Bribing foreign officials is a violation of the US law Foreign Corrupt Practices Act. So it's surprising that he would admit this to a journalist.
Right, but according to the fastcompany article he's revoked his US citizenship to be a Belize permanent resident and seems to have gone to great pains to make his assets completely untouchable to the US what with the 5 civil suits pending against him.
There's quite alot of foreshadowing in the fastcompany article:
Then there is the $1 million patrol boat he donated to the Belizean coast guard. (In a letter to The New York Times, he described it as an act of philanthropy; later, he tells me he had to bribe members of the coast guard to prevent them from hassling his ferry business: "This is a third-world country. I had to bribe a whole bunch of folks.
indicating that he routinely gives large, overt, public bribes to get whatever he wants in Belize
Then there's this:
"And so a pair of police officers came to visit him. "We are sorry that we have to tell you to stop building that wall," they said. "I am sorry that I have to tell you that I am going to build it anyway," he told them, and they left. To McAfee, this exchange was proof of the evolved level of discourse in Belize, where a person is largely left to do as he pleases. . . At the time, I thought that he was simply being argumentative. But McAfee seems to want freedom without limitation. Needless to say, few of us exercise this sort of freedom. It tends to be very expensive."
Either he is willfully ignoring the fact that this seems to have been a small-time shakedown attempt or he is completely oblivious to it. Did he really think Belize patrolmen (note, not the environmental cops) are so genuinely concerned about shoreline regulations?? He doesn't seem to realize by being so brazen about describing large bribes to the press he's just inviting even bigger, less polite shake-downs in the future, which sounds exactly like what (unfortunately) just went down. Did he really think that request for a campaign contribution for the guy employing police hitsquads was purely optional when bribes for building permits, import permits, business titles, etc. for his dozens of shell companies were not?
Sure, it still sucks, and I feel sorry for him, but it really does sound like he specifically chose Belize because he liked how pliable the laws were if you had money and it never occurred to him that cuts both ways...
Dead tissue is useless tissue. Nothing in nature moves when it's dead unless it's being pushed. The moment metabolic activity has stopped (in humans, about three minutes after the heart stops) bacteria and other recyclers begin to do their jobs, destroying the ability of critical cells to function. Once rigor mortis sets in, three to four hours later, the body is completely incapable of being moved through electrical (or nervous) stimulation, as the muscles (which operate on a principle similar to a forklift) become fused due to the absence of ATP. When rigor mortis fades, 2-3 days after death, these frozen parts are destroyed, and the muscle cells are just useless bags of mush. In short, reanimating dead tissue is completely out of the question for anything short of a bad deus ex machina in a Hollywood film.
If you want a zombie, think less dead, more infected. There are lots of parasites that screw with behaviour in a dramatic way, and guarantee the animal will die in the near future. Worry about those. (And never travel to Africa.)
Great examples, I'd like to add the most zombie-relevant one, though, the wasp parasite that mind-controls a "zombie" spider into making a specially designed nest for the larva with its silk spinner, and then it parks itself in the center to be a snack larva when they hatch (it is still alive as Samantha points out, just somehow mind controlled via some injected toxin).
http://www.damninteresting.com/mind-controlling-wasps-and-zombie-spiders/
here's a whole gallery of zombie-insect examples:
http://discovermagazine.com/photos/04-zombie-animals-and-the-parasites-that-control-them
I assume you mean specifically a strain of bird flu which would be more harmful to humans, for use as a weapon. The answer in this case is that it isn't very prohibitive in terms of equipment; a well-stocked lab, general-purpose biology lab could probably be put together for under half a million dollars: thermal cyclers are cheap, reagents are cheap, incubators are cheap, pipettes are cheap. The most expensive piece would be the hardware to do DNA sequencing to confirm what changes have occurred; technically you could just leave this out. This would not be a particularly safe working environment, however; a BSL 3 lab (the kind appropriate to studying contagious human diseases) would be much more expensive to put together and easily cost a couple of million dollars. For test subjects, as morbid as this is, I'd probably recommend pigs or stray cats, both of which are known to be susceptible.
Much more challenging would be the task of getting well-trained researchers who are willing to engineer such a weapon. The people with substantial knowledge of influenza are either doctors (under the Hippocratic Oath) or PhDs in the life sciences (who got their knowledge because they were expressly interested in helping people.) You might also have a lot of trouble getting the equipment in the first place, since some more expensive pieces require licenses to operate.
A simpler route for the aspiring supervillian would be naturally supporting evolution through eugenics: infect a population of pigs with the disease, and then place the corpses of the pigs who die first into the next population, ad infinitum. This sort of process has been used commercially to make genetically-modified crops more resistant to disease and herbicides. For this, all you'd need is a big enough warehouse, a lot of pigs, and the various facilities to maintain them all. Perhaps also a clipboard or two.
The second route may appear to be slower, but I'm not sure if we know enough about the flu genome that directly modifying it would really make us any more efficient at getting it to do something specifically bad.
I would add a couple of zeroes to the estimate. You need an animal facility for studying emerging infectious diseases, as only the diseases that are so well understood that we can already treat them typically have established cell-culture models (and even them my pathogen colleagues don't trust them much). Sure, maybe you are in a 3rd world country where there is no PETA/OSHA/CDC etc and you are working for a despot. You still need containment to keep infected animals separate from healthy ones or you can't experiment. You still need to keep your PhD-equivalent researchers from constantly getting sick and dying (not because you care about them but because they are hard to replace). And anyone well educated enough to be useful will be acutely aware of how dangerous it is to work closely with sick animals without containment facilities. So you need a biocontainment lab along the lines of the beginnings of the movie "outbreak". Of which there are a few thousand in the world, so it's well within the means of a rogue nation-state or well connected corporation, but unlikely for garage terrorists because they will probably get really sick before they could make any progress on something weaponizable. Even the well-regulated containment labs in the states have tons of near-misses all the time, you can only imagine how hazardous to your health it would be to work without protections. I think at this point terrorists with a death wish are still probably better off trying to stuff IEDs in their underpants than playing with infectious agents without proper facilities.
Lastly, I'll point that although it only takes a PCR machine and some off-the-shelf chemicals to make recombinant E. coli, the procedures for making specific changes to virus genomes are a heck of a lot more complicated. So although you could theoretically cultivate and mutate a viruses you found in the wild using non-highly trained technicians, if you wanted to make the specific changes in the redacted papers you'd need PhD. level virologists to do it for you. To boot, it probably would fizzle because the authors have since clarified the mutations they identified only increase airborne transmission, they weren't actually that lethal to the ferrets. So people are much more worried about the precendent they are setting for how future findings are disseminated or classified rather than the exact findings in this set of papers (specifically, that we had no procedure or guidelines at all). The authors speculate that any similarly equipped facility (on the order of dozens worldwide that specialize in flu/ferret work) could replicate their work in six months or so given all the details, but they were much more worried about these mutations occurring naturally by chance in the future than a garage-terrorist group doing it first.
So what we have here is that public health experts say it's more important we address the inevitable natural evolution of the bug into something more dangerous by telling third world hospitals exactly what mutations to look for so we can have an early warning system, whereas security experts say any risk, however small, of terrorists using this data should be avoided at all costs. We'll see which side wins. .
I find it slightly ominous that you call data-driven research a thing of the past; I just got through a course that hailed it as a Big Deal—though the class's attitude was that it was a process for finding a hypothesis, not really testing one. Given that a full human gene expression microarray really is quite excessive for pointing fingers at only a handful of genes (those could be done through much cheaper RT-PCR, after all) my instinct is still to suspect that they're not as organized as you or I might like them to be—or, at least, they're prepared to fall back, and since they're grinding up such a valuable resource already, decided to go for broke with the gene chips, to make sure any negative confirmations they generate are as useful as possible.
Don't get me wrong, I think genechips are awesome tools. I've seen some really nice work on elucidating what changes at different points in the cell cycle, for example, that really couldn't have been done with anything else. But just because it's a high-throughput tool that could be used to brute force things doesn't mean we don't have to pay scientists to think anymore. I think genomics really planted the idea in people's heads that if you collected the data first, other people would be able to make it useful later, but then you have the luxury of there being a definite consensus sequence of an organism. With genechips, the results you get can depend alot on where you decide to focus your attention, I would argue if you don't know what to look for you just won't find it.
If these big, multi-center consortium projects had some sort of arrangement where after they identify "interesting" things they could then go in a more detailed study and pick the interesting things apart, that would be something. But they don't, because the people who are good at pushing the technological hi-throughput capabilities are usually not the people who know what a biologically interesting results might look like or where to look for them and that could be fatal if the community these projects are supposed to be serving have no ability to tell the ship it's headed in the wrong direction.
There's a great editorial from a personal hero of mine Sean Eddy (of pFam fame, we overlapped a bit when he was in St. Louis). He has a great point about how science is evolving to where ee completely divorce the people who have the technical knowledge of how to do an experiment with the people who care about the end results and why this might not be such a good idea.
http://selab.janelia.org/publications/Eddy05b/Eddy05b-reprint.pdf
I was at a conference lately where basically all the bigwigs were predicting the death of data-driven research simply due to a lack of bang for the buck an age of very tight pursestrings and technology that outdates itself in a matter of months. And there was a consortium guy there, whose passionate defense of it was "well, it kept the lights on in my lab so I could do the other cool stuff I wanted to do. Oh, and we standardized on data formats and have a central repository, that's good, right?"
With big disorders like autism and schizophrenia, where the underlying causes are so complex that we haven't yet found them, the story generally seems to be the case that we throw microarrays at them just in case, not because we have substantive reason to believe that a hypothesis might be sound. If these studies fail to yield anything, then that's all well and good: we know the problem is either an aberration in the networks which is too complex and subtle for us to detect, or we've narrowed it down to one of the other major things that can go wrong, like epigenetics, a good old wholesome mutation (which could be picked up Mendelianly with linkage analysis), environmental exposure, or prions. The language you used was very certain (e.g. 'prove what they want to show') and I just wanted to emphasize that, while such thinking may be the unfortunate reality of grant-writing, determining that schizophrenia can't be detected on a mRNA-based microarray is almost as significant. (As an undergrad I have the luxury of not thinking about the miserable reality of how competitive research can be. Out of the mouths of babes, if you will.)
Hmmm, I have to disagree here, and not because of cynical grant realities per se. .
Consider if I was a grant reviewer, and you're proposing to grind up valuable donated brain tissues from dead patients (which is pretty much irreplaceable and in high demand since not alot of people donate their bodies to science anymore). You are proposing an experiment where each sample will require a separate 500-1000K$ genechip to measure the mrna levels (they are not generally re-useable). You need samples from multiple patients to establish a profile that is representative of the disease state (and not specific to one individual). You probably have multiple tissues you could choose from within the brain. You need controls to establish a profile for the healthy state. You need multiple replicates for statistical significance. That's easily in the mid five-figure range for the consumables alone for a single set of experiments, to say nothing of the cost of acquiring and processing the tissues. I'm not going to fund you if you have no hypothesis you are trying to prove other than "we might find something interesting with genechips", that's what we call a very expensive fishing trip. Even if there's lots of grant money around, I will go to the next application in the pile and give the slot to anyone who can convince me they have a hypothesis worth testing (any hypothesis, it doesn't even have to be exciting, it doesn't have to be right, but it should be well thought out).
The drug industry used to do alot of this, what we call "hypothesis-free" research (I think they called it "data driven" research, as in, we'll collect the data first and come up with a hypothesis later). I would argue this doesn't follow the scientific method which allows us to refine a hypothesis given a set of observation until it ends up revealing something new. A well designed experiment will allow you to learn something even if the hypothesis turns out to be false, because it's systematic and tests something from multiple angles, whereas a poorly designed genechip experiment can end up telling us nothing in particular because there's often more noise than signal. . .
Anyway that's my 2 cents. You will certainly see alot of fishing trip type of research out there in the literature, especially from the period when genechips were brand new and you could get anything published just by using one. And there are still plenty of projects like that trying to recruit bioinformaticists to come in and miraculously save the day by finding something interesting in those very expensive datasets that don't show anything (I was in a hospital where they spent a few million dollars taking genechips on all surgery patients pre and post-op, for example, with no particular hypothesis in mind). I suggest avoiding those projects with a 12-foot pole.
Ack! I got carried away. My original intent on replying to this thread was to plug a good book I've been reading that summarizes how all the classic experiments from the 30-60's showed what we know today about how mRNA works and how it is regulated. For me at least, it's much more interesting to read than a dry textbook that just presents the end results as facts handed down from on high (such textbooks also tend to get outdated rather quickly, whereas understanding the logic behind the classic experiments will never be outdated).
http://www.amazon.com/RNA-Indispensable-Molecule-James-Darnell/dp/1936113198
check your university's library, you ought to be able to get it from interlibrary loan at least.
Heyo -- thanks for the heads-up on Twitter. I'm the sysadmin at a small university department, and I work with scientsts studying gene expression. They're good and patient people, but sometimes I feel a bit like I'm questioning the foundations of their work...which feels either rude or ignorant.
First off, I'd always been under the impression that DNA was only/mainly used during reproduction -- a cell divides under DNA direction, some bit of the cell is the machinery that makes whatever protein is needed during its life, and DNA isn't involved much after that. However, I'm starting to understand (I think...) that I've got it all wrong. My understanding now that gene expression can basically turn on a dime, and that *this* is the usual way a cell makes a protein: something happens to a cell, it says "Whoah, I need protein X", and it starts transcribing the DNA so it can manufacture it (modulo things like gene regulation). This process can take very little time (hours or less). Have I got that right?
Second: one of the things they study is datasets of gene expression in post-mortem brains. (Well, technically I guess I've got that wrong, since genes aren't expressed post-mortem...
What I don't understand:
a) Since time passes between death and sequencing, how much fidelity does/can this have do what was going on at the point of death?
b) Even if it is a good indication of what was going on at death, how does that relate to a long-term illness like schizophrenia when (assuming I've got this bit right) gene expression can turn on and off in a very short time? I realize there are (ahem) ethical problems with doing brain biopsies on living subjects, and that post-mortem is the best that can be done -- but how good can it be?
Many, many thanks for your time. Any questions about system administration, let me know.
Hope you don't mind me hijacking this thread, I think it's a great service Samantha is providing here. I just wanted to add a few comments as someone who has sadly seen alot of sloppy gene-chip experiments going on (but also some very nice ones).
It's really encouraging to hear that you are taking an active interest in what your scientific collaborators are trying to show. You'll be that much better equipped to help them prove what they want to show if you are roughly on the same page as them - something alot of scientists overlook when they delegate out the technical stuff they don't know how to do themselves. You might find that the group you are working with has some graduate students or maybe postdocs (i.e. probably whoever you have day-to-day contact with who actually does the experiments and hands you with the datasets) that would be much more available to answering your questions than the big bosses who have to consult a calendar to even see if they have time to meet with you.
As a biophysicist (but importantly not a neuroscientist), I can still say that I am not aware of any consensus on what causes schizophrenia other than it must have both a genetic and an environmental component (i.e. having relatives that had it greatly increases your risk, as does certain types of substance abuse). Therefore it is absolutely a central assumption of your collaborators' research that some key component is due to a long-term up or down-regulation of expressed mRNA's, that's certainly not an established fact anywhere in the literature although there is speculation and circumstantial evidence and it might be a favorite hypothesis in the field. I am 100% certain that a large portion of the grant proposal that funded this research was devoted to justifying this assumption and that it will be the first question out of the mouths of peer-reviewer of any papers that come out of it, so I can only assume that very persuasive arguments were made since microarrays are expensive.
I can give an example of an over-simplified hypothesis that, nonetheless, would be a home run to your collaborators if they could prove it. Certain drugs that interfere with neurotransmitter receptors (ketamines?) can induce schizophrenia-like symptoms, so maybe one component of schizophrenia is something that systematically lowers mRNA levels of the neutrotransmitters that interact with ketamines so there are less of them in the brain. It would have to be chronic and long-term to make a huge difference to cognition (surface receptor concentrations take along time to build up as they are expensive to make) so such a scenario would in fact show up in the mRNA levels. Or maybe something upstream that helps promote production of a neurotransmitter (like an activator) gets down regulated and has the same end effect. But I can also make up hypothesis that don't involve mRNA's at all - What if reduced neurotransmitter function is caused by some sort of protein misfolding due to a genetic mutation, so they end up being recycled instead of on the cell surface? Or what if it's an adverse reaction to something else in the environment that interferes with receptor function as opposed to merely diminishing their numbers? As Samantha pointed out, people measure mRNA levels mainly because the technology exists, whereas it simply doesn't for alot of other important processes.
Off the top of my head, there are super-lots of other assumptions that would have to be worked out as well, even assuming there is no significant degradation of the mRNA after death (which as Samantha points out, requires freezing to be absolutely sure, but AFAIK you don't freeze donated organs, since mammalian cells don't handle freezing and thawing very well). Will mRNA expression levels at death have more to do with the dying process than the underlying long-term neurological condition? Would it affect all neurons or just a certain type from a certain part of the brain? What is the false-positive rate on the gene chips themselves? (I've read alot of commercial ones have errors on them). These are all questions that a cell biologist/neuroscientist would be able to answer far better than I (i.e. the lab you are working with). But I would characterize your concerns about "questioning the foundations of their work" as totally legitimate questions since they are relying on you to help them sort the signal from the noise - a task that would be much easier if you know what assumptions are being tested by the controls and where to look first when you get a new dataset.
Good luck with your work!
His definitions require replication with variations. So if someone found a way to suppress genetic mutation in humans, we would not be alive right? An artificial creation can also not be alive unless it can reproduce? Does factory production count? It seems we can shorten his definition even more if we embrace his bias:
Life is: from evolution.
I don't object to evolution, but I don't think it's correct to define life by this existing process. Or am I missing something?
There IS a blatant agenda here, and it has nothing to do with defining life.
This type of paper is what I would call "borderline scholarship". It was done by a real scientist, passed "real" peer review, and even ended up in a "real" journal (more on that in a bit). But I would estimate this sort of work took maybe one weekend in a library and 20 minutes in excel. "Top science" this is not. It was picked up by JBSD, a washed-up journal that used to publish edgy stuff a few decades ago, and has lately decided that the way to regain relevance in age of science-by-press-release is to publish edgy sounding papers (no matter the quality of their content), invite two dozen "expert commentaries" from actual experts in the field, make a press release, hope it gets picked up by popular media (such as slashdot) and then watch their citation index go up the wazoo.
It doesn't matter that most of the two-dozen expert comments are basically rehashes of "why is this being published, again, and why was I asked to comment on it?". Hey, it's such an edgy paper, 20 experts "couldn't wait" to submit their comments, and if they are not familiar with the publication they don't realize their commentary just got counted as an actual citation for the original paper and upped the citation index for the journal itself.
Oh, and make it "open access" to sound like they are so generous as to let the public in on this amazing breakthrough (actually, this is a journal that long ago stopped being able to charge anyone to subscribe to them).
As is typical from such self-serving PR exercises, I actually learned more from the criticisms than from the actual paper.
Here's what Eugene Koonin says, and he's the one that proved life exists in three separate branches (prokaryotes, eukaryotes, and archaea). So he's thought about this alot more deeply than TFA.
http://www.jbsdonline.com/mc_images/category/4317/4-koonin-jbsd_29_4_2012.pdf
Yet, all its simplicity and appeal notwithstanding, the minimalist definition appears to be neither necessary nor sufficient, not even internally consistent. A simple implication of information theory (and more fundamentally, thermodynamics) is that error-free replication (more precisely, any information transmission process) is impossible (5). Hence the phrase self-reproduction with variation is actually redundant because any replication process will be characterized by some intrinsic error rate. The problem is exactly the opposite: it has been shown by Eigen and others that for stable information transfer (inheritance) down the chain of generations to be sustained, the error rate must not exceed a certain critical value known as error catastrophe or mutational meltdown threshold (6, 7). Thus, a necessary condition for life to evolve is not simply replication and not ‘replication with variation’ (a tautology) but replication with an error rate below the sustainability threshold.
And here's a snippet from the response from evolutionary biologist Richard Egel, author of "Origins of Life: The Primal Self-Organization", so yeah, he's thought alot about this question too:
http://www.jbsdonline.com/mc_images/category/4317/8-egel-jbsd_29_4_2012.pdf
In summary, the statistical vocabulary approach of Tifonov (1) to extract a simple defining formula for the intrinsic complexity of life amounts to an enchanting exercise on the border between basic science and aphoristic poetry. I was somewhat reminded of my first visit to the United States in the mid sixties, when a frenzy florished among high school kids to come up with the most fanciful variation on “Happiness is
How is it, then, that, say, in Poland you can do medical school as a 6 year integrated program, starting straight out of high school, while in the U.S. you need an undergrad degree followed by what, 5 more years? I don't think that the polish model produces any worse doctors...
I agree completely it could be done in 6 years in terms of the curriculum itself and once you've isolated the right student pool (med school here is 4 years, BTW, not 5, and there is not much to do your 4th year except applying and interviewing for residencies). But for a variety of competing interests in the US it is much harder to image a universal shift to 6-year integrated programs succeeding. Given that even the doctors that graduate last in their class here still have an automatic ticket to earning potentials in the top 1% of society, pre-med students will continue to bend to whatever admissions criteria are thrown their way.
I think the real question that differentiates the two models is if it's easier to judge on paper whether an 18 year old high school graduate vs a 22 year old who has attended college is going to make the final cut to be a successful doctor.
Consider that in the US, less than 50% of medical school applicants (i.e. premeds) are accepted to any medical school at all. Combined with the fact that somewhere between 60 and 80% of college freshman declaring pre-med intentions change their mind before even getting to the point of applying to medical school (either due to a change of heart or being "weeded out" by the pre-med curriculum). Medical schools have little incentive to increase their student capacity (due to vested interests such as maintaining their "elite" rankings and limiting the overall number of licensed physicians competing for jobs) so a universal shift to a 6-year integrated programs would also mean having to sift through an order of magnitude more applicants with much less data to compare them by (high schools in the US being notoriously uneven in quality and, on average, well below European standards in terms of college preparedness).
In the US, dropping out of med-school is NOT an option due to the obscene amount of loans one needs. Conversely, medical schools here covet high graduation rates to improve their standings, so try to do all their weed-out in the application process and then try their hardest to make sure everyone who is accepted makes it through. So within that framework, I think it's easier to judge candidates who proven university academic track record rather than just a high school diploma.
Maybe it works in poland because the secondary education system is more uniform? I would still expect a model like the Polish one would have to compensate for students who just don't prove to be up to the task by failing a substantial portion of them out over that 6-year period. I don't think that's necessarily better or worse than the US system, but given how the system is set up here (where rankings mean everything and students often have to go a quarter million dollars in debt to finance their M.D.) there's little incentive for medical schools here to change their requirement until society collectively decides that we need more doctors who are paid less rather than a restricted number of super-specialists who earn stratospheric sums.
MD degree is to long and the school mindset may be to much drilled in to people. Going to med school do they really need a full 4 year BA with all the filler classes before med school? Why not 2-3 years and then Med school? Now I can see what that setting in a class room for years with lot's of tests and some stuff that you will never use can do to your mindsets. Testes become more about craning for the test then studying the full topics. Now some of this comes from poor tests and the other part comes from the tech the test idea.
Well, it wasn't always this way. Used to be, you didn't need a B.A. to enter medical school. Heck, you didn't even need to have any contact with real patients before you set up your own practice (i.e. no residency or clerkships). Medical schools used to be giant diploma mills that would take any paying student. Accreditation and board certification were a complete joke.
Then the civil war came along, many of those doctors were drafted to help the army, and to the horror of wounded soldiers everywhere, it soon became clear that your chances of survival were often *better* if you were not treated at all than if you were allowed to be operated on by one of these diploma mill graduates with no real qualifications.
Since then, all medical schools have required a bachelor's degree.
I entirely agree one could theoretically teach all the relevant pre-med material in 2-3 years, nothing is stopping anyone from simply finishing a B.A. a year early if they want. Most pre-meds I knew could have too, they just chose not to because they wanted to live a little before going to med school, or buff their resume and get into a really good one.
And sure, you can always argue pre-meds are being weeded out with only slightly relevant material (yes, orgo II, I'm looking at you). But, you know what? I aced that class without really understanding it and all it took was applying a few key chemical concepts and a fair bit of rote memorization. If you can't hack that, I don't want you interpreting my MRI scan or prescribing me an immunomodulator that might or might not interact with my heart medication.
Our business in life is not to succeed but to continue to fail in high spirits. -- Robert Louis Stevenson
