At the recent Boskone, a panel discussed why some of us are writing science fiction on Earth, rather than some distant star. My reason is that science has multiple frontiers, in many dimensions–such as the interior of living cells. Now, scientists at Albert Einstein can watch the molecules of memory move within a neuron. The Science report is here.
Postdoc Hye Yoon Park worked with Robert Singer (and a long list of collaborators, as always) to construct a mouse in which the memory molecules can be seen. The molecules (moving white dots–click video) are messenger RNA, the RNA copies of an archival DNA gene. The gene expresses the messenger RNA to specify beta-actin protein, synthesized by a ribosome. But the amount of mRNA is what determines how much beta-actin gets made. And where the RNA goes–there goes the protein. Beta-actin transport within a neuron (nerve cell) is associated with extending the dendrites, the spine-like projections that connect to other neurons and help form memories.
So how did Park make this special mouse with fluorescence-tagged mRNA?
As usual, she used that Nobel-winning protein, GFP (Green Fluorescent Protein, originally made by a jellyfish, now made by bacteria, mice, plants, in every scientist’s lab). First, the MCP mouse (light green) was made “transgenic” by inserting the gene specifying GFP into its genome. This was done using a lentiviral vector–the research equivalent of those life-saving gene therapy vectors made from HIV (the AIDS virus, remember). The vector is constructed to contain the gene encoding GFP, located between two lentiviral integration sites. But in this case the GFP gene is “fused” (its sequence attached to) the sequence for another protein, MCP. MCP is the coat protein of a bacteriophage (a kind of virus that infects bacteria). If this starts to sound mixed up, remember this is the postmodern Franken-gene era; every useful gene gets constructed out of bits and pieces from wherever.
Now a different mouse also gets constructed (the gray one above) in which the mRNA for beta actin has some extra sequence fused, called the MBS sequence. The MBS sequence of RNA specifically binds to MCP protein.
Next–unbelievable though it may sound–the next step is actually to cross breed the two lucky mice (yes, they get to have fun the time-honored traditional way). I guess in vitro IVF could do as well, but many mouse breeders actually still do the old fashioned thing, usually picking up a male mice by the tail from one bin, and a female mouse by the tail from another bin. As a result (aside) many lab-bred mouse strains evolve low vision, because the ones that don’t see the hand coming for the tail get to breed.
Anyway, the result is the (dark green) mouse, whose neurons express both the GFP-fused MCP phage coat protein and the MBS tagged mRNA sequence that binds the fluorescent GFP-MCP protein. So wherever beta-actin mRNA goes, the GFP is sure to bind and light up fluorescent. Watch the cool video. Where the mRNA goes, and how it stores memories, is a story for another day.
The X-Prize Foundation is best known for the Ansari-funded prize for repeatable spaceflight for a hu/manned craft, in 2004. Now there’s a Google Xprize to be won for putting a rover on the moon by 2015. The design above is by Astrobotic.
But the foundation supports other kinds of prizes–including prizes in life science. The Brain-Machine prize will reward a “reliable, non-harmful interface between the digital world and the human cortex.” In other words, a cyborg; or the future Toynet world of Frontera. Other prizes reward health sensors and organogenesis. There’s even a Jurassic prize for guess what.
Suppose we combine the two fields of space exploration and artificial life? I’d like to see a self-printout prize: A prize for a rover-printer that can print out a working copy of itself. A sort of lunar cockroach–once you set down one, you’ll never need to send another.
What Xprize would you like to see?
The USA FDA has scheduled hearings on designer babies. Once you start hearings, you know there’s only one way down the rabbit hole. Or up the mountain, depending on your perspective. As we recall from Frontera 3D, in our increasingly inward-directed universe, down and up are always the same.
The aim of the proposed therapies is to help women who cannot conceive healthy children, owing to defective mitochondria in their eggs. Mitochondria–which carry their own chromosomes–have been the sleeper factor in IVF modification. Mitochondria, being derived by evolution from bacterial passengers, have a borderline status–more than cytoplasm, yet not part of the Mendelian nuclear DNA. In some cases, it’s possible to fix a mother’s eggs by injecting functional mitochondria from another woman’s egg cytoplasm. The only alternative women have is for their male partner to fertilize donor eggs from a different woman. The child then has the father’s sperm, but none of the mother’s genes. Nuclear gene therapy would make it possible to “fix” the future baby by providing the mother’s own nuclear genes.
But now, according to the NYTimes, the FDA is considering allowing modification of “nuclear material.” The mother’s nuclear chromosomes will replace the nucleus of the egg donor, while maintaining the donor cytoplasm and mitochondria. At first glance, it’s not clear how the nuclear option differs from what we do already, providing donor cytoplasm from genetically healthy eggs. But the future implications are interesting. If we replace a donor nucleus in full, why not replace one in part? A single chromosome, perhaps, encoding human growth hormone? Or the eye color genes?
The NYTimes Op Ed ponderously considers the possible ramifications such as possible side effects for the baby. Side effects are a minor concern IMHO, as any baby conceived in the back seat of a car has more pressing concerns for its future. But the future in which we increasingly design our children is worth considering. Why not future children with perfect pitch, synesthesia and prehensile tails?
If the thought gives you pause, try reading Beyond Therapy–not the play, but the biotech ethics report commissioned by W. Bush before 9/11. We forget that before 9/11 the USA’s primary preoccupation was stem cell research, with a surprisingly unpredictable array of partisans for and against. Beyond Therapy is well worth a read, if only for the eloquence of it prose and the earnestness of its devotion to hu/man tradition. I always assign it for Bio Sci Fi. And then we go on to celebrate our future children’s synesthesia.
Well, I was going to write up the latest amazing news on memory molecules, but it will have to wait. A remarkable piece of true news (no, it’s not April 1st yet) has somehow managed to escape major notice. To quote from NYT:
“Around noon on a recent Friday, Donor Five, a healthy 31-year-old, walked across M.I.T.’s frigid, wind-swept campus to a third-floor restroom to make a contribution to public health. Less than two hours later, a technician blended the donor’s stool into preparations that looked like chocolate milk. The material was separated and stored in freezers at an M.I.T. microbiology lab, awaiting shipment to hospitals around the country. Each container was carefully labeled: Fecal Microbiota Preparation.
“Nearly a year ago, Mark Smith, a 27-year-old doctoral candidate, and three colleagues launched OpenBiome, the nation’s first human stool bank. Its mission: to provide doctors with safe, inexpensive fecal material from screened donors to treat patients with Clostridium difficile, a gastrointestinal infection that kills at least 14,000 Americans a year. ‘People are dying, and it’s crazy because we know what the solution is’ Mr. Smith said ….” Continued here.
Before Boskone, I visited my friends in Cambridge, who build transgenic blood cells and figure out the mysteries of cell signaling. Meanwhile, our Harvard friends construct termite robots.
These adorable Lego-like robots supposedly scurry like termites stochastically building the termite equivalent of Highclere castle. Termite mounds are visible from space—though I wonder how great a claim that is now that satellites can read your book over your shoulder, but never mind.
This evening’s Boskone panel is about the rising seas, which are destined to overcome Boston. The termite robots might be helpful to build levees or repair them in case of a breach. But I wonder if termites are the best model. What about those army ants that build “bivouacs” of their own bodies?
The bivouac is made of the living ants linking their legs and bodies into a living mass that contains and protects the queen and larvae. It’s impressive—I believe this sort of behavior inspired the wall-climbing zombie masses of World War Z. While more sinister in appearance, perhaps, than the termite Lego-bots, I think the robots building themselves into the breach offer a more interesting approach to robot construction. More about such robots—and army ants—in my current Frontera novel.
An undergraduat at U. Arizona may have spotted the first signs of flowing water on Mars–Today, not billions of years ago.
The student, Lujendra Ojha, now pursuing graduate work at Georgia Institute of Technology, published a report of dark streaks on a crater that had no known explanation. The streaks appear and disappear seasonally, consistent with water flowing and drying up.
If the water is flowing, it must be very salty, like the high salt waters that support halophilic archaea, microbes on Earth that grow in concentrated salt. You can find haloarchaea in an evaporating pond; as the salt concentrates, the less salt-tolerant microbes fall apart, and their nutrients are consumed by the more tolerant halophiles. Haloarchaea also augment their respiration with photosynthesis; an adaptation used by the space-habitat purple microbes of The Highest Frontier. Halophiles are studied by my colleagues Priya and Shiladitya DasSarma as models for extraterrestrial life.
The Ham versus Nye interview is the latest adventure in the misbegotten aim of trying to reason with creationists. You know they’re in trouble when the creationists cite my textbook–Microbiology: An Evolving Science–which interviews Richard Lenski, director of the twenty-year bacterial evolution experiment. It doesn’t get better than this. Any thoughtful person reading that interview–and maybe the rest of the book–can only get swept up into the amazing epic adventure that evolution actually is.
The point Ham was trying to make when he cited the Lenski interview is that the ability of E. coli to metabolize citrate is not a “new trait.” Perhaps not so novel in the global sense, since a similar trait (using different enzymes) evolved in other bacteria such as Salmonella. But, more globally yet–what is E. coli? In nature, E. coli has what’s called an “open pangenome” (see our Chapter 17). An open pangenome means that if you sample E. coli bacteria in nature, you will find that every isolate has a few genes (not one, more like 300 or so) that occur in none other of the isolates you’ve found so far. Keep going, and in theory you will find an infinite number of new genes in evolving E. coli.
So, Mr. Ham, guess what: E. coli hasn’t evolved just one new trait. It’s evolved new traits to infinity.