Category Archives: Science

prions, mad cows and memes

Years ago, when I was in school, there were two sources of transmissible disease: bacteria an viruses. This idea was so well entrenched that it was very hard to suggest that there might be a third category. Of course, congenital disease and poisons cause disease, too, but these are nottransmissible. In the last 10 years, a new kind of disease-causing element was isolated: the prion. Even 5 years ago it was a contentious issue, but my sense of the landscape is that the consensus has been reached: there are proteins that mis-form and then cause other proteins to mis-form.

It’s known that these proteins get from one animal to another through cannibalism. If a mad cow eats another mad cow, it spreads the disease. How the mis-folded proteins get from the gut to the brain remains a mystery as best I have heard. I’d be really interested to learn of new findings in that area. In any case, there were some rumors in 2004 that there might be a more virulent form of prion disease in caribou, but I never heard any more about it. Interesting trivia, prions and some spider silk proteins are both amyloids.

I ramble on about this to illustrate a point: extremely unlikely things (flukes) can have a strong impact if they are in an environment that is “propagative”. I’ll illustrate with a flower analogy then talk about prions again. Let’s say I have a hundred acres of fresh, beautiful, irrigated, tilled soil. It’s ready for seed, but it’s in the middle of a desert and there are no seeds. It’s isolated. The event of a single seed (the size of a grain of sand) falling in that huge hundred acres would be impossible to notice. If you looked for seeds with a magnifying glass, you could look for your whole life and never see one land. But if you just wait and look for flowers, you have a much better chance of inferring that a plant has landed. Probably if a seed lands you won’t notice. You might not even notice the first plant. But given a few growing seasons, you will see a whole patch of earth covered with all of that one seed’s great grandchildren. The event was rare, but its consequences grow very quickly in that fertile ground.

Now let’s return to prions. The seed is a single protein molecule mis-folding. It causes other proteins to mis fold. That means that the fertile ground upon which this seed has fallen is the cow’s brain. And the plant that grows is madness. If cow’s brains are isolated, that’s not a big deal for anyone but that cow. But if the cow’s brains are brought into proximity to other cow’s brains, then that one seed (no matter how rare) will take up the whole space eventually.

Eventually, I’d like to talk about memes on this space. Memes are like flowers and prions and seeds. Given fertile space, they spread. The consequences of that are entirely dependent on the type of meme. Some are beneficial and some are detrimental; some are slow to grow while others spread quickly. They are ideas that jump from one mind to another. As humans, we can choose the memes for which we make our minds a habitat. That is one of our greatest gifts.

More to come.

-Peter

Heparin, analytical chemists to the rescue, and how bias could hurt open science

I was really impressed by the science that tracked down the problem with the contaminated heparin. It made me think of the enormity of coming up with good data in contentious issues like this. I have to wonder what this kind of issues a loaded question like “is this heparin contaminated?” would present for open science.

For people who are unfamiliar, heparin is a drug derived from meat animals that prevents blood coagulation. It’s really important for dialysis patients because in dialysis, blood is passed through a machine to remove the wastes that would usually go out as urine. The machine doesn’t like coagulated blood, an your body doesn’t want the coagulated blood back. So it’s important that it stay un-coagulated. Given that, heparin is pretty important. A bunch of people got sick taking heparin recently (66 died, sadly) and it was up to the analytical chemists to figure out why. It turned out that an impurity was causing the adverse reaction, but the impurity was so similar to the real heparin that it was being missed by the usual tests. In fact, thee have been some allegations that the impurity was deliberately introduced because it is cheaper, and in standard tests will show up as the legitimate compound.

So, to get this figured out, the FDA did something clever. They gave a bunch of samples of the questionable heparin and the good heparin to some analytical chemists, but they didn’t tell the chemists which was which. Two groups of chemists looked for a contaminant and found the same thing independently. The fact that they both found the same impurity in the same sample is good evidence. But without knowing in the first place which sample caused health problems made the conclusion all the stronger.

But I would like to point out that this kind of science is hard. We’re looking at a lot of work, yes. But in this kind of business, it’s so murky and so easy to be biased that careful people need to blind themselves to the facts that might affect their interpretations. I’ve been reading a lot about open science recently, and I think it’s a marvelous idea: share data the way people share code so that the maximum good can come from whatever work people are doing. The problem with the idea is that whole “science is hard” thing. If people start sharing preliminary data, and they have biases and they share these biases, we could end up with open sciecne discrediting itself pretty fast. Unlike broken code that just doesn’t work, broken science can persist for a long time. It would be a shame to see something so promising become the home of charlatans and the self-delusional.

-Peter

spider silk proteins, microfluidics, and cool stuff that is small

A pair of German groups collaborated to produce an artificial spinarette. They made very small tubes (called Microfluidics by those in the business) into which they injected engineered spider silk proteins produced in bacteria. The obvious cool tings aside (e.g. arachnoweave armor) there are several interesting scientific oddities. The first is in the aggregation of protein eADF3. According to the article, at low concentrations it forms aggregates. But if you add shear flow (like forcing it through a small channel or a spinarette) it makes fibers instead of particles. That’s pretty strange.
Here’s something else. The protein aggregates in salt water under static conditions into tiny particles. These particles unfold and dissolve in pure water. The the fibers made of the same stuff in the same conditions stable in pure water. Something pretty drastic has changed about how those proteins are structured when they assemble under the shear conditions in the flow of that microfluidically confined stream. Indeed, spectroscopy shows a high beta-sheet content of the fibers, although I didn’t see anything about the beta-sheet content of the particles.
But these authors go one step further. A two part mixture of two silk proteins, both found in spiders (the above mentioned eADF3 and another, eADF4) produce a twisted fiber of higher strength and similarity to the natural product of a spider. If you’ve ever watched a nature show and seen a spider at work, you’ll know that they have to pull the silk tightly when they are spinning in order to make it strong; this explains why. The shear forces of the fluid moving through the spider’s little orifice are really important. Maybe that’s another step toward that arachnoweave armor. That and that d3o stuff (like a d3o Hat to protect your head) would make a product fit for Batman.

It’s not recombinant spider silk, but the D3O videos are worth looking at, if you have not already.

-Peter

Durable goods, maintenance, the maker ethos, and the first inroad to voluntary simplicity

Durable goods:

Real durable goods last and can be repaired and maintained.Then there are consumables, things you use for a while then throw away.The problem is that some things, in order to be competitive in price, look like durables but actually are designed to be consumables.Take air conditioners for example.

The laboratory where I work bought a a consumer-quality air conditioner for ~$500.It was supposed to run in a hot lab to take the thermal stress of some of the equipment.Within a year it had failed.It seems that the fail point was a single motor among 3 or 4 of the motors in there.Now, there might be a cascade failure situation.But in the end, it’s probably one motor replacement and the thing is back in shape.But we can’t get that one motor.The company won’t sell us just a part, and they want $75 plus transportation to have a rep come look at it without any guarantee he will be able to do anything.

So, what we have here is a disturbingly common situation of a consumable product masquerading as a durable product.What that means is that AC units used to be considered something you install, maintain, fix and keep around.It was durable.Maybe it cost $1000, but you expect that with $100 per year maintenance, it will last forever.Well, this AC unit only cost $500! A great deal! Except it wasn’t a durable good.It doesn’t cost $100 per year to maintain, it has to be fully replaced every year.

This is a different business model.How this works: produce the cheapest possible product in order to compete for foolish consumers’ attention.People are going to impulse buy on credit, so they are not investigating what is the best deal.So the lowest sticker price is going to get the sale.And, if the product is cheap and breaks, that’s all the better.Since it had a very limited warranty and no plan for maintenance (this thing doesn’t even have screws – it’s snapped together) it was virtually guaranteed to produce a second sale quite soon after.

Now I’m far from being the first to notice this trend; there is a growing subculture of people who are saying they want to be anti-consumers.They want to conserve and maintain.It’s a service-oriented culture that looks at making things last rather than making more things.I like that mentality for lots of reasons.It means more thought has to go into the product.It means less stress on the environment.It makes people more aware of their purchases and happy with their decisions.It’s a lower stress, higher reward lifestyle for more people. The people involved are contributing directly to the quality of each others’ lives rather than trying to produce as much crap as possible and trick each other into buying it.

-Peter

P.S. Here’s the Rev. Billy of the Church of Stop Shopping to break it down.

The internet and peer review

I went to look at some old Ze Frank videos and see what that guy was up to after my last post. As usual, he’s hard at work organizing a cavalcade of entertainments. One thing that I ran into on a tangent was an article on First Monday about Ze Franks’s experiment. I had forgotten about First Monday. It’s a peer reviewed journal about… well, I was never sure what it was about. I read some articles there at some point and never really caught a theme. So that’s fine, not all journals need a theme, but it does raise issues about what constitutes a peer.

I can’t keep up with all of my professional reading much less some theme-free tangential journal, no matter how interesting one article might be per issue. So I forgot the whole thing. But now I’m reminded, so I’ll tell you about it. The whole peer review system in general is a strange one. If you want to get into a fight after an academic seminar, bring up peer review.

It’s (almost) always anonymous, and there was a court case recently in which a journal was asked to reveal who the reviewers were for a published study and they refused. The idea is that if you’re anonymous, you will be more likely to give your honest, critical opinion. It’s supposed to keep reviewers safe from the repercussions of a bad review.

There’s lots of people saying the whole system is outdated. I would compare it to judging a youtube video by the first 3 comments. In case you’re wondering, the single deepest pit of scum and villainy in the known universe is the youtube comment area. It sucks away my faith in humanity whenever I read it, so I generally do not. This relates to a theory of the internet presented Mike “Gabe” Krahulik (NSFW).

Back to the subject at hand, we’re in an age when continuous peer review in real time is happening constantly all over the internet. The academic community is using a century-old social technology because the consequences of moving to something else are unknown. And, as youtube illustrates, some of those consequences are horrific. So, I sympathize.

-Peter