Washing your hands with endocrine disruptors

A new study came out of UC Davis this week titled: "Triclocarban enhances testosterone action: A new type of endocrine disruptor?" This article, published in the journal Endocrinology, describes new evidence that triclocarbon, one of the primary active ingredients in "anti-bacterial" household products, acts as an endocrine disruptor. The authors found that triclocarban increased expression of genes normally responsive to testosterone (in human cells) and increased the size of testosterone-responsive organs such as the prostate (in mice).

Studies like this often rely on unrealistically high doses of their drug of choice in order to elicit such dramatic effects. These authors assert that their dosage was no more than 3 times higher than a human would receive from washing with a triclocarban-containing body wash product, which is remarkable. Considering how trivial the inclusion of these compounds in personal products is, I see no reason to continue using them.

I already avoid these anti-bacterial products because they're a crass marketing ploy that plays on one of the many paralyzing fears that control Americans. Washing with warm water and soap is already extremely effective at decontaminating skin from bacteria and viruses. Most of the microbes out there are harmless in the first place. In the meantime, these anti-bacterial chemicals contribute to antibiotic resistance and distract people from the truly important tactics in public health. Anti-bacterial chemicals have also been found to accumulate in agricultural fields, as they're not broken down in water treatment. It's anybody's guess what consequence that could have...

The science is still out on whether there's any real danger from casual exposure to these chemicals, but like the putative endocrine disruptors that leach from microwaved plastic, I see no reason to take the chance. These aren't game-changing technologies and I can easily do without them. It's little inconvenience for me to drink my coffee out of a cup made of something besides polycarbonate. Something, incidentally, that won't make my coffee taste weird.

How meat and GMC FlexFuel are starving the 3rd world

The current issue of The Economist has some interesting articles on damage done to global economies and the rural poor by 1st world subsidies.

"The end of cheap food" sums it up pretty well and "Cheap no more" elaborates.

The facts and chain of logic square with what I know about ag systems. I especially appreciate their repeated point that if you want to subsidize the poor (e.g. by making sure the poor in the US can afford food), you should do it directly, not by monkeying with the market. Coincidentally, an ad on NPR today remarked that US subsidies are focused on food that aren't especially healthy either, which is true. I think Talk of the Nation tomorrow is actually focusing on the Farm Bill, so I'll likely write more then.

At any rate, I've heard multiple arguments against our ag subsidies but only two for them. I think I can pretty much discount the first; that we need subsidies to keep food affordable. Americans use to spend a much greater proportion of their income on food than they do today, and our middle class rose all the same. The second argument, that we need subsidies to ensure a domestic food supply, I doubt strongly. North America has pretty remarkable ag resources (good soils and climates) and already dominates world markets in many non-subsidized "specialty crops," e.g. almonds. The US does a lot more with ag than grain.

Science for fun or profit

The journal Nature has a weekly column that addresses job prospects of scientists. As a grad student anxiously looking forward to a real job, I check in on it weekly. One of the regular features is the brief musing of some young scientist on their day to day struggles and realizations.

This week's column includes the writings of a post doctoral plant geneticist. She reflects on the ambivalence of a friend who works in industry and the possibility of making the transition herself. The final line invokes a common sentiment: "For me, the hardest adjustment is the notion that science is profit, and that this has great influence on one's research."

I am continually frustrated by this attitude and its implication that "real" scientists are motivated purely by an insatiable thirst for knowledge. Although it's possible that this woman merely wishes to do the most practical good she can for humanity without the constraints of a business model, most academics who express this sentiment show an equal disdain for both profitable and altruistic technological applications. It is implied that any effort to use your knowledge cheapens its acquisition.

If science really was simply the quest for knowledge, then it would be placed by any rational society in the same box as philosophy and the arts; luxuries worthy of funding when extra resources are available. I'd like to see how much a molecular biologist (who can easily spend thousands of dollars a day) could accomplish on a poet's stipend. In the end, all of biology pretty much comes down to medicine and agriculture. The NIH, NSF, USDA and all other science funding agencies wouldn't exist if they didn't represent such a valuable investment to the citizens of United States who pay for them.

Expecting all fellow scientists to be motivated solely by curiosity is not only arrogant and unrealistic, but threatens the scientific infrastructure of the United States. We will maintain our first-tier research position only as long as we continue to translate our science into the practical technology that our citizens expect us to produce. We should celebrate (and advertise to the public!) when scientists are able to make a return on society's investment in them. The love of learning is useful trait for a scientist to have, but it shouldn't be a goal. If your research, at some point down the line, doesn't contribute to a product that someone's willing to spend their paycheck on, then your research wasn't worth doing.

New Timeline

I was wishing for extra time and I guess I got it.

My boss mentioned today that I should be telling potential postdoc PIs that I'll be done by next fall. I still think I can be done by June if I continue to write as I run my final experiments, but I agree that it's better to be conservative. He said that it was fine that I plan to start contacting people now but that I don't really need to. Although I don't want to be one of those grad students scrambling for a postdoc right up to the last minute, I won't even hit the 6 month mark until December (or March!).

Either way, I think I can take a few days off and lighten up on myself. I'm feeling pretty burned out. Work's been really hectic this week. I'm in the until-recently unfathomable position of having more experimental tissue available than I can process before it goes bad. I'd hate to waste it when I was doing without for so long.

My projects are going well though. I just submitted a minor publication that my one boss has had in his inbox for the better part of a year. Even though it's small, it'll be my first "first author" pub, which is kinda exciting. I think I'll take the night off and let my focus for the next two days simplly be making the best use of the few hundred tomato seedlings sitting on my desk....

Biofuels = scam?

I've heard a lot of bad things about biofuels.

Most of the arguments come down to:
1) the whole process is even less efficient/more polluting than our current technologies
2) there's not enough land to produce all this biomass unless we stop growing crops for food

I have also heard frequent references to the 'corn ethanol' lobby with conspiratorial overtones against Coca-Cola, Detroit, and Iowa.

I've generally been sympathetic to the anti-biofuels crowd since it squares more with my experiences and I've heard more numbers from them. I came across something that may change my mind though. As I was trolling for postdoc labs the other day, I stopped by Chris Somerville's lab website. He's a very prominent plant biologist who's specialized in cell wall biology and, at least recently, improving plant structure to optimize biofuel technology. He has a link to a presentation titled "The Future of Biofuels" on his site. I wish I could see his actual presentation, but the slides alone present some significant evidence of the viability of biofuels.

He begins by displaying charts demonstrating that most of our energy comes from fossil fuels, and that these fuels are associated with political/economic instability and climate change. Eight (referenced) graphs lay out a convincing introduction that fossil fuels are a problem that requires an immediate solution. Finally, he runs through the usual suspects of alternative energy with some advantages and limitations of each (nothing new here).

He then begins addressing the different forms of energy conversion that fall under the umbrella of "biomass." There are actually multiple ways to make biomass into energy, and different plants show great differences in efficiency. He lists the three main ways to turn biomass into energy as burning, conversion to syngas, and conversion to ethanol and other fuels. He then shows several slides diagramming the cellulose structure of plant cell walls. There's little writing, but I imagine here he makes the point that cellulose, being I believe the most abundant biological chemical on the planet, has great potential to produce energy if we can develop a way to process it.

One of the reasons why contemporary biomass to ethanol conversion is so terribly inefficient is because we haven't developed technologies that allow us to access cellulose and lignin - the primary (and virtually indestructible) components of the plant "skeleton." I wish there was more text on this part of the presentation, but I infer the overall point as being that advances in technology will radically increase the amount of energy we can get out of biomass. This is completely plausible.

He then addresses the land issue. He first makes the point of reminding us that modern crops are much more productive than their progenitors, and that biotechnology promises greater gains. He then shows how we can get large amounts of biomass from agricultural wastes. His best point, and the one that I find novel and compelling is that many of these biomass crops could be grown on marginal land. Arable land occupies a tiny percentage of the Earth's land surface area (and shrinking thanks to unsustainable practices and suburbs!). Biomass crops, having different profit margins and yield objectives, could be economically harvested from land that doesn't support crops. They generally would receive neither added fertilizer or irrigation. This brings to mind a paper I read on the potential of salt-tolerant plants as crops. We have no shortage of watered, sunny land (e.g. coastal deserts) with too much salt for conventional crops. This could be a great resource for specially bred/engineered biomass crops.

My favorite chart in his presentation is a map of the United States with colors illustrating which biomass crops could be grown most easily in each region. One of the most aesthetically pleasing parts of this chart are the implication that more or less "natural" ecosystems of forests and prairies could be managed for an economic return. For the most part grasses and trees are matched up with regions of the US where they (or close relatives) are native. I love the idea of living in an area that provides economic support for large spaces of nearly-wild prairie and woodland that are managed minimally.

Eco-agriculture, the idea that crops can be managed like a diverse, wild ecosystem (and the foundation of organic agricultural ideals), is worthless in most agricultural settings, but shows some promise in biofuels. You don't need to manage a crop very carefully if your end use is to burn it.

His final conclusions are:
Biomass conversion is capable of providing a very large proportion of our energy needs
Current energy crops have not yet been optimized
Current technologies to process energy crops have not been optimized
"There are no insurmountable problems to achieving cost-effective, carbon-neutral solar energy production from plants."

On the eco-agriculture side, he says that biomass ag will be especially low-impact because:
Fewer chemical inputs are needed
Energy crops could be grown in mixed cultivation (e.g. with native plants) and harvested late to increase biodiversity.

I think I buy it.

Plumalmondterine

My one boss is involved in this big peach breeding project that's been running for, I think, decades. He's responsible for disease screening assays on thousands of fruits from different crosses that are produced each summer. One of the universal benefits of working in an ag lab is that we get lots of leftovers every week.

This week's peaches were pretty interesting. A bunch of them looked like normal nectarines, but when you bit into them, they tasted more like plums and had deep red-purple flesh. The skin was a little rubbery like a plum too. We thought this was pretty remarkable until we got down to the pit. There was an almond inside! It was like a fruit that came with a dessert at the end!

This week's peaches turned out to be hybrids between peach and almond trees (all three of these trees are very closely related to each other, in the genus Prunus - along with apricots and cherries). This got me thinking about the extent to which our food supply is made up of completely artificially-selected genetic freaks. Much of what we eat barely resembles any plant you could find growing wild out in the woods. Traditional breeding techniques have produced varieties far more bizarre and "unnatural" than anything so far engineered with molecular biology techniques. One day that won't be true, but currently our genetic engineering is pretty simplistic.

It's kinda funny that the vast majority of people are much more concerned about genetic engineering than traditional breeding right now despite the safety record of GMOs, which is arguably better. This is completely understandable. I think it's a really good example of how common sense intuition often turns out to be a pretty unreliable method of divining reality. People were really scared of vaccines when they were invented too. This was another technology that sounds like a really terrible idea at first, but turns out to be an invaluable tool when you have the nitty gritty down. These are both normal first reactions for rational people, I think. At least in comparison to more far-out ideas like "intuiting."

Intuiting is a term that some mycophiles have used to describe the putative (and false!) idea that humans can determine if a wild mushroom is poisonous or edible by their impression of it. I guess some people are really eager to find shortcuts around such boring pursuits as scholarship. Why study which potential foods will kill you if you think you can just believe you have an innate ability to sense if something is "good" or "bad" for you? The naive idea that the world is split into dialectic opposites of black and white points toward the gray.

There's a lot of subtle variation in the botanical world. Sometimes single species of fungi or plants exhibit huge ranges in concentrations of potentially poisonous or toxic chemicals. Wild almonds are toxic because they produce cyanide when broken. It's thought that domesticated almonds (which obviously don't produce cyanide) are descended from a mutant wild almond that failed to produce cyanide.

I don't think the metabolic pathways and regulation for cyanide production are really known in Prunus. When my friend who works in an almond lab heard that me and my lab mate had tasted the apparent peach almond he was a little alarmed. Apparently this kind of haywire genetic mixing happens a lot in Prunus species and it's happened before that a fruit is produced that looks like chimera of a few different fruits that we think of as distinct.

I still think this would be a great variety for the supermarket or farmer's market. It's a hell of a lot better than a "Grapple" at any rate. In the end, with breeding or GMOs, it all comes down to empirical testing. You can't always predict whether something is a good idea just based on experience or established theories. New foods and new versions of old foods just need to have an eye kept on them to make sure no unexpected poisons or other hazards creep in.

Do this, and all this new fruit will need is a name.

Devourer of Radiation

I'm surprised that I had forgotten about this story until I caught up on my article reading list this afternoon.

Ionizing Radiation...Enhances the Growth of Fungi - PL0S 0ne

(this open access journal is part of a audacious federal project worthy of its own post...coming soon)

But anyway, here's the punchline:

Some fungi may be capable of consuming radiation.

The story:

Melanin (the pigment in your skin that protects you from the sun) is an amorphous aromatic polymer that plays many different roles in many different organisms. Fungi use melanin both as a shield against the environment and a weapon against hosts (another story I intend to follow up on). Melanin has been well documented to shield cells from the damaging energy of electromagnetic radiation, such as UV light, by both absorbing and scattering photons and electrons. The authors of this paper set out on this topic with the hope of characterizing the physico-chemical changes that take place when melanin molecules intercept light.

In the process of their experimentation, they noticed that three species of melanized fungi grew significantly more (by four measures) when they were irradiated than when they were not. They also observed that melanin was capable of increasing the redox reaction of NADH and ferricyanide when irradiated (by passing electrons between the two chemicals).

Towards the end, the authors review previous indirect evidence for the idea that radiation is beneficial for the growth of some melanized fungi. One species has been found to be radiotropic - preferentially growing towards sources of radiation. This organism, Cryptococcus cladosporiodes, has become very common in the region surrounding Chernobyl since the meltdown. In both lab and field studies, other species of melanized fungi have been found to grow towards radionuclide-cotaminated soil particles, which were then apparently consumed.

So it may be possible that some melanized fungi are able to live off radiation (both electromagnetic and from decaying radioactive particles), I presume, by capturing photons/electrons like chlorophyll pigments and passing them down the electron transport chain.

Maybe we can turn all the nuclear waste holding tanks around the country into fungal fermenters instead of fighting the NIMBY monster of Yucca Mountain.

Orthotydeus lambi!

One of the most interesting talks I saw at APS was David Gadoury's "Very small sheep." He began by describing how his group failed to detect significant epidemics of powdery mildew (a plant-infecting fungus) on a wild species of grape (a plant that is very susceptible in conventional agriculture). In greenhouse experiments, these wild grapes were just as susceptible as agricultural grapes to powdery mildew when inoculated. They discovered that a species of wild mite, that occurs throughout the United States, control powdery mildew of wild grapes by roaming their leaves and grazing heavily on the spores and mycelium of the parasitic fungus.

They then asked themselves if these mites lived in commercial grape fields, and if not, if something could be done to encourage their presence. They first suspected that the mites were absent from commercial grape varieties because these varieties have many fewer "hairs" than the wild species - and these mites are thought to rely on these hairs in order to hide from predatory mites. But despite having fewer "hairs," known as domatia, mites seemed just as happy to live on commercial varieties - in fields that weren't sprayed with pesticides...

Agricultural grapes are routinely treated with pesticides to control damaging insects and fungi, so they ran an experiment comparing mite populations in grape fields treated with different pesticides. Ironically the "organic" fungicide, sulfur, killed the mites, but some of advanced synthetic fungicides didn't hurt the mites, at least not at lower application rates. One member of the audience, possibly hoping for an organic solution, asked if mites might be found that were resistant to sulfur. David replied that it was not possible, and that you might as likely find an organism that's resistant to "fire" - reflecting the extreme toxicity of this "organic" biocide.

They then tried to see if mites could control powdery mildew in the absence of pesticides. It turns out they could - but not to economically acceptable levels. In the end, the best treatment was a low level of fungicide that controlled powdery mildew partially, yet allowed mites to exist to control the rest. Not a pesticide-free solution but certainly better than the original!

San Diego Conference 2007 - no, not comic con

Well, I just got back from the APS conference in San Diego this afternoon. Several of my colleagues felt somewhat let down by this meeting. It seemed that many of the talks and posters lacked the quality of, at least, last year's meeting in Quebec City. I imagine it was just bad luck which labs decided not to attend this year. At any rate I have two stories in preparation for you.

The first was a pretty exciting talk by David Gadoury of Cornell. Biocontrol, the use of predatory/parasitic organisms to control pests in place of pesticides, has long been a holy grail of plant pathology. His talk described (a very rare!) example of a native organism controlling severe epidemics of a serious plant disease in a mainstream agricultural crop. Successful biocontrol is virtually unprecedented as it is, but this talk interested me additionally for the system's apparent sheer practicality, and interesting interactions with pesticide applications (hint* synthetic helps, organic ruins!). more coming soon...

The second story I have is based on a presentation by Dennis Avery of the Hudson Institute. He started off his presentation with a scathing assessment of several "green" solutions to the status quo such as organic ag and biofuels. To the extent that he spoke within subjects I've studied (~80% of his points), he was dead on (with very clever and informative examples) but he also ventured onto potentially thinner ice - e.g. denouncing any correlation between human artifacts (specifically elevated CO2 levels) and global warming. I've never really taken the time to look at the evidence for this myself, but after his talk I feel this is pretty intellectually (and literally) lazy. The way the media has handled scientific topics from organic ag to stem cells really calls for everyone to start taking more responsibility to critically evaluate "facts" that they're presented with.

At any rate, the story I'm preparing will include some research into the goals and financial backers of this institute and associated individuals. At the very least, I'll share my notes from his presentation (hopefully with some stats-checking and link to his power point file).

I'll follow up with a look into the primary source evidence for anthropogenic global warming. In the unlikely case that we don't have good evidence that human industry causes significant global warming, it would be foolish to waste conservation cash and effort on this specific goal.

cheers!

Humanized moss and cheap drugs

For the first few millions years of our existence we got our chemicals directly from other organisms or the ground. People managed to come up with a lot of clever ways to extract, purify and modify these chemicals over the years since to make useful stuff: leather, beer, bronze, paper, vulcanized rubber, and the plastics of the great synthetic chemistry boon of the first half of the last century. It's been even more incredible what ingenuity people have demonstrated in identifying chemicals with medicinal properties in the organisms around them - and improving them. The significance of penicillin was not lost on the scientists who noticed it clearing colonies around the little ascomycete that produces it, but it didn't start saving soldiers until an ambitious germplasm collection and breeding project resulted in an isolate that produced prodigious quantities of the antibiotic, and synthetic chemistry altered its chemical nature to protect it from stomach acid. It's a testament to this triumph that those of us born since have such a cavalier attitude toward "infection." Lacerations are rarely fatal in the developed world these days.

Scientific medicine has begun to turn on the fulcrum of molecular/personalized medicine. Enormous investments have been made to determine the chemical signals that make the difference between a well-behaved, healthy cell and cancerous or infected ones. Increasingly, chemicals have been identified that radically affect the procession of disease, but they are often too complex to be synthesized economically by traditional synthetic organic chemistry.

As there's nothing new under the sun, we're back to looking at plants for our medicines. Organisms make chemicals. It's what they do. Chemicals that would be exceedingly expensive to produce in a test tube are routinely produced in our own bodies. So what happens when a chemical in our body is found, under certain conditions, to cure?

Bioreactors are (largely still hypothetical) organisms that has been genetically engineered to produce chemicals we value - medicines, industrial feedstocks, foods, and fibers. Medicine leads the way since we pay the most for it. Several systems have been successfully used/proposed to produce these engineered chemicals. These include transgenic animals, liquid culture of mammal cells, liquid culture of bacterial or fungal cells, or plants. Each has pros and cons. Plants for example can be grown (in agricultural settings) far cheaper than any other bioreactor, but present a high containment risk (i.e. if you have a transgene that you REALLY don't want to escape into the natural world, you're better off in a BSL-4 factory than some field out in Iowa).

And here's what I really am here to write about: An article I came across the other day that suggests that moss may be the ideal bioreactor*. I hadn't realized it was in the running. In a few decades, when you're being kept alive with cutting edge drugs that used to cost millions of dollars a gram, you may have that green stuff to thank.

Many of the advantages of moss also exist in "true" plants, but there are additional ones.

1. Plants (like mammals) can produce complex, multi-part, and highly modified chemicals. Bacteria and fungi generally produce simpler and generally less 'animal-like' chemicals.
2. In contained cell culture, plants can be grown much cheaper than animal or microbe cells
   
3. Plant bioreactors won't be accidentialy contaminated with human pathogens

The most exciting part of this story is that moss is very amenable to genetic engineering - it has a small genome, and responds readily to many tools in the genetic engineer's toolbox. One of the main drawbacks to plant bioreactors is that style in which they add sugar groups onto their proteins (glycosylation) - they tend to be recognized by the human immune system, producing (rarely but significantly) serious allergic reactions. But mosses can still grow normally when their plant-specific glycosylation pathway is heavily altered. Mosses can be humanized, replacing their molecular gears and cams piecemeal with animal versions that are more compatible with us. They can be engineered to produce complicated, specific chemicals, CHEAPLY! in big tanks, without the risks associated with putting things in your body - such as infection and allergic shock.

* Current Opinion in Plant Biology 2004 7:166-170

Welcome!

I've started this blog to document my last year (*theoretically) of graduate school and my pursuit of a postdoctoral position, and (again theoretically) a real life. I'll be writing about the process and the thoughts I come across along the way.


gene safari

1. a pointless exercise in genomic stamp collecting.
2. a study with no planned or fortuitous application to theory or practice.
   

no, the seminar was awful. he just showed us a slide show of his most recent gene safari


upcoming chapters...

• Humanized moss
• How to destroy/save the world with agricultural biotechnology
• Death of a Discipline - a view from inside
• Why organic agriculture is bad for you, the planet, and the future of human decency
  

enjoy!