November 28, 2007

Reputations On (the) Line

Shrinepracticalethics: Honest Opinions or Bullying? is another of my practical ethics posts. This time about on-line rating systems for teachers. Teacher's unions hate them, but at least in Germany they are protected as free speech. I argue that they are relevant as a way of balancing the formal power of teachers with informal reputation power, and that persistent pseudonyms might make everybody happy.

However, there is an issue I did not have the space to get into: local versus global reputations.

We have always had reputations, and they are essential for the function of society. Without reputations trust would not be possible, and economy would be highly inefficient. In the past reputations were always local to groups, subject to constant reappraisal. Today we have emerging global reputations outside our own group. These global reputations suffer both from lack of context, lack of reappraisal and a high degree of noisiness. The teacher evaluation may be due to temporary affect, and be interpreted very differently by parents, administrators, pupils and teachers. Evaluations may remain long after the situation has changed. And it is easy to lie.

The combination of Internet, free expression and effective search systems means that online, global reputations are inevitable. The problem is that we tend to treat them as local reputations. They are not reliable, consistent, frequently updated or reflecting a particular group. Hence we need to learn to look for the reputation of reputation sources: is someone saying something about me anonymously on an open forum, or doing it under his own name?

We ought to collectively (out of enlightened self interest) look into the possibility of not just making distributed reputation systems but ways of estimating reputation source reliabilities and aggregate scattered reputation pieces appropriately. Much of this is likely already being done in collaborative evaluation research, but to make any kind of software work we also need the social interest and understanding why it should be used. Just as we have gradually learned not to trust something because it is printed or on-line, we need to build a memetic immune system against low-quality reputation fragments. That may prove very tricky, since reputations are just the kind of "hot" social and emotional fact that we tend to fall for.

Posted by Anders3 at 11:41 PM | Comments (0)

November 27, 2007

I have been Varholed

andersvarhol.pngCollection: Masterminds of contemporary Transhumanism is an artwork/portrait gallery by Günter Bachelier that takes pictures of transhumanists and evolves them. I'm honoured to be part of it, in the form of 2000 versions of myself.

I think I would be terribly embarrassed by a traditional portrait; I imagine I would find faults in me or the portrait whenever I saw it (a bit like watching oneself on TV). This approach feels much better: there are numerous possibilities, not all are perfect, but by expanding into the sea of possible selves and possible portraits the overall effect is a kind of meta-portrait. It is not tied so strongly to me, right here, right now in front of the computer, but rather to the complex net entity Anders.Sandberg that extends through time and space. And as a transhumanist I of course find that entity much more interesting than the tea-drinking monkey hammering away at the keyboard.

Posted by Anders3 at 06:00 PM | Comments (0)

Hyperbolic Cover

I'm on the cover of Science News. Or rather, my graphics is there. I did an illustration for the article Shadow World: Science News Online, Nov. 17, 2007 showing a sphere on the Poincare disc with a hyperbolic tessellation.

It is fun to play with hyperbolic tessellations. I recommend Dmitry Brant's program for interactive play. I wonder if one could make an interesting tic-tac-toe game for such a surface? For the 5,4 tiling there are extra diagonals that may make it harder to block the other player.

As for string-particle duality I have no clue. I love duality relationships in mathematics and physics, but I do not understand even string theory so I don't know how to handle the theory described in the article (is that tic-tac-TOE?). However, it seems one could at least make an interesting dual generalisation of tic-tac-toe played on a tessellation by looking at the corresponding game played on the dual tessellation. Instead of putting markers on the polygons, one puts markers on the corners. This is the same for a square tiling in Euclidean space, but in hyperbolic space some fun possibilities may open up.

Posted by Anders3 at 02:49 PM | Comments (0)

November 22, 2007

No Such Thing as a Fair Coin?

cointoss.pngDiaconis, P., Holmes, S. and Montgomery, R. Dynamical Bias in the Coin Toss, SIAM Review vol 49:2, pp 211-235 analyses the process of flipping a coin. Even when vigorously flipped the coin turns out to come up more often the same way as it started. The discrepancy is small - p=0.51 for same side up, something which it would take about 250,000 trial flips to check - but it is hard to get away from.

The reason, as described in the paper, is that the fairness of a throw is dependent on the angle between the rotation axis and the normal of the coin. Imagine a coin thrown straight up, rotating around a vertical axis. Such a coin would of course land with the same face up, being 100% unfair. A coin rotating around an axis through its edge would on the other hand tend to be fair (if it rotated enough times that initial uncertainty in the flip became magnified enough). But a coin with a rotation axis inbetween would be somewhat unfair. The analysis gets a bit more complex due to precession, but it seems that averaged over all rotation axes we get a bias towards same side up. Experimental testing then seemed to confirm this dynamics.

Of course, if the original top side is hidden things become fair again.

Posted by Anders3 at 07:57 PM | Comments (0)

November 21, 2007

Cryo Britannia

DNA coinOn CNE I blog about the bioliberal autumn we have had in the UK. The BMA's report Boosting your brainpower: Ethical aspects of cognitive enhancements is a must read (OK, I helped out in its development, but only to a minuscule extent).

Then there has of course been John Harris book Enhancing Evolution (will it be the #1 transhumanist Newtonmas present this year?) and the usual activities for us at the FHI and Uehiro Centre. Guess why I have not been blogging so much?

Of course, there have been some interesting counterarguments too. A few weeks back we had Michael Sandel over to lecture about accepting the Given (I better blog about that interesting topic). I'm also looking forward to RSA ethical futures event "Boundaries to Human Enhancement" December 3.

I actually think there is something happening on this island biopolitically. The question is if we can get to the point Britannia waives the rules on enhancement?

Posted by Anders3 at 07:06 PM | Comments (0)

Systematic Sloppiness

Cognitive HazardMy first post at Practicalethics is practicalethics: It is 10 O'clock, do you know what your cells are? - about the amazingly persistent problem of contaminated cell lines. It has been known about for more than 40 years, people have spent years fighting it, yet it persists. This is a nasty example of how systematic sloppiness can become in human institutions.

Of course, today in the UK the big news is of course that the government lost 25 million child benefit records on two discs - including names, dates of birth, bank and address details. This is of course another great example of monumental institutional sloppiness and tardiness (the discs have been lost since 18 October, and the banks were alerted 12-18 november).

Hmm, for a going rate among identity thieves (according to a UK newspaper I saw) of £10-50 for the bank details of a person, those discs are worth at least 72.5-362.5 million pounds given the stated number of accounts. Even if they are well encrypted (which everybody seems to doubt) that would be worth a significant decryption effort. Maybe the Storm supercomputer will get hired?

Sloppiness seems to be the natural state of human thinking and action. It takes special effort to avoid, and non-sloppiness is a rather noteworthy situation. That is why people remark about meticulous scientists or precise bureaucrats. The consequences of sloppiness depends on the variance of utility between similar choices in a context. In everyday life it does not make much difference: in science, managing millions of people or life-or-death situations it does. Maybe a cognitive enhancement against sloppiness, something that gives us the mental and physical energy to jump through all the hoops would help us much more to live in our complex world than a mere memory enhancement?

Posted by Anders3 at 06:36 PM | Comments (0)

Ignoring the Children for the Clones

A clone of clonesLast week on CNE I was blogging about the reproductive cloning legislation study by the United Nations University's Institute of Advanced Studies. They suggested more international legislation. Apparently not because there is too much cloning going on, but simply because so many countries make anti-cloning legislation.

The real problem here is that anti-cloning legislation is getting introduced for all the wrong reasons. Defending human dignity, identity or traditional biology are problematic foundations for laws given how little agreement there is about their nature or normativity. But current cloning methods are likely to be inefficient and risky for the health of the cloned child, making reproductive cloning unacceptable in any civilized society for the foreseeable (near) future. So it would make more sense to push for laws preventing the unnecessary risking of children's health rather than stopping reproductive cloning. That would achieve both the aim of curtailing reproductive cloning as well as any other dangerous practice. But yuck-based legislation efforts does not care much for that kind of rationality.

It is all a bit like making cigarette smoking illegal while ignoring pipe, cigar and marijuana smoking because they have other cultural connotations.

Posted by Anders3 at 12:50 AM | Comments (0)

November 13, 2007

Paternalistic Elitist Egalitarians vs Envious Non-Elitist Liberals

Support the hospitalLast week I blogged on CNE about the proposed law in Germany that would deny covering the cost for medical treatment for complications from beauty operation or piercing.

I'm of two minds about this. As a libertarian I think we should carry the costs of what we do. If people want to enhance themselves they should pay for that, and if things go wrong they should pay for that (or have insurance, where they will pay premiums).

That is fine in libertopia. But in Germany (and most other European countries) we have mandatory health insurance systems. This means not just healthcare altruism where we all pay for ensuring that everybody gets a chance of treatment, but also an incentive of worrying about the neighbour's health - if he is doing something to risk it, I'm going to have to pay a small part of the cost. Politicians and other authorities get a strong incentive to be paternalistic and keep people not just healthy but also from doing anything dangerous or unhealthy. As the healthcare costs grow to more and more of the GDP, expect not just smoking, alcohol and obesity to end up in the sights, but also generally risky behavior, exposing oneself to conditions that might cause dementia or expensive chronic disease and so on. Not to mention potentially risky medical enhancements.

Having to pay for a health insurance for everybody and then extra insurance (or direct costs) for oneself if one wants to enhance would make this more expensive than just paying directly for the enhancement and risk management. That is, it would become a more elitist thing. The German proposal might have as effect (if it passes) to make plastic surgery remain a status symbol signalling that one is significantly richer than most. And a similar treatment of enhancement may also help them remain expensive and inaccessible to the masses. Anti-enhancement thinkers would no doubt solve this by banning enhancement, but that only means that now only rich medical tourists or criminals are enhanced.

On the other hand, paying for all medical issues would cost the insurance system an arbitrary amount of money. It has to clearly state its limits. Michael Sandel claimed in a talk that health is a finite goal, once we are healthy nothing more needs to be done. This is clearly untrue, since there are always those that cannot be helped fully and will always benefit from ever more expensive treatments, and even when the basic problems are fixed we desire that extra little bit of health. Any medical insurance system must admit to its limitations and state them.

The problem is of course that few politicians want to be responsible for telling a suffering group that their ailment is not important enough to cover - even when that is rational.

As I see it the choice (or rather, a chance to interpolate) is between an egalitarian system that will promote elite advantage, or a system that accepts inequality but does not give the elite an advantage. The first system will try to expand its coverage for political reasons and become ever more expensive, making it paternalistic and willing to meddle in people's lives. People will be unhappy if their ailments are not in the cake and will try to expand their slice at somebody else's expense. The second one allows more freedom, but will leave many people unhappy because they still cannot afford what they want, and now they have nobody to blame.

Maybe that is the truly important thing to redistribute: blame. If blame is optimally redistributed we are all happy, right?

Posted by Anders3 at 05:56 PM | Comments (0)

November 07, 2007

Magnetic Delays

Big proton quadrupoleThis week on CNE: the EU finally realized that the Physical Agents Directive made much use of MRI impossible. Sanity wins after three years and lots of lobbying to stop a proposal that solves a non-problem.

It is interesting to see how the precautionary principle (invoked to set exposure limits to magnetic fields) is not seen as applicable to EU directives, where harm has to be demonstrated. Applying the principle to policymaking would be quite rational: in the absence of evidence that a proposed policy would be helpful and not have deleterious side effects, it ought not to be passed. Maybe the Commission could argue for a proactionary approach.

Posted by Anders3 at 01:46 AM | Comments (0)

November 03, 2007

The Early Bird gets the Caffeine Pill

The Benefits of CoffeeThis week I have experimented with a new way of getting up in the morning. My problem is that Anders-Sleepy has different goals than Anders-Awake, and is quite adept at resetting the alarm clock. Now I, Anders-Awake, has found a way around this self:

I set my alarm to 6:00 and 8:00. At 6:00 I go up, take a 50mg caffeine pill, and go to bed again. Then I sleep and wake up rested and energetic around 8.

In my case the time for the pill to start working seems to be 1.5 hours. A dose of one pill ensures that I wake up (but still yawning) while two pills makes me start the day much more quickly. The added benefit is of course a regular sleep schedule.

I ran into the problem of a late night one of the days, where I remained awake until 3:30. In this case I adjusted the program slightly, taking the pill at 7:00 and sleeping to 8:30, this seemed to work and the rest of the day was efficient. I became tired earlier in the evening, which was fixed by going to sleep earlier.

Using caffeine to combat sleep inertia is not my idea; a study has shown that it works for naps. Music may also help.

Posted by Anders3 at 12:58 PM | Comments (0)

November 02, 2007

Another Mighty Mouse

Dynamism of a Squirrel on GravelYet another impressive mouse, described in Over-expression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse, Hakimi et al., 10.1074/jbc.M706127200 Journal of Biological Chemistry.

These mice rely more on fatty acids as a source of energy and produce less lactate. They move around a lot normally and could, run 6 km on a threadmill (normal mice ran 0.2 km). They eat 60% more than controls, but apparently remain fit and trim. To make things even better, they live longer and reproduce even at 21-30 months of age.

The extra nutrient need is a likely explanation why this genotype has not appeared in the wild - it only works in a rich environment (and hence answers the evolutionary optimality challenge by a changed tradeoff). The overexpression apparently promoted development of type 1 muscle fibers similarly to the marathon mice.

Seems like this trick ought to work in humans, but as the paper notes, we better check what the effect is on the mind first. But I would not say no to a lot of extra energy and activity - getting calories has never been simpler.

Posted by Anders3 at 02:19 PM | Comments (0)

November 01, 2007

Top 10 Genetic Enhancements

I recently got asked for my list of top genetic enhancements that have already been done in mammals (and hence could presumbaly be done in humans). Here is my list:

1. The Doogie Mouse. Better memory through overexpression of NMR2B. A very simple, yet good demonstration of how plastic our memory system is. Since then several other ways of enhancing memory genetically have been found, with slightly different effects on different types of memory, forgetting and side effects.

Tang, Y. P., E. Shimizu, et al. (1999). "Genetic enhancement of learning and memory in mice." Nature 401(6748): 63-69.

Tang Y, Wang H, Feng R, Kyin M, Tsien J (2001). "Differential effects of enrichment on learning and memory function in NR2B transgenic mice". Neuropharmacology 41 (6): 779–90. PMID 11640933

Wei, F., G. D. Wang, et al. (2001). "Genetic enhancement of inflammatory pain by forebrain NR2B overexpression." Nature Neuroscience 4(2): 164-169.

Wang, H. B., G. D. Ferguson, et al. (2004). "Overexpression of type-1 adenylyl cyclase in mouse forebrain enhances recognition memory and LTP." Nature Neuroscience 7(6): 635-642.

Routtenberg, A., I. Cantallops, et al. (2000). "Enhanced learning after genetic overexpression of a brain growth protein." Proceedings of the National Academy of Sciences of the United States of America 97(13): 7657-7662.

Tan, D. P., Q. Y. Liu, et al. (2006). "Enhancement of long-term memory retention and short-term synaptic plasticity in cbl-b null mice." Proceedings of the National Academy of Sciences of the United States of America 103(13): 5125-5130.

2. Color vision mice. Adding human photopigment allows (at least females) to see new colors. This is extra interesting since it shows the brain can adapt to the signals from a new sense, at least when growing up with it.

Gerald H. Jacobs, Gary A. Williams, Hugh Cahill, Jeremy Nathans, Emergence of Novel Color Vision in Mice Engineered to Express a Human Cone Photopigment, Science 23 March 2007: Vol. 315. no. 5819, pp. 1723 - 1725

3. Methuselah mice. By reducing growth hormone levels long-lived dwarf mice can be produced. The current record holder survived 4 years 11 months and 3 weeks, while normal mice have a two year lifespan.

A. Bartke, H. Brown-Borg, J. Mattison, B. Kinney, S. Hauck, C. Wright, Prolonged longevity of hypopituitary dwarf mice. Exp. Gerontol. 36, 21-28 (2001)

Bartke A, Brown-Borg H. Life extension in the dwarf mouse. Curr Top Dev Biol. 2004;63:189-225.

4. Monogamous voles. Normally non-monogamous voles can be turned monogamous (and more social) by changing the vassopressin V1a receptor.

Young L. J., Nilsen R., Waymire K. G., MacGregor G. R. and Insel T. R. 1999 Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole. Nature 400, 766–768.

Landgraf R., Frank E., Aldag J. M., Neumann I. D., Sharer C. A., Ren X. et al. 2003 Viral vector-mediated gene transfer of the vole V1a vasopressin receptor in the rat septum: improved social discrimination and active social behaviour. Eur. J. Neurosci. 18, 403–411.

Pitkow L. J., Sharer C. A., Ren X., Insel T. R., Terwilliger E. F. and Young L. J. 2001 Facilitation of affiliation and pair-bond formation by vasopressin receptor gene transfer into the ventral forebrain of a monogamous vole. J. Neurosci. 21, 7392–7396

Lim M. M., Wang Z., Olazábal D. E., Ren X., Terwilliger E. F. and Young L. J. 2004 Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature 429, 754–757.

5 Regenerating MRL mice (OK, a case of accidental breeding rather than genetic engineering, and it involves at least 20 genes). These mice regenerate holes punched in their ears as well as some injuries to heart muscle.

Heber-Katz, E. 1999. The regenerating mouse ear. Seminars in Cell & Develop. Biol. 10:415-420.

Heber-Katz E, Leferovich J, Bedelbaeva K, Gourevitch D, and Clark L (2004) The scarless heart and the MRL mouse. Phil. Trans. R. Soc. Lond. B 359:785-793.

John M. Leferovich, Khamilia Bedelbaeva, Stefan Samulewicz, Xiang-Ming Zhang, Donna Zwasdagger , Edward B. Lankforddagger , and Ellen Heber-Katz, Heart regeneration in adult MRL mice, PNAS August 14, 2001 vol. 98 no. 17 9830-9835

6. Schwarzenegger mice and Belgian blue cows. Strength through myostatin knockout. This has occasionally happened naturally in humans and cattle.

Lee SJ, McPherron AC. Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci USA 2001: 98: 9306–9311

Whittemore LA, Song K, Li X, Aghajanian J, Davies M, Girgenrath S, Hill JJ, Jalenak M, Kelley P, Knight A, Maylor R, O'Hara D, Pearson A, Quazi A, Ryerson S, Tan XY, Tomkinson KN, Veldman GM, Widom A, Wright JF, Wudyka S, Zhao L, Wolfman NM, Inhibition of myostatin in adult mice increases skeletal muscle mass and strength. Biochem Biophys Res Commun. 2003 Jan 24;300(4):965-71.

McPherron, AC, SJ Lee. Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci USA 1997, 94:12457

Grobet, L, LJR Martin, D Poncelet, et al. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nature Genet 1997, 17:71.

Schuelke M, Wagner KR, Stolz LE, Hubner C, Riebel T, Komen W, Braun T., Tobin JF, Lee SJ. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med 2004: 350: 2682–2688.

Lee SJ (2007) Quadrupling Muscle Mass in Mice by Targeting TGF-ß Signaling Pathways. PLoS ONE 2(8)

7 The hard working monkeys. Work discipline through a blocked dopamine D2 gene? Monkeys tend to slack off until they get close to a reward they have to work for. If injected with a DNA construct that blocks the D2 receptor they worked at an even rate. This is likely less a case of workaholism and more a case of specific memory impairment for how rewarding situations look. Still, adjusting the dopamine system is likely to enable boosts of motivation.

Zheng Liu, Barry J. Richmond, Elisabeth A. Murray, Richard C. Saunders, Sara Steenrod, Barbara K. Stubblefield, Deidra M. Montague, and Edward I. Ginns, DNA targeting of rhinal cortex D2 receptor protein reversibly blocks learning of cues that predict reward, PNAS  August 17, 2004  vol. 101  no. 33, 12336–12341 

8 Anticancer mice. These mice (the result of a lucky mutation) have immune systems that kill cancer cells efficiently and can even help other mice through blood transfusions.

Cui Z, Willingham MC, Hicks AM, Alexander-Miller MA, Howard TD, Hawkins GA, Miller MS, Weir HM, Du W, DeLong CJ. Spontaneous regression of advanced cancer: identification of a unique genetically determined, age-dependent trait in mice. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6682-7.

Hicks AM, Riedlinger G, Willingham MC, Alexander-Miller MA, Von Kap-Herr C, Pettenati MJ, Sanders AM, Weir HM, Du W, Kim J, Simpson AJG, Old LG, Cui Z. Transferable anticancer innate immunity in spontaneous regression/complete resistance mice. PNAS E-published May 8, 2006.

9 Antiobesity mice. These mice are protected from getting obese and diabetic from their diet by their lack of acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1). Their fat tissue can even reduce obesity and glucose buildup in other mice if transplanted. There are other strains protected from obesity by lack of other proteins, and a strain that have more adiponectin that put all excess fat into their blubber, remaining healthy despite turning very obese.

Smith SJ, et al. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking DGAT. Nat. Genet. 2000;25:87–90

Chen HC, et al. Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglylcerol acyltransferase 1. J. Clin. Invest. 2002;109:1049–1055. doi:10.1172/JCI200214672.

Chen HC, Jensen DR, Myers HM, Eckel RH, Farese RV Jr. Obesity resistance and enhanced glucose metabolism in mice transplanted with white adipose tissue lacking acyl CoA:diacylglycerol acyltransferase 1. J Clin Invest. 2003 Jun;111(11):1715-22.

Li-Jun Ma, Su-Li Mao, Kevin L. Taylor, Talerngsak Kanjanabuch, YouFei Guan, YaHua Zhang, Nancy J. Brown, Larry L. Swift, Owen P. McGuinness, David H. Wasserman, Douglas E. Vaughan, and Agnes B. Fogo, Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1, Diabetes 53:336-346, 2004

Mounib Elchebly, Paul Payette, Eva Michaliszyn, Wanda Cromlish, Susan Collins, Ailsa Lee Loy, Denis Normandin, Alan Cheng, Jean Himms-Hagen, Chi-Chung Chan, Chidambaram Ramachandran, Michael J. Gresser, Michel L. Tremblay, Brian P. Kennedy, Increased Insulin Sensitivity and Obesity Resistance in Mice Lacking the Protein Tyrosine Phosphatase-1B Gene, Science 5 March 1999: Vol. 283. no. 5407, pp. 1544 - 1548

Ja-Young Kim, Esther van de Wall, Mathieu Laplante, Anthony Azzara, Maria E. Trujillo, Susanna M. Hofmann, Todd Schraw, Jorge L. Durand, Hua Li, Guangyu Li, Linda A. Jelicks, Mark F. Mehler, David Y. Hui, Yves Deshaies, Gerald I. Shulman, Gary J. Schwartz and Philipp E. Scherer. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. Journal of Clinical Investigation 117(Sept. 4):2621-2637. 2007

10 Marathon mice. These mice have more expression of PPARδ in their muscles, which makes them turn into type I (slow twitch) fibers that work well for long-distance running. The miche have more endurance and - even when not training - increased resistance to obesity.

Wang YX, Zhang CL, Yu RT, Cho HK, Nelson MC, et al. (2004) Regulation of Muscle Fiber Type and Running Endurance by PPARδ. PLoS Biol 2(10): e294

Some other runner-ups are IGF-1 gene therapy to slow age-related loss of muscle function, mice with calorie-restriction like metabolism improving longevity and heart condition, green fluorescent mice, mice with increased cerebral cortex size and the high EPO levels found in the family of Eero Mäntyranta, giving them extra blood hemoglobin.

Barton-Davis, E.R., Shoturma, D.I., Musaro, A., Rosenthal, N. and Sweeney, H.L. Viral mediated expression of IGF-I blocks the aging-related loss of skeletal muscle function, Proc. Natl. Acad. Sci. USA 95: 15603-15607, 1998.

Anthony M. Payne, Zhenlin Zheng, María Laura Messi, Carol E. Milligan, Estela González and Osvaldo Delbono, Motor neurone targeting of IGF-1 prevents specific force decline in ageing mouse muscle, J. Physiol. 2006;570;283-294 2005

Lin Yan, Dorothy E. Vatner, J. Patrick O'Connor, Andreas Ivessa, Hui Ge, Wei Chen, Shinichi Hirotani, Yoshihiro Ishikawa, Junichi Sadoshima,, and Stephen F. Vatner, Type 5 Adenylyl Cyclase Disruption Increases Longevity and Protects Against Stress, Cell, Vol 130, 247-258, 27 July 2007

Hadjantonakis AK, Gertsenstein M, Ikawa M, Okabe M, Nagy A. Generating green fluorescent mice by germline transmission of green fluorescent ES cells. Mech Dev. 1998 Aug;76(1-2):79-90.

Anjen Chenn and Christopher A. Walsh, Regulation of Cerebral Cortical Size by Control of Cell Cycle Exit in Neural Precursors, Science 297 (5580): 365-369

de la Chapelle A, Traskelin AL, Juvonen E. (1993). "Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis." Proc Natl Acad Sci U S A. 90(10):4495-9.

I, for one, welcome our new rodent overlords.

Addendum November 1 2007: The "brainbow" mouse that expresses several fluoroscent proteins at random in neurons is another impressive modification, although it (like the other fluoroscent animals) is not an enhancement per se - at least not until it starts to be used for aesthetic purposes.

Jean Livet, Tamily A. Weissman, Hyuno Kang, Ryan W. Draft, Ju Lu, Robyn A. Bennis, Joshua R. Sanes1 & Jeff W. Lichtman, Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system, Nature 450, 56-62

Addendum November 2 2007: Mice overexpressing a carboxykinase in muscle have a different energy metablism, making them both marathon mice, more physically active and longer lived.

Parvin Hakimi, Jianqi Yang, Gemma Casadesus, Duna Massillon, Fatima Tolentino-Silva, Colleen K. Nye, Marco E. Cabrera, David R. Hagen, Christopher B. Utter, Yacoub Baghdy, David H. Johnson, David L. Wilson, John P. Kirwan, Satish C. Kalhan, and Richard W. Hanson, Over-expression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse, Journal of Biological Chemistry, online November 9, 2007.
Posted by Anders3 at 05:24 PM | Comments (0)

The Law of Expected Unintended Consequences

Self-evolving systemYesterday I attended a talk by Laith Yakob who described some of his current research on the ecology of controlling dengue fever. The best way of doing that is to control the populations of the Aedes aegypti mosquito. A very elegant way is the sterile insect technique: a large number of sterile insects are released, making most eggs nonviable and the next generation smaller. By releasing sterile insects each breeding season eventually the fertile insects dwindle to zero. It has been quite successful, and using sterile males this ought to be able to remove Aedes. No toxins, no risk of building up resistance, specific to one species.

Not so fast, Yakob warned. Aedes larvae compete with each other for food, making only a small number survive in each breeding clutch. Fewer viable eggs = fewer larvae = less competition = more survival. Running this through a population model he found that adding sterile males to the population could boost it by up to 70%! If enough sterile insects are released it will of course still collapse, but in a realistic situation this will only happen near the release sites. Nearby the boosting effect occurs. Oops.

The solution is likely genetically modified mosquitos. If they carry a dominant mutation that is lethal during the pupal stage the boosting of population does not happen. Similarly, a mutation that kills off any female will also cause a declining population. Of course, for breeding purposes it must be turned off, but that can be done using an artificial substance not found in nature. This is being explored by the company Oxitec, who not unsurprisingly appeared in the talk.

A far more elegant method than breeding insecticide-resistant females and covering them with insecticide.

I think this lecture demonstrated the utility of having detailed population models of different species. For once we can avoid a costly mistake and instead come up with a better solution. Similarly genetic engineering allows a targeted solution rather than just breeding and hoping for the best. Improved ability to predict and intervene, that is the way of making the law of unintended consequences predictable.

Posted by Anders3 at 12:18 AM | Comments (0)