Standard Pages (they don't change often)

Tuesday, November 26, 2013

Bitter fruit. Or not.

It's gotten a bit chilly in the Gulf Coast, and that usually means a few things. Oyster season is here, and Gulf oysters are cheap, plentiful and delicious. It's also the thick of the Texas citrus season, and among the varieties grown here is the somewhat famous Rio Red grapefruit. What you may not know is that it is the product of using radiation to scramble the plant DNA.

This type of wholesale mutagenesis seems to sit fairly well amongst people who are concerned about genetically engineered (GE) plants. Although commercialized GE plants have specific traits with well known modifications, critics often cite the possibility of unintended consequences. Yet what could be more rife with unplanned results than random mutagenesis - yet these practices don't bear the scrutiny and political handwringing that GE plants do.

So, how would we go about developing grapefruit nowadays? A little lesson then in science transparency. The choice of selecting the Rio Red was to find a less bitter grapefruit. As it turns out, the main bitter component in citrus is a type of isoflavonone glycoside - I won't go into the long specific chemical names. Suffice it to say that there are two related compounds, very similar to each other. But one is bitter, the other is tasteless. And how bitter citrus is depends on the ratio of these two. Which is made by two different genes, creatively named Cm1,2RhaT (bitter) and Cs1,6RhaT (tasteless). And so, modifying just how these two genes are controlled or programmed determines the bitterness levels of most citrus. This is the power of leveraging the power of modern biochemistry and genomics. We can understand and modify to get a specific change with greater control than in the past.

Tuesday, November 19, 2013

Incentive for Poo

People have a tendency to jump on these diet fads whenever scientific evidence shows even preliminary glimmers in a certain direction. Once a social structure forms around this diet notion, the trend tends to persist even if the science goes contrary to the original conclusion. Be it gluten-free, low carb, paleo, ketogenic, calorie restrictive — most of these start with some kind of scientific or quasi-scientific notion, and is extrapolated to cult status. Getting to the start of such a movement would be a fascinating observation.

And maybe we are at the start of such a new fad. But I dare people to get started on this. In September, the team of Jeff Gordon in Washington University, headed by Vanessa Ridaura, published a tour de force article in Science. It's worth describing in some detail. First, a little background: if you aren't aware by now, a human body is really a constellation of microbial communities in addition to the human cells. There are about 10 bacterial cells for every human cell, and one of the more recent changes in our thinking is that some microbes aren't just friends, they are us. Alterations in the microbiota, by antibiotics or by other means, have drastic effects on human health. We are only recently starting to understand this, that it can affect everything from immunity to behavior.

In this paper, the group located some obesity discordant identical twins. That means finding twins who are genetically identical, but one is thin, and the other is, well, plump, and collected poop from both of them. Then they seeded the gut bacteria - ok, they fed the poop to genetically inbred mice that had been cleared of endogenous bacteria. Now they have incubators of the microbiota from the humans. The mice were then both fed the same diet - low fat, high fiber - guess what? Mice seeded with thin poop stayed thin, plump poop, got increased adiposity (that's scientifically accurate term for "got fatter").

Figure from the paper illustrating the experiment

This buys into this idea that the bacteria lining the gut is the gateway of nutrients into the body. It's the population that determines what eventually makes it into the system. It also says that obesity is potentially communicable. Or is it? The investigators then co-housed the mice. If obesity is transmissible, then if the mice are co-housed, the mice seeded with "plump poop" can transmit the bacteria to the mice seeded with "thin poop", and then everyone gets fat and happy.

The exact opposite happened. Co-housing prevented mice seeded with "plump poop" from getting fat. Seems that it's thin-ness that is communicable, and that it can in fact prevent obesity. The paper goes into dramatic detail analyzing the specific biochemical pathways that are different between the two microbiological populations, pinpointing the subpopulation of bacterial species that may be the biggest contributors, and even modeling the biochemistry underlying the potential differences in digestion. But I doubt if most people will try to understand it to that detail. This is sufficient preliminary information to make "thin people poop" the next crazy diet fad. 

So much for the scary aspects of eating shit

Disclaimer: this is very preliminary work - this is to illustrate how basic science works, and to highlight an exciting development that has fundamental implications for our understanding of human physiology. This is not an endorsement to go around eating poop indiscriminately.

Friday, November 8, 2013

Chicken Perplexity

Matzoh ball pho from Eatsie Boys, Houston, TX
Antibiotics in food is one of the most emotionally charged topics when discussing modern agriculture (certainly words like "ticking time bomb" don't help in the fear department). But antibiotics and biology are a scientifically complicated issue. A quick review: what we colloquially call antibiotics comprise a range of compounds that are intended to interfere with microbial growth but minimally interfere with human (and related host animals) physiology. Many of these (and the matching resistance mechanisms) are indigenous to the competition among the different microbe species, and we humans have just appropriated a subset of these for our use. Nonetheless, most people seem to operate on the assumption that, by default, there are no antibiotics in the wild unless introduced by humans, that all antibiotics are functionally equivalent, and that resistance is "created" by exposure.

This misunderstanding can, of course, be aggravated by poor science reporting. The New York Times recently published an article (authored by Stephanie Strom) reporting the survey of the antibiotic resistant bacteria found supermarket, kosher, organic, or "raised without antibiotics (RWA) chicken in the New York City area. She summarized the results thusly:
Almost twice as many of the kosher chicken samples tested positive for antibiotic-resistant E. coli as did the those from conventionally raised birds. And even the samples from organically raised chickens and those raised without antibiotics did not significantly differ from the conventional ones.
The same conclusions are being echoed by various other outlets, from Salon to the Jewish Weekly (some writers focus on the fact that the lead author, Jack Millman, is 17 years old). But I found some problems upon reading of the paper published in F1000 Research (and responsibly linked). First is that the authors reported the resistant microbes as a percentage of isolates - they didn't report it as absolute values. Meaning that unless they had sampled equally among the different categories of chicken, this can be radically different. For example, if there were 100 conventionally raised birds sampled, and 10 kosher birds, but 5 were resistant in both samples, the kosher birds would come up as 50% while the conventional would be 5%. Reporting the total population number is important to interpretation.

But the second sentence will perplex most: after all, "organic" should include an exclusion of antibiotics, while RWA means that the birds could still be raised conventionally just without the use of commercial antibiotics. And yet, the resistance levels weren't significantly different from conventional - how can this be so?

The key could be how the samples were procured. The authors had gathered 213 chicken samples - in order to manage this large set of samples, they decided on a single bacterium per sample. This, alone, should raise alarm bells. But this is how they did it: they took a chicken leg from each sample, dropped in a sterile bag with MacConkey broth, and incubated it overnight. MacConkey broth is a growth medium for bacteria, but most bacteria are actually unculturable - that is, for more than 90% of bacterial species we don't even know how to grow them in controlled laboratory conditions. MacConkey broth is designed specifically to grow lactose fermenting bacteria - this is called a selection regimen. Only certain bacteria will be favored to grow in these conditions. Why? Because the authors wanted to focus on a well studied workhorse: E. coli. And I have a whole different article on why E. coli can be a confusing bug to study.

Chicken soup, from Pecking Order, Chicago, IL
That's not the only issue. The generation time for E. coli is about 20 minutes. That's how much time, on average, it takes for one cell to become two. Assuming a 10 hour overnight incubation, that's 30 generations. And from the resulting set of surviving descendants (do that math - but it's easily in the millions) they picked one cell for subsequent tests to see if they could be positively identified as E. coli. And if it passed that test, that's the one they tested for antibiotic resistance as representative for that chicken sample.

Imagine if you're comparing cities. If you took one person from any city in the world, at random, and presumed to judge the characteristics of the population of that city from this one sample, it wouldn't be valid. Now, instead of that one person, you decided to take a descendant from a selected number of residents many generations later. I find it hard to think that it would be representative of the original population.

This, I fear, is the weakest part of this study. The authors technically sampled less than one cell per sample and extrapolated their conclusions to the original. This is not a rigorous study design. But the authors didn't try to oversell their results - the journalists who reporting on this jumped to very broad conclusions, often bringing angst regarding the kosher bird process - I am not even going to discuss the fact that the authors disclosed that their classification system was intentionally skewed to report more antibiotic resistant bacteria than not. Bottom line: there's insufficient information in this study to conclude one way or the other.

I did learn that there's a practice of injecting some antibiotics in eggs prior to the chick hatching, although the paper implied that this is standard practice. In truth, this is "off label" use, meaning that it isn't an approved practice.

Monday, November 4, 2013

Fixing up labels

The electoral battle rages in Washington over I-522 - the proposed law requiring the labeling of foods containing genetically modified organisms. My own objection to such a law is pretty evident, primarily because it is unscientific and unjust. What baffles me sometimes is how cavalier some people are with regards to food labeling. The "just label it" and similar campaigns make it seem like labeling is at once trivial and essential (the phrase "fighting labeling" is also often used as a strawman argument, as if opponents to the law are preventing people from voluntarily labeling the food). 

I have come to realize that the state of food (and by extension, supplement) labeling is in such a poor and confusing state that it's easy to trivialize it. The difference, of course, is that mandated labels carry the penalty and force of law, and should not be treated lightly. Take, for example, coconut water. Practically unheard of a few years ago, bottled and canned coconut water now has dedicated shelves in major grocery stores in the US. 

And a common label and tactic is to report coconut water as a "natural" sports drink, that it hydrates better than water. This, of course, is untrue: truth behind the coconut water craze. It isn't difficult to figure out that the main hydrating component for coconut water is, well, the water. The fact that it is mostly composed of water. 

That doesn't prevent folks from making a coconut water concentrate - where the main hydrating component is reduced - to chug quickly. I guarantee you that this is no way more hydrating than water. 

But, of course, we can take this to the ultimate level of ridiculousness.

Behold - Coconut water powder. Completely dehydrated coconut water - and yet it is labeled for "hydration on the go". 
If such labeling is casually present, no wonder people don't think the addition of a nonsensical label is  worth objecting to. Except in this case, it's about coercion. These manufacturers chose to add the nonsensical label. I-522 will compel and coerce food producers to add a nonsensical label even if they don't want to. People of Washington, please vote NO on I-522.

By the way, coconut water really comes from a hard to peel fruit like this, not a can.  May need a machete to cut open.