2007: The Transmurine year

It seems that 2007 was a good year to be a lab mouse.

Some outstanding developments in cell biology, genetics, evo-devo, and several other branches of Biology, have improved the murine condition and given more lifespan, strength or stamina to mice. Exactly what we, transhumanists hope to achieve for our own kind. These mice, as the Betterhumans motto says, are “better than well”.

We were used to seeing mice with impaired functions, some of them extremely dysfunctional and with shocking phenotypes. Often they died before long, destroyed by its own conditions, after a painful life. Now, after understanding better the mechanisms of several body systems, after gaining a better viewpoint of genetic regulatory circuits, we have begun to tinker more delicately and exquisitely with the genes of these mice, now with superb results that give us hope and further enthusiasm for the promise of enhancing human capacities. This new generation of mice is only the beginning of a new era of improved mammals that will beat their natural counterparts in several aspects and aren't impaired in any sense, compared to them.

The first of these mice is only a mouse with scientific and aesthetic value, as its phenotype is not visible and not useful for itself, but to us, human experimenters. The Brainbow mice express genes for Green, Yellow, Red and Cyan. Fluorescent Proteins are coupled to the Cre/lox recombination systems. A probabilistic recombination event renders these genes functional and the combined expression of several (but not all at the same time, as the recombination is an stochastic event, different in every cell) different genes create as many as 90 possible shades of colors for each neuron (or any other cell). The differential gene expression and coloring of each cell allow experimenters to keep track of individual cells, which have the same color across all their lengths. Yes, this modification is not helpful to its bearers, but surely is interesting, beautiful and offers interesting body modification perspectives if it were possible to achieve in adult individuals rather than only in embryos. Coupling the expression of Cre to a Turing Pattern-like expression system would lead to extremely interesting skin color patterns, similar in shape to tigers or leopards, but with many different colors in a random way. Maybe we could even figure how to tweak cell receptors and gene expression to create fractal patterns on skin. Maybe in the future tattoos will be induced spreading different substances over the skin, one for each color, and maybe this gene expression could be turned off and return skin to its normal state. In any case, this is good news for Morphological Freedom fans.

I already commented on another post about one of the star mice from this year, the myostatin deficient mice that develop four times more muscle than regular mice. In this case, possibly we could mimic the effects of the alterations using drugs that modulate the activity of these proteins and therefore we would not need any gene modification to have the effect in humans. Possibly these drugs will be heavily regulated and their use for other than medical conditions as muscular dystrophy, deemed illegal, however, they are going to be used for other purposes, whether we like it or not. Again, I would say that the honest thing to do would be to end the hypocrisy and allow this kind of modification to be used in professional sports, but only limited to a league of enhanced athletes, separated from regular athletes, as pairing unaided persons with the ones who use this kind of tech would be unfair. What will happen with public attention to both leagues? Would it lead to a mass approval and support of transhumanist points of views, once the people realize that their beloved sport heroes are de facto transhumans? I do not have the slightest idea, but certainly that is going to be very interesting.

The overexpression of the SAC domain of the prostate apoptosis response-4 gene causes resistance to tumors in mice, both spontaneous and induced by oncogenes. The SAC domain seems to induce apoptosis when the cell machine gets out of control, not in normal or immortalized cells, where proliferation is out of control. This apoptosis is independent of p53 and other tumor supressor genes. The specificity of the action is conferred by Protein Kinase A, an enzyme that has increased activity in tumoral cells. The overexpression of SAC does not affect the growth, development or lifespan of mice, that stay tumor free and normal in every other sense.

Maybe the most impressive performance of the year is the one from PEPCK-mus mice. These mice overexpress the enzyme PEPCK in muscle, that converts Phosphoenol Pyruvate to Oxalacetate, generating ATP from ADP in the process and bypassing lactic acid production. This might sound dull and uninteresting, but the effects are simply breathtaking. PEPCK-mus mice can run more than ten times the normal distance that regular mice can run, at higher speeds. The levels of lactic acid in the cells of these mice remain the same during heavy exercise as during rest. Here's the video of the comparison between both mice:



Simply impressive. I barely have words to describe what I feel when I see this. These mice also remain fertile for a longer time and live longer than normal mice. These are truly transmice, improved, enchanced. However, there are problems, as they eat more food (but they stay fit) and have slightly more agressive behaviour. These drawbacks must be studied in depth before we can port the mechanism to humans (And it might be not possible due to physiological differences), but overall, the sole fact that it is possible to achieve such effects overexpressing a single gene is tremendously encouraging.

I think that the experiment that will beat the current M Prize holder is already on its course or will begin in 2008 and that even more interesting mice will show up this year at an even faster pace. Maybe we are at the point where we need a metric that accounts for the number of modified genes in a mouse, the number of ways in that it differs from regular mice and how different it is. Maybe a better option is some ratio between the number of genes modified and the number of pathways that are affected by these genes, multiplied by some measure of longevity. Maybe this hypothetical number is impossible to calculate, as we would have to assign values to staying cancer-free, running for longer, seeing in the ultraviolet region, or being able to photosynthetize and digest cellulose. This is utterly absurd, but maybe we could find a measure other than the lifespan of the enhanced mice, maybe the resistance of cultured cells to carcinogenic agents, its behavior concerning fasting or radiation poisoning. It is a complex issue but I still think it would be worthy to acknowledge the fact that as a result of several extensive modifications these new mice show improved phenotypes. The crux of the problem, I guess, is that we would be trying to assign values to what we think that ultimately would lead to improved humans themselves, and there is no single concept of what it means to be “better” when options, situations and viewpoints are almost endless. But even for something as widely adopted as Moore's law, measuring the speed of the processor alone, without accounting for software requirements is not a reliable way to predict end-user experience, as a relatively new processor with Windows Vista can do much worse than an older one running an older version of Windows or a lightweight distro of Linux, so maybe sticking to a number as a guide of what's inside the mouse is not as crazy as it sounds.

When will the Transhuman Year arrive? Hard to say. All these developments have been used to create new animals, not applied to an existing mouse that then changed its phenotype. Before we can benefit form this research we still have to develop safe ways of transfecting genes into existing animals and triggering their expression in a controlled fashion. Current viral vectors are unreliable and dangerous, however, even if safer methods are developed, they still will have to go through a regulatory nightmare before we are able to use them, unless unethical paradises and biotech havens arise, probably in developing countries. A way to get funding for clinical tests and support a successful industry before human application of the tech is ready could be use the technology in pets: life extension, rejuvenation, enhancing of beloved pets, selling colorful kittens, extra fast greyhounds for racing, developing dogs and cats that will live for longer but that won't reproduce unless given a pill, avoiding the need of neutering processes. This temporary and selective sterilization would be fairly easy to develop given that we have safe transfection vectors. Then it could be applied to existing animals, inoculating the vector on them and maybe help to solve the problem of urban canine overpopulation. I think that a lot of people would buy these treatments for their pets, if the alternative is death or hurting them with unnecessary organ removals, and that revenue could be used to fund further research in humans.

It has been a good year for H+ ideas, a good year for scientific research and a good year for mice. There are a lot of unsolved issues and a lot of problems that require not tech solutions but political and social ones. Sadly we cannot do much about it, other than keep trying to give education and critical thinking tools to as many people as possible. Expose people to other world views and experiences, so they realize that life can be different, can be improved. That leaders should be accountable for their actions and that the real wealth of nations lies not on the land, the industry or even on computers, but on human ingenuity and love for knowledge.