It wasn't the Mayo Clinic and they have this to say: "Oil of oregano has received a great deal of attention, with proponents claiming it can treat a variety of illnesses, including sinus disorders. Like many spices, oregano does have some antibacterial and antifungal properties — making it at least plausible that it might help or prevent some sinus problems caused by bacteria and fungi. Unfortunately, there have been no published trials that have looked at oil of oregano specifically for this use. For this reason, it isn't known what role, if any, oil of oregano plays in treating or preventing sinusitis." Or at least that's James T. Li, M.D., Mayo clinic asthma and allergy specialist has to say on the Clinic's webpage. Current as of Aug 29, 2009.
As for the crack about big pharma, bullshit. Traditional treatments have attracted a lot of investigation for the last couple of decades. If (if!) you find out that the traditional treatment works, then you can isolated the active compound(s) and patent and sell that.
With a few exceptions like carbonates, cyanide salts, or allotropes of carbon (graphite, diamond, buckyball, etc), if it contains carbon it's an organic molecule. Since there aren't all that many molecules that meet these exceptions it's pretty safe to apply the rule: they found a crapload of different organic molecules.
A different news writeup (the actual paper isn't available yet on PNAS, not even online) says millions of compounds, including 70 different amino acids. It'll be interesting as details unfold.
Not quite. There's at least one well-documented quick-draw contest: between"Wild Bill" Hickcok and Davis Tutt on July 21, 1865 in Springfield, Missouri. It's not clear who drew first.
Since evolution at the simplest level is change in allele frequency over time, let's take a look at your example using the very simplest case: fur color as a Mendelian trait: one gene two alleles. Let's also say that white fur is recessive (w) and the black fur is dominant (B), and there is no selective pressure other than your cat killing machine and no cats are born.
Pre selection: 90 black cats (BB) and 9 white cats (ww)
Post selection: 1 black cat (BB) and 9 white cats (ww)
Pre selection, the black fur allele comprises 90.9% of the gene pool, white fur 9.1%.
Post selection, the black fur allele comprises 10% of the gene pool, white fur 90%.
So you clearly have a change in allele frequency, and therefore have clear-cut evolution. Let's change the experiment a little. Above it is assumed that all black cats have two black fur genes, which is going to show the biggest change in allele frequency possible under this experiment. Let's look at the other end, where all black cats are heterozygous for fur color.
Pre selection: 90 black cats (Bw) and 9 white cats (ww)
Post selection: 1 black cat (Bw) and 9 white cats (ww)
Pre selection, the black fur allele comprises 45.5% of the gene pool, white fur 54.5%.
Post selection, the black fur allele comprises 5% of the gene pool, white fur 95%.
So again we clearly have a change in allele frequency and therefore clearly have evolution, no matter what the case for the original gene pool as we've covered both extremes.
Now you're correct that in the absence of any other evolutionary mechanism the proportion of black cats will increase if the cats start mating. If we simply randomize the gametes (ignoring the impact of the small population size) from the first example where the black cats are homozygous for the trait we'll have 19% black cats in the next generation (1% BB, 18% Bw) and 81% white cats (ww). However we're at the Hardy-Weinberg equilibrium; in the absence of any evolutionary mechanisms the allele frequencies will not change any further, it's still 10% B and 90% w.
It's not that selection != evolution. As demonstrated above it is possible that selection ==evolution. In a more realistic environment there are other factors at play but selection is still one of the most important evolutionary mechanisms.
Before I jumped from a molecular biology department and into an entomology lab, I think I had a similar perspective. Nobody does research on caterpillars. Why would they? Insects are a bunch of squirmy, unpleasant, gross bugs. That's a pretty common view and goes back a while too. Lamarck's (one of the guys credited with creating the term "biology," the guy who came up with the term "invertebrates," and same guy who came up with Lamarckian evolution in the late 1700's) peers made fun of him for studying things that crawl in the dirt. But people study insects, insects are important. In comparison mammals are a minor clade, a mere curiosity, were it not for the fact that we happen to be mammals.
The number one through 995,123.8 of the top agricultural pests are insects. Some of the greatest spreaders of human disease are insects. Rats get most of the coverage about the Bubonic Plague/Black Death, but they're a couple steps removed: Bubonic Plague is caused by the bacterium Y. pestis, carried and introduced to humans by bites from fleas, which are carried on flea transporters (rats), which spread to the New World on rat transporters (ships). Malaria, Dengue Fever, Yellow Fever, Chikungunya, and several other diseases are all spread by the heat-seaking flying syringes aka mosquitoes. Ticks transmit a couple varieties of encephalitis-causing viruses, as well as the bacteria that cause Lyme disease. Sand fleas spread the protozoan parasite that causes Leishmaniasis. Bedbugs are on their way back in a big way and can spread at least 20 different diseases, including potentially Chagas (which can also be spread by assassin bugs) and Hepatitis B.
Besides being of great interest with respect to human health and agriculture insects are also useful as model organisms. Everybody here who's had Biology 101 has heard of the genetic experiments on fruit flies (which are ongoing), but there are other model organisms as well. Off the top of my head I can think of Manduca sexta (commonly called tobacco hornworm, also a moth), Tribolium castaneum (red flour beetle), and Bombyx mori (silk worm, also a moth). Manduca's used as a model organism in neuroscience as it's huge (larvae up to 4 inches long), raising is quick, easy, and cheap, and they're easy to dissect (and without all the regulatory issues that vertebrate researchers have to deal with). It, and other insects, are also used in immunology research as some of the same proteins and pathways exist in moths and humans, for instance the Toll-like receptor/Interlukin-1 receptor superfamily. Insects are probably still the most important organisms when it comes to understanding the molecular biology underlying development; Hox genes were discovered in fruit flies. Lots of people are studying insects, caterpillars even, but funding...well that's an issue. Personally I think we could cut the cancer budget by a third and still have a lot of fat left over. But then I'm not in a cancer lab.
Either that or it's pretending it's a nautilus. Octopi are relatives (same class, Cephalopoda) of nautiluses, which are the only extant cephalopods with an external shell...that's secreted by the animal and not made of coconut.
"My opinion was always if the taxpayers pay for it, the taxpayers own it. Research, patents and discoveries and even software. At a minimum the government should be able to transfer licenses from one branch to another. If your research is that valuable, don't take federal money. A lot of universities are taking federal money for research and then selling those discoveries to companies that sell them back to the taxpayers."
All academic researchers are desperately scrambling for any kind of money to keep themselves and associates employed and doing science. Federal grants in my area of research have fallen to 10% success rates, and some don't manage to hit 5%. That's one in ten (or less) grant proposals get funded, and getting worse every year. To stay afloat academics increasingly take up public-private partnerships and/or patent and sell ideas. The lab I work in has done both and that funding has provided around a third of our operating budget. It's also the most dependable source of income and it's percentage will surely increase given the sorry state of federal granting agencies. While traditional funding sources have been cratering, patents provide $45 million a year for my university's research budget. You want all fully or partially government-funded research to be public? Triple the federal research budget and adjust each year for inflation. As long as I'm having a pipe dream I'd also like so-called state universities to have a mandatory minimum floor of 33% of their operating budget to come from their state. Some don't get 10%.
Even if all that were to happen there's a still a down side. One of the missions of the university is to train scientists. With professorships at universities typically having 300 applicants for each available position very, very few scientists will go an academic route; many more will go into private industry. The patent process and public-private partnerships besides providing desperately needed funding also serve as an introduction to non-academic research and is productive training itself. That's an argument to be made for increased use of patents and public-private partnerships to further the education of the next generation of scientists.
"The real issue is that much of the funding is going to projects which aren't going to be completed before the funding runs out."
That's not the way it works. For starters there's rarely, if ever, a definitive "end point" for a study. There's always something more that could be done; it's a piss-poor paper that doesn't bring out new issues to explore. Running out of money or key personnel moving on to a new position often times is the end where whatever you've got is bundled up into a publication(s). If it isn't at the level of a..."least publishable unit" then it might sit around for a year or three until the principal investigator can scrounge up time or more often the case money to get it to that LPU point.
"Many if not most of those projects will then be scrambling for funding..."
This is what academic scientists call "situation normal" or "Wednesday" it's how the game doesn't work for about the last 15 years or so, and getting worse every year. You are constantly scrambling for money, any money, to keep yourself and your staff employed and doing science.
Are the Copenhagen and Everett interpretations of quantum mechanics supported by evidence? Do the underlying theories explain the evidence and make potentially falsifiable predictions that flow from the conceptual underpinnings of the individual theories? If yes, then either theory, even if one or both are overthrown are contributing positively to science. Now compare that to Intelligent Design (assuming that is likely your position). Behe's "Darwin's Black Box" was published in 1996. Johnson's "Darwin on Trial" was published in 1991. "Of Pandas and People" was first published in 1989 having morphed into "Intelligent Design" from earlier straight up creationist drafts dating to 1983. It is now 2009, almost 2010. Proponents of ID have, as of yet, to come up with any evidence. They have also not said what such evidence would even look like. Actual working scientists like me have done more: we explain what a human or human-like intelligence would do, then state the plain truth that no such evidence has been found. If you don't believe me then check out NCBI which has free public access to all genes sequenced using public moneys, and start searching for that designer(s). ID proponents have failed to come up with falsifiable predictions that are produced from the theoretical framework of ID. That's probably because they have yet, after 26 years to come up with a scientific theory of ID. Despite these four scientifically fatal flaws, ID flourishes. There are dozens of popular books on the subject. There are speaking tours. There are even movies like "Expelled" shown in movie theaters. There are court cases, media blitzes, and conservative politicians must kowtow to it. The Templeton Foundation begs, literally begs to give money to ID researchers...but can't find anyone to fund. In this granting environment, a "good" grant has six times as many applicants as it has successful awardees. For ID proponents, allegedly scientists, to let money go begging insults all of science and everyone working in it. Yet you complain of suppression when nothing could be further from the case.
The human tailbone is most certainly vestigial. Vestigial does not mean useless; it means that it once had a given function (external tail in this case) but no longer performs that function, but does not mean that it doesn't perform a different function. In humans, our coccyx is usually comprised of 3-5 vertebrae, which are usually fused into two or three segments. Not all function in muscle attachment, as is unsurprising given the variability in the structure. People have been born with nine calcified bones in the coccyx (plus cartilaginous structures), and external tails complete with articulating vertebrae (five's the record as far as I know) have been reported in the medical literature. People have also been born without a coccyx at all, although like external tails this is rare. Removal of the coccyx is called a coccygectomy (say that to your five year old!) and can be done on the whole or just a part of the structure with little or no side effects.
"If a genetically-modified human were cloned today, would that clone be outside common ancestry?"
There are limits to what we know how to do. We've figured out how to do mammalian cloning (with some caveats and high inefficiency; Dolly the sheep for example). We could, if we expended sufficient effort, take chromosomes from different people and probably produce a viable clone from that, but the ancestry could be traced: It wouldn't be mom and pop, but mom(s) and dad(s). We could get a bit more exotic than that, by swapping out say the human citrate synthase gene and replacing it with one from a different species, so the resulting organism's heritage would be mom(s)+dad(s)+other species contributor. Venturing out more into science fiction than actual genetics it might be possible to construct an artificial genome that would produce something that for all intensive purposes is a fully functional and viable human, yet have lower sequence identity to humans than chimps do (~98%) by removing or modifying endogenous retroviral sequences, mucking about with introns, and introduction of alternative codons in protein coding regions or even some swapping of whole genes with closely related species. The more changes the more of a bitch it will be to accomplish but is not totally beyond the realm of what is at least conceivable, if not possible quite just yet. Anyway the resulting artificial human genome could have low sequence identity with any other human genome yet could still be identifiably human as in chromosome 1 has genes x,y,z arranged this way or minimally expressed in a way that is the same spatial and temporal pattern in naturally occurring humans. It wouldn't fit in with common ancestry aside from being able to trace the bits and pieces. So the short of it would be that yes a constructed human genome could violate common ancestry to various degrees. Would it be human, well, people could certainly argue over that, even if the resulting organism could pass as a human unless you had your DNA sequencer handy.
"Would it be designed?"
Trivially, yes, in that we have a reason (um, presumably), a method, and a goal, but the more exotic the human-like genome the more we'd turn to random mutation and artificial selection to get our artificial human genome to function. That's what we do now for vastly simpler problems.
"Do we know this hasn't happened in the distant past?"
The scenario above for making our more outlandish artificial human genome has us taking a starting point (human genome), modify individual nucleotides to produce neutral or highly conservative mutations, we remove (or add) noncoding elements that also have no or negligible effect, or we swap out human gene X for, say, gorilla gene X (and then test and if necessary modify to make it work). Changes like that are easily detectable by comparing genome sequences, and are comparable to swapping, adding, and subtracting parts from a golf cart, a go cart, and a 57 Chevy to make a vehicle of some sort. However if someone(s) at some time(s) muddled with DNA(s) for some reason(s), there is no evidence that this has occurred. We see no plants with mitochondria that are clearly more related to those from a wolf than those from a rose, no apes with highly modified feather genes used to produce hair, and no bacteria sporting TCA pathways that were clearly dropped in from fish. Instead we see a pattern of nested hierarchy indicative of common descent. The mouse gene for citrate synthase is more closely related to rat citrate synthase than it is to human citrate synthase, those in turn are much more closely related to turkey citrate synthase than one from bacteria. You can do this with any gene you like and you will observe a common pattern of nested hierarchies, which is required for evolution and common descent to be true. The same will go for gene expression patterns, developmental patterns, etc. Can we unambiguously state that no designer fiddled about even though there's no evidence in support of the idea? No, but neither can we unambiguously state we're not brains floating in jars hooked up to an artificial reality. Both ideas are similarly useless to science.
I wonder if the lab had an even harder time getting approval for raising a colony of mosquitoes known to be infected with malaria than getting approval for infecting volunteers with malaria. I work in an entomology lab that specializes in the yellow fever mosquito Aedes aegypti. As a part of that work, we maintain a colony of mosquitoes. For us, we just have a pair of percivals (incubator that controls temperature, light, humidity, some also control CO2 levels) that we raise the insects in at different life stages. We always have on hand at least eggs which can last months but usually also a few cages (glorified tupperware with heavy cloth mesh) of adults that are being mated to produce eggs, and frequently trays full of water to grow larvae. A handful of mosquitoes are usually loose and getting bit happens ~daily and is just accepted as an occupational hazard. A few people in lab actually no longer have an allergic response to a mosquito bite due to constant exposure. I think we're maybe a little cavalier about all of that, but we don't have, or need, any kind of special containment as the adults are not infected with any pathogen. But these guys are intentionally raising mosquitoes and then at some point introducing the malaria pathogen to them. While young female adult mosquitoes normally get the pathogen by biting an infected person, there must be a controlled way of doing this. I'm just wondering how they manage to have a high enough level of control to pass review. A glove box alone won't cut it as access to the chamber is typically just an inner and an outer hatch--too easy for a mosquito to get through. Maybe they had to rig it up with a refrigeration unit. If you cool insects down, they get much slower. We use chill plates (peltier coolers--it's not just for CPUs!) to immobilize adult mosquitoes for microinjections or microsurgery. However even with a refrigeration unit as precaution there seems to be a risk of accidental release. Damn, I want to see their setup.
There are already a dozen or more level 4 biohazard (there's no such thing as a level 5 biohazard) facilities either under construction or already in operation in the US. Several are in major cities, such as Atlanta (headquarters of the Centers for Disease Control), Bethesda (Washington, D.C. metro area and also headquarters of the National Institutes of Health), Boston, Cincinnati, and also Stony Brook (to a New Yorker it's on the Moon, to everyone else it's on Long Island and therefore spitting distance of 10's of millions), San Antonio, Richmond, and Los Angeles. The only level 4 biohazard facility that I know of that I think is in a poor location is located on an island. Galveston, TX to be specific. It's most famous for the hurricane in 1900 which is still the worst national disaster in the US. Hurricane Ike in 2008 produced a big enough surge to go around it sea wall, and it was only a Cat 2 storm.
An isolated island in the middle of nowhere is a boneheaded idea. First you're going to have to get the island, and isolated islands are typically small which will severely limit facility size, or are located in arctic regions. Both are highly susceptible to harsh weather, for a small tropical island it could be completely covered with water from even a minor tropical storm because elevation won't be much greater than a few feet, and did I mention the arctic for option B? Next, you're going to have to import all building material, and in the process of construction drive to extinction the majority of native species. Your construction will have to provide not only for the level 4 facility itself, but also ALL support facilities. Power plant, housing, recreational facility, docks, repair and maintenance depots, airport, waste handling, water purification, and barracks. Yes, barracks. A remote island facility with level 4 biohazards and no defense force? Gee if I were a terrorist I know where I'd go! Now let's think recruitment. Very few people are going to be willing to live on this remote island fortress year round, especially without their families. Those that do are going to demand a king's ransom and will only be willing to do it for a few years before leaving and will also be early in their careers. However the idea of working on and off in shifts won't work either. From personal experience research projects take years to complete when working full time. You walk away from one for even a week and it will take time to get it back on track. No sane researcher would take a job where you'd rotate on for 3-6 months and then rotate off. You'd spend all your time on the island frantically trying to get research up and running, and all time off trying not to get divorced. So you get vastly higher costs (both startup and annual), vastly worse security, nigh impossible recruitment for shift employees which are going to be borderline psychotic in a short while due to the mind-breaking stress from both impossible working conditions and impossible personal/family life, while your year-round workers will have zero retention, and both sets will demand massive salaries and benefits. All that, and work will proceed at a snail's pace if you're lucky.
If you search for the terms "evolution" and "hiv" on pubmed you get nearly 5,000 papers back. That's just one disease. One of the big problems about most, probably all, diseases caused by some kind of pathogen is that they have huge population sizes and grow very fast. Evolution can move damn fast under those situations, and that's why we've got multiple-antibiotic resistant bugs out there that didn't exist 30 years ago. If you're working in epidemiology or virology or any disease-related field you're de facto doing evolutionary biology research. Also, given Kansas' infamous pro-creationism leanings it will be much harder to recruit scientists there. Any scientist with children would be reluctant to move there because they would worry about science-deniers on the board of education tampering with their kid's education. I doesn't help in recruiting those of us without kids, either.
"If any (non-trivial) treatment consisting of specifically folding proteins is found, then there will be exactly one way to produce said drug : genetic manipulation. Only a genetically modified cell will be able to produce those custom proteins."
This is not necessarily the case. We can predict with reasonable accuracy (about 80%) what sort of secondary structure (alpha helix, beta sheet, or coil, basically) a protein will have based solely on the protein sequence. For example, if you were to put the protein sequence lkgtlgqdvidirtlgskgvftfdpgftst, into Jpred you get this prediction:
LKGTLGQDV IDIRT LGSKGV FTF DPGFTST
------------------EEEEE-------------EEE
Where E is the code for beta sheet, and the dash is coil. Jpred is smart enough to also search through the Protein Data Bank and see if that sequence belongs to a protein that has already had it's structure solved, which is the case here. I told Jpred to go on with the prediction anyway, and by comparison to the known protein structure iIt doesn't do horribly bad, correctly predicting that most of this sequence is coil, getting close with the first bit of sheet secondary structure, and misinterpreting the second sheet bit when it should be another type of structure (a turn--several different ones are defined but make up only small amounts of structure, being largely transitions between the other secondary structure types). However as the example sort of hints at, protein structure can be squishy. If your protein is an enzyme, then it must bind substrate, catalyze a reaction, and release product. There will be some structural change that accompanies this, meaning that small molecules can have an impact on protein structure. Sometimes but not often this can involve radical change. I knew a guy a few years ago who designed a protein, such that he could control the secondary structure of a short stretch by the addition of a small molecule. If present, part A was helix, part B was coil. If absent, part A was coil, part B was helix. I'm running out of time, but there are also examples in nature of a protein in the course of it's biological function that has parts swap between sheet and helix structure. Lastly, we come to diseases caused by misfolding proteins. The mutations are often small ones, that disrupt proper folding of structural proteins. It may be possible to treat disorders at least to some extent by introducing a small molecule that will favor the properly folded state as opposed to the disease-causing improperly folded protein state (I'm thinking of Lou Gehrig's disease aka amyotrophic lateral sclerosis, ALS). Such a small molecule probably can't do anything about existing misfolded protein stuck in a plaque in the cell, but the small molecule might interact with protein as it is being made or before it joins the plaque and prevent an increase in the plaque size. It is at least conceivable that a conventional drug treatment could affect this part of ALS and halt or slow the progression of the disease.
"Now if I could just find a use for all those damn AOL CDs in the attic."
CD FIGHT!!! Seriously it's a lot of fun as long as nobody minds a few scratches. Back, oh god, 10 years ago a friend of mine interned at Microsoft and was on their developer network. If Microsoft made a CD for distribution anywhere in the world, any version, he got it. He had 300+ by year's end. We had about 15 guys in the dorm hucking CD's down the hall and stairwells. Everybody still had the correct number of eyes and nobody needed stitches, just a couple bandaids. And what else are you going to do with Windows 98 OSR 50.2.4.6.A-4 in Swahili?
Maybe not. Host:pathogen interaction is already pretty tricky, which is why it's a big deal when you get something that jumps the species barrier (even the name's suggestive). Now you're going vector:pathogen:host which makes it much more complicated. Some mosquitoes are vectors of some diseases, some are vectors for others. The mosquito we use in my lab, Aedes aegypti, can carry the dengue fever virus, yellow fever virus, and chikungunya virus, but not the malaria pathogen (a protozoan, not a virus).
You're mistaken. Mosquito species can show marked preferences for what poor critter they like to get a blood meal from. For instance Anopheles gambiae almost exclusively feeds off of humans, and also is a major vector in the spread of the malaria pathogen. Others have their own preferences to varying different extents. Interestingly, all mosquitoes exclusively feed off of warm-blooded animals. They're also ancient, dating back around to when dinosaurs were walking around. Might have fed off them too.
You're right on one point though: evolution of resistance to the vaccine is probably inevitable, just a question of how long it will take and what we can come up with while it buys us some time. In the tropics you can have IIRC up to 25 generations of mosquitoes in a single year. Multiply that by the huge population size and you can get some pretty rapid evolution. That's increasingly a problem for insecticides (not just for mosquitoes) and there's increasing interest in the development of new ones these days.
I think you're mistaken. I'm applying for one of these grants right now, and the way I read it was that you must spend all the cash in one year, but if you've got a bit left over then you can get up to a six month extension to spend the remainder. The only extra funding is the $million if your work is really promising after the first year. And as others have pointed out even for a typically underpaid postdoc $100k in a year will only cover salary, benefits, and looking at my last grant application about $35k left over for chemicals, supplies, and etc. I would personally need somewhere in the range of another $30k-50k a year to cover my chemicals, supplies, and user fee costs. Not that I wouldn't be jumping up and down for about a week if I got one of these grants.
I think there's a kind of a sliding scale of ownership: a rented apartment is less than an owned trailer home in rented lot, is less than a condo, is less than a house+lot. Actually I suppose there's a still greater level of ownership: house in town (with home owner's association) is less than a house in town (no Jr. Fascists) is less than a farm/ranch. With the lowest level if you're unlucky you could be barely half a step above a condo. With the highest...it's your land. No, I take that back. It's your fucking land and you can do with it whatever you want so long as it's not illegal, or at least not Illegal and the neighbor's don't know and wouldn't care if they did. You can put up signs that say "Trespassers will be shot. Survivors will be shot again." to your hearts content. You can paint your house bright pink. Plant corn in your front yard, right next to the two story tall metal sculpture. Have chickens and fresh eggs. Have a goat mow your lawn for you. A still (little i-illegal). Let your dogs roam around and urinate on the whole outdoors as far as you own (You can join in too. It's fun.). Now that's ownership. Owning four walls, er, your share of four walls in an apartment building, not so much. If the economics made sense I could see myself doing it but it's just not the same.
I forgot to include that there are movies of proteins during catalysis by using Laue diffraction, and I've been lucky enough to see a talk where they speaker showed such a movie. While I can't at the moment find a good example I did find this large.pdf of a powerpoint presentation. Scroll down to page 17 and you can start to see a little bit of what's going on in the case of release of carbon monoxide from myoglobin. Which has some broader relevance as carbon monoxide poisoning results from that molecule binding to hemoglobin and out-competing oxygen. Got published in Nature too.
Well for high-speed crystallography it isn't so much that data collection is the problem (for most applications). You can collect a high-quality data set of a protein at APS in under a half an hour. The real bottlenecks in x-ray crystallography is, was, and unfortunately most likely always will be protein crystallization. Way back in the day when protein crystallography was just starting, it was thought to be somewhat bizarre for proteins to crystallize. Fast forward four or five decades and now if your protein is reasonably soluble, reasonable stable, and has a definite structure (not all proteins have a well-defined structure and just flop about in a range of states), then you can probably get it to crystallize well enough to solve the structure. But it might take a long time to pull off, years even. But that's only for soluble proteins. If a protein is normally in the cell membrane, it is much, much harder. A cell membrane is basically soap. Soap doesn't crystallize. There are only a few structures of integral membrane proteins despite a lot of work on the problem. Also proteins that only have one domain or even just a helix poking into the membrane can be tricky--they're usually done by just removing the offending membrane bit but often suffer from solubility problems.
For part two, lasers produce monochromatic light. One technique for doing real-time x-ray crystallography involves using polychromatic x-rays. Normally you get a single, specific, monochromatic wavelength (, or at least close enough that for data processing you largely ignore everything else. The resulting diffraction pattern looks something like that seen on wikipedia's page. That page and links are actually pretty good. However you can use a broader spectrum of x-rays and get a different diffraction pattern due to having different wavelengths of light hitting your protein crystal over the course of the exposure, or a Laue diffraction image (ignore the color--computer added). Interpreting Laue diffraction's significantly harder because you also have to take into account that you have basically multiple different wavelengths of light producing multiple different, overlapping diffraction patterns. Unlike monochromatic diffraction patterns, which require exposure times of at least tenths of a second even at APS (or potentially hours on a weaker rotating anode x-ray source like at an individual lab), Laue diffraction can be measured in picoseconds--on the time scale of chemical reactions catalyzed by enzymes. A few groups have done time-resolved x-ray crystallography with reactions by building up series of Laue images. You can't do it for everything, though. Data processing problems aside you typically need a chemical reaction that can be triggered by light. Also, proteins frequently undergo structural reorientations during catalysis--the change will have to be small enough so that the packing of proteins in the crystal lattice will not be affected. Time-resolved x-ray crystallography using Laue diffraction is never going to be widely used, but the results can still be very exciting.
What these guys have in mind and how practical it is I don't know since I've somewhat shifted away from protein x-ray crystallography. I do remember going to a conference a few years ago where some guys wanted to use a single molecule to collect data on--by blasting the bajesus (that's a technical term) out of it with an extremely short, extremely massive burst of x-rays. They had the problem though of ripping off basically all of the electrons in the process, IIRC. Even at weak home rotating anode x-ray sources you still have to worry about radiation damaging your crystal (and affecting your resulting model of the protein), but blasting away all the electrons? That's like comparing a flyswatter and a tactical nuke.
That's not all that funny. I know someone who went on sabbatical to a Chinese university a couple years ago. They're building brand new high-tech bioscience labs but not the necessary infrastructure to support them properly. There were no facilities at that particular university, one of the top ten in China, for handling hazardous waste. Hazardous liquids are just poured down the drain, nothing for disposal was autoclaved. He saw a peasant (his term) poking through the trash and yes, eat the agar out of a petri dish. The rest of the trash is often picked over by other peasants for any sort of plastic that could be reused or recycled. What's left just got mixed in with other municipal trash at the dump. What's even scarier is that they're building a level three biohazard facility nearby, right in the middle of the city.
A comment on your point 2: in the paper in nature they cite a paper, which has a cite to another paper that has the protein production and purification methods. It seems to be common practice for recombinant hemoproteins to spike the culture media with a heme precursor to crank up it's production. That precursor is listed at $142.50 per gram in my Sigma catalog. The authors may or may not have spiked their culture with it; materials and methods details in Nature papers are extremely brief or like here cite a paper that cites a paper. Anyway, if they did use a heme precursor that adds expense, if they didn't, the proteins produced will have less of the heme which is required for oxygen binding.
As for points 5 &etc., that's critical. A pint or two of blood replacement coursing through your veins triggering an immune response couldn't possibly be good. But yeah you're right, that's not what the authors are really at for this paper. The word "blood" isn't even in the Nature article!
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It wasn't the Mayo Clinic and they have this to say: "Oil of oregano has received a great deal of attention, with proponents claiming it can treat a variety of illnesses, including sinus disorders. Like many spices, oregano does have some antibacterial and antifungal properties — making it at least plausible that it might help or prevent some sinus problems caused by bacteria and fungi. Unfortunately, there have been no published trials that have looked at oil of oregano specifically for this use. For this reason, it isn't known what role, if any, oil of oregano plays in treating or preventing sinusitis." Or at least that's James T. Li, M.D., Mayo clinic asthma and allergy specialist has to say on the Clinic's webpage. Current as of Aug 29, 2009.
As for the crack about big pharma, bullshit. Traditional treatments have attracted a lot of investigation for the last couple of decades. If (if!) you find out that the traditional treatment works, then you can isolated the active compound(s) and patent and sell that.
With a few exceptions like carbonates, cyanide salts, or allotropes of carbon (graphite, diamond, buckyball, etc), if it contains carbon it's an organic molecule. Since there aren't all that many molecules that meet these exceptions it's pretty safe to apply the rule: they found a crapload of different organic molecules.
A different news writeup (the actual paper isn't available yet on PNAS, not even online) says millions of compounds, including 70 different amino acids. It'll be interesting as details unfold.
Not quite. There's at least one well-documented quick-draw contest: between"Wild Bill" Hickcok and Davis Tutt on July 21, 1865 in Springfield, Missouri. It's not clear who drew first.
Since evolution at the simplest level is change in allele frequency over time, let's take a look at your example using the very simplest case: fur color as a Mendelian trait: one gene two alleles. Let's also say that white fur is recessive (w) and the black fur is dominant (B), and there is no selective pressure other than your cat killing machine and no cats are born.
Pre selection: 90 black cats (BB) and 9 white cats (ww)
Post selection: 1 black cat (BB) and 9 white cats (ww)
Pre selection, the black fur allele comprises 90.9% of the gene pool, white fur 9.1%.
Post selection, the black fur allele comprises 10% of the gene pool, white fur 90%.
So you clearly have a change in allele frequency, and therefore have clear-cut evolution. Let's change the experiment a little. Above it is assumed that all black cats have two black fur genes, which is going to show the biggest change in allele frequency possible under this experiment. Let's look at the other end, where all black cats are heterozygous for fur color.
Pre selection: 90 black cats (Bw) and 9 white cats (ww)
Post selection: 1 black cat (Bw) and 9 white cats (ww)
Pre selection, the black fur allele comprises 45.5% of the gene pool, white fur 54.5%.
Post selection, the black fur allele comprises 5% of the gene pool, white fur 95%.
So again we clearly have a change in allele frequency and therefore clearly have evolution, no matter what the case for the original gene pool as we've covered both extremes.
Now you're correct that in the absence of any other evolutionary mechanism the proportion of black cats will increase if the cats start mating. If we simply randomize the gametes (ignoring the impact of the small population size) from the first example where the black cats are homozygous for the trait we'll have 19% black cats in the next generation (1% BB, 18% Bw) and 81% white cats (ww). However we're at the Hardy-Weinberg equilibrium; in the absence of any evolutionary mechanisms the allele frequencies will not change any further, it's still 10% B and 90% w.
It's not that selection != evolution. As demonstrated above it is possible that selection ==evolution. In a more realistic environment there are other factors at play but selection is still one of the most important evolutionary mechanisms.
Before I jumped from a molecular biology department and into an entomology lab, I think I had a similar perspective. Nobody does research on caterpillars. Why would they? Insects are a bunch of squirmy, unpleasant, gross bugs. That's a pretty common view and goes back a while too. Lamarck's (one of the guys credited with creating the term "biology," the guy who came up with the term "invertebrates," and same guy who came up with Lamarckian evolution in the late 1700's) peers made fun of him for studying things that crawl in the dirt. But people study insects, insects are important. In comparison mammals are a minor clade, a mere curiosity, were it not for the fact that we happen to be mammals.
The number one through 995,123.8 of the top agricultural pests are insects. Some of the greatest spreaders of human disease are insects. Rats get most of the coverage about the Bubonic Plague/Black Death, but they're a couple steps removed: Bubonic Plague is caused by the bacterium Y. pestis, carried and introduced to humans by bites from fleas, which are carried on flea transporters (rats), which spread to the New World on rat transporters (ships). Malaria, Dengue Fever, Yellow Fever, Chikungunya, and several other diseases are all spread by the heat-seaking flying syringes aka mosquitoes. Ticks transmit a couple varieties of encephalitis-causing viruses, as well as the bacteria that cause Lyme disease. Sand fleas spread the protozoan parasite that causes Leishmaniasis. Bedbugs are on their way back in a big way and can spread at least 20 different diseases, including potentially Chagas (which can also be spread by assassin bugs) and Hepatitis B.
Besides being of great interest with respect to human health and agriculture insects are also useful as model organisms. Everybody here who's had Biology 101 has heard of the genetic experiments on fruit flies (which are ongoing), but there are other model organisms as well. Off the top of my head I can think of Manduca sexta (commonly called tobacco hornworm, also a moth), Tribolium castaneum (red flour beetle), and Bombyx mori (silk worm, also a moth). Manduca's used as a model organism in neuroscience as it's huge (larvae up to 4 inches long), raising is quick, easy, and cheap, and they're easy to dissect (and without all the regulatory issues that vertebrate researchers have to deal with). It, and other insects, are also used in immunology research as some of the same proteins and pathways exist in moths and humans, for instance the Toll-like receptor/Interlukin-1 receptor superfamily. Insects are probably still the most important organisms when it comes to understanding the molecular biology underlying development; Hox genes were discovered in fruit flies. Lots of people are studying insects, caterpillars even, but funding...well that's an issue. Personally I think we could cut the cancer budget by a third and still have a lot of fat left over. But then I'm not in a cancer lab.
Either that or it's pretending it's a nautilus. Octopi are relatives (same class, Cephalopoda) of nautiluses, which are the only extant cephalopods with an external shell...that's secreted by the animal and not made of coconut.
"My opinion was always if the taxpayers pay for it, the taxpayers own it. Research, patents and discoveries and even software. At a minimum the government should be able to transfer licenses from one branch to another. If your research is that valuable, don't take federal money. A lot of universities are taking federal money for research and then selling those discoveries to companies that sell them back to the taxpayers."
All academic researchers are desperately scrambling for any kind of money to keep themselves and associates employed and doing science. Federal grants in my area of research have fallen to 10% success rates, and some don't manage to hit 5%. That's one in ten (or less) grant proposals get funded, and getting worse every year. To stay afloat academics increasingly take up public-private partnerships and/or patent and sell ideas. The lab I work in has done both and that funding has provided around a third of our operating budget. It's also the most dependable source of income and it's percentage will surely increase given the sorry state of federal granting agencies. While traditional funding sources have been cratering, patents provide $45 million a year for my university's research budget. You want all fully or partially government-funded research to be public? Triple the federal research budget and adjust each year for inflation. As long as I'm having a pipe dream I'd also like so-called state universities to have a mandatory minimum floor of 33% of their operating budget to come from their state. Some don't get 10%.
Even if all that were to happen there's a still a down side. One of the missions of the university is to train scientists. With professorships at universities typically having 300 applicants for each available position very, very few scientists will go an academic route; many more will go into private industry. The patent process and public-private partnerships besides providing desperately needed funding also serve as an introduction to non-academic research and is productive training itself. That's an argument to be made for increased use of patents and public-private partnerships to further the education of the next generation of scientists.
"The real issue is that much of the funding is going to projects which aren't going to be completed before the funding runs out."
That's not the way it works. For starters there's rarely, if ever, a definitive "end point" for a study. There's always something more that could be done; it's a piss-poor paper that doesn't bring out new issues to explore. Running out of money or key personnel moving on to a new position often times is the end where whatever you've got is bundled up into a publication(s). If it isn't at the level of a..."least publishable unit" then it might sit around for a year or three until the principal investigator can scrounge up time or more often the case money to get it to that LPU point.
"Many if not most of those projects will then be scrambling for funding..."
This is what academic scientists call "situation normal" or "Wednesday" it's how the game doesn't work for about the last 15 years or so, and getting worse every year. You are constantly scrambling for money, any money, to keep yourself and your staff employed and doing science.
Are the Copenhagen and Everett interpretations of quantum mechanics supported by evidence? Do the underlying theories explain the evidence and make potentially falsifiable predictions that flow from the conceptual underpinnings of the individual theories? If yes, then either theory, even if one or both are overthrown are contributing positively to science. Now compare that to Intelligent Design (assuming that is likely your position). Behe's "Darwin's Black Box" was published in 1996. Johnson's "Darwin on Trial" was published in 1991. "Of Pandas and People" was first published in 1989 having morphed into "Intelligent Design" from earlier straight up creationist drafts dating to 1983. It is now 2009, almost 2010. Proponents of ID have, as of yet, to come up with any evidence. They have also not said what such evidence would even look like. Actual working scientists like me have done more: we explain what a human or human-like intelligence would do, then state the plain truth that no such evidence has been found. If you don't believe me then check out NCBI which has free public access to all genes sequenced using public moneys, and start searching for that designer(s). ID proponents have failed to come up with falsifiable predictions that are produced from the theoretical framework of ID. That's probably because they have yet, after 26 years to come up with a scientific theory of ID. Despite these four scientifically fatal flaws, ID flourishes. There are dozens of popular books on the subject. There are speaking tours. There are even movies like "Expelled" shown in movie theaters. There are court cases, media blitzes, and conservative politicians must kowtow to it. The Templeton Foundation begs, literally begs to give money to ID researchers...but can't find anyone to fund. In this granting environment, a "good" grant has six times as many applicants as it has successful awardees. For ID proponents, allegedly scientists, to let money go begging insults all of science and everyone working in it. Yet you complain of suppression when nothing could be further from the case.
The human tailbone is most certainly vestigial. Vestigial does not mean useless; it means that it once had a given function (external tail in this case) but no longer performs that function, but does not mean that it doesn't perform a different function. In humans, our coccyx is usually comprised of 3-5 vertebrae, which are usually fused into two or three segments. Not all function in muscle attachment, as is unsurprising given the variability in the structure. People have been born with nine calcified bones in the coccyx (plus cartilaginous structures), and external tails complete with articulating vertebrae (five's the record as far as I know) have been reported in the medical literature. People have also been born without a coccyx at all, although like external tails this is rare. Removal of the coccyx is called a coccygectomy (say that to your five year old!) and can be done on the whole or just a part of the structure with little or no side effects.
"If a genetically-modified human were cloned today, would that clone be outside common ancestry?"
There are limits to what we know how to do. We've figured out how to do mammalian cloning (with some caveats and high inefficiency; Dolly the sheep for example). We could, if we expended sufficient effort, take chromosomes from different people and probably produce a viable clone from that, but the ancestry could be traced: It wouldn't be mom and pop, but mom(s) and dad(s). We could get a bit more exotic than that, by swapping out say the human citrate synthase gene and replacing it with one from a different species, so the resulting organism's heritage would be mom(s)+dad(s)+other species contributor. Venturing out more into science fiction than actual genetics it might be possible to construct an artificial genome that would produce something that for all intensive purposes is a fully functional and viable human, yet have lower sequence identity to humans than chimps do (~98%) by removing or modifying endogenous retroviral sequences, mucking about with introns, and introduction of alternative codons in protein coding regions or even some swapping of whole genes with closely related species. The more changes the more of a bitch it will be to accomplish but is not totally beyond the realm of what is at least conceivable, if not possible quite just yet. Anyway the resulting artificial human genome could have low sequence identity with any other human genome yet could still be identifiably human as in chromosome 1 has genes x,y,z arranged this way or minimally expressed in a way that is the same spatial and temporal pattern in naturally occurring humans. It wouldn't fit in with common ancestry aside from being able to trace the bits and pieces. So the short of it would be that yes a constructed human genome could violate common ancestry to various degrees. Would it be human, well, people could certainly argue over that, even if the resulting organism could pass as a human unless you had your DNA sequencer handy.
"Would it be designed?"
Trivially, yes, in that we have a reason (um, presumably), a method, and a goal, but the more exotic the human-like genome the more we'd turn to random mutation and artificial selection to get our artificial human genome to function. That's what we do now for vastly simpler problems.
"Do we know this hasn't happened in the distant past?"
The scenario above for making our more outlandish artificial human genome has us taking a starting point (human genome), modify individual nucleotides to produce neutral or highly conservative mutations, we remove (or add) noncoding elements that also have no or negligible effect, or we swap out human gene X for, say, gorilla gene X (and then test and if necessary modify to make it work). Changes like that are easily detectable by comparing genome sequences, and are comparable to swapping, adding, and subtracting parts from a golf cart, a go cart, and a 57 Chevy to make a vehicle of some sort. However if someone(s) at some time(s) muddled with DNA(s) for some reason(s), there is no evidence that this has occurred. We see no plants with mitochondria that are clearly more related to those from a wolf than those from a rose, no apes with highly modified feather genes used to produce hair, and no bacteria sporting TCA pathways that were clearly dropped in from fish. Instead we see a pattern of nested hierarchy indicative of common descent. The mouse gene for citrate synthase is more closely related to rat citrate synthase than it is to human citrate synthase, those in turn are much more closely related to turkey citrate synthase than one from bacteria. You can do this with any gene you like and you will observe a common pattern of nested hierarchies, which is required for evolution and common descent to be true. The same will go for gene expression patterns, developmental patterns, etc. Can we unambiguously state that no designer fiddled about even though there's no evidence in support of the idea? No, but neither can we unambiguously state we're not brains floating in jars hooked up to an artificial reality. Both ideas are similarly useless to science.
I wonder if the lab had an even harder time getting approval for raising a colony of mosquitoes known to be infected with malaria than getting approval for infecting volunteers with malaria. I work in an entomology lab that specializes in the yellow fever mosquito Aedes aegypti. As a part of that work, we maintain a colony of mosquitoes. For us, we just have a pair of percivals (incubator that controls temperature, light, humidity, some also control CO2 levels) that we raise the insects in at different life stages. We always have on hand at least eggs which can last months but usually also a few cages (glorified tupperware with heavy cloth mesh) of adults that are being mated to produce eggs, and frequently trays full of water to grow larvae. A handful of mosquitoes are usually loose and getting bit happens ~daily and is just accepted as an occupational hazard. A few people in lab actually no longer have an allergic response to a mosquito bite due to constant exposure. I think we're maybe a little cavalier about all of that, but we don't have, or need, any kind of special containment as the adults are not infected with any pathogen. But these guys are intentionally raising mosquitoes and then at some point introducing the malaria pathogen to them. While young female adult mosquitoes normally get the pathogen by biting an infected person, there must be a controlled way of doing this. I'm just wondering how they manage to have a high enough level of control to pass review. A glove box alone won't cut it as access to the chamber is typically just an inner and an outer hatch--too easy for a mosquito to get through. Maybe they had to rig it up with a refrigeration unit. If you cool insects down, they get much slower. We use chill plates (peltier coolers--it's not just for CPUs!) to immobilize adult mosquitoes for microinjections or microsurgery. However even with a refrigeration unit as precaution there seems to be a risk of accidental release. Damn, I want to see their setup.
There are already a dozen or more level 4 biohazard (there's no such thing as a level 5 biohazard) facilities either under construction or already in operation in the US. Several are in major cities, such as Atlanta (headquarters of the Centers for Disease Control), Bethesda (Washington, D.C. metro area and also headquarters of the National Institutes of Health), Boston, Cincinnati, and also Stony Brook (to a New Yorker it's on the Moon, to everyone else it's on Long Island and therefore spitting distance of 10's of millions), San Antonio, Richmond, and Los Angeles. The only level 4 biohazard facility that I know of that I think is in a poor location is located on an island. Galveston, TX to be specific. It's most famous for the hurricane in 1900 which is still the worst national disaster in the US. Hurricane Ike in 2008 produced a big enough surge to go around it sea wall, and it was only a Cat 2 storm.
An isolated island in the middle of nowhere is a boneheaded idea. First you're going to have to get the island, and isolated islands are typically small which will severely limit facility size, or are located in arctic regions. Both are highly susceptible to harsh weather, for a small tropical island it could be completely covered with water from even a minor tropical storm because elevation won't be much greater than a few feet, and did I mention the arctic for option B? Next, you're going to have to import all building material, and in the process of construction drive to extinction the majority of native species. Your construction will have to provide not only for the level 4 facility itself, but also ALL support facilities. Power plant, housing, recreational facility, docks, repair and maintenance depots, airport, waste handling, water purification, and barracks. Yes, barracks. A remote island facility with level 4 biohazards and no defense force? Gee if I were a terrorist I know where I'd go! Now let's think recruitment. Very few people are going to be willing to live on this remote island fortress year round, especially without their families. Those that do are going to demand a king's ransom and will only be willing to do it for a few years before leaving and will also be early in their careers. However the idea of working on and off in shifts won't work either. From personal experience research projects take years to complete when working full time. You walk away from one for even a week and it will take time to get it back on track. No sane researcher would take a job where you'd rotate on for 3-6 months and then rotate off. You'd spend all your time on the island frantically trying to get research up and running, and all time off trying not to get divorced. So you get vastly higher costs (both startup and annual), vastly worse security, nigh impossible recruitment for shift employees which are going to be borderline psychotic in a short while due to the mind-breaking stress from both impossible working conditions and impossible personal/family life, while your year-round workers will have zero retention, and both sets will demand massive salaries and benefits. All that, and work will proceed at a snail's pace if you're lucky.
If you search for the terms "evolution" and "hiv" on pubmed you get nearly 5,000 papers back. That's just one disease. One of the big problems about most, probably all, diseases caused by some kind of pathogen is that they have huge population sizes and grow very fast. Evolution can move damn fast under those situations, and that's why we've got multiple-antibiotic resistant bugs out there that didn't exist 30 years ago. If you're working in epidemiology or virology or any disease-related field you're de facto doing evolutionary biology research. Also, given Kansas' infamous pro-creationism leanings it will be much harder to recruit scientists there. Any scientist with children would be reluctant to move there because they would worry about science-deniers on the board of education tampering with their kid's education. I doesn't help in recruiting those of us without kids, either.
"If any (non-trivial) treatment consisting of specifically folding proteins is found, then there will be exactly one way to produce said drug : genetic manipulation. Only a genetically modified cell will be able to produce those custom proteins."
This is not necessarily the case. We can predict with reasonable accuracy (about 80%) what sort of secondary structure (alpha helix, beta sheet, or coil, basically) a protein will have based solely on the protein sequence. For example, if you were to put the protein sequence lkgtlgqdvidirtlgskgvftfdpgftst, into Jpred you get this prediction:
LKGTLGQDV IDIRT LGSKGV FTF DPGFTST
------------------EEEEE-------------EEE
Where E is the code for beta sheet, and the dash is coil. Jpred is smart enough to also search through the Protein Data Bank and see if that sequence belongs to a protein that has already had it's structure solved, which is the case here. I told Jpred to go on with the prediction anyway, and by comparison to the known protein structure iIt doesn't do horribly bad, correctly predicting that most of this sequence is coil, getting close with the first bit of sheet secondary structure, and misinterpreting the second sheet bit when it should be another type of structure (a turn--several different ones are defined but make up only small amounts of structure, being largely transitions between the other secondary structure types). However as the example sort of hints at, protein structure can be squishy. If your protein is an enzyme, then it must bind substrate, catalyze a reaction, and release product. There will be some structural change that accompanies this, meaning that small molecules can have an impact on protein structure. Sometimes but not often this can involve radical change. I knew a guy a few years ago who designed a protein, such that he could control the secondary structure of a short stretch by the addition of a small molecule. If present, part A was helix, part B was coil. If absent, part A was coil, part B was helix. I'm running out of time, but there are also examples in nature of a protein in the course of it's biological function that has parts swap between sheet and helix structure. Lastly, we come to diseases caused by misfolding proteins. The mutations are often small ones, that disrupt proper folding of structural proteins. It may be possible to treat disorders at least to some extent by introducing a small molecule that will favor the properly folded state as opposed to the disease-causing improperly folded protein state (I'm thinking of Lou Gehrig's disease aka amyotrophic lateral sclerosis, ALS). Such a small molecule probably can't do anything about existing misfolded protein stuck in a plaque in the cell, but the small molecule might interact with protein as it is being made or before it joins the plaque and prevent an increase in the plaque size. It is at least conceivable that a conventional drug treatment could affect this part of ALS and halt or slow the progression of the disease.
No, that's only the theoretical half of it. The other half is the experimental: "What happens when I poke it with a stick?"
"Now if I could just find a use for all those damn AOL CDs in the attic."
CD FIGHT!!! Seriously it's a lot of fun as long as nobody minds a few scratches. Back, oh god, 10 years ago a friend of mine interned at Microsoft and was on their developer network. If Microsoft made a CD for distribution anywhere in the world, any version, he got it. He had 300+ by year's end. We had about 15 guys in the dorm hucking CD's down the hall and stairwells. Everybody still had the correct number of eyes and nobody needed stitches, just a couple bandaids. And what else are you going to do with Windows 98 OSR 50.2.4.6.A-4 in Swahili?
Maybe not. Host:pathogen interaction is already pretty tricky, which is why it's a big deal when you get something that jumps the species barrier (even the name's suggestive). Now you're going vector:pathogen:host which makes it much more complicated. Some mosquitoes are vectors of some diseases, some are vectors for others. The mosquito we use in my lab, Aedes aegypti, can carry the dengue fever virus, yellow fever virus, and chikungunya virus, but not the malaria pathogen (a protozoan, not a virus).
You're mistaken. Mosquito species can show marked preferences for what poor critter they like to get a blood meal from. For instance Anopheles gambiae almost exclusively feeds off of humans, and also is a major vector in the spread of the malaria pathogen. Others have their own preferences to varying different extents. Interestingly, all mosquitoes exclusively feed off of warm-blooded animals. They're also ancient, dating back around to when dinosaurs were walking around. Might have fed off them too.
You're right on one point though: evolution of resistance to the vaccine is probably inevitable, just a question of how long it will take and what we can come up with while it buys us some time. In the tropics you can have IIRC up to 25 generations of mosquitoes in a single year. Multiply that by the huge population size and you can get some pretty rapid evolution. That's increasingly a problem for insecticides (not just for mosquitoes) and there's increasing interest in the development of new ones these days.
I think you're mistaken. I'm applying for one of these grants right now, and the way I read it was that you must spend all the cash in one year, but if you've got a bit left over then you can get up to a six month extension to spend the remainder. The only extra funding is the $million if your work is really promising after the first year. And as others have pointed out even for a typically underpaid postdoc $100k in a year will only cover salary, benefits, and looking at my last grant application about $35k left over for chemicals, supplies, and etc. I would personally need somewhere in the range of another $30k-50k a year to cover my chemicals, supplies, and user fee costs. Not that I wouldn't be jumping up and down for about a week if I got one of these grants.
I think there's a kind of a sliding scale of ownership: a rented apartment is less than an owned trailer home in rented lot, is less than a condo, is less than a house+lot. Actually I suppose there's a still greater level of ownership: house in town (with home owner's association) is less than a house in town (no Jr. Fascists) is less than a farm/ranch. With the lowest level if you're unlucky you could be barely half a step above a condo. With the highest...it's your land. No, I take that back. It's your fucking land and you can do with it whatever you want so long as it's not illegal, or at least not Illegal and the neighbor's don't know and wouldn't care if they did. You can put up signs that say "Trespassers will be shot. Survivors will be shot again." to your hearts content. You can paint your house bright pink. Plant corn in your front yard, right next to the two story tall metal sculpture. Have chickens and fresh eggs. Have a goat mow your lawn for you. A still (little i-illegal). Let your dogs roam around and urinate on the whole outdoors as far as you own (You can join in too. It's fun.). Now that's ownership. Owning four walls, er, your share of four walls in an apartment building, not so much. If the economics made sense I could see myself doing it but it's just not the same.
I forgot to include that there are movies of proteins during catalysis by using Laue diffraction, and I've been lucky enough to see a talk where they speaker showed such a movie. While I can't at the moment find a good example I did find this large .pdf of a powerpoint presentation. Scroll down to page 17 and you can start to see a little bit of what's going on in the case of release of carbon monoxide from myoglobin. Which has some broader relevance as carbon monoxide poisoning results from that molecule binding to hemoglobin and out-competing oxygen. Got published in Nature too.
Well for high-speed crystallography it isn't so much that data collection is the problem (for most applications). You can collect a high-quality data set of a protein at APS in under a half an hour. The real bottlenecks in x-ray crystallography is, was, and unfortunately most likely always will be protein crystallization. Way back in the day when protein crystallography was just starting, it was thought to be somewhat bizarre for proteins to crystallize. Fast forward four or five decades and now if your protein is reasonably soluble, reasonable stable, and has a definite structure (not all proteins have a well-defined structure and just flop about in a range of states), then you can probably get it to crystallize well enough to solve the structure. But it might take a long time to pull off, years even. But that's only for soluble proteins. If a protein is normally in the cell membrane, it is much, much harder. A cell membrane is basically soap. Soap doesn't crystallize. There are only a few structures of integral membrane proteins despite a lot of work on the problem. Also proteins that only have one domain or even just a helix poking into the membrane can be tricky--they're usually done by just removing the offending membrane bit but often suffer from solubility problems.
For part two, lasers produce monochromatic light. One technique for doing real-time x-ray crystallography involves using polychromatic x-rays. Normally you get a single, specific, monochromatic wavelength (, or at least close enough that for data processing you largely ignore everything else. The resulting diffraction pattern looks something like that seen on wikipedia's page. That page and links are actually pretty good. However you can use a broader spectrum of x-rays and get a different diffraction pattern due to having different wavelengths of light hitting your protein crystal over the course of the exposure, or a Laue diffraction image (ignore the color--computer added). Interpreting Laue diffraction's significantly harder because you also have to take into account that you have basically multiple different wavelengths of light producing multiple different, overlapping diffraction patterns. Unlike monochromatic diffraction patterns, which require exposure times of at least tenths of a second even at APS (or potentially hours on a weaker rotating anode x-ray source like at an individual lab), Laue diffraction can be measured in picoseconds--on the time scale of chemical reactions catalyzed by enzymes. A few groups have done time-resolved x-ray crystallography with reactions by building up series of Laue images. You can't do it for everything, though. Data processing problems aside you typically need a chemical reaction that can be triggered by light. Also, proteins frequently undergo structural reorientations during catalysis--the change will have to be small enough so that the packing of proteins in the crystal lattice will not be affected. Time-resolved x-ray crystallography using Laue diffraction is never going to be widely used, but the results can still be very exciting.
What these guys have in mind and how practical it is I don't know since I've somewhat shifted away from protein x-ray crystallography. I do remember going to a conference a few years ago where some guys wanted to use a single molecule to collect data on--by blasting the bajesus (that's a technical term) out of it with an extremely short, extremely massive burst of x-rays. They had the problem though of ripping off basically all of the electrons in the process, IIRC. Even at weak home rotating anode x-ray sources you still have to worry about radiation damaging your crystal (and affecting your resulting model of the protein), but blasting away all the electrons? That's like comparing a flyswatter and a tactical nuke.
That's not all that funny. I know someone who went on sabbatical to a Chinese university a couple years ago. They're building brand new high-tech bioscience labs but not the necessary infrastructure to support them properly. There were no facilities at that particular university, one of the top ten in China, for handling hazardous waste. Hazardous liquids are just poured down the drain, nothing for disposal was autoclaved. He saw a peasant (his term) poking through the trash and yes, eat the agar out of a petri dish. The rest of the trash is often picked over by other peasants for any sort of plastic that could be reused or recycled. What's left just got mixed in with other municipal trash at the dump. What's even scarier is that they're building a level three biohazard facility nearby, right in the middle of the city.
A comment on your point 2: in the paper in nature they cite a paper, which has a cite to another paper that has the protein production and purification methods. It seems to be common practice for recombinant hemoproteins to spike the culture media with a heme precursor to crank up it's production. That precursor is listed at $142.50 per gram in my Sigma catalog. The authors may or may not have spiked their culture with it; materials and methods details in Nature papers are extremely brief or like here cite a paper that cites a paper. Anyway, if they did use a heme precursor that adds expense, if they didn't, the proteins produced will have less of the heme which is required for oxygen binding.
As for points 5 &etc., that's critical. A pint or two of blood replacement coursing through your veins triggering an immune response couldn't possibly be good. But yeah you're right, that's not what the authors are really at for this paper. The word "blood" isn't even in the Nature article!