Thinking while sick

Back when I watched TV, which is many years ago, I would sometimes watch Star Trek. My least favorite character was Mr. Spock. My objection to Spock was that he was extremely foolish in a way that he should have been smart enough to recognize and correct. His foolishness was based in his refusal to admit the importance of understanding emotion and psychology. He would respond to any statement about feelings influencing actions with, "That's illogical," without considering the fact that these statements were also true. Feelings do influence behavior, and to deny that fact, or fail to act on it is illogical.

I was thinking about this last night in the context of the placebo effect. The placebo effect is surprisingly powerful, very easy to demonstrate convincingly, and I've never heard a plausible argument for how the physiology behind it works. There is also good evidence for a negative placebo effect, that believing something will harm you can make it somewhat harmful.

This was on my mind because I have been sick for the last two weeks, with a cold bad enough to keep me from getting much of anything done, and people have started to suggest various home remedies that I am sure don't work. However, because of the placebo effect, I wish I did believe they worked. My inherent skepticism keeps me from gaining the demonstrable benefits of almost any worthless snake-oil. On the other hand my previous experience of frequent and lengthy sickness convinces me that I am likely to stay sick, surely contributing to a negative placebo effect.

It was these thoughts, plus snippets of the Norse myths Iris has been reading to me before bed, that I went to sleep. And what a strange pair of dreams I. First, I dreamed I was in a bar or hall with long wooden tables. Some of my deceased male relatives were there, as were many other people I didn't know. I knew I had only been there long ago, as a child. A man at another table stood, called for attention, and pointed at me. "Look who's come back," he announced mockingly, "Why if it isn't Daniel, the heir to a long proud line of atheists!" I was going to argue, but I woke.

Next, I dreamt that my left thumb-nail had gotten very long and ragged. As I tried to cut it, it started to expanded, unfold and then unroll itself, until it was as big as a post card. It had been tightly folded and wrapped, growing into itself. I cut it off amazed that it could have gotten so big and ingrown without my realizing, and at how compactly wrapped it had been. Looking at my thumb I saw a slot under the skin, maybe a half inch deep just above the nail where the furled and folded nail had rested. Inside the hollow there were areas where minute green plants had started to grow, and areas with many small bloody scabs. I was happy to be able to rinse it clear, and with that I again woke, feeling well rested and fully awake for the first time in weeks.

How do I interpret this? I've decided that simply believing that the placebo effect is helping should be enough to cause the placebo effect to actually help, and that something as simple as a dream of cleansing should be enough to trigger this positive cycle. At present, I am not interested in hearing alternative explanations.

My very first robot

We've just gotten a Roomba. For those of you who don't know, this is one of those vacuum-cleaner robots. It has some obvious advantages (and disadvantages) as compared to just using a normal vacuum. First, I can turn it on and then go back to my sickbed while it cleans the floors. Push a button on the top and it vacuums the whole room. It is low enough to get under and behind the couches and beds, picking up huge amounts of dust and hair in the process. It is fun to watch when one has a fever.
On the downside, the thing is an idiot. In theory it has various "robot behaviors" that help it to efficiently clean the whole room, but in practice it seems to pretty much bounce around the room at random, occasionally following a wall successfully. I should specify that the version we have (440) is probably not as good at navigating as the latest versions (610). It does eventually find its way to most corners of the room, although it took about 45 minutes of bouncing around to have covered our living room fairly well, even after I put up the chairs, trash-can, etc. It doesn't see, and doesn't seem to make a map of where it has and hasn't gone, so it will repeatedly miss clumps of dust sitting in the middle of the floor. Some of these it never got. It has a very small dirt compartment, so after one room it was completely full, although I admit most of that dirt came from under couches where I don't usually get.
On a single charge it did our living room, hallway, office and most of our bedroom, although it needed to be emptied after each room. I left it doing the bedroom while I took a shower. Half way through the shower it started making a rather pathetic beeping. It was under the middle of the bed and had picked up so much lint and hair that its brushes and wheels could not longer turn. I pulled it out with a broom and had to take the thing half apart to clean all the hair wrapped around everything. Oh the plus side, it hasn't looked so clean under our bed in months I suppose with regular Roomba-ing the dust won't accumulate to the point that it becomes a navigational hazard.

With time these things and their competitors will become more advanced and less clueless. In movies and books we always go straight to humanoid sentient robots, without the intermediate step of a self-propelled vacuum cleaner taking two minutes to find its way out from under the desk. This is like the Precambrian ancestor of R2D2.

H1: The universe is 96% aliens.

Most good scientists are deeply impressed by, and even excited about, how little we yet know, how much there still is to find out. Our science and technology are impressive accomplishments, but still very much in their infancy as compared to what is possible.

Imagine, if you will, a tremendously technologically advanced civilization, whose technology just continues to advance. What is the end point? What do they and their technology look like after billions of years of rapid technological advance? I think it is safe to say that we don't know. It clearly wouldn't be anything that we currently have the science or technology to understand. As Arthur C. Clarke wrote, "Any sufficiently advanced technology is indistinguishable from magic." We wouldn't understand this alien technology or what it did any more than Cro-Magnons would understand a wireless modem. This hyper-advanced civilization would presumably have explored ever nook, cranny and loophole in the physical laws that govern the universe and transformed their technology and themselves beyond recognition. We likely wouldn't even recognize it or them as technology or life. We might not even recognize them or their technology as normal matter or energy, although after billions of years they would likely have transformed large parts of the universe itself.

Which brings me back to how little we currently know. Modern cosmology assigns only 4% of the mass/energy in the universe to "normal" matter, the kind we know anything about. 22% is thought to be "dark matter" and the remainder, 74%, is "dark energy." We know little about dark matter and next to nothing about dark energy, except that they are necessary to make our equations work out. Putting to one side the plausibility that the equations are wrong, we are free to speculate on what is going on with that other 96% that we can't see but suspect is there. My preferred hypothesis is that the universe is 96% aliens. Which is a somewhat silly way of saying that other life-forms may have transformed some large portion of the mass and energy in the universe into forms we don't understand. Why should a civilization with the most advanced technology we can pretend to conceive of be expected to leave things as they found them? If conservation of mass/energy is one of the rules they can't get around, couldn't a big crowded universe of aliens be expected to convert a large portion of its limiting resource into whatever form allows them to use this resource most efficiently? Dark matter releases no detectable radiation, and as such leaks no mass/energy. This would also help to explain why SETI can't detect any aliens. A civilization that hoards mass and energy isn't going to go blaring electromagnetism all over the place.

Why under this hypothesis would 4% of the matter be left as boring old stars, dust, black holes and light? Perhaps these things serve some function for the dark aliens. Or maybe we, and everything we can see, are a designated nature preserve with strictly enforced limits on poaching. To try to answer this last question is to move from pure speculation to pure fancy, so your guess is as good as mine.

Evolutionary challenges to gene engeneering a better human

My friend Terry is a bioengineer, as well as a part time futurist. Much of what people in his field work on (as judged by what Terry talks about when he puts on his futurist hat and has a couple of glasses of wine) is thinking about how to modify the human genome to increase our lifespan and healthspan (I just made up the word healthspan, but I bet someone out there is already using it). Much of my work is to understand how and why we evolved to have the lifespan and healthspan we currently do. My understanding of my work is not promising to my understanding of this part of Terry's colleagues' work. In my view, bioengineering a much longer lived human will be extraordinarily difficult for several reasons.

First, we have a great many systems that seem to fail at about the same age, and there are good evolutionary reasons why this should be. Why bother building a femur that last longer than your heart, or your brain, or your pancreas? So to engineer a much longer-lived human, one has to be prepared to make a large number of changes to see a small effect. Terry counters that there will inevitably be some low-hanging fruit, and I concede this point. Simply by editing out some of the purely harmful mutations in the human gene-pool, we can probably extend average life span by a few months or maybe a couple of years. But because so many things fail at similar ages, no one or two or 100 changes could give us healthy 150 year olds.

Second, many individual genes have an enormous number of different effects in a wide range of systems, tissues and traits. When a gene has more than one effect, this is called pleiotropy, and we are chock full of pleiotropies, most of which we don't yet know about or understand. DNA is not like a blueprint, where you can just erase one wall, re-route a few wires, and draw in a new door. It is more like a vastly sprawling and disorganized system of interacting computer applications, add-ons, duplicates, and operating systems (only without any comprehensible order, annotation or easily understood compartmentalization). Something which functions as part of an unnecessary application may also be used in several disparate parts of the operating system. Modify a line of code and all sorts of unintended things can happen. Evolution has fine-tuned this system of interactions through millions of generations of trial and error, with emphasis on the error. Our best computer simulations are barely able to comprehend the folding of a single amino acid string into a protein, let alone a whole cell or organ or human, and animal models only go so far. So the process to modify evolution's optimization would not be fun, fast or clean. Our various bits are tuned to work together, and most potential single modifications can only move us away from that local optimum.

Terry counters that in many cases what evolution was tuning was utility in the form of health/strength/life vs. cost in the form of calories. A large part of the theory of life-history evolution is based on models where developing organisms have limited nutritional resources to invest in important tasks like growing, healing and reproducing. If one assumes unlimited calories are available, one can theoretically grow, reproduce and heal maximally all at the same time. And in Terry's view (which I can't help but see the wisdom in) anyone who can afford to play with the human genome can also afford plenty of potato chips. For the relevant population, calories are no longer limiting. In fact, we go out of our way to burn extra calories now. Spending calories lavishly to buy a few extra years of life or more garish secondary sexual traits is a win-win. The bioengineers of the future will have the advantage over evolution, because they won't have to worry about one of the main constraints evolution was dealing with, calorie restriction. So we may have to change a few things at once to make it all work well together, but we can do that. We can, in my imagining of Terry's thinking, reengineer the organism to its new environment.

It occurred to me last night that there is third, bigger and more insurmountable barrier to re-tuning. One that is not just a technological limitation: Breeding. Humans have been known to breed with each other, and in doing so they mix their genomes. You have half the genome of your biological father and half the genome of your biological mother. Imagine if your uber-mench father had a carefully altered suite of genes, and your mother was a good old-fashioned non-GMO woman. What do you get? You get half a carefully altered genome mixed with genes they were never designed to interact with. Chances are, you have all sorts of wacky health problems, and greatly reduced longevity. It would be like taking half the code of Mac OS 9 and half the code of OS X and expecting a stable operating system.

This means that every change and group of changes would have to be carefully designed to be back-compatible. The alternatives are gene altering the entire human population (which would never ever ever ever work (and I very rarely use that many "ever"s in a row)) or engineering the longevous new humans to be incapable of interbreeding with the old model. They'd have to start by separating off one population as a seperate species, Homo terrii, and only thereafter get serious about reengineering.

So suppose the engineers decide they want to make everything back compatible?
I'm not convinced this would work either. Most mutations are bad for you not only because they break a piece of the system, but because they make a new piece that doesn't work with what is already there. Requiring back compatibility means we have to have every piece work with not only the old set of genes and the new set of genes, but every possible combination of old and new. Evolution, largely free from constraints of time, funding and ethics, accomplishes this by letting those individuals who have bad combinations die out until there are very few harmful combinations possible. To extend the computer code analogy, this would be like trying to write OS XI in such a way that if one blended the code with OS X, it would still work. It is possible to do, but XI would end up looking an awful lot like X, too similar to be more than a service update.

This leaves only the option of creating a population incapable of breeding with normal humans and altering their genes extensively to try to overcome a large number of age-limiting factors at once. Again my understanding of evolution suggests a major difficulty. To do this successfully, one would need a large population all gene-altered simultaneously, to avoid inbreeding effects. One can't start a new population with just a few individuals and expect that species to have a decent chance of surviving well. Even if the species does make it through, there is likely to be an extended period of decreased lifespan and healthspan while the inbreeding kinks work themselves out and the population increases in size and genetic diversity.

Without doubting that bioengineers will continue to make things that seem impossible become projects of undergraduates, I consider it highly unlikely they will achieve any very significant advances in human longevity in the next few decades.

(NOTE: I sent this to Terry for comment or objection some time ago but he has been busy with 'job' and 'editing the book.' I take his failure to offer a substantive reply as evidence that in some basement deep under campus, his department is already failing to build an immortal human.)

Catnip -> Olfaction -> Happy

My Friend Terry Johnson is a lecturer in Bioengeneering at UC Berkeley. He also writes the Ask a Biogeek column for io9.com. Now he is one of the judges for their Mad Science Contest: Build a Lifeform. And, in investigating my idea for an artificial organism, I came across this abstract:

Hart BL, Leedy MG.1985. Analysis of the catnip reaction: mediation by olfactory system, not vomeronasal organ. Behav Neural Biol. 44(1):38-46.

Pet owners and behavioral scientists alike are fascinated by unique behavioral reactions that cats show in the presence of catnip. These experiments explored the possibility that the catnip reaction might be triggered by chemosensory stimulation of the vomeronasal organ. In the chewing and mouthing of the catnip source, substances might be dissolved in saliva and transported to the vomeronasal organ. The rolling and rubbing during a catnip reaction might be a sexual response activated by the accessory olfactory system since the system projects to parts of the brain involved in mediation of sexual behavior. However, removal of the vomeronasal organ did not attenuate any of the behavioral reactions to catnip. Olfactory bulbectomy immediately eliminated catnip responding, revealing that the chemosensory stimulus evoking the catnip reaction is undoubtedly mediated through the main olfactory system. Catnip activates behavioral elements associated with several species-specific behaviors, including sniffing and chewing as associated with oral appetitive behavior, rolling and rubbing characteristic of female sexual behavior, batting the catnip source characteristic of play behavior, and a type of kicking associated with predatory behavior. These behavioral reactions occur randomly and intermittently.

The moral of the story seems to be that:
A. Cats respond to catnip through their olfaction, the type of smelling that humans do fairly well, rather than through the vomeronasal organ, the part of smelling that humans don't seem to do at all.
B. Catnip elicits from cats behaviors associated with almost every active things cats enjoy (eating, playing, sex and hunting). Catnip does not elicit the calming and resting behaviors such as self-grooming and napping that cats also enjoy. Catnip also does not elict behavior associated with things cats don't enjoy (fighting, danger, housechoirs).

Based on this, and my own observations, it seems likely that catnip is a quick-acting stimulant, extremely pleasant to the cat and absorbed through the olfactory epithelium.

Stefanie Schwartz, in her book "Psychoactive Herbs in Veterinary Medicine" list some other useful facts. Catnip response is not associated with any know histological or physiological effect, (meaning that while it certainly does something in the body, it is something subtle) catnip is not toxic even at relatively high doses, and the physiological and psychological effects are very different in cats than in humans. In humans, catnip is mild sedative, and smoked catnip is said to have similar psychtrophic effects to smoke marijiana. In cats, it is clearly a stimulant. In neither species does it have any known side effects.

Nepetalactone, the active ingredient, is also aparrently a powerful insect repellant, driving off both lice and cockroaches many times more powerfully than does DEET.