As people who think hard about how evolution works, this is annoying!

So, in sum, I think there's a lot to this field. That alone should sell it.

Anne Buchanan said...

Exactly. Thanks for unpicking this, Holly.

Steve said...

Holly, I completely agree that the quote is over-stating the case. However, the biosynthesis of a milk component does raise the question of what value that component might provide to a child.

Holly Dunsworth said...

That is a valid question, for sure. However, my complaint isn't about "overstating" an evolutionary case, it's about misrepresenting evolution, period. If everything is in a constant state of adaptation, there is no evolution going forward and there has been no evolution to get us here since everything was always in a state of adaptation until now too.

Holly Dunsworth said...

Ugh. I don't even like what I wrote ^. Just wanted to make sure my complaint wasn't perceived to be about "overstating" or against scientifically investigating components of milk.

Anne Buchanan said...

And no one asked me, but I would agree that it's an interesting question. It's just that it's impossible to know _why_ there are oligosaccharides in breast milk. The explanation that it was because of some selective pressure to feed microbes in the infant's gut is perfectly plausible. But that doesn't make it probable and certainly doesn't make it so. Determining selective reasons for something that happened eons ago has to be pure speculation, and goes way beyond the data.