Monday, July 28, 2008

The DNA Network

The DNA Network

Sex & SMBE in 2009 [evolgen]

Posted: 28 Jul 2008 04:00 PM CDT

SMBE2009_small.jpg

The University of Iowa is hosting next year's meeting of the Society of Molecular Biology and Evolution, SMBE 2009. I usually go to the annual SMBE conference, and I was probably going to attend SMBE 2009. Now I'm definitely going. Why? Because John Logsdon just announced that they'll be hosting a pre-conference meeting on the Evolution of Sex and Recombination.

The Sex & Recombination meeting was supposed to happen this summer, and it was scheduled for the week prior to the Evolution 2008 conference in Minnesota. But mother nature interrupted, and the flooded campus was in no state to host the conference (coitus interruptis as John calls it). So it's really good to hear that they'll be able to have the meeting in 2009. Hopefully I'll have some sexy results to present.

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Models, Ideologies and Self-Denial [The Daily Transcript]

Posted: 28 Jul 2008 02:39 PM CDT

As a scientist, I traffic in data, ideas, models and theories.

I spend a lot of time thinking about how the whole process works. And many scientists and science philosophers have thought about this as well. One inescapable fact: humans tend to duck, deny and fool themselves into believing certain ideas even when data points the other way. It's the little voice in our head that says "I am not biased, it's everyone else." Humans are highly prone to much cognitive dissonance. It's just that in science you must confront this reality head on, all the time.

These tendencies exist everywhere and are held in check by institutional mechanisms. In the sciences and most of academia, this tendency is countered by our most treasured currency, trust. Scientists are known to be very skeptical individuals, this reflects the fact that in the scientific world trust must be earned. We all struggle in the lab to get results and generate theories that can advance the field we're in. These theories and models can then be tested further directly or indirectly. If your experiments are uncontrolled, unreliable, your results do not jive with other published results or your models have very little or no predictive power, you will never establish the trust that is required to succeed. The assessment of a particular scientist's reputation is aided by the many scientific institutions, such as publishers (who need to build up their own reputation), peer reviewers, tenure committees and a constant stream of new data from competing labs. Sometimes a mistake does happen (cold fusion being the best example), sometimes it's deliberate, sometimes it's sloppyness, but in the long run these problems are weeded out, science marches on. Within this framework most scientists learn to be careful with their experiments and their interpretations - after all their reputations are in play and the steady march of science doesn't give a damn.

In other arenas, such as in American political discourse, the cognitive dissonance that plagues human thought is rampant.

What is the difference between these two worlds? Why are they so different? Who is to blame?

A finger could be pointed at the main stream media (apparently now known as the traditional media). They have been seen as playing the role of public critic/skeptic and as the fact finder. However over the last eight years they've mostly played the role of stenographers and cheerleaders. Some may even claim that they've always played this second role - and to a certain extent they may be right. But it's definitely been worse in recent times.

Part of the problem is that those in position of influence within these institutions have forgotten how messy the human mind is. They forget that it is easy to fool yourself - the human mind easily gravitates towards ideas that are convenient. I guess there is no equivalent to the steady march of science. It seems to be all about short term profit and not long term reputation. And recently the whole situation in the MSM has been aggravated by the proliferation of political pundits. This is not only to forget the problems of ideology, but to fully embrace it.

Iraq is the enemy? They've must have helped Bin Laden. The schools are bad? Let the invisible hand of the free market magically fix things. You don't like the president's plan? You must be a traitor. These are simple thoughts that conveniently support the thinker's own inner bias. The pundits who spout these ideas are supposedly experts in every subject, but in the end are nothing but apparatchiks for the powers that be. These hacks are a case study in ideology-gone-wild.

Why did this happen?

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Mass v Gas and the Biomass Buzz [Sciencebase Science Blog]

Posted: 28 Jul 2008 07:00 AM CDT

Biomass on the road to RouenThere are two main schools of thought when it comes to oil supply. There are those who believe that oil supplies are strictly limited and that we have passed the peak and will soon (40 to 60 years) run out of oil with which to power our vehicles. Then are those who believe supplies could last much longer than current predictions suggest. The latter school of thought believes there are either reserves that are simply too expensive to extract at today’s oil prices but they will be tapped ultimately or they believe that new sources will be found as the pressure rises. There is actually a third school of thought: those who believe oil is not a fossil fuel at all, but a continuously renewed material that will never run out, but that’s a different story.

During the 20th century and now into the 2000s, petroleum has predominated in fuelling transport hinging on the enormous growth of chemical engineering and chemical technology since the beginning of the industrial revolution. Currently, fuels from crude oil is used to fulfil 96 to 98% of the worldwide energy demand for cars, ships and planes.

Whichever school makes the grade in the end shouldn’t really matter, as Chemical engineers Maria Sudiro and Alberto Bertucco of the University of Padova, Italy, and many others have pointed out:

The currently known reserves of methane and of coal exceed those of crude oil by factors of about 1.5 and 25, respectively.

They reckon any analysis of fuel supply and the potential for using biomass as a so-called renewable source is not quite as clearcut as one might imagine. They explain that the problem of producing synthetic liquid fuels by alternative routes to conventional petrochemical means is mixed. The industrial processes of Gas To Liquid (GTL), Coal To Liquid (CTL), and Biomass To Liquid (BTL) use natural gas, coal, and biomass as feedstocks, respectively, all with varying efficiencies and resulting energy densities.

Now, writing in the International Journal of Alternative Propulsion (2008, 2, 13-25), the researchers have modelled each process on a weight basis per unit of feedstock (natural gas, coal and biomass/wood). For hypothetical plants running at a production rate of 100 tonnes per hour, they found that yields are about 70, almost 33 and just under 17%, respectively. Moreover, the carbon dioxide emitted per unit mass of liquid fuel is a relatively low at 0.9 kg for GTL, almost 5 kg for CTL, and over 6 kg for BTL processes. So, on the face of it, it would seem that gas-to-liquid fuel
beats
coal and
biomass hands down
in terms
of efficiency and
carbon footprint
gas-to-liquid fuel beats coal and biomass hands down in terms of efficiency and carbon footprint.

Of course, in some sense, the use of biomass can be thought of as carbon neutral as it is purportedly a renewable resource. However, such fudging of any analysis always seems to ignore the environmental impact of sourcing the biomass, whether that is the assimilation of waste for conversion, the planting of fuel crops, and the energy use and waste products of the conversion process. So, truly no solution is entirely clearcut when one takes into account the complete lifecycle of the fuel production process, well-to-wheel, as it were.

At first, site gas to liquid, may not seem necessarily to be the perfect option. This is especially so if one takes into account costs and political issues, such as access to a ready supply for any region hoping to exploit GTL. As such, the Padova team has evaluated production costs of synthetic fuel in a GTL process. They considered two different scenarios: the case of a production plant close to a natural gas supply. The second case is of a GTL plant remote from the country with the gas supply.

Their financial analysis reveals that the return on investment for a GTL plant with a local supply occurs in less than two and a half years, whereas it is almost seven years if the supply is in a country remote to the manufacturer. They conclude that given our reliance on oil, its derivatives, and putatively petroleum substitutes (and despite hybrid and hydrogen):

The economical and financial analysis has shown that it is extremely convenient to invest in a GTL plant located in countries where natural gas is available at a low price, thanks to the favourable return of investment.

It could be that as biomass becomes more accessible, possibly to the detriment of food and water supply, that the BTL approach to fuel becomes more viable. However, given the abundance of natural gas and the potential to release that from locked in sources, such as frozen methane hydrates, GTL could be the way forward for some regions of the world faced with dwindling oil supplies, especially given the lower carbon footprint compared with liquid fuels derived from coal or biomass.

Sudiro, M., Bertucco, A. (2008). Production of synthetic gasoline and diesel fuels by alternative processes using natural gas, coal and biomass: process simulation and economic analysis. International Journal of Alternative Propulsion, 2(1), 13-25. DOI:

a

Mass v Gas and the Biomass Buzz

Notes of a Biology Watcher [Bitesize Bio]

Posted: 28 Jul 2008 05:27 AM CDT

My all-time favorite biology writer would, without a doubt, be Lewis Thomas. Twenty-odd years before anyone had conceived of blogging, much less blogging about science, Lewis Thomas was publishing a handful of books that were on science, creative and pithy, and little more than a collection of loosely-connected essays. Lives of a Cell: Notes of a Biology Watcher is the most popular of his books, and is amusing light reading that will entertain biologists of all fields.

Throughout the book, Thomas reveals truly extraordinary facts about biology and microbiology that tend to leave the reader in actual awe. Another of his books, The Medusa and the Snail: More Notes of a Biology Watcher, is in the same vein. For Lives of a Cell, one Amazon reviewer gave this description:

it seems to me that one common theme of several of the chapters has to do with communication — oral, chemical, behavioral, and genetic. Other possible themes include the fact that humans are “not all that.” That we are part of the global system, not running it. Another possibility includes the idea that everything can be an analogy of the way that a cell works — organelles, membranes, cellular processes, products, and so forth.

Medium ImageAs the Wiki entry for Lewis Thomas points out, another interesting quote from Lives was an observation very similar to James Lovelock’s Gaia hypothesis:

I have been trying to think of the earth as a kind of organism, but it is no go. I cannot think of it this way. It is too big, too complex, with too many working parts lacking visible connections. The other night, driving through a hilly, wooded part of southern New England, I wondered about this. If not like an organism, what is it like, what is it most like? Then, satisfactorily for that moment, it came to me: it is most like a single cell.

And so on. His books are insightful and thought-provoking, and use non-techical prose that is uncommon for a person of science. The light-hearted tone makes his books among my favorite light-reading.

Lewis Thomas (1913-1993) himself spent most of his illustrious medical career as a medical researcher and administrator at Yale Medical School, NYU School of Medicine, and the Memorial Sloan-Kettering Institute.

Out of touch... [The Gene Sherpa: Personalized Medicine and You]

Posted: 28 Jul 2008 05:08 AM CDT

Sorry about that. I have been busy writing a book that will hit to store shelves in a couple of months. Here's an excerpt................... "If you were looking for a college level description of...

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Wine Fraud: So Pre-Biotech. []

Posted: 28 Jul 2008 02:03 AM CDT

vinofraud.jpg

Reading The Billionaire’s Vinegar got us thinking that biotech should shortly be relegating wine counterfeiting — any kind of agricultural fraud, really — to the scrap-heap of history. You shell out $3,000 for a bottle of precious Mourvedre? Darned straight you want proof. Companies like Applied DNA Solutions are working on the particulars right now.

Where is human evolution heading? [HENRY » genetics]

Posted: 28 Jul 2008 12:46 AM CDT

Nancy Shute in USNews:

If you judge the progress of humanity by Homer Simpson, Paris Hilton, and Girls Gone Wild videos, you might conclude that our evolution has stalled—or even shifted into reverse. Not so, scientists say. Humans are evolving faster than ever before, picking up new genetic traits and talents that may help us survive a turbulent future.

Mess up CCR2 using zinc finger nucleases and prevent HIV? [Yann Klimentidis' Weblog]

Posted: 27 Jul 2008 11:16 PM CDT

this is pretty cool...using zinc finger nucleases to mimic the protective effect of the CCR5delta32 mutation against HIV infection.
The fourth author has a hell of a first name!

Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases
Elena E Perez, Jianbin Wang, Jeffrey C Miller, Yann Jouvenot, Kenneth A Kim, Olga Liu1, Nathaniel Wang, Gary Lee, Victor V Bartsevich, Ya-Li Lee, Dmitry Y Guschin, Igor Rupniewski, Adam J Waite, Carmine Carpenito, Richard G Carroll, Jordan S Orange, Fyodor D Urnov, Edward J Rebar, Dale Ando, Philip D Gregory, James L Riley, Michael C Holmes & Carl H June
Nature Biotechnology 26, 808 - 816 (2008)
Abstract: Homozygosity for the naturally occurring 32 deletion in the HIV co-receptor CCR5 confers resistance to HIV-1 infection. We generated an HIV-resistant genotype de novo using engineered zinc-finger nucleases (ZFNs) to disrupt endogenous CCR5. Transient expression of CCR5 ZFNs permanently and specifically disrupted 50% of CCR5 alleles in a pool of primary human CD4+ T cells. Genetic disruption of CCR5 provided robust, stable and heritable protection against HIV-1 infection in vitro and in vivo in a NOG model of HIV infection. HIV-1-infected mice engrafted with ZFN-modified CD4+ T cells had lower viral loads and higher CD4+ T-cell counts than mice engrafted with wild-type CD4+ T cells, consistent with the potential to reconstitute immune function in individuals with HIV/AIDS by maintenance of an HIV-resistant CD4+ T-cell population. Thus adoptive transfer of ex vivo expanded CCR5 ZFN–modified autologous CD4+ T cells in HIV patients is an attractive approach for the treatment of HIV-1 infection.

Do we know how Velcade doesn't work? [Omics! Omics!]

Posted: 27 Jul 2008 09:25 PM CDT

In my recent piece on the proteasome inhibitor Argyrin A, a commenter (okay, so far THE commenter) noted something I can't argue with, that there is not a well nailed-down understanding of why proteasome inhibition is lethal to tumor cells. I probably should write up a further exploration of how they might work, but I really need to skim the literature for any new findings (so far, nothing stunning).

As Yogi Berra might say, Velcade (bortezomib) is effective in cancer except when it isn't. Indeed, in cell lines in culture the stuff is devastating, but that certainly isn't what's seen in the clinic. In that setting, there is this obnoxious tease of a signal in Phase I (remember, in oncology Phase I is tried in patients with the disease, not with healthy volunteers as in most indications) followed by cruel let-down in Phase II. Even in diseases where the drug works, such as myeloma, it doesn't work in all patients and some patients become resistant. Perhaps that resistance is the key to the puzzle: understand how tumors stop being sensitive and you'd understand the ones which are never sensitive to start with.

Three recent papers (in Blood, J Pharmacol Exp Ther & Exp Hematol) have found the same mechanism for this transition. Alas, none are free & I've only read the abstract (one of many reasons to swing by the MIT library soon All point to overexpression and/or mutation in PSMB5, the proteasome subunit which binds Velcade. Two of the papers report different point mutations, but both in the Velcade binding pocket and in at least one a reduced affinity for Velcade was demonstrated. Game, set & match?

Well, perhaps not. First of all, all three studies are in cell lines, two in closely related ones. As noted above, cell lines are highly imperfect for exploring proteasome inhibition in particular (and not uniformly reliable for oncotherapeutic pharmacology in general). Judging from the abstracts, none of them went fishing around in patient samples, or if they did they came up dry. Given that PSMB5 is an obvious candidate gene for bortezomib resistance, I'm pretty sure this one's been hammered on hard by my former colleagues. Nobody likes to publish the Journal of Negative Results, which I'm pretty sure is where it would end up. Almost certainly some patients will be found who went from sensitivity to resistance due to mutations in PSMB5, but at the moment it's not the long-awaited (and much desired/needed) central hypothesis of why proteasome inhibition works and which patients it should be used in.

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